WorldWideScience

Sample records for human cancer development

  1. Assessing global transitions in human development and colorectal cancer incidence.

    Science.gov (United States)

    Fidler, Miranda M; Bray, Freddie; Vaccarella, Salvatore; Soerjomataram, Isabelle

    2017-06-15

    Colorectal cancer incidence has paralleled increases in human development across most countries. Yet, marked decreases in incidence are now observed in countries that have attained very high human development. Thus, in this study, we explored the relationship between human development and colorectal cancer incidence, and in particular assessed whether national transitions to very high human development are linked to temporal patterns in colorectal cancer incidence. For these analyses, we utilized the Human Development Index (HDI) and annual incidence data from regional and national cancer registries. Truncated (30-74 years) age-standardized incidence rates were calculated. Yearly incidence rate ratios and HDI ratios, before and after transitioning to very high human development, were also estimated. Among the 29 countries investigated, colorectal cancer incidence was observed to decrease after reaching the very high human development threshold for 12 countries; decreases were also observed in a further five countries, but the age-standardized incidence rates remained higher than that observed at the threshold. Such declines or stabilizations are likely due to colorectal cancer screening in some populations, as well as varying levels of exposure to protective factors. In summary, it appears that there is a threshold at which human development predicts a stabilization or decline in colorectal cancer incidence, though this pattern was not observed for all countries assessed. Future cancer planning must consider the increasing colorectal cancer burden expected in countries transitioning towards higher levels of human development, as well as possible declines in incidence among countries reaching the highest development level. © 2017 UICC.

  2. The global cancer burden and human development: A review.

    Science.gov (United States)

    Fidler, Miranda M; Bray, Freddie; Soerjomataram, Isabelle

    2017-06-01

    This review examines the links between human development and cancer overall and for specific types of cancer, as well as cancer-related risk-factors and outcomes, such as disability and life expectancy. To assess human development, the Human Development Index was utilized continuously and according to four levels (low, medium, high, very high), where the low and very high categories include the least and most developed countries, respectively. All studies that assessed aspects of the global cancer burden using this measure were reviewed. Although the present cancer incidence burden is greater in higher Human Development Index countries, a greater proportion of the global mortality burden is observed in less developed countries, with a higher mean fatality rate in the latter countries. Further, the future cancer burden is expected to disproportionally affect less developed regions; in particular, it has been estimated that low and medium Human Development Index countries will experience a 100% and 81% increase in cancer incidence from 2008 to 2030, respectively. Disparities were also observed in risk factors and average health outcomes, such as a greater number of years of life lost prematurely and fewer cancer-related gains in life expectancy observed in lower versus higher Human Development Index settings. From a global perspective, there remain clear disparities in the cancer burden according to national Human Development Index scores. International efforts are needed to aid countries in social and economic transition in order to efficiently plan, implement and evaluate cancer control initiatives as a means to reduce the widening gap in cancer occurrence and survival worldwide.

  3. Human Papillomavirus and the Development of Different Cancers.

    Science.gov (United States)

    Gao, Ge; Smith, David I

    2017-03-01

    Human papillomaviruses (HPV) are responsible for the development of almost all cervical cancers. HPV is also found in 85% of anal cancer and in 50% of penile, vulvar, and vaginal cancers, and they are increasingly found in a subset of head and neck cancers, i.e., oropharyngeal squamous cell carcinomas (OPSCC). The model for how HPV causes cancer is derived from several decades of study on cervical cancer, and it is just presumed that this model is not only completely valid for cervical cancer but for all other HPV-driven cancers as well. Next-generation sequencing (NGS) has now provided the necessary tools to characterize genomic alterations in cancer cells and can precisely determine the physical status of HPV in those cells as well. We discuss recent discoveries from different applications of NGS in both cervical cancer and OPSCCs, including whole-genome sequencing and mate-pair NGS. We also discuss what NGS studies have revealed about the different ways that HPV can be involved in cancer formation, specifically comparing cervical cancer and OPSCC.

  4. The pig as a large preclinical model for therapeutic human anti-cancer vaccine development

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

    2016-01-01

    Development of therapeutic cancer vaccines has largely been based on rodent models and the majority failed to establish therapeutic responses in clinical trials. We therefore used pigs as a large animal model for human cancer vaccine development due to the large similarity between the porcine...... and human immunome. We administered peptides derived from porcine IDO, a cancer antigen important in human disease, formulated in Th1-inducing adjuvants to outbred pigs. By in silico prediction 136 candidate IDO-derived peptides were identified and peptide-SLA class I complex stability measurements revealed...

  5. A global view on cancer incidence and national levels of the human development index.

    Science.gov (United States)

    Fidler, Miranda M; Soerjomataram, Isabelle; Bray, Freddie

    2016-12-01

    Socioeconomic factors are associated with cancer incidence through complex and variable pathways. We assessed cancer incidence for all cancers combined and 27 major types according to national human development levels. Using GLOBOCAN data for 184 countries, age-standardized incidence rates (ASRs) were assessed by four levels (low, medium, high, very high) of the Human Development Index (HDI), a composite index of life expectancy, education, and gross national income. A strong positive relationship between overall cancer incidence and HDI level was observed. When comparing the ASR in very high HDI regions with that in low HDI regions, we observed a positive association ranging from 2 to 14 and 2 to 11 times higher in males and females, respectively, depending on the cancer type. Positive dose-response relationships between the ASR and HDI level were observed in both sexes for the following cancer types: lung, pancreas, leukemia, gallbladder, colorectum, brain/nervous system, kidney, multiple myeloma, and thyroid. Positive associations were also observed for testicular, bladder, lip/oral cavity, and other pharyngeal cancers, Hodgkin lymphoma, and melanoma of the skin in males, and corpus uteri, breast, and ovarian cancers and non-Hodgkin lymphoma in females. A negative dose-response relationship was observed for cervical and other pharyngeal cancers and Kaposi sarcoma in females. Although the relationship between incidence and the HDI remained when assessed at the country-specific level, variations in risk within HDI levels were also observed. We highlight positive and negative associations between incidence and human development for most cancers, which will aid the planning of cancer control priorities among countries undergoing human development transitions. © 2016 UICC.

  6. Chromatin Memory in the Development of Human Cancers

    OpenAIRE

    Yao, Yixin; Des Marais, Thomas L; Costa, Max

    2014-01-01

    Cancer is a complex disease with acquired genomic and epigenomic alterations that affect cell proliferation, viability and invasiveness. Almost all the epigenetic mechanisms including cytosine methylation and hydroxymethylation, chromatin remodeling and non-coding RNAs have been found associate with carcinogenesis and cancer specific expression profile. Altered histone modification as an epigenetic hallmark is frequently found in tumors. Understanding the epigenetic alterations induced by car...

  7. Human Development Inequality Index and Cancer Pattern: a Global Distributive Study.

    Science.gov (United States)

    Rezaeian, Shahab; Khazaei, Salman; Khazaei, Somayeh; Mansori, Kamyar; Sanjari Moghaddam, Ali; Ayubi, Erfan

    2016-01-01

    This study aimed to quantify associations of the human development inequality (HDI) index with incidence, mortality, and mortality to incidence ratios for eight common cancers among different countries. In this ecological study, data about incidence and mortality rates of cancers was obtained from the Global Cancer Project for 169 countries. HDI indices for the same countries was obtained from the United Nations Development Program (UNDP) database. The concentration index was defined as the covariance between cumulative percentage of cancer indicators (incidence, mortality and mortality to incidence ratio) and the cumulative percentage of economic indicators (country economic rank). Results indicated that incidences of cancers of liver, cervix and esophagus were mainly concentrated in countries with a low HDI index while cancers of lung, breast, colorectum, prostate and stomach were concentrated mainly in countries with a high HDI index. The same pattern was observed for mortality from cancer except for prostate cancer that was more concentrated in countries with a low HDI index. Higher MIRs for all cancers were more concentrated in countries with a low HDI index. It was concluded that patterns of cancer occurrence correlate with care disparities at the country level.

  8. BAD-mediated apoptotic pathway is associated with human cancer development.

    Science.gov (United States)

    Stickles, Xiaomang B; Marchion, Douglas C; Bicaku, Elona; Al Sawah, Entidhar; Abbasi, Forough; Xiong, Yin; Bou Zgheib, Nadim; Boac, Bernadette M; Orr, Brian C; Judson, Patricia L; Berry, Amy; Hakam, Ardeshir; Wenham, Robert M; Apte, Sachin M; Berglund, Anders E; Lancaster, Johnathan M

    2015-04-01

    The malignant transformation of normal cells is caused in part by aberrant gene expression disrupting the regulation of cell proliferation, apoptosis, senescence and DNA repair. Evidence suggests that the Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway influences cancer chemoresistance. In the present study, we explored the role of the BAD-mediated apoptotic pathway in the development and progression of cancer. Using principal component analysis to derive a numeric score representing pathway expression, we evaluated clinico-genomic datasets (n=427) from corresponding normal, pre-invasive and invasive cancers of different types, such as ovarian, endometrial, breast and colon cancers in order to determine the associations between the BAD-mediated apoptotic pathway and cancer development. Immunofluorescence was used to compare the expression levels of phosphorylated BAD [pBAD (serine-112, -136 and -155)] in immortalized normal and invasive ovarian, colon and breast cancer cells. The expression of the BAD-mediated apoptotic pathway phosphatase, PP2C, was evaluated by RT-qPCR in the normal and ovarian cancer tissue samples. The growth-promoting effects of pBAD protein levels in the immortalized normal and cancer cells were assessed using siRNA depletion experiments with MTS assays. The expression of the BAD-mediated apoptotic pathway was associated with the development and/or progression of ovarian (n=106, pcancers, as well as with ovarian endometriosis (n=20, pcancer cells compared to the immortalized normal cells, whereas PP2C gene expression was lower in the cancer compared to the ovarian tumor tissue samples (n=76, pcancer cells. The BAD-mediated apoptotic pathway is thus associated with the development of human cancers likely influenced by the protein levels of pBAD.

  9. Establishing the pig as a large animal model for vaccine development against human cancer

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

    2015-01-01

    Immunotherapy has increased overall survival of metastatic cancer patients, and cancer antigens are promising vaccine targets. To fulfill the promise, appropriate tailoring of the vaccine formulations to mount in vivo cytotoxic T cell (CTL) responses toward co-delivered cancer antigens is essential...... and the porcine immunome is closer related to the human counterpart, we here introduce pigs as a supplementary large animal model for human cancer vaccine development. IDO and RhoC, both important in human cancer development and progression, were used as vaccine targets and 12 pigs were immunized with overlapping...... peptides predicted to bind to SLA-1*04:01, −1*07:02, −2*04:01, −2*05:02, and/or −3*04:01. This identified 89 stable (t½ ≥ 0.5 h) peptide-SLA complexes. By IFN-γ release in PBMC cultures we monitored the vaccine-induced peptide-specific CTL responses, and found responses to both IDO- and Rho...

  10. Molecular diagnosis of human papillomavirus in the development of cervical cancer

    OpenAIRE

    Lourdes Gutiérrez-Xicoténcatl; Tanya Plett-Torres; Claudia L Madrid-González; Vicente Madrid-Marina

    2009-01-01

    Cervical cancer (CC) is a major public health problem in developing countries and its most significant etiological risk factor is infection by the human papillomavirus (HPV). The main approach to date for the prevention of CC has been through screening programs, using the cervical smear (PAP test) to detect precursory lesions. The sensitivity and specificity of the PAP smear depend on the skills of the observer to recognize and classify a variety of cellular abnormalities. The development of ...

  11. Endothelial protein C receptor function in murine and human breast cancer development.

    Directory of Open Access Journals (Sweden)

    Florence Schaffner

    Full Text Available Several markers identify cancer stem cell-like populations, but little is known about the functional roles of stem cell surface receptors in tumor progression. Here, we show that the endothelial protein C receptor (EPCR, a stem cell marker in hematopoietic, neuronal and epithelial cells, is crucial for breast cancer growth in the orthotopic microenvironment of the mammary gland. Mice with a hypomorphic allele of EPCR show reduced tumor growth in the PyMT-model of spontaneous breast cancer development and deletion of EPCR in established PyMT tumor cells significantly attenuates transplanted tumor take and growth. We find expansion of EPCR(+ cancer stem cell-like populations in aggressive, mammary fat pad-enhanced human triple negative breast cancer cells. In this model, EPCR-expressing cells have markedly increased mammosphere- and tumor-cell initiating activity compared to another stable progenitor-like subpopulation present at comparable frequency. We show that receptor blocking antibodies to EPCR specifically attenuate in vivo tumor growth initiated by either EPCR(+ cells or the heterogenous mixture of EPCR(+ and EPCR(- cells. Furthermore, we have identified tumor associated macrophages as a major source for recognized ligands of EPCR, suggesting a novel mechanism by which cancer stem cell-like populations are regulated by innate immune cells in the tumor microenvironment.

  12. Strategies for Developing Oral Vaccines for Human Papillomavirus (HPV) Induced Cancer using Nanoparticle mediated Delivery System.

    Science.gov (United States)

    Uddin, Mohammad Nasir; Kouzi, Samir A; Hussain, Muhammad Delwar

    2015-01-01

    Human Papillomaviruses (HPV) are a diverse group of small non-enveloped DNA viruses. Some HPVs are classified as low-risk as they are very rarely associated with neoplasia or cancer in the general population, and cause lenient warts. Other HPVs are considered as high-risk types because they are responsible for several important human cancers, including cervical cancer, a large proportion of other anogenital cancers, and a growing number of head and neck cancers. Transmission of HPV occurs primarily by skin-to-skin contact. The risk of contracting genital HPV infection and cervical cancer is influenced by sexual activity. Currently two prophylactic HPV vaccines, Gardasil® (Merck, USA) and Cervarix® (GlaxoSmithKline, UK), are available and recommended for mass immunization of adolescents. However, these vaccines have limitations as they are expensive and require cold chain storage and trained personnel to administer them by injection. The use of nano or micro particulate vaccines could address most of these limitations as they are stable at room temperature, inexpensive to produce and distribute to resource poor regions, and can be administered orally without the need for adjuvants in the formulation. Also it is possible to increase the efficiency of these particulate vaccines by decorating the surface of the nano or micro particulates with suitable ligands for targeted delivery. Oral vaccines, which can be delivered using particulate formulations, have the added potential to stimulate mucosa-associated lymphoid tissue located in the digestive tract and the gut-associated lymphoid tissue, both of which are important for the induction of effective mucosal response against many viruses. In addition, oral vaccines provide the opportunity to reduce production and administration costs and are very patient compliant. This review elaborately discusses different strategies that can be pursued to develop a nano or micro particulate oral vaccine for HPV induced cancers and

  13. Human development index is associated with mortality-to-incidence ratios of gastrointestinal cancers.

    Science.gov (United States)

    Hu, Qi-Da; Zhang, Qi; Chen, Wei; Bai, Xue-Li; Liang, Ting-Bo

    2013-08-28

    To identify the role of human development in the incidence and mortality rates of gastrointestinal cancers worldwide. The age-standardized incidence and mortality rates for gastrointestinal cancers, including cancers of the esophagus, stomach, pancreas, liver, gallbladder, and colorectum, were obtained from the GLOBOCAN 2008 database and United States Cancer Statistics (USCS) report. The human development index (HDI) data were calculated according to the 2011 Human Development Report. We estimated the mortality-to-incidence ratios (MIRs) at the regional and national levels, and explored the association of the MIR with development levels as measured by the HDI using a modified "drug dose to inhibition response" model. Furthermore, countries were divided into four groups according to the HDI distribution, and the MIRs of the four HDI groups were compared by one-way ANOVA followed by the Tukey-Kramer post-hoc test. State-specific MIRs in the United States were predicted from the estimated HDI using the fitted non-linear model, and were compared with the actual MIRs calculated from data in the USCS report. The worldwide incidence and mortality rates of gastrointestinal cancers were as high as 39.4 and 54.9 cases per 100000 individuals, respectively. Linear and non-linear regression analyses revealed an inverse correlation between the MIR of gastrointestinal cancers and the HDI at the regional and national levels (β < 0; P = 0.0028 for regional level and < 0.0001 for national level, ANOVA). The MIR differed significantly among the four HDI areas (very high HDI, 0.620 ± 0.033; high HDI, 0.807 ± 0.018; medium HDI, 0.857 ± 0.021; low HDI, 0.953 ± 0.011; P < 0.001, one-way ANOVA). Prediction of the MIRs for individual United States states using best-fitted non-linear models showed little deviation from the actual MIRs in the United States. Except for 28 data points (9.93% of 282), the actual MIRs of all gastrointestinal cancers were mostly located in the prediction

  14. Cancer incidence and mortality are associated with human development index and health setups in Africa.

    Science.gov (United States)

    Pervaiz, Ruqiya; Faisal, Faisal

    2017-06-29

    This study aimed to analyse the correlation between cancer incidence and mortality and the Human Development Index (HDI) in Africa. Furthermore, to analyse the variations in cancer Mortality to Incidence Ratio (MIR) based on health care systems in African countries. Cancer incidence and mortality data for 53 countries were obtained from GLOBOCAN database. Country-wise data on National-HDI were obtained from Human Development Report 2015. Health System Attainment (HSA) data were acquired from World Health Report 2000. The parametric data were analysed by Pearson-correlation and Linear-regression analysis for the effect of HDI and HSA on MIR in African Countries. One-way ANOVA was used to test the differences of MIR in each HDI group. All analyses were performed in SPSS version 20. An inverse correlation was revealed by cancer MIR with both HDI (r=-0.897, p<0.001) and HSA (r=-0.750, p<0.001). A significantly low MIR was reported from high HDI countries compared to medium and low HDI countries by one-way ANOVA analysis (p<0.001). Linear regression analysis also reported a negative effect of MIR with both HDI (adjusted R(2)=0 0.801, β=-0.897, p<0.001) and HSA (adjusted R(2)=0.554, β=-0.750, p<0.001). Based on their HDIs, different African countries has different health system attainments, which is the cause of variations in MIR in these countries. To control their cancer burden, these low and medium HDI countries should focus on improvement of their economic status and policies making, regarding the provision of better health systems to the masses. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  15. Human papillomaviruses and cancer.

    Science.gov (United States)

    Haedicke, Juliane; Iftner, Thomas

    2013-09-01

    Human papillomaviruses (HPV) are small oncogenic DNA viruses of which more than 200 types have been identified to date. A small subset of these is etiologically linked to the development of anogenital malignancies such as cervical cancer. In addition, recent studies established a causative relationship between these high-risk HPV types and tonsillar and oropharyngeal cancer. Clinical management of cervical cancer and head and neck squamous cell carcinomas (HNSCCs) is largely standardized and involves surgical removal of the tumor tissue as well as adjuvant chemoradiation therapy. Notably, the response to therapeutic intervention of HPV-positive HNSCCs has been found to be better as compared to HPV-negative tumors. Although the existing HPV vaccine is solely licensed for the prevention of cervical cancer, it might also have prophylactic potential for the development of high-risk HPV-associated HNSCCs. Another group of viruses, which belongs to the beta-HPV subgroup, has been implicated in nonmelanoma skin cancer, however, the etiology remains to be established. Treatment of HPV-induced nonmelanoma skin cancer is based on local excision. However, topically applied immune-modulating substances represent non-surgical alternatives for the management of smaller cutaneous tumors. In this review we present the current knowledge of the role of HPV in cancer development and discuss clinical management options as well as targets for the development of future intervention therapies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Incidence and mortality of kidney cancers, and human development index in Asia; a matter of concern.

    Science.gov (United States)

    Arabsalmani, Masoumeh; Mohammadian-Hafshejani, Abdollah; Ghoncheh, Mahshid; Hadadian, Fatemeh; Towhidi, Farhad; Vafaee, Kamran; Salehiniya, Hamid

    2017-01-01

    The incidence and mortality of kidney cancer have steadily increased by 2%- 3% per decade worldwide, and an increased risk of kidney cancer has been observed in many Asian countries. The information on the incidence and mortality of a disease and its distribution is essential for better planning for prevention and further studies. This study aimed to assess the incidence and mortality of kidney cancer and their correlation with the human development index (HDI) in Asia. This ecological study was based on GLOBOCAN data Asia for assessment the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI and its details that include life expectancy at birth, mean years of schooling and gross national income (GNI) per capita. We use of correlation bivariate method for assessment the correlation between ASIR and ASMR with HDI and its components. A total of 121 099 kidney cancer cases were recorded in Asian countries in 2012.Overall, 80 080 cases (66.12%) were males. Sex ratio was 1.95. The three countries with the highest number of new patients were china (66 466 cases), Japan (16 830 cases), India(9658 cases), respectively. Positive correlation were seen between HDI and ASIR of kidney cancer 0.655 (P = 0.001), and HDI and ASMR of kidney cancer 0.285 (P = 0.055). A positive relationship between ASIR and the HDI was seen. The relationship is due to risk factors in countries with high development such as older age, smoking, hypertension, obesity, and diet. However, ASMR showed no significant relationship with HDI.

  17. Translating discovery in zebrafish pancreatic development to human pancreatic cancer: biomarkers, targets, pathogenesis, and therapeutics.

    Science.gov (United States)

    Yee, Nelson S; Kazi, Abid A; Yee, Rosemary K

    2013-06-01

    Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer.

  18. Characteristic Gene Expression Profiles of Human Fibroblasts and Breast Cancer Cells in a Newly Developed Bilateral Coculture System

    Directory of Open Access Journals (Sweden)

    Takayuki Ueno

    2015-01-01

    Full Text Available The microenvironment of cancer cells has been implicated in cancer development and progression. Cancer-associated fibroblast constitutes a major stromal component of the microenvironment. To analyze interaction between cancer cells and fibroblasts, we have developed a new bilateral coculture system using a two-sided microporous collagen membrane. Human normal skin fibroblasts were cocultured with three different human breast cancer cell lines: MCF-7, SK-BR-3, and HCC1937. After coculture, mRNA was extracted separately from cancer cells and fibroblasts and applied to transcriptomic analysis with microarray. Top 500 commonly up- or downregulated genes were characterized by enrichment functional analysis using MetaCore Functional Analysis. Most of the genes upregulated in cancer cells were downregulated in fibroblasts while most of the genes downregulated in cancer cells were upregulated in fibroblasts, indicating that changing patterns of mRNA expression were reciprocal between cancer cells and fibroblasts. In coculture, breast cancer cells commonly increased genes related to mitotic response and TCA pathway while fibroblasts increased genes related to carbohydrate metabolism including glycolysis, glycogenesis, and glucose transport, indicating that fibroblasts support cancer cell proliferation by supplying energy sources. We propose that the bilateral coculture system using collagen membrane is useful to study interactions between cancer cells and stromal cells by mimicking in vivo tumor microenvironment.

  19. Human Viruses and Cancer

    Directory of Open Access Journals (Sweden)

    Abigail Morales-Sánchez

    2014-10-01

    Full Text Available The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt’s lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers.

  20. Pathways involved in Drosophila and human cancer development: the Notch, Hedgehog, Wingless, Runt, and Trithorax pathway.

    Science.gov (United States)

    Geissler, Klaus; Zach, Otto

    2012-05-01

    Animal models are established tools to study basic questions of biology in a systematic way. They have greatly facilitated our understanding of the mechanisms by which nature forms and maintains organisms. Much of the knowledge on molecular changes underlying the development of organisms originates from research in the fruit fly model Drosophila melanogaster. Vertebrate models including the mouse and zebrafish model, but also other animal models coming from different corners of the animal kingdom have shown that much of the basic machinery of development is essentially identical, not just in all vertebrates but in all major phyla of invertebrates too. Moreover, key elements of this machinery have been demonstrated to be involved in recurrent molecular abnormalities detected in tumor-tissue from patients, indicating their implication in the genesis of human cancer. Thus, research in this field has become a common topic for both biologists and hemato-oncologists. In this review, we summarize current knowledge on some of these key elements and molecular pathways such as Notch, Hedgehog, Wingless, Runt, and Trithorax that have been originally described and studied in animal models and which seem to play a major role in the pathophysiology and targeted management of human cancer.

  1. Basics of tumor development and importance of human papilloma virus (HPV for head and neck cancer [

    Directory of Open Access Journals (Sweden)

    Klussmann, Jens Peter

    2012-12-01

    Full Text Available [english] Head and Neck Squamous Cell Carcinomas (HNSCC are the 6 most common cancers worldwide. While incidence rates for cancer of the hypopharynx and larynx are decreasing, a significant increase in cancer of the oropharynx (OSCC is observed. Classical risk factors for HNSCC are smoking and alcohol. It has been shown for 25 to 60% of OSCC to be associated with an infection by oncogenic human papilloma viruses (HPV. The development of “common” cancer of the head and neck is substantially enhanced by an accumulation of genetic changes, which lead to an inactivation of tumor suppressor genes or activation of proto-oncogenes. A more or less uniform sequence of different DNA-damages leads to genetic instability. In this context, an early and frequent event is deletion on the short arm of chromosome 9, which results in inactivation of the p16-gene. In contrast, for HPV-induced carcinogenesis, expression of the viral proteins E6 and E7 is most important, since they lead to inactivation of the cellular tumor-suppressor-proteins p53 and Rb. The natural route of transoral infection is a matter of debate; peroral HPV-infections might be frequent and disappear uneventfully in most cases. Smoking seems to increase the probability for developing an HPV-associated OSCC. The association of HNSCC with HPV can be proven with established methods in clinical diagnostics. In addition to classical prognostic factors, diagnosis of HPV-association may become important for selection of future therapies. Prognostic relevance of HPV probably surmounts many known risk-factors, for example regional metastasis. Until now, no other molecular markers are established in clinical routine. Future therapy concepts may vary for the two subgroups of patients, particularly patients with HPV-associated OSCC may take advantage of less aggressive treatments. Finally, an outlook will be given on possible targeted therapies.

  2. Global Inequalities in Cervical Cancer Incidence and Mortality are Linked to Deprivation, Low Socioeconomic Status, and Human Development

    Directory of Open Access Journals (Sweden)

    Gopal K. Singh, PhD

    2012-11-01

    Full Text Available Objective: This study examined global inequalities in cervical cancer incidence and mortality rates as a function of cross-national variations in the Human Development Index (HDI, socioeconomic factors, Gender Inequality Index (GII, and healthcare expenditure.Methods: Age-adjusted incidence and mortality rates were calculated for women in 184 countries using the 2008 GLOBOCAN database, and incidence and mortality trends were analyzed using the WHO cancer mortality database. Log-linear regression was used to model annual trends, while OLS and Poisson regression models were used to estimate the impact of socioeconomic and human development factors on incidence and mortality rates.Results: Cervical cancer incidence and mortality rates varied widely, with many African countries such as Guinea, Zambia, Comoros, Tanzania, and Malawi having at least 10-to-20-fold higher rates than several West Asian, Middle East, and European countries, including Iran, Saudi Arabia, Syria, Egypt, and Switzerland. HDI, GII, poverty rate, health expenditure per capita, urbanization, and literacy rate were all significantly related to cervical cancer incidence and mortality, with HDI and poverty rate each explaining >52% of the global variance in mortality. Both incidence and mortality rates increased in relation to lower human development and higher gender inequality levels. A 0.2 unit increase in HDI was associated with a 20% decrease in cervical cancer risk and a 33% decrease in cervical cancer mortality risk. The risk of a cervical cancer diagnosis increased by 24% and of cervical cancer death by 42% for a 0.2 unit increase in GII. Higher health expenditure levels were independently associated with decreased incidence and mortality risks.Conclusions and Public Health Implications: Global inequalities in cervical cancer are clearly linked to disparities in human development, social inequality, and living standards. Reductions in cervical cancer rates are achievable by

  3. Two novel human NUMB isoforms provide a potential link between development and cancer.

    Science.gov (United States)

    Karaczyn, Aldona; Bani-Yaghoub, Mahmud; Tremblay, Roger; Kubu, Chris; Cowling, Rebecca; Adams, Tamara L; Prudovsky, Igor; Spicer, Douglas; Friesel, Robert; Vary, Calvin; Verdi, Joseph M

    2010-12-01

    We previously identified four functionally distinct human NUMB isoforms. Here, we report the identification of two additional isoforms and propose a link between the expression of these isoforms and cancer. These novel isoforms, NUMB5 and NUMB6, lack exon 10 and are expressed in cells known for polarity and migratory behavior, such as human amniotic fluid cells, glioblastoma and metastatic tumor cells. RT-PCR and luciferase assays demonstrate that NUMB5 and NUMB6 are less antagonistic to NOTCH signaling than other NUMB isoforms. Immunocytochemistry analyses show that NUMB5 and NUMB6 interact and complex with CDC42, vimentin and the CDC42 regulator IQGAP1 (IQ (motif) GTPase activating protein 1). Furthermore, the ectopic expression of NUMB5 and NUMB6 induces the formation of lamellipodia (NUMB5) and filopodia (NUMB6) in a CDC42- and RAC1-dependent manner. These results are complemented by in vitro and in vivo studies, demonstrating that NUMB5 and NUMB6 alter the migratory behavior of cells. Together, these novel isoforms may play a role in further understanding the NUMB function in development and cancer.

  4. Two novel human NUMB isoforms provide a potential link between development and cancer

    Directory of Open Access Journals (Sweden)

    Prudovsky Igor

    2010-12-01

    Full Text Available Abstract We previously identified four functionally distinct human NUMB isoforms. Here, we report the identification of two additional isoforms and propose a link between the expression of these isoforms and cancer. These novel isoforms, NUMB5 and NUMB6, lack exon 10 and are expressed in cells known for polarity and migratory behavior, such as human amniotic fluid cells, glioblastoma and metastatic tumor cells. RT-PCR and luciferase assays demonstrate that NUMB5 and NUMB6 are less antagonistic to NOTCH signaling than other NUMB isoforms. Immunocytochemistry analyses show that NUMB5 and NUMB6 interact and complex with CDC42, vimentin and the CDC42 regulator IQGAP1 (IQ (motif GTPase activating protein 1. Furthermore, the ectopic expression of NUMB5 and NUMB6 induces the formation of lamellipodia (NUMB5 and filopodia (NUMB6 in a CDC42- and RAC1-dependent manner. These results are complemented by in vitro and in vivo studies, demonstrating that NUMB5 and NUMB6 alter the migratory behavior of cells. Together, these novel isoforms may play a role in further understanding the NUMB function in development and cancer.

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

    Science.gov (United States)

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

    2015-04-01

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

  6. Incidence and mortality of kidney cancer and its relationship with HDI (Human Development Index) in the world in 2012.

    Science.gov (United States)

    Mohammadian, Maryam; Pakzad, Reza; Towhidi, Farhad; Makhsosi, Behnam Reza; Ahmadi, Abbas; Salehiniya, Hamid

    2017-01-01

    Kidney cancer is among the cancers that have the highest growth rate in all age and racial groups in the world and is as the most deadly type of urinary tract cancer. Since awareness about this cancer incidence status and mortality is essential for better planning, this study aimed to investigate the incidence and mortality rate of kidney cancer and its relationship with the development index in the world in 2012. This study was an ecological study conducted based on GLOBOCAN project of the World Health Organization (WHO) for the countries in the world. The correlation between Standardized Incidence Rates (SIRs) and Standardized Mortality Rates (SMRs) of kidney cancer with HDI and its components was assessed using SPSS18. In total, 337,860 incidence cases (213,924 were men and 123,936 women) and 143,406 deaths (90,802 cases in men and 52,604 in women) of kidney cancer were recorded in 2012. A positive correlation of 0.731 was seen between SIR of kidney cancer and HDI (p≤0.001). Also, a negative correlation of 0.627 was seen between SMR of kidney cancer and HDI (p≤0.001). The incidence and mortality rate of kidney cancer is higher in developed countries. A significant positive correlation has been seen between the standardized incidence and mortality rate of kidney cancer with the Human Development Index and its components. We need more studies to examine variation in incidence and mortality of kidney cancer and its related factors in the world.

  7. Tart cherry anthocyanins inhibit tumor development in Apc(Min) mice and reduce proliferation of human colon cancer cells.

    Science.gov (United States)

    Kang, Soo-Young; Seeram, Navindra P; Nair, Muraleedharan G; Bourquin, Leslie D

    2003-05-08

    Anthocyanins, which are bioactive phytochemicals, are widely distributed in plants and especially enriched in tart cherries. Based on previous observations that tart cherry anthocyanins and their respective aglycone, cyanidin, can inhibit cyclooxygenase enzymes, we conducted experiments to test the potential of anthocyanins to inhibit intestinal tumor development in Apc(Min) mice and growth of human colon cancer cell lines. Mice consuming the cherry diet, anthocyanins, or cyanidin had significantly fewer and smaller cecal adenomas than mice consuming the control diet or sulindac. Colonic tumor numbers and volume were not significantly influenced by treatment. Anthocyanins and cyanidin also reduced cell growth of human colon cancer cell lines HT 29 and HCT 116. The IC(50) of anthocyanins and cyanidin was 780 and 63 microM for HT 29 cells, respectively and 285 and 85 microM for HCT 116 cells, respectively. These results suggest that tart cherry anthocyanins and cyanidin may reduce the risk of colon cancer.

  8. The pig as a model for therapeutic human anti-cancer vaccine development, elucidating the T-cell reactivity against IDO and RhoC

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

    Immunotherapy against cancer has shown increased overall survival of metastatic cancer patients and is a promising new vaccine target. For this to succeed, appropriate tailoring of vaccine formulations to mount in vivo cytotoxic T cell (CTL) responses towards co-delivered cancer antigens...... is important. Previous development of therapeutic cancer vaccines has largely been based on studies in mice and the majority of these candidate vaccines failed to establish therapeutic responses in subsequent human clinical trials. Since the porcine immunome is more closely related to the human counterpart, we...... here introduce pigs as a superior large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, both known to be important in human cancer development and progression, were used as vaccine targets. Pigs were...

  9. Overview of Human Papillomavirus-Based and Other Novel Options for Cervical Cancer Screening in Developed and Developing Countries

    NARCIS (Netherlands)

    Cuzick, Jack; Arbyn, Marc; Sankaranarayanan, Rengaswamy; Tsu, Vivien; Ronco, Guglielmo; Mayrand, Marie-Helene; Dillner, Joakim; Meijer, Chris J. L. M.

    2008-01-01

    Screening for cervical cancer precursors by cytology has been very successful in countries where adequate resources exist to ensure high quality and good coverage of the population at risk. Mortality reductions in excess of 50% have been achieved in many developed countries; however the procedure is

  10. Overview of Human Papillomavirus-Based and Other Novel Options for Cervical Cancer Screening in Developed and Developing Countries

    NARCIS (Netherlands)

    Cuzick, Jack; Arbyn, Marc; Sankaranarayanan, Rengaswamy; Tsu, Vivien; Ronco, Guglielmo; Mayrand, Marie-Helene; Dillner, Joakim; Meijer, Chris J. L. M.

    2008-01-01

    Screening for cervical cancer precursors by cytology has been very successful in countries where adequate resources exist to ensure high quality and good coverage of the population at risk. Mortality reductions in excess of 50% have been achieved in many developed countries; however the procedure is

  11. Expression and new exon mutations of the human Beta defensins and their association on colon cancer development.

    Directory of Open Access Journals (Sweden)

    Abdelhabib Semlali

    Full Text Available The development of cancer involves genetic predisposition and a variety of environmental exposures. Genome-wide linkage analyses provide evidence for the significant linkage of many diseases to susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Human β-defensins (hBDs are important molecules of innate immunity. This study was designed to analyze the expression and genetic variations in hBDs (hBD-1, hBD-2, hBD-3 and hBD-4 and their putative association with colon cancer. hBD gene expression and relative protein expression were evaluated by Real-Time polymerase chain reaction (qPCR and immunohistochemistry, respectively, from 40 normal patients and 40 age-matched patients with colon cancer in Saudi Arabia. In addition, hBD polymorphisms were genotyped by exon sequencing and by promoter methylation. hBD-1, hBD-2, hBD-3 and hBD-4 basal messenger RNA expression was significantly lower in tumor tissues compared with normal tissues. Several insertion mutations were detected in different exons of the analyzed hBDs. However, no methylation in any hBDs promoters was detected because of the limited number of CpG islands in these regions. We demonstrated for the first time a link between hBD expression and colon cancer. This suggests that there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs and the potential development of colon cancer.

  12. The development of an integrated platform to identify breast cancer glycoproteome changes in human serum.

    Science.gov (United States)

    Zeng, Zhi; Hincapie, Marina; Haab, Brian B; Hanash, Samir; Pitteri, Sharon J; Kluck, Steven; Hogan, Jason M; Kennedy, Jacob; Hancock, William S

    2010-05-07

    Protein glycosylation represents one of the major post-translational modifications and can have significant effects on protein function. Moreover, changes in the carbohydrate structure are increasingly being recognized as an important modification associated with cancer etiology. In this report, we describe the development of a proteomics approach to identify breast cancer related changes in either concentration and/or the carbohydrate structures of glycoprotein(s) present in blood samples. Diseased and healthy serum samples were processed by an optimized sample preparation protocol using multiple lectin affinity chromatography (M-LAC) that partitions serum proteins based on glycan characteristics. Subsequently, three separate procedures, 1D SDS-PAGE, isoelectric focusing and an antibody microarray, were applied to identify potential candidate markers for future study. The combination of these three platforms is illustrated in this report with the analysis of control and cancer glycoproteomic fractions. Firstly, a molecular weight based separation of glycoproteins by 1D SDS-PAGE was performed, followed by protein, glycoprotein staining, lectin blotting and LC-MS analysis. To refine or confirm the list of interesting glycoproteins, isoelectric focusing (targeting sialic acid changes) and an antibody microarray (used to detect neutral glycan shifts) were selected as the orthogonal methods. As a result, several glycoproteins including alpha-1B-glycoprotein, complement C3, alpha-1-antitrypsin and transferrin were identified as potential candidates for further study.

  13. Human papillomavirus and cervical cancer.

    Science.gov (United States)

    Crosbie, Emma J; Einstein, Mark H; Franceschi, Silvia; Kitchener, Henry C

    2013-09-07

    Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and clears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16, 18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved.

  14. Cells Lines vs. Animals Studies for Developing New Therapeutic Strategies in Human Pancreatic Cancer?

    Directory of Open Access Journals (Sweden)

    Raffaele Pezzilli

    2006-05-01

    Full Text Available In the past, most of the knowledge gained regarding the physiology and the pathology of the pancreas has been evaluated in experimental studies on animals especially on rats/mice. This approach has been criticized in recent years because most of the data obtained from animals cannot be fully applied to humans [1]. A new approach to the physiology and pathology of the pancreas comes from studying its molecular biology, and the results obtained seem to be more reliable than those obtained in animals. An example of this assumption comes from studies on pancreatic ductal adenocarcinoma: this cancer seems to result from a progressive accumulation of mutations in genes such as K-ras, CDKN2A, p53, BRCA2, p164ink, and SMAD4 [2]; in particular, the SMAD4 mutations which result in the constitutive activation of transforming growth factor b1 signalling, are generally considered to be responsible for the desmoplastic response, which includes upregulated expression of the extracellular matrix, and type I collagen [3, 4, 5, 6]. Grzesiak et al. [7, 8] have also shown that a2b1 integrin-mediated adhesion on type I collagen promotes a malignant phenotype in FG pancreatic cells, as defined by increased proliferation and haptokinetic cell migration, downregulated expression and localization of E-cadherin and b-catenin in cell-cell contacts, increased phosphorylation of GSK3b and PKB/Akt, and downregulated expression of PTHrP, IL-6, and IL-8 as compared to fibronectin, type IV collagen, laminin, or vitronectin. These results are in agreement with previous studies demonstrating that type I collagen downregulates E-cadherin expression in Panc-1, BxPC-3, and PaTu8988s pancreatic cancer cells, resulting in increased proliferation and migration compared to fibronectin.

  15. Human Cancer Models Initiative | Office of Cancer Genomics

    Science.gov (United States)

    The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer research.

  16. Serglycin in human cancers

    Institute of Scientific and Technical Information of China (English)

    Xin-Jian Li; Chao-Nan Qian

    2011-01-01

    Serglycin belongs to a family of small proteoglycans with Ser-Gly dipeptide repeats,and it is modified with different types of glycosaminoglycan side chains.Intracellular serglycin affects the retention and secretion of proteases,chemokines,or other cytokines by physically binding to these factors in secretory granules.Extracellular serglycin has been found to be released by several types of human cancer cells,and it is able to promote the metastasis of nasopharyngeal carcinoma cells.Serglycin can bind to CD44,which is another glycoprotein located in cellular membrane.Serglycin's function of promoting cancer cell metastasis depends on glycosylation of its core protein,which can be achieved by autocrine as well as paracrine secretion mechanisms.Further investigations are warranted to elucidate serglycin signaling mechanisms with the goal of targeting them to prevent cancer cell metastasis.

  17. HCSD: the human cancer secretome database

    Science.gov (United States)

    Feizi, Amir; Banaei-Esfahani, Amir; Nielsen, Jens

    2015-01-01

    The human cancer secretome database (HCSD) is a comprehensive database for human cancer secretome data. The cancer secretome describes proteins secreted by cancer cells and structuring information about the cancer secretome will enable further analysis of how this is related with tumor biology. The secreted proteins from cancer cells are believed to play a deterministic role in cancer progression and therefore may be the key to find novel therapeutic targets and biomarkers for many cancers. Consequently, huge data on cancer secretome have been generated in recent years and the lack of a coherent database is limiting the ability to query the increasing community knowledge. We therefore developed the Human Cancer Secretome Database (HCSD) to fulfil this gap. HCSD contains >80 000 measurements for about 7000 nonredundant human proteins collected from up to 35 high-throughput studies on 17 cancer types. It has a simple and user friendly query system for basic and advanced search based on gene name, cancer type and data type as the three main query options. The results are visualized in an explicit and interactive manner. An example of a result page includes annotations, cross references, cancer secretome data and secretory features for each identified protein. Database URL: www.cancersecretome.org. PMID:26078477

  18. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  19. Mechanisms of virus immune evasion lead to development from chronic inflammation to cancer formation associated with human papillomavirus infection

    Directory of Open Access Journals (Sweden)

    Masachika Senba

    2012-10-01

    Full Text Available Human papillomavirus (HPV has developed strategies to escape eradication by innate and adaptive immunity. Immune response evasion has been considered an important aspect of HPV persistence, which is the main contributing factor leading to HPV-related cancers. HPV-induced cancers expressing viral oncogenes E6 and E7 are potentially recognized by the immune system. The major histocompatibility complex (MHC class I molecules are patrolled by natural killer cells and CD8+ cytotoxic T lymphocytes, respectively. This system of recognition is a main target for the strategies of immune evasion deployed by viruses. The viral immune evasion proteins constitute useful tools to block defined stages of the MHC class I presentation pathway, and in this way HPV avoids the host immune response. The long latency period from initial infection to persistence signifies that HPV evolves mechanisms to escape the immune response. It has now been established that there are oncogenic mechanisms by which E7 binds to and degrades tumor suppressor Rb, while E6 binds to and inactivates tumor suppressor p53. Therefore, interaction of p53 and pRb proteins can give rise to an increased immortalization and genomic instability. Overexpression of NF-kB in cervical and penile cancers suggests that NF-kB activation is a key modulator in driving chronic inflammation to cancer. HPV oncogene-mediated suppression of NF-kB activity contributes to HPV escape from the immune system. This review focuses on the diverse mechanisms of the virus immune evasion with HPV that leads to chronic inflammation and cancer.

  20. Differentiation of Neonatal Human-Induced Pluripotent Stem Cells to Prostate Epithelial Cells: A Model to Study Prostate Cancer Development

    Science.gov (United States)

    2014-06-01

    1 AD_________________ Award Number: W81XWH-12-1-0189 TITLE: Differentiation of Neonatal Human...CONTRACT NUMBER Differentiation of Neonatal Human Induced Pluripotent Stem Cells to Prostate Epithelial Cells: A Model to Study Prostate Cancer...13. SUPPLEMENTARY NOTES 14. ABSTRACT We set out to establish conditions for differentiation of human neonatal foreskin skin fibroblast

  1. SAV1 represses the development of human colorectal cancer by regulating the Akt-mTOR pathway in a YAP-dependent manner.

    Science.gov (United States)

    Jiang, Jianwu; Chang, Wei; Fu, Yang; Gao, Yongshun; Zhao, Chunlin; Zhang, Xiefu; Zhang, Shuijun

    2017-08-01

    SAV1 is a human homologue of Salvador that contains two protein-protein interaction modules known as WW domains and acts as a scaffolding protein. SAV1 participates in the development of diverse types of cancer. We aimed to investigate the role of SAV1 in human colorectal cancer. Human colorectal cancer samples were used to study the expression of SAV1 and YAP. Loss-of-function and gain-of-function strategies were used to study the effects of SAV1 on colorectal cancer cell growth. Rapamycin was used to treat cells and mice to investigate the effect of mTOR signalling. SAV1 represses the development of colorectal cancer by inhibiting the Akt-mTOR signalling in a YAP-dependent manner. The mRNA and protein levels of SAV1 are down-regulated in human colorectal cancer tissues compared with adjacent non-cancer tissues. SAV1 knockdown promotes the growth of colorectal cancer cells in vitro and in vivo, whereas SAV1 overexpression leads to opposing results. SAV1 represses the activation of the Akt-mTOR signalling, and rapamycin treatment blunts the effects of SAV1 on in vitro and in vivo growth of colorectal cancer cells. Finally, we show that SAV1 promotes the phosphorylation and inactivation of YAP, which contributes to the effect of SAV1 on Akt-mTOR signalling pathway. SAV1 is a repressor during the development of human colorectal cancer by inhibiting the YAP-Akt-mTOR signalling pathway. © 2017 John Wiley & Sons Ltd.

  2. Multivariate analysis of countries' government and health-care system influences on opioid availability for cancer pain relief and palliative care: more than a function of human development.

    Science.gov (United States)

    Gilson, Aaron M; Maurer, Martha A; Lebaron, Virginia T; Ryan, Karen M; Cleary, James F

    2013-02-01

    Many international governmental and nongovernmental organizations regard unrelieved cancer pain as a significant global public health problem. Although opioids such as morphine are considered essential medicines in the provision of palliative care and for treating cancer pain, especially when the pain is severe, low- and middle-income countries often lack such medications. The primary aim of this study was to examine countries' government and health-care system influences on opioid availability for cancer pain and palliative care, as a means to identify implications for improving appropriate access to prescription opioids. A multivariate regression of 177 countries' consumption of opioids (in milligrams/death from cancer and AIDS) contained country-level predictor variables related to public health, including Human Development Index, palliative care infrastructure, and health system resources and expenditures. Results were highly explanatory (adjusted R(2) = 82%) and Human Development Index was the most predictive variable when controlling for all other factors in the statistical model (B = 11.875, confidence interval = 10.216, 13.534, p Human Development Index. However, Human Development Index is not the most policy-relevant factor, and this finding should be reconciled against the reality that many countries with low or medium Human Development Index have succeeded in creating and sustaining a health-care system to strengthen cancer pain care and palliative care, including through the appropriate use of essential prescription opioids.

  3. Human Development, Human Evolution.

    Science.gov (United States)

    Smillie, David

    One of the truly remarkable events in human evolution is the unprecedented increase in the size of the brain of "Homo" over a brief span of 2 million years. It would appear that some significant selective pressure or opportunity presented itself to this branch of the hominid line and caused a rapid increase in the brain, introducing a…

  4. Human Development Report 1991: Financing Human Development

    OpenAIRE

    United Nations Development Programme, UNDP

    1991-01-01

    Lack of political commitment rather than financial resources is often the real barrier to human development. This is the main conclusion of Human Development Report 1991 - the second in a series of annual reports on the subject.

  5. Elucidating the T-cell reactivity against porcine IDO and RhoC to establish the pig as an animal model for vaccine development against human cancer

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon;

    is a requirement for activation of CTLs. Previously, the development of therapeutic anti-cancer vaccines have largely been based on rodent models, in particular mice; however the majority of these fail to establish a therapeutic response once put into clinical trials. Pigs have the potential of serving as a model...... superior to rodents as they are more closely related to humans in terms of immunology and physiology. Here, we introduce pigs as a supplementary large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, two tumor...... antigens previously identified as important players in human cancer development and progression, were used as vaccine targets. Using peptide-MHC-I binding predictors we identified IDO-derived and RhoC-derived candidate peptides potentially binding to five different broadly distributed SLA molecules. We...

  6. HCSD: the human cancer secretome database

    DEFF Research Database (Denmark)

    Feizi, Amir; Banaei-Esfahani, Amir; Nielsen, Jens

    2015-01-01

    database is limiting the ability to query the increasing community knowledge. We therefore developed the Human Cancer Secretome Database (HCSD) to fulfil this gap. HCSD contains >80 000 measurements for about 7000 nonredundant human proteins collected from up to 35 high-throughput studies on 17 cancer...... types. It has a simple and user friendly query system for basic and advanced search based on gene name, cancer type and data type as the three main query options. The results are visualized in an explicit and interactive manner. An example of a result page includes annotations, cross references, cancer...

  7. The kinetic mechanism of Human Thymidine Phosphorylase - a molecular target for cancer drug development.

    Science.gov (United States)

    Deves, Candida; Rostirolla, Diana Carolina; Martinelli, Leonardo Kras Borges; Bizarro, Cristiano Valim; Santos, Diogenes Santiago; Basso, Luiz Augusto

    2014-03-04

    Human Thymidine Phosphorylase (HTP), also known as the platelet-derived endothelial cell growth factor (PD-ECGF) or gliostatin, catalyzes the reversible phosphorolysis of thymidine (dThd) to thymine and 2-deoxy-α-d-ribose-1-phosphate (2dR1P). HTP is a key enzyme in the pyrimidine salvage pathway involved in dThd homeostasis in cells. HTP is a target for anticancer drug development as its enzymatic activity promotes angiogenesis. Here, we describe cloning, expression, and purification to homogeneity of recombinant TYMP-encoded HTP. Peptide fingerprinting and the molecular mass value of the homogenous protein confirmed its identity as HTP assessed by mass spectrometry. Size exclusion chromatography showed that HTP is a dimer in solution. Kinetic studies revealed that HTP displayed substrate inhibition for dThd. Initial velocity and isothermal titration calorimetry (ITC) studies suggest that HTP catalysis follows a rapid-equilibrium random bi-bi kinetic mechanism. ITC measurements also showed that dThd and Pi binding are favorable processes. The pH-rate profiles indicated that maximal enzyme activity was achieved at low pH values. Functional groups with apparent pK values of 5.2 and 9.0 are involved in dThd binding and groups with pK values of 6.1 and 7.8 are involved in phosphate binding.

  8. Colon cancer associated transcripts in human cancers.

    Science.gov (United States)

    Chen, Yincong; Xie, Haibiao; Gao, Qunjun; Zhan, Hengji; Xiao, Huizhong; Zou, Yifan; Zhang, Fuyou; Liu, Yuchen; Li, Jianfa

    2017-08-02

    Long non-coding RNAs serve as important regulators in complicated cellular activities, including cell differentiation, proliferation and death. Dysregulation of long non-coding RNAs occurs in the formation and progression of cancers. The family of colon cancer associated transcripts, long non-coding RNAs colon cancer associated transcript-1 and colon cancer associated transcript-2 are known as oncogenes involved in various cancers. Colon cancer associated transcript-1 is a novel lncRNA located in 8q24.2, and colon cancer associated transcript-2 maps to the 8q24.21 region encompassing rs6983267. Colon cancer associated transcripts have close associations with clinical characteristics, such as lymph node metastasis, high TNM stage and short overall survival. Knockdown of them can reverse the malignant phenotypes of cancer cells, including proliferation, migration, invasion and apoptosis. Moreover, they can increase the expression level of c-MYC and oncogenic microRNAs via activating a series of complex mechanisms. In brief, the family of colon cancer associated transcripts may serve as potential biomarkers or therapeutic targets for human cancers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Effects of Human Development Index and Its Components on Colorectal Cancer Incidence and Mortality: a Global Ecological Study.

    Science.gov (United States)

    Khazaei, Salman; Rezaeian, Shahab; Khazaei, Somayeh; Mansori, Kamyar; Sanjari Moghaddam, Ali; Ayubi, Erfan

    2016-01-01

    Geographic disparity for colorectal cancer (CRC) incidence and mortality according to the human development index (HDI) might be expected. This study aimed at quantifying the effect measure of association HDI and its components on the CRC incidence and mortality. In this ecological study, CRC incidence and mortality was obtained from GLOBOCAN, the global cancer project for 172 countries. Data were extracted about HDI 2013 for 169 countries from the World Bank report. Linear regression was constructed to measure effects of HDI and its components on CRC incidence and mortality. A positive trend between increasing HDI of countries and age-standardized rates per 100,000 of CRC incidence and mortality was observed. Among HDI components education was the strongest effect measure of association on CRC incidence and mortality, regression coefficients (95% confidence intervals) being 2.8 (2.4, 3.2) and 0.9 (0.8, 1), respectively. HDI and its components were positively related with CRC incidence and mortality and can be considered as targets for prevention and treatment intervention or tracking geographic disparities.

  10. Report: Human cancer genetics

    Institute of Scientific and Technical Information of China (English)

    LI Marilyn; ALBERTSON Donna

    2006-01-01

    The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. They will also review presymptomatic testing of hereditary cancers, and the application of expression profiling to identify patients likely to benefit from particular therapeutic approaches.

  11. Human cancer genetics*

    OpenAIRE

    2006-01-01

    The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. They will also review presymptomatic testing of hereditary cancers, and the application of expression profiling to identify patients likely to benefit from particular therapeutic approaches.

  12. Development of LC-QTOF-MS method for human lung tissue fingerprinting. A preliminary application to nonsmall cell lung cancer.

    Science.gov (United States)

    Ciborowski, Michal; Kisluk, Joanna; Pietrowska, Karolina; Samczuk, Paulina; Parfieniuk, Ewa; Kowalczyk, Tomasz; Kozlowski, Miroslaw; Kretowski, Adam; Niklinski, Jacek

    2017-09-01

    The major histologic subtypes of non-small cell lung cancer (NSCLC) include adenocarcinoma (ADC), squamous cell lung carcinoma (SCC), and large-cell carcinoma (LCC). Clinical trials of targeted agents and newer chemotherapy agents yielded differences in outcomes according to histologic subgroups providing a rationale for histology-based treatment in NSCLC. Currently, NSCLC subtyping is performed based on histopathological examinations and immunohistochemistry. However available methods leave about 10% of NSCLC cases as not otherwise specified. The purpose of this study was development of an LC-QTOF-MS method for human lung tissue metabolic fingerprinting that could discriminate NSCLC histological subtypes and propose biomarkers candidates that could support proper NSCLC diagnosis. Metabolites were extracted with acetonitrile or methanol/ethanol and different chromatographic conditions were tested. In the final method 10 mg of lung tissue was homogenized with 50% methanol and metabolites were extracted with acetonitrile. Metabolites were separated on C8-RP and HILIC columns. About 3500 and 2000 of metabolic features (in both ion modes) were detected with good repeatability (CV Lung tumor and control tissue samples obtained from NSCLC patients were analyzed with developed methodology. Acylcarnitines, fatty acids, phospholipids, and amino acids were found more abundant in tumor as compared to control tissue. Acylcarnitines, lysophospholipids, creatinine, creatine, and alanine were identified as potential targets enabling classification of NSCLC subtypes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Exploring disparities in incidence and mortality rates of breast and gynecologic cancers according to the Human Development Index in the Pan-American region.

    Science.gov (United States)

    Martínez-Mesa, J; Werutsky, G; Michiels, S; Pereira Filho, C A S; Dueñas-González, A; Zarba, J J; Mano, M; Villarreal-Garza, C; Gómez, H; Barrios, C H

    2017-08-01

    To evaluate whether a country's Human Development Index (HDI) can help explain the differences in the country's breast cancer and gynecological cancer incidence and mortality rates in the Pan-American region. Ecological analysis. Pan-American region countries with publicly available data both in GLOBOCAN 2012 and the United Nations Development Report 2012 were included (n = 28). Incidence and mortality rates age-standardized per 100,000 were natural log-transformed for breast cancer, ovarian cancer, corpus uteri cancer, and cervical cancer. The mortality-to-incidence ratio (MIR) was calculated for each site. Pearson's correlation test and a simple linear regression were performed. The HDI showed a positive correlation with breast cancer and ovarian cancer incidence and mortality rates, respectively, and a negative correlation with cervical cancer incidence and mortality rates. The HDI and corpus uteri cancer showed no association. MIR and the HDI showed a negative correlation for all tumor types except ovarian cancer. An increment in 1 HDI unit leads to changes in cancer rates: in breast cancer incidence β = 4.03 (95% confidence interval [CI] 2.61; 5.45) P < 0.001, breast cancer mortality β = 1.76 (95% CI 0.32; 3.21) P = 0.019, and breast cancer-MIR β = -0.705 (95% CI 0.704; 0.706) P < 0.001; in cervical cancer incidence β = -3.28 (95% CI -4.78; -1.78) P < 0.001, cervical cancer mortality β = -4.63 (95% CI -6.10; -3.17) P < 0.001, and cervical cancer-MIR β = -1.35 (95% CI -1.83; -0.87) P < 0.001; in ovarian cancer incidence β = 3.26 (95% CI 1.78; 4.75) P < 0.001, ovarian cancer mortality β = 1.82 (95% CI 0.44; 3.20) P = 0.012, and ovarian cancer-MIR β = 5.10 (95% CI 3.22; 6.97) P < 0.001; in corpus uteri cancer incidence β = 2.37 (95% CI -0.33; 5.06) P = 0.83, corpus uteri cancer mortality β = 0.68 (95% CI -2.68; 2.82) P = 0.96, and corpus uteri cancer-MIR β = -2.30 (95% CI -3.19; -1.40) P < 0.001. A

  14. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  15. Developments in Colorectal Cancer Screening

    Science.gov (United States)

    ... JavaScript on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Past Issues / Summer 2016 Table of Contents Dr. ... patients know to help determine the best colon cancer screening test for them? Colonoscopy is considered the gold ...

  16. Jordan Adjusted Human Development

    OpenAIRE

    Ababsa, Myriam

    2014-01-01

    Jordan Human Development Index (HDI) and Adjusted Human Development Index (IHDI) In 1990, the United Nations Development Programme designed a Human Development Index composed of life expectancy at birth, level of education and gross domestic product (GDP) per capita. In 2011, the UNDP ranked Jordan 95th out of 187 countries with a human development index of 0.698, up from 0.591 in 1990, making it the leading medium-range country for human development (fig. VIII.1). In 2010, the inequality adj...

  17. [Human papilloma virus and cervical cancer. An historical review on the development of research on cancer of the cervix uteri in Venezuela].

    Science.gov (United States)

    García-Tamayo, Jorge; Molina, Julia; Blasco-Olaetxea, Eduardo

    2010-06-01

    The history on the relationship of VPH infection and cervical cancer was examined. Findings were initially reported in Maracaibo(1971), later in Mexico(1973) and thereafter several studies on the ultrastructure and immunohistochemistry of VPH infection and its role on cervical cancer were described. The ultrastructural findings of viral particles of HPV and their proteins, as well as their role in the incorporation of the viral genome to the human cervical cells were also described. Glycoproteins on the surface of cervical cells were reviewed and their importance on HPV infection was related to p16, blood group antigens and early genetic changes in the cell cycle with loss of heterozigocity, all of which, stimulated by the high risk HPV infection lead to cervical cancer.

  18. Human Papillomavirus in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Anna Rosa Garbuglia

    2014-08-01

    Full Text Available Human papillomavirus (HPV is currently considered to be a major etiologic factor, in addition to tobacco and alcohol, for oropharyngeal cancer (OPC development. HPV positive OPCs are epidemiologically distinct from HPV negative ones, and are characterized by younger age at onset, male predominance, and strong association with sexual behaviors. HPV16 is the most prevalent types in oral cavity cancer (OCC, moreover the prevalence of beta, and gamma HPV types is higher than that of alpha HPV in oral cavity.

  19. In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

    Science.gov (United States)

    Genetic background plays a dominant role in mammary gland development and breast cancer (BrCa). Despite this, the role of genetics is only partially understood. This study used strain-dependent variation in an inbred mouse mapping panel, to identify quantitative trait loci (QTL) underlying structura...

  20. Cancer stem cells in human gastrointestinal cancer.

    Science.gov (United States)

    Taniguchi, Hiroaki; Moriya, Chiharu; Igarashi, Hisayoshi; Saitoh, Anri; Yamamoto, Hiroyuki; Adachi, Yasushi; Imai, Kohzoh

    2016-11-01

    Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the main causes of cancer-related deaths. Gastrointestinal cancers are the most common malignancies and still the most frequent cause of cancer-related mortality worldwide. Because gastrointestinal CSCs are also thought to be resistant to conventional therapies, an effective and novel cancer treatment is imperative. The first reported CSCs in a gastrointestinal tumor were found in colorectal cancer in 2007. Subsequently, CSCs were reported in other gastrointestinal cancers, such as esophagus, stomach, liver, and pancreas. Specific phenotypes could be used to distinguish CSCs from non-CSCs. For example, gastrointestinal CSCs express unique surface markers, exist in a side-population fraction, show high aldehyde dehydrogenase-1 activity, form tumorspheres when cultured in non-adherent conditions, and demonstrate high tumorigenic potential in immunocompromised mice. The signal transduction pathways in gastrointestinal CSCs are similar to those involved in normal embryonic development. Moreover, CSCs are modified by the aberrant expression of several microRNAs. Thus, it is very difficult to target gastrointestinal CSCs. This review focuses on the current research on gastrointestinal CSCs and future strategies to abolish the gastrointestinal CSC phenotype.

  1. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of

  2. Oncogenes and human cancer

    NARCIS (Netherlands)

    E.C.P. Heisterkamp (Nora); J.H.C. Groffen (John)

    1984-01-01

    textabstractThe first demonstrations that cancer could have an infectious nature was by Ellerman and Bang (1) ~ who showed that leukemia in chickens was transmissible with cell-free extracts and by Rous (2), who found in a similar fashion that naturally occurring chicken sarcomas were transmissible.

  3. Progress and controversies in developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    Speiser Daniel E

    2005-04-01

    Full Text Available Abstract Immunotherapy has become a standard approach for cancer management, through the use of cytokines (eg: interleukin-2 and monoclonal antibodies. Cancer vaccines hold promise as another form of immunotherapy, and there has been substantial progress in identifying shared antigens recognized by T cells, in developing vaccine approaches that induce antigen-specific T cell responses in cancer patients, and in developing new technology for monitoring immune responses in various human tissue compartments. Dramatic clinical regressions of human solid tumors have occurred with some cancer vaccines, but the rate of those responses remains low. This article is part of a 2-part point:counterpoint series on peptide vaccines and adoptive therapy approaches for cancer. The current status of cancer vaccination, and associated challenges, are discussed. Emphasis is placed on the need to increase our knowledge of cancer immunobiology, as well as to improve monitoring of cellular immune function after vaccination. Progress in both areas will facilitate development of effective cancer vaccines, as well as of adoptive therapy. Effective cancer vaccines promise to be useful for treatment and prevention of cancer at low cost and with low morbidity.

  4. Prevalence of Telomerase Activity in Human Cancer

    Directory of Open Access Journals (Sweden)

    Chi-Hau Chen

    2011-05-01

    Full Text Available Telomerase activity has been measured in a wide variety of cancerous and non-cancerous tissue types, and the vast majority of clinical studies have shown a direct correlation between it and the presence of cancerous cells. Telomerase plays a key role in cellular immortality and tumorigenesis. Telomerase is activated in 80–90% of human carcinomas, but not in normal somatic cells, therefore, its detection holds promise as a diagnostic marker for cancer. Measurable levels of telomerase have been detected in malignant cells from various samples: tissue from gestational trophoblastic neoplasms; squamous carcinoma cells from oral rinses; lung carcinoma cells from bronchial washings; colorectal carcinoma cells from colonic luminal washings; bladder carcinoma cells from urine or bladder washings; and breast carcinoma or thyroid cancer cells from fine needle aspirations. Such clinical tests for telomerase can be useful as non-invasive and cost-effective methods for early detection and monitoring of cancer. In addition, telomerase activity has been shown to correlate with poor clinical outcome in late-stage diseases such as non-small cell lung cancer, colorectal cancer, and soft tissue sarcomas. In such cases, testing for telomerase activity can be used to identify patients with a poor prognosis and to select those who might benefit from adjuvant treatment. Our review of the latest medical advances in this field reveals that telomerase holds great promise as a biomarker for early cancer detection and monitoring, and has considerable potential as the basis for developing new anticancer therapies.

  5. Cancer Metabolomics and the Human Metabolome Database

    Directory of Open Access Journals (Sweden)

    David S. Wishart

    2016-03-01

    Full Text Available The application of metabolomics towards cancer research has led to a renewed appreciation of metabolism in cancer development and progression. It has also led to the discovery of metabolite cancer biomarkers and the identification of a number of novel cancer causing metabolites. The rapid growth of metabolomics in cancer research is also leading to challenges. In particular, with so many cancer-associate metabolites being identified, it is often difficult to keep track of which compounds are associated with which cancers. It is also challenging to track down information on the specific pathways that particular metabolites, drugs or drug metabolites may be affecting. Even more frustrating are the difficulties associated with identifying metabolites from NMR or MS spectra. Fortunately, a number of metabolomics databases are emerging that are designed to address these challenges. One such database is the Human Metabolome Database (HMDB. The HMDB is currently the world’s largest and most comprehensive, organism-specific metabolomics database. It contains more than 40,000 metabolite entries, thousands of metabolite concentrations, >700 metabolic and disease-associated pathways, as well as information on dozens of cancer biomarkers. This review is intended to provide a brief summary of the HMDB and to offer some guidance on how it can be used in metabolomic studies of cancer.

  6. Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines

    DEFF Research Database (Denmark)

    Nielsen, Sonja K; Møllgård, Kjeld; Clement, Christian A

    2008-01-01

    Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant Hh signaling is associated with several pancreatic diseases. Here we investigated the link between Hh signaling and primary cilia in the human developing pancreatic ducts and in cultures of human pancreatic duct...

  7. Development of cancer immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y

    1999-04-01

    To increase the curative rate of cancer patients, we developed ideal biological response modifier from medicinal plants: Ginsan, KC68IId-8, KC-8Ala, KG-30. Ginsan activated natural killer cell activity of spleen cells more than 5.4 times than lentinan, 1.4 times than picibanil. Radioprotective activity of Ginsan is stronger than WR2721, glucan, and selenium. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of A20 tumor cells was also augmented by transfection with B7.1 gene. The immunosuppression of gamma-irradiation was due to the reduction of Th1 sytokine gene expression through STAT pathway. These research will devote to develop new cancer immunotherapy and to reduce side effect of cancer radiotherapy and chemotherapy.

  8. Optimization of human cancer radiotherapy

    CERN Document Server

    Swan, George W

    1981-01-01

    The mathematical models in this book are concerned with a variety of approaches to the manner in which the clinical radiologic treatment of human neoplasms can be improved. These improvements comprise ways of delivering radiation to the malignan­ cies so as to create considerable damage to tumor cells while sparing neighboring normal tissues. There is no unique way of dealing with these improvements. Accord­ ingly, in this book a number of different presentations are given. Each presentation has as its goal some aspect of the improvement, or optimization, of radiotherapy. This book is a collection of current ideas concerned with the optimization of human cancer radiotherapy. It is hoped that readers will build on this collection and develop superior approaches for the understanding of the ways to improve therapy. The author owes a special debt of thanks to Kathy Prindle who breezed through the typing of this book with considerable dexterity. TABLE OF CONTENTS Chapter GENERAL INTRODUCTION 1. 1 Introduction 1...

  9. Water pipe smoking and human oral cancers.

    Science.gov (United States)

    Rastam, Samer; Li, Fu-Min; Fouad, Fouad M; Al Kamal, Haysam M; Akil, Nizar; Al Moustafa, Ala-Eddin

    2010-03-01

    While cigarette smoking is recognized as an important risk factor in human oral cancers, the effect of water pipe smoking (WPS) on these cancers is not known. WPS is very common in the young adult population, especially in the Middle East, and has been associated with several respiratory problems. However, to date, there have been no studies examining the association between WPS and the progression of human oral cancers. Currently, the role of WPS in human oral cancers remains uncertain because of the limited number of investigations. This raises the question of whether WPS plays a significant role in the development of human oral carcinomas. In this paper, we propose the hypothesis that human oral normal epithelial cells are vulnerable to persistent WPS; moreover, WPS could play an important role in the initiation of a neoplastic transformation of human normal oral epithelial cells. Therefore, we believe that an international collaboration of epidemiological and clinical studies as well as cellular and molecular biology investigations is necessary to answer this important question.

  10. HUMAN CANCER IS A PARASITE SPREAD VIA INTRUSION IN GENOME

    Directory of Open Access Journals (Sweden)

    Sergey N. Rumyantsev

    2013-03-01

    Full Text Available The present article is devoted to further development of new paradigm about the biology of human cancer: the hypothesis of parasitic nature, origin and evolution of the phenomenon. The study included integrative reconsidering, and reinterpretation of the make-ups, traits and processes existing both in human and animal cancers. It was demonstrated that human cancer possesses nearly analogous set of traits characteristic of transmissible animal cancer. Undoubted analogies are seen in the prevalence, clinical exposure, progression of disease, origin of causative agents, immune response against invasion and especially in the intrinsic deviations of the leading traits of cancerous cells. Both human and animal cancers are highly exceptional pathogens. But in contrast to contagious animal cancers the cells of of human cancer can not pass between individuals as usual infectious agents. Exhaustive evidence of the parasitic nature and evolutionary origin of human cancer was revealed and interpreted. In contrast to animal cancer formed of solitary cell lineage, human cancer consists of a couple of lineages constructed under different genetic regulations and performed different structural and physiological functions. The complex make-up of cancer composition remains stable over sequential propagation. The subsistence of human cancer regularly includes obligatory interchange of its successive forms. Human cancer possesses its own biological watch and the ability to gobble its victim, transmit via the intrusion of the genome, perform intercommunications within the tumor components and between the dispersed subunits of cancer. Such intrinsic traits characterize human cancer as a primitively structured parasite that can be classified in Class Mammalians, Species Genomeintruder malevolent (G.malevolent.

  11. Development and characterization of two human triple-negative breast cancer cell lines with highly tumorigenic and metastatic capabilities.

    Science.gov (United States)

    Su, Yanrong; Pogash, Thomas J; Nguyen, Theresa D; Russo, Jose

    2016-03-01

    Triple-negative breast cancer (TNBC) is a group of cancer with high diversity, limited therapies, and poor prognosis. TNBC cell lines and animal models provide effective tools for studies and drug discovery. Here, we report the development of two TNBC cell lines (XtMCF and LmMCF) based on our existing cell model that consists of normal breast epithelial cell line MCF10F, estradiol-transformed cells trMCF, and Boyden chamber-selected tumorigenic cells bsMCF. The XtMCF and LmMCF cell line were derived from xenograft and lung metastasis of bsMCF cells, respectively. The bsMCF, XtMCF, and LmMCF cells have undergone epithelial-mesenchymal transition (EMT), exhibiting a mesenchymal-like feature. In vivo studies showed XtMCF and LmMCF cells were highly tumorigenic and metastatic. The injection of 5 × 10(4) cells to CB17/SCID mice mammary fat pad produced xenografts in 9/9 mice and tumors reached 10 millimeters in diameter in 5 weeks. The injection of 1 × 10(6) XtMCF or 8 × 10(4) LmMCF cells into the mice tail vein was sufficient to form extensive lung metastases in 4 weeks. The two new cell lines exhibited CD44(+) /CD49f(+) and CD44(+) /EpCAM(+) cancer stem cell (CSC) characteristics, and the EGF-like domain of EpCAM was cleaved off. Together with the normal and early transformed counterparts, herein we provide a complete cancer model for the study of initiation, evolution, and identification of new therapeutics for TNBC. The finding that EGF-like domain of EpCAM was cleaved off in cells which have undergone EMT suggests this cleavage may be involved in the EMT process and the cancer stem cell properties of these cells.

  12. Viruses and human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gallo, R.C.; Haseltine, W.; Klein, G.; Zur Hausen, H.

    1987-01-01

    This book contains papers on the following topics: Immunology and Epidemiology, Biology and Pathogenesis, Models of Pathogenesis and Treatment, Simian and Bovine Retroviruses, Human Papilloma Viruses, EBV and Herpesvirus, and Hepatitis B Virus.

  13. Septin mutations in human cancers

    Directory of Open Access Journals (Sweden)

    Elias T Spiliotis

    2016-11-01

    Full Text Available Septins are GTP-binding proteins that are evolutionarily and structurally related to the RAS oncogenes. Septin expression levels are altered in many cancers and new advances point to how abnormal septin expression may contribute to the progression of cancer. In contrast to the RAS GTPases, which are frequently mutated and actively promote tumorigenesis, little is known about the occurrence and role of septin mutations in human cancers. Here, we review septin missense mutations that are currently in the Catalog of Somatic Mutations in Cancer (COSMIC database. The majority of septin mutations occur in tumors of the large intestine, skin, endometrium and stomach. Over 25% of the annotated mutations in SEPT2, SEPT4 and SEPT9 belong to large intestine tumors. From all septins, SEPT9 and SEPT14 exhibit the highest mutation frequencies in skin, stomach and large intestine cancers. While septin mutations occur with frequencies lower than 3%, recurring mutations in several invariant and highly conserved amino acids are found across different septin paralogs and tumor types. Interestingly, a significant number of these mutations occur in the GTP-binding pocket and septin dimerization interfaces. Future studies may determine how these somatic mutations affect septin structure and function, whether they contribute to the progression of specific cancers and if they could serve as tumor-specific biomarkers.

  14. DBGC: A Database of Human Gastric Cancer.

    Science.gov (United States)

    Wang, Chao; Zhang, Jun; Cai, Mingdeng; Zhu, Zhenggang; Gu, Wenjie; Yu, Yingyan; Zhang, Xiaoyan

    2015-01-01

    The Database of Human Gastric Cancer (DBGC) is a comprehensive database that integrates various human gastric cancer-related data resources. Human gastric cancer-related transcriptomics projects, proteomics projects, mutations, biomarkers and drug-sensitive genes from different sources were collected and unified in this database. Moreover, epidemiological statistics of gastric cancer patients in China and clinicopathological information annotated with gastric cancer cases were also integrated into the DBGC. We believe that this database will greatly facilitate research regarding human gastric cancer in many fields. DBGC is freely available at http://bminfor.tongji.edu.cn/dbgc/index.do.

  15. Vascular endothelial growth factor receptor-1 in human cancer: concise review and rationale for development of IMC-18F1 (Human antibody targeting vascular endothelial growth factor receptor-1).

    Science.gov (United States)

    Schwartz, Jonathan D; Rowinsky, Eric K; Youssoufian, Hagop; Pytowski, Bronislaw; Wu, Yan

    2010-02-15

    The human vascular endothelial growth factor receptor-1 (VEGFR-1, or Flt-1) is widely expressed in normal and pathologic tissue and contributes to the pathogenesis of both neoplastic and inflammatory diseases. In human cancer, VEGFR-1 mediated signaling is responsible for both direct tumor activation and angiogenesis. VEGFR-1 mediated activation of nonmalignant supporting cells, particularly stromal, dendritic, hematopoietic cells, and macrophages, is also likely important for cancer pathogenesis. VEGFR-1 is also hypothesized to enable the development of cancer metastases by means of activation and premetastatic localization in distant organs of bone marrow-derived hematopoietic progenitor cells, which express VEGFR-1. IMC-18F1 is a fully human IgG(1) antibody that binds to VEGFR-1 and has been associated with the inhibition of cancer growth in multiple in vitro and human tumor xenograft models. The preliminary results of phase 1 investigations have also indicated a favorable safety profile for IMC-18F1 at doses that confer antibody concentrations that are associated with relevant antitumor activity in preclinical models.

  16. The incidence and mortality of lip and oral cavity cancer and its relationship to the 2012 Human Development Index of Asia

    Directory of Open Access Journals (Sweden)

    Amir Tiyuri

    2017-02-01

    Full Text Available Introduction: Lip and oral cavity cancer is one of the most prevalent cancers in Asia and considered to be a major public health problem due to the low survival rate. Because of the importance of access to information about this cancer (including incidence, mortality rate and relation to socioeconomic indicators, this study aims at investigating the incidence and mortality of lip and oral cavity cancer and its relationship with the Human Development Index (HDI of Asia (from 2012. Method: This study was an ecological study in Asia for assessment of the correlation between age-specific incidence rate (ASIR and age-specific mortality rate (ASMR with the HDI and its components which include: life expectancy at birth, mean years of schooling and gross national income (GNI per capita. Data on the standardized incidence ratio (SIR and the standardized mortality ratio (SMR for every Asian country for the year 2012 were obtained from the global cancer project and data on the HDI and its components were extracted from the World bank site.  We used a bivariate method for assessment of the correlation between the SIR and SMR with the HDI and its individual components. Statistical significance was assumed if P<0.05. All reported P-values were two-sided. Statistical analyses were performed using SPSS (Version 15.0, SPSS Inc.. Results: A total incidence of 162,506 cases and 95,005 deaths were recorded in Asian countries in 2012. Countries with the highest SIR (per 100,000 were the following: Maldives (11, Sri Lanka (10.3, Pakistan (9.8, Bangladesh (9.4, and India (7.2. The highest SMR was observed in the following countries: Pakistan (5.9, Bangladesh (5.6, Afghanistan (5.1, India (4.9, and Maldives (4.1. The correlation between SIR of lip and oral cavity cancer and HDI was -0.378 (p=0.010, with life expectancy at birth at -0.324 (p=0.028, mean years of schooling at -0.283 (p=0.057, and level of income per each person of the population at -0.279 (p=0

  17. Human pancreas development.

    Science.gov (United States)

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

  18. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng

    2012-01-01

    Full Text Available Multiple layers of suppressive components including regulatory T (TReg cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TReg cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TReg cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TReg cells in preclinical and clinical settings.

  19. Marketing Human Resource Development.

    Science.gov (United States)

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  20. Marketing Human Resource Development.

    Science.gov (United States)

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  1. Human papillomavirus and gastrointestinal cancer: A review

    Science.gov (United States)

    Bucchi, Dania; Stracci, Fabrizio; Buonora, Nicola; Masanotti, Giuseppe

    2016-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention. PMID:27672265

  2. The Isolation and Characterization of Human Prostate Cancer Stem Cells

    Science.gov (United States)

    2015-05-01

    IGF1, SOX15, BMPR1B, TGFBR1, etc), which fall into distinct GO categories including SC, development, stress response, and wound healing (unpublished...prostate cancer through the elucidation of the role of cancer stem cells in the pathogenesis of the disease. During the past year, we have made the...studies, ii) in vitro co-culture of human prostate cancer cells (established cell lines and primary patient samples) with human prostate fibroblasts

  3. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, Des

    2009-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  4. Human mammary fibroblasts stimulate invasion of breast cancer cells in a three-dimensional culture and increase stroma development in mouse xenografts

    Directory of Open Access Journals (Sweden)

    Olsen Charlotta J

    2010-08-01

    Full Text Available Abstract Introduction Tumour phenotype is regulated in a complex fashion as a result of interactions between malignant cells and the tumour stroma. Fibroblasts are the most abundant and perhaps most active part of the tumour stroma. A better understanding of the changes that occur in fibroblasts in response to the presence of malignant cells may lead to the development of new strategies for cancer treatment. We explored the effects of fibroblasts on the growth and invasion of mammary carcinoma tumour cells in vitro and in vivo. Methods In order to analyse secreted factors that affect invasive abilities of breast cancer cells we co-cultured human mammary fibroblasts (HMF3s and cancer cells (MCF7S1 in three-dimensional (3D growth conditions devoid of heterogeneous cell-cell contact. To study the possible influence of fibroblasts on MCF7S1 cancer cell growth in vivo we co-injected HMF3s and MCF7S1 cells in Balb/c nu/nu mice. Results In 3D co-culture both HMF3s and MCF7S1 cells demonstrated enhanced invasion into a Matrigel matrix. This was correlated with enhanced expression of the metastasis promoting S100A4 protein in fibroblasts, stimulation of the matrix metalloproteinase (MMP-2 activity, and enhanced secretion of a range of different cytokines. Orthotopic injection of oestrogen-dependent MCF7S1 cancer cells together with fibroblasts showed stimulation of tumour growth in mice without an external oestrogen supply. The resulting tumours were characterized by increased development of extracellular matrix, as well as an increase of murine S100A4 concentration and activity of MMP-2 in the tumour interstitial fluid. Conclusion Stimulation of the invasive phenotype of tumour cells in 3D co-cultures with fibroblasts could be correlated with increased production of S100A4 and MMP-2. We propose that enhanced development of mouse host-derived tumour stroma in a MCF7S1 co-injection xenograft model leads to oestrogen independency and is triggered by the

  5. Reprogramming of human cancer cells to pluripotency for models of cancer progression

    Science.gov (United States)

    Kim, Jungsun; Zaret, Kenneth S

    2015-01-01

    The ability to study live cells as they progress through the stages of cancer provides the opportunity to discover dynamic networks underlying pathology, markers of early stages, and ways to assess therapeutics. Genetically engineered animal models of cancer, where it is possible to study the consequences of temporal-specific induction of oncogenes or deletion of tumor suppressors, have yielded major insights into cancer progression. Yet differences exist between animal and human cancers, such as in markers of progression and response to therapeutics. Thus, there is a need for human cell models of cancer progression. Most human cell models of cancer are based on tumor cell lines and xenografts of primary tumor cells that resemble the advanced tumor state, from which the cells were derived, and thus do not recapitulate disease progression. Yet a subset of cancer types have been reprogrammed to pluripotency or near-pluripotency by blastocyst injection, by somatic cell nuclear transfer and by induced pluripotent stem cell (iPS) technology. The reprogrammed cancer cells show that pluripotency can transiently dominate over the cancer phenotype. Diverse studies show that reprogrammed cancer cells can, in some cases, exhibit early-stage phenotypes reflective of only partial expression of the cancer genome. In one case, reprogrammed human pancreatic cancer cells have been shown to recapitulate stages of cancer progression, from early to late stages, thus providing a model for studying pancreatic cancer development in human cells where previously such could only be discerned from mouse models. We discuss these findings, the challenges in developing such models and their current limitations, and ways that iPS reprogramming may be enhanced to develop human cell models of cancer progression. PMID:25712212

  6. The use of matrigel has no influence on tumor development or PET imaging in FaDu human head and neck cancer xenografts

    DEFF Research Database (Denmark)

    Fliedner, Frederikke P.; Hansen, Anders Elias; Jorgensen, Jesper T.

    2016-01-01

    is currently available. This study evaluates the potential effect of matrigel use in a human head and neck cancer xenograft model (FaDu; hypopharyngeal carcinoma) in NMRI nude mice. The FaDu cell line was chosen based on its frequent use in studies of cancer imaging and tumor microenvironment. Methods: NMRI...

  7. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  8. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  9. T Cell Coinhibition and Immunotherapy in Human Breast Cancer

    OpenAIRE

    Janakiram, Murali; Abadi, Yael M.; Sparano, Joseph A.; Zang, Xingxing

    2012-01-01

    Costimulation and coinhibition generated by the B7 family and their receptor CD28 family have key roles in regulating T lymphocyte activation and tolerance. These pathways are very attractive therapeutic targets for human cancers including breast cancer. Gene polymorphisms of B7x (B7-H4/B7S1), PD-1 (CD279), and CTLA-4 (CD152) are associated with increased risk of developing breast cancer although the underlying mechanisms are unclear. In human breast cancer microenvironment, up-regulation of ...

  10. Telomerase activity in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, J.

    2000-10-01

    The overall goal of this collaborative project was to investigate the role in malignant cells of both chromosome telomeres, and telomerase, the enzyme that replicates telomeres. Telomeres are highly conserved nucleoprotein complexes located at the ends of eucaryotic chromosomes. Telomere length in somatic cells is reduced by 40--50 nucleotide pairs with every cell division due to incomplete replication of terminal DNA sequences and the absence of telomerase, the ribonucleoprotein that adds telomere DNA to chromosome ends. Although telomerase is active in cells with extended proliferative capacities, including more than 85% of tumors, work performed under this contract demonstrated that the telomeres of human cancer cells are shorter than those of paired normal cells, and that the length of the telomeres is characteristic of particular types of cancers. The extent of telomere shortening ostensibly is related to the number of cell divisions the tumor has undergone. It is believed that ongoing cell proliferation leads to the accumulation and fixation of new mutations in tumor cell lineages.Therefore, it is not unreasonable to assume that the degree of phenotypic variability is related to the proliferative history of the tumor, and therefore to telomere length, implying a correlation with prognosis. In some human tumors, short telomeres are also correlated with genomic instabilities, including interstitial chromosome translocation, loss of heterozygosity, and aneuoploidy. Moreover, unprotected chromosome ends are highly recombinogenic and telomere shortening in cultured human cells correlates with the formation of dicentric chromosomes, suggesting that critically short telomeres not only identify, but also predispose, cells to genomic instability, again implying a correlation with prognosis. Therefore, telomere length or content could be an important predictor of metastatic potential or responsiveness to various therapeutic modalities.

  11. Benzyl Isothiocyanate Inhibits Epithelial-Mesenchymal Transition in Cultured and Xenografted Human Breast Cancer Cells

    OpenAIRE

    Sehrawat, Anuradha; Singh, Shivendra V.

    2011-01-01

    We showed previously that cruciferous vegetable constituent benzyl isothiocyanate (BITC) inhibits growth of cultured and xenografted human breast cancer cells, and suppresses mammary cancer development in a transgenic mouse model. We now demonstrate, for the first time, that BITC inhibits epithelial-to-mesenchymal transition (EMT) in human breast cancer cells. Exposure of estrogen-independent MDA-MB-231 and estrogen-responsive MCF-7 human breast cancer cell lines and a pancreatic cancer cell ...

  12. Incidence and Mortality of Liver Cancer and their Relationship with the Human Development Index in the World

    Directory of Open Access Journals (Sweden)

    Masoumeh Arabsalmani

    2016-09-01

    Full Text Available Background: Information on the incidence and mortality of liver cancer can be useful for health programs and research activities, and with regard to the possible role of the HDI and liver cancer, this study aimed to investigate incidence and mortality from the cancer and their relationship with the indicator and its components in 2012 in world. Methods: In this ecologic study, data were extracted from GLOBOCAN in 2012. Data on HDI and its components were extracted from the World Bank. The number and standardized incidence and mortality rates of liver cancer were reported by regions in the world. Data were analyzed by SPSS software and Correlation coefficient test. Results: There was a total of 782,451 incidence cases. Of these patients, 228, 082 cases (29.15 % were women and 554, 369 cases (70.85 % men, and there were 745,533 deaths. Of the deaths, 224, 492 cases (30.11 % occurred in women and 521, 041 cases (69.89 % men were recorded in the world in 2012. Results showed that there was a significant inverse correlation between age-specific incidence rate ( ASIR and HDI (r=-0.345, p and #8804;0.001, as well significant inverse correlation was seen between age-specific mortality rate (ASMR, and HDI and its components. Conclusion: Liver cancer incidence and mortality are higher in the medium HDI countries. The relationship between the standardized incidence and mortality of liver cancer with HDI and its components, including life expectancy at birth, mean years of schooling and income level per person was significantly negative. [Biomed Res Ther 2016; 3(9.000: 800-807

  13. Development of drug-loaded chitosan hollow nanoparticles for delivery of paclitaxel to human lung cancer A549 cells.

    Science.gov (United States)

    Jiang, Jie; Liu, Ying; Wu, Chao; Qiu, Yang; Xu, Xiaoyan; Lv, Huiling; Bai, Andi; Liu, Xuan

    2017-08-01

    In this study, biodegradable chitosan hollow nanospheres (CHN) were fabricated using polystyrene nanospheres (PS) as templates. CHN were applied to increase the solubility of poorly water-soluble drugs. The lung cancer drug paclitaxel (PTX), which is used as a model drug, was loaded into CHN by the adsorption equilibrium method. The drug-loaded sample (PTX-CHN) offered sustained PTX release and good bioavailability. The state characterization of PTX by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) showed that the PTX absorbed into CHN existed in an amorphous state. An in vitro toxicity experiment indicated that CHN were nontoxic as carriers of poorly water-soluble drugs. The PTX-CHN produced a marked inhibition of lung cancer A549 cells proliferation and encouraged apoptosis. A cell uptake experiment indicated that PTX-CHN was successfully taken up by lung cancer A549 cells. Furthermore, a degradation experiment revealed that CHN were readily biodegradable. These findings state clearly that CHN can be regarded as promising biomaterials for lung cancer treatment.

  14. Human papillomaviruses and skin cancer.

    Science.gov (United States)

    Smola, Sigrun

    2014-01-01

    Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 120 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood. The clinical relevance of genus beta-PV infection has clearly been demonstrated in patients suffering from epidermodysplasia verruciformis (EV), a rare inherited disease associated with ahigh rate of skin cancer. In the normal population genus beta-PV are suspected to have an etiologic role in skin carcinogenesis as well but this is still controversially discussed. Their oncogenic potency has been investigated in mouse models and in vitro. In 2009, the International Agency for Research on Cancer (IARC) classified the genus beta HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. This chapter will give an overview on the knowns and unknowns of infections with genus beta-PV and discuss their potential impact on skin carcinogenesis in the general population.

  15. Developing Anticancer Copper(II) Pro-drugs Based on the Nature of Cancer Cells and the Human Serum Albumin Carrier IIA Subdomain.

    Science.gov (United States)

    Gou, Yi; Qi, Jinxu; Ajayi, Joshua-Paul; Zhang, Yao; Zhou, Zuping; Wu, Xiaoyang; Yang, Feng; Liang, Hong

    2015-10-01

    To synergistically enhance the selectivity and efficiency of anticancer copper drugs, we proposed and built a model to develop anticancer copper pro-drugs based on the nature of human serum albumin (HSA) IIA subdomain and cancer cells. Three copper(II) compounds of a 2-hydroxy-1-naphthaldehyde benzoyl hydrazone Schiff-base ligand in the presence pyridine, imidazole, or indazole ligands were synthesized (C1-C3). The structures of three HSA complexes revealed that the Cu compounds bind to the hydrophobic cavity in the HSA IIA subdomain. Among them, the pyridine and imidazole ligands of C1 and C2 are replaced by Lys199, and His242 directly coordinates with Cu(II). The indazole and Br ligands of C3 are replaced by Lys199 and His242, respectively. Compared with the Cu(II) compounds alone, the HSA complexes enhance cytotoxicity in MCF-7 cells approximately 3-5-fold, but do not raise cytotoxicity levels in normal cells in vitro through selectively accumulating in cancer cells to some extent. We find that the HSA complex has a stronger capacity for cell cycle arrest in the G2/M phase of MCF-7 by targeting cyclin-dependent kinase 1 (CDK1) and down-regulating the expression of CDK1 and cyclin B1. Moreover, the HSA complex promotes MCF-7 cell apoptosis possibly through the intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway, accompanied by the regulation of Bcl-2 family proteins.

  16. Atopy and development of cancer

    DEFF Research Database (Denmark)

    Skaaby, Tea; Nystrup Husemoen, Lise Lotte; Roswall, Nina

    2014-01-01

    BACKGROUND: Atopy is the familial or personal propensity to develop IgE antibodies against environmental allergens. Atopy, theoretically, could both prevent and promote the development of cancer. However, evidence from epidemiologic studies has been inconclusive. OBJECTIVE: We investigated...... the longitudinal association between atopy and the incidence of total and specific types of cancers of 5 Danish population-based studies. METHODS: Atopy was defined as serum specific IgE positivity against inhalant allergens. A total of 14,849 persons were followed up prospectively by linkage to the Danish Cancer...... Registry. We used Cox regression analysis, and risk was expressed as hazard ratios (HR) (95% CIs) for persons with atopy versus those without atopy. RESULTS: There were 1919 incident cancers (median follow-up, 11.8 years). There were no statistically significant associations between atopy and risk of any...

  17. One Health and cancer: A comparative study of human and canine cancers in Nairobi

    Directory of Open Access Journals (Sweden)

    Nyariaro Kelvin Momanyi

    2016-11-01

    Full Text Available Aim: Recent trends in comparative animal and human research inform us that collaborative research plays a key role in deciphering and solving cancer challenges. Globally, cancer is a devastating diagnosis with an increasing burden in both humans and dogs and ranks as the number three killer among humans in Kenya. This study aimed to provide comparative information on cancers affecting humans and dogs in Nairobi, Kenya. Materials and Methods: Dog data collection was by cancer case finding from five veterinary clinics and two diagnostic laboratories, whereas the human dataset was from the Nairobi Cancer Registry covering the period 2002-2012. The analysis was achieved using IBM SPSS Statistics® v.20 (Dog data and CanReg5 (human data. The human population was estimated from the Kenya National Census, whereas the dog population was estimated from the human using a human:dog ratio of 4.1:1. Results: A total of 15,558 human and 367 dog cancer cases were identified. In humans, females had higher cancer cases 8993 (an age-standardized rate of 179.3 per 100,000 compared to 6565 in males (122.1 per 100,000. This order was reversed in dogs where males had higher cases 198 (14.9 per 100,000 compared to 169 (17.5 per 100,000 in females. The incident cancer cases increased over the 11-year study period in both species. Common cancers affecting both humans and dogs were: Prostate (30.4, 0.8, the respiratory tract (8.3, 1.3, lymphoma (5.6, 1.4, and liver and biliary tract (6.3, 0.5, whereas, in females, they were: Breast (44.5, 3.6, lip, oral cavity, and pharynx (8.8, 0.6, liver and biliary tract (6.5, 1.2, and lymphoma (6.0, 0.6, respectively, per 100,000. Conclusion: The commonality of some of the cancers in both humans and dogs fortifies that it may be possible to use dogs as models and sentinels in studying human cancers in Kenya and Africa. We further infer that developing joint animalhuman cancer registries and integrated cancer surveillance systems may

  18. The role of neutering in cancer development.

    Science.gov (United States)

    Smith, Annette N

    2014-09-01

    Increased discussion on the influence of neutering on cancer development has been recently prompted with several studies that seem to indicate that incidence of some cancers may be increased with castration or spaying in our canine populations. Although the data are thought-provoking, we may not be able to extrapolate findings in single dog breeds to the entire species. Additionally, societal and humane issues related to pet overpopulation, as well as the incidence of other noncancerous diseases, behavior issues, and potentially decreased overall lifespan in unaltered animals must be taken into consideration before wholesale rejection of neutering in pets. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Prevalence of Human Papillomavirus in endometrial cancer

    DEFF Research Database (Denmark)

    Olesen, Tina Bech; Svahn, Malene Frøsig; Faber, Mette Tuxen

    2014-01-01

    HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.......HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer....

  20. Expression of polarity genes in human cancer.

    Science.gov (United States)

    Lin, Wan-Hsin; Asmann, Yan W; Anastasiadis, Panos Z

    2015-01-01

    Polarity protein complexes are crucial for epithelial apical-basal polarity and directed cell migration. Since alterations of these processes are common in cancer, polarity proteins have been proposed to function as tumor suppressors or oncogenic promoters. Here, we review the current understanding of polarity protein functions in epithelial homeostasis, as well as tumor formation and progression. As most previous studies focused on the function of single polarity proteins in simplified model systems, we used a genomics approach to systematically examine and identify the expression profiles of polarity genes in human cancer. The expression profiles of polarity genes were distinct in different human tissues and classified cancer types. Additionally, polarity expression profiles correlated with disease progression and aggressiveness, as well as with identified cancer types, where specific polarity genes were commonly altered. In the case of Scribble, gene expression analysis indicated its common amplification and upregulation in human cancer, suggesting a tumor promoting function.

  1. Antiangiogenic Steroids in Human Cancer Therapy

    OpenAIRE

    2005-01-01

    Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of ...

  2. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

    Torrente, Mariela C.; Rodrigo, Juan P.; Haigentz, Missak; Dikkers, Frederik G.; Rinaldo, Alessandra; Takes, Robert P.; Olofsson, Jan; Ferlito, Alfio

    2011-01-01

    Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we revie

  3. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

    Torrente, Mariela C.; Rodrigo, Juan P.; Haigentz, Missak; Dikkers, Frederik G.; Rinaldo, Alessandra; Takes, Robert P.; Olofsson, Jan; Ferlito, Alfio

    2011-01-01

    Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we revie

  4. Human papillomavirus infections in laryngeal cancer

    NARCIS (Netherlands)

    Torrente, M.C.; Rodrigo, J.P.; Haigentz Jr., M.; Dikkers, F.G.; Rinaldo, A.; Takes, R.P.; Olofsson, J.; Ferlito, A.

    2011-01-01

    Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we revie

  5. Human papillomavirus infections in laryngeal cancer

    NARCIS (Netherlands)

    Torrente, M.C.; Rodrigo, J.P.; Haigentz Jr., M.; Dikkers, F.G.; Rinaldo, A.; Takes, R.P.; Olofsson, J.; Ferlito, A.

    2011-01-01

    Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we

  6. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

    Torrente, Mariela C.; Rodrigo, Juan P.; Haigentz, Missak; Dikkers, Frederik G.; Rinaldo, Alessandra; Takes, Robert P.; Olofsson, Jan; Ferlito, Alfio

    Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we

  7. TP53 mutations, expression and interaction networks in human cancers.

    Science.gov (United States)

    Wang, Xiaosheng; Sun, Qingrong

    2017-01-03

    Although the associations of p53 dysfunction, p53 interaction networks and oncogenesis have been widely explored, a systematic analysis of TP53 mutations and its related interaction networks in various types of human cancers is lacking. Our study explored the associations of TP53 mutations, gene expression, clinical outcomes, and TP53 interaction networks across 33 cancer types using data from The Cancer Genome Atlas (TCGA). We show that TP53 is the most frequently mutated gene in a number of cancers, and its mutations appear to be early events in cancer initiation. We identified genes potentially repressed by p53, and genes whose expression correlates significantly with TP53 expression. These gene products may be especially important nodes in p53 interaction networks in human cancers. This study shows that while TP53-truncating mutations often result in decreased TP53 expression, other non-truncating TP53 mutations result in increased TP53 expression in some cancers. Survival analyses in a number of cancers show that patients with TP53 mutations are more likely to have worse prognoses than TP53-wildtype patients, and that elevated TP53 expression often leads to poor clinical outcomes. We identified a set of candidate synthetic lethal (SL) genes for TP53, and validated some of these SL interactions using data from the Cancer Cell Line Project. These predicted SL genes are promising candidates for experimental validation and the development of personalized therapeutics for patients with TP53-mutated cancers.

  8. Development of a stably transfected estrogen receptor-mediated luciferase reporter gene assay in the human T47D breast cancer cell line.

    Science.gov (United States)

    Legler, J; van den Brink, C E; Brouwer, A; Murk, A J; van der Saag, P T; Vethaak, A D; van der Burg, B

    1999-03-01

    Development of an estrogen receptor-mediated, chemical-activated luciferase reporter gene-expression (ER-CALUX) assay was attempted by stable transfection of luciferase reporter genes in a number of cell lines. Stable transfection of the chimeric Gal4 estrogen receptor and luciferase gene constructs in MCF-7 breast cancer and Hepa.1c1c7 mouse hepatoma cell lines, as well as transfection of a newly constructed luciferase reporter gene pEREtata-Luc in the ECC-1 human endometrial cell line, resulted in constitutive, non-estradiol-inducible clones. Stable transfection of pEREtata-Luc in the T47D breast cancer cell line, however, resulted in an extremely sensitive, highly responsive cell line. Following a 24-h exposure to estradiol (E2), stably transfected T47D.Luc cells demonstrated a detection limit of 0.5 pM, an EC50 of 6 pM, and a maximum induction of 100-fold relative to solvent controls. No clear reduction in responsiveness has been found over extended culture periods (50 passages). Anti-estrogens ICI 182,780, TCDD, and tamoxifen inhibited the estradiol-mediated luciferase induction. Genistein, nonylphenol, and o,p'DDT were the most potent (pseudo-)estrogens tested in this system (EC50 100, 260, and 660 nM, respectively). Determination of interactive effects of the (pseudo-)estrogens nonylphenol, o,p'DDT, chlordane, endosulfan, dieldrin, and methoxychlor revealed that, in combination with 3 pM E2, (pseudo-)estrogens were additive. Slightly more than additive effects (less than 2-fold) were found for combinations of dieldrin and endosulfan tested in the range of 3 to 6 microM. At these concentrations, the combination of endosulfan and chlordane demonstrated additive interaction. The ER-CALUX assay with T47D cells can provide a sensitive, responsive, and rapid in vitro system to detect and measure substances with potential (anti-)estrogenic activity.

  9. DNA damage checkpoint recovery and cancer development

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Haiyong [First affiliated hospital, Zhejiang University, School of medicine, Cancer Center, 79 Qingchun Road, Hangzhou 310003 (China); Zhang, Xiaoshan [Department of Genetics, University of Texas M.D. Anderson Cancer Center, Department of Genetics Unit 1010, 1515 Holcombe Blvd. Houston, TX 77030 (United States); Teng, Lisong, E-mail: lsteng@zju.edu.cn [First affiliated hospital, Zhejiang University, School of medicine, Cancer Center, 79 Qingchun Road, Hangzhou 310003 (China); Legerski, Randy J., E-mail: rlegersk@mdanderson.org [Department of Genetics, University of Texas M.D. Anderson Cancer Center, Department of Genetics Unit 1010, 1515 Holcombe Blvd. Houston, TX 77030 (United States)

    2015-06-10

    Cell cycle checkpoints were initially presumed to function as a regulator of cell cycle machinery in response to different genotoxic stresses, and later found to play an important role in the process of tumorigenesis by acting as a guard against DNA over-replication. As a counterpart of checkpoint activation, the checkpoint recovery machinery is working in opposition, aiming to reverse the checkpoint activation and resume the normal cell cycle. The DNA damage response (DDR) and oncogene induced senescence (OIS) are frequently found in precancerous lesions, and believed to constitute a barrier to tumorigenesis, however, the DDR and OIS have been observed to be diminished in advanced cancers of most tissue origins. These findings suggest that when progressing from pre-neoplastic lesions to cancer, DNA damage checkpoint barriers are overridden. How the DDR checkpoint is bypassed in this process remains largely unknown. Activated cytokine and growth factor-signaling pathways were very recently shown to suppress the DDR and to promote uncontrolled cell proliferation in the context of oncovirus infection. In recent decades, data from cell line and tumor models showed that a group of checkpoint recovery proteins function in promoting tumor progression; data from patient samples also showed overexpression of checkpoint recovery proteins in human cancer tissues and a correlation with patients' poor prognosis. In this review, the known cell cycle checkpoint recovery proteins and their roles in DNA damage checkpoint recovery are reviewed, as well as their implications in cancer development. This review also provides insight into the mechanism by which the DDR suppresses oncogene-driven tumorigenesis and tumor progression. - Highlights: • DNA damage checkpoint works as a barrier to cancer initiation. • DDR machinary response to genotoxic and oncogenic stress in similar way. • Checkpoint recovery pathways provide active signaling in cell cycle control. • Checkpoint

  10. Potential Prognostic Markers for Human Prostate Cancer

    Science.gov (United States)

    2001-03-01

    Prostate 35: 185-192, 1998 osteoblasts on prostate carcinoma proliferation and chemo- 32. Trikha M, Cai Y, Grignon D, Honn KV: Identification taxis ...Markers for Human Prostate Cancer PRINCIPAL INVESTIGATOR: Bruce R. Zetter, Ph.D. CONTRACTING ORGANIZATION: Children’s Hospital Boston, Massachusetts...March 2001 Final (1 Sep 98 - 28 Feb 01) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Potential Prognostic Markers for Human Prostate Cancer DAMD17-98-1

  11. Defining the cellular precursors to human breast cancer

    Science.gov (United States)

    Keller, Patricia J.; Arendt, Lisa M.; Skibinski, Adam; Logvinenko, Tanya; Klebba, Ina; Dong, Shumin; Smith, Avi E.; Prat, Aleix; Perou, Charles M.; Gilmore, Hannah; Schnitt, Stuart; Naber, Stephen P.; Garlick, Jonathan A.; Kuperwasser, Charlotte

    2012-01-01

    Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM+) and basal/myoepithelial (CD10+). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM+ epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10+ cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10+ breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues. PMID:21940501

  12. Human papillomavirus in cervical cancer and oropharyngeal cancer: One cause, two diseases.

    Science.gov (United States)

    Berman, Tara A; Schiller, John T

    2017-06-15

    Human papillomavirus (HPV) causes greater than 5% of cancers worldwide, including all cervical cancers and an alarmingly increasing proportion of oropharyngeal cancers (OPCs). Despite markedly reduced cervical cancer incidence in industrialized nations with organized screening programs, cervical cancer remains the second most common cause of death from cancer in women worldwide, as developing countries lack resources for universal, high-quality screening. In the United States, HPV-related OPC is only 1 of 5 cancers with a rising incidence since 1975 and now has taken over the cervix as the most common site of HPV-related cancer. Similar trends follow throughout North America and Europe. The need for early detection and prevention is paramount. Despite the common etiologic role of HPV in the development of cervical cancer and HPV-associated OPC, great disparity exists between incidence, screening modalities (or lack thereof), treatment, and prevention in these 2 very distinct cohorts. These differences in cervical cancer and HPV-associated OPC and their impact are discussed here. Cancer 2017;123:2219-2229. © 2017 American Cancer Society. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  13. Epigenetic changes in virus-associated human cancers

    Institute of Scientific and Technical Information of China (English)

    Hsin Pai LI; Yu Wei LEU; Yu Sun CHANG

    2005-01-01

    Epigenetics of human cancer becomes an area of emerging research direction due to a growing understanding of specific epigenetic pathways and rapid development of detection technologies. Aberrant promoter hypermethylation is a prevalent phenonmena in human cancers. Tumor suppressor genes are often hypermethylated due to the increased activity or deregulation of DNMTs. Increasing evidence also reveals that viral genes are one of the key players in regulating DNA methylation. In this review, we will focus on hypermethylation and tumor suppressor gene silencing and the signal pathways that are involved, particularly in cancers closely associated with the hepatitis B virus, simian virus 40 (SV40), and Epstein-Barr virus. In addition, we will discuss current technologies for genome-wide detection of epigenetically regulated targets, which allow for systematic DNA hypermethylation analysis. The study of epigenetic changes should provide a global view of gene profile in cancer, and epigenetic markers could be used for early detection,prognosis, and therapy of cancer.

  14. Expression of Axl and its prognostic significance in human breast cancer

    OpenAIRE

    Jin, Gaoyuan; Wang, Zhenzhen; Wang, Jianguang; Zhang, Like; CHEN Yanbin; Yuan, Pengfei; Liu, Dechun

    2016-01-01

    Breast cancer is the most common malignant cancer and second leading cause of cancer-related death among women, and its prevalence continues to increase. Axl overexpression has been identified in the many types of human cancer, and it has been demonstrated to participate in signaling pathways related to carcinogenesis and cancer development. In the present study, Axl expression was examined by performing immunohistochemical staining in 60 breast cancer tumors and 40 benign breast lesions (25 ...

  15. Biological stoichiometry in human cancer.

    Directory of Open Access Journals (Sweden)

    James J Elser

    Full Text Available BACKGROUND: A growing tumor in the body can be considered a complex ecological and evolutionary system. A new eco-evolutionary hypothesis (the "Growth Rate Hypothesis", GRH proposes that tumors have elevated phosphorus (P demands due to increased allocation to P-rich nucleic acids, especially ribosomal RNA, to meet the protein synthesis demands of accelerated proliferation. METHODOLOGY/PRINCIPAL FINDINGS: We determined the elemental (C, N, P and nucleic acid contents of paired malignant and normal tissues from colon, lung, liver, or kidney for 121 patients. Consistent with the GRH, lung and colon tumors were significantly higher (by approximately two-fold in P content (fraction of dry weight and RNA content and lower in nitrogen (N:P ratio than paired normal tissue, and P in RNA contributed a significantly larger fraction of total biomass P in malignant relative to normal tissues. Furthermore, patient-specific differences for %P between malignant and normal tissues were positively correlated with such differences for %RNA, both for the overall data and within three of the four organ sites. However, significant differences in %P and %RNA between malignant and normal tissues were not seen in liver and kidney and, overall, RNA contributed only approximately 11% of total tissue P content. CONCLUSIONS/SIGNIFICANCE: Data for lung and colon tumors provide support for the GRH in human cancer. The two-fold amplification of P content in colon and lung tumors may set the stage for potential P-limitation of their proliferation, as such differences often do for rapidly growing biota in ecosystems. However, data for kidney and liver do not support the GRH. To account for these conflicting observations, we suggest that local environments in some organs select for neoplastic cells bearing mutations increasing cell division rate ("r-selected," as in colon and lung while conditions elsewhere may select for reduced mortality rate ("K-selected," as in liver and

  16. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  17. Human Papilloma Viruses and Breast Cancer – Assessment of Causality

    Science.gov (United States)

    Lawson, James Sutherland; Glenn, Wendy K.; Whitaker, Noel James

    2016-01-01

    High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case–control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is “specificity.” HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers. PMID:27747193

  18. Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts

    Science.gov (United States)

    Cheng, Michelle; Ho, Samantha; Yoo, Jun Hwan; Tran, Deanna Hoang-Yen; Bakirtzi, Kyriaki; Su, Bowei; Tran, Diana Hoang-Ngoc; Kubota, Yuzu; Ichikawa, Ryan; Koon, Hon Wai

    2015-01-01

    Background Cathelicidin (LL-37 in humans and mCRAMP in mice) represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. Methods We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial–mesenchymal transition (EMT) of colon cancer cells and fibroblast-supported colon cancer cell proliferation. Results Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-β1-induced EMT of colon cancer cells. Media conditioned by the human colonic CCD-18Co fibroblasts promoted human colon cancer HT-29 cell proliferation. Cathelicidin pretreatment inhibited colon cancer cell proliferation mediated by media conditioned by human colonic CCD-18Co fibroblasts. Cathelicidin disrupted tubulin distribution in colonic fibroblasts. Disruption of tubulin in fibroblasts reduced fibroblast-supported colon cancer cell proliferation. Conclusion Cathelicidin effectively inhibits colon cancer development by interfering with EMT and fibroblast

  19. Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies.

    Science.gov (United States)

    Hwang, Pei-Ing; Wu, Huan-Bin; Wang, Chin-Di; Lin, Bai-Ling; Chen, Cheng-Tao; Yuan, Shinsheng; Wu, Guani; Li, Ker-Chau

    2011-09-01

    To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue. By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific Gene Expression Templates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis.Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity. These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.

  20. Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies

    Directory of Open Access Journals (Sweden)

    Yuan Shinsheng

    2011-09-01

    Full Text Available Abstract Background To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue. Results By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific Gene Expression Templates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis. Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity. Conclusions These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.

  1. Developing human technology curriculum

    Directory of Open Access Journals (Sweden)

    Teija Vainio

    2012-10-01

    Full Text Available During the past ten years expertise in human-computer interaction has shifted from humans interacting with desktop computers to individual human beings or groups of human beings interacting with embedded or mobile technology. Thus, humans are not only interacting with computers but with technology. Obviously, this shift should be reflected in how we educate human-technology interaction (HTI experts today and in the future. We tackle this educational challenge first by analysing current Master’s-level education in collaboration with two universities and second, discussing postgraduate education in the international context. As a result, we identified core studies that should be included in the HTI curriculum. Furthermore, we discuss some practical challenges and new directions for international HTI education.

  2. The influence of polymorphisms of glutathione S-transferases M1 and M3 on the development of human urothelial cancer.

    Science.gov (United States)

    Golka, Klaus; Schmidt, Tobias; Seidel, Thilo; Dietrich, Holger; Roemer, Hermann C; Lohlein, Dietrich; Reckwitz, Thomas; Sokeland, Jurgen; Weistenhofer, Wobbeke; Blaszkewicz, Meinolf; Selinski, Silvia

    2008-01-01

    Cigarette smoking is the most important risk factor for development of transitional cell carcinoma of the urinary bladder. The effect of polymorphisms of glutathione S-transferases M1 (GSTM1) and M3 (GSTM3) on the influence of cigarette smoking on urinary bladder carcinogenesis was investigated. In total, 293 bladder cancer patients from hospitals in Dortmund and Wittenberg as well as 176 patients without any malignancy from a Department of Surgery from Dortmund were genotyped for GSTM1 and GSTM3 according to standard PCR/RFLP methods. Smoking habits were quantified by a standardized interview. The proportion of GSTM1 negative cases was 63% in the entire bladder cancer cases group compared to 50% in controls. The GSTM3*A/*A genotype was 76% in cancer cases versus 74% in controls. Smokers and ex-smokers were overrepresented in bladder cancer cases. A significant association between smoking status and GSTM1 or GSTM3 genotype was not detected. The elevated proportion of GSTM1 negative bladder cancer cases shows an effect of this polymorphic enzyme on development of bladder cancer. In contrast to other studies, an influence of GSTM1 on the risk due to cigarette smoking was not observed.

  3. Gene transcriptional networks integrate microenvironmental signals in human breast cancer.

    Science.gov (United States)

    Xu, Ren; Mao, Jian-Hua

    2011-04-01

    A significant amount of evidence shows that microenvironmental signals generated from extracellular matrix (ECM) molecules, soluble factors, and cell-cell adhesion complexes cooperate at the extra- and intracellular level. This synergetic action of microenvironmental cues is crucial for normal mammary gland development and breast malignancy. To explore how the microenvironmental genes coordinate in human breast cancer at the genome level, we have performed gene co-expression network analysis in three independent microarray datasets and identified two microenvironment networks in human breast cancer tissues. Network I represents crosstalk and cooperation of ECM microenvironment and soluble factors during breast malignancy. The correlated expression of cytokines, chemokines, and cell adhesion proteins in Network II implicates the coordinated action of these molecules in modulating the immune response in breast cancer tissues. These results suggest that microenvironmental cues are integrated with gene transcriptional networks to promote breast cancer development.

  4. Arsenic Exposure and the Induction of Human Cancers

    Directory of Open Access Journals (Sweden)

    Victor D. Martinez

    2011-01-01

    Full Text Available Arsenic is a metalloid, that is, considered to be a human carcinogen. Millions of individuals worldwide are chronically exposed through drinking water, with consequences ranging from acute toxicities to development of malignancies, such as skin and lung cancer. Despite well-known arsenic-related health effects, the molecular mechanisms involved are not fully understood; however, the arsenic biotransformation process, which includes methylation changes, is thought to play a key role. This paper explores the relationship of arsenic exposure with cancer development and summarizes current knowledge of the potential mechanisms that may contribute to the neoplastic processes observed in arsenic exposed human populations.

  5. Autonomic nerve development contributes to prostate cancer progression.

    Science.gov (United States)

    Bauman, John; McVary, Kevin

    2013-11-01

    In a significant translational study, Magnon et al. investigated the role that the autonomic nervous system plays in the development and spread of prostate cancer in both mice and human models. The study shows different roles for both branches of the autonomic nervous system, with the sympathetic system promoting early stages of tumorigenesis, and the parasympathetic system promoting cancer dissemination. This information could lead to important new foundations for treatment, therapies and management of prostate cancer.

  6. Novel innate cancer killing activity in humans

    Directory of Open Access Journals (Sweden)

    Lovato James

    2011-08-01

    Full Text Available Abstract Background In this study, we pilot tested an in vitro assay of cancer killing activity (CKA in circulating leukocytes of 22 cancer cases and 25 healthy controls. Methods Using a human cervical cancer cell line, HeLa, as target cells, we compared the CKA in circulating leukocytes, as effector cells, of cancer cases and controls. The CKA was normalized as percentages of total target cells during selected periods of incubation time and at selected effector/target cell ratios in comparison to no-effector-cell controls. Results Our results showed that CKA similar to that of our previous study of SR/CR mice was present in human circulating leukocytes but at profoundly different levels in individuals. Overall, males have a significantly higher CKA than females. The CKA levels in cancer cases were lower than that in healthy controls (mean ± SD: 36.97 ± 21.39 vs. 46.28 ± 27.22. Below-median CKA was significantly associated with case status (odds ratio = 4.36; 95% Confidence Interval = 1.06, 17.88 after adjustment of gender and race. Conclusions In freshly isolated human leukocytes, we were able to detect an apparent CKA in a similar manner to that of cancer-resistant SR/CR mice. The finding of CKA at lower levels in cancer patients suggests the possibility that it may be of a consequence of genetic, physiological, or pathological conditions, pending future studies with larger sample size.

  7. Decorin in Human Colon Cancer: Localization In Vivo and Effect on Cancer Cell Behavior In Vitro.

    Science.gov (United States)

    Nyman, Marie C; Sainio, Annele O; Pennanen, Mirka M; Lund, Riikka J; Vuorikoski, Sanna; Sundström, Jari T T; Järveläinen, Hannu T

    2015-09-01

    Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational. © The Author(s) 2015.

  8. Developing Human Resources through Actualizing Human Potential

    Science.gov (United States)

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  9. Oral contraceptives, human papillomavirus and cervical cancer.

    Science.gov (United States)

    La Vecchia, Carlo; Boccia, Stefania

    2014-03-01

    Oncogenic human papillomavirus is the key determinant of cervical cancer, but other risk factors interact with it to define individual risk. Among these, there is oral contraceptive (OC) use. A quantitative review of the link between OCs and cervical cancer was performed. Long-term (>5 year) current or recent OC use has been related to an about two-fold excess risk of cervical cancer. Such an excess risk, however, levels off after stopping use, and approaches unity 10 or more years after stopping. The public health implications of OC use for cervical cancer are limited. In any case, such implications are greater in middle-income and low-income countries, as well as in central and eastern Europe and Latin America, where cervical cancer screening and control remain inadequate.

  10. Strategies in cancer vaccines development.

    Science.gov (United States)

    Cunto-Amesty, Gina; Monzavi-Karbassi, Behjatolah; Luo, Ping; Jousheghany, Fariba; Kieber-Emmons, Thomas

    2003-05-01

    The recent definition of tumour-specific immunity in cancer patients and the identification of tumour-associated antigens have generated renewed enthusiasm for the application of immune-based therapies for the treatment of malignancies. Recent developments in cancer vaccines have also been based on an improved understanding of the cellular interactions required to induce a specific anti-tumour immune response. Consequently, a number of cancer vaccines have entered clinical trials. Targeting broad-spectrum tumour-associated antigens has emerged as a strategy to lower the risk of tumour escape due to the loss of specific nominal antigen. Amongst the most challenging of tumour-associated antigens to which to target in active specific immunotherapy applications are carbohydrate antigens. As carbohydrates are intrinsically T-cell-independent antigens, more novel approaches are perhaps needed to drive specific-T-cell-dependent immune responses to carbohydrate antigens. In this context peptide mimetics of core structures of tumour-associated carbohydrate antigens might be developed to augment immune responses to these broad-spectrum antigens.

  11. Pre-clinical Orthotopic Murine Model of Human Prostate Cancer.

    Science.gov (United States)

    Shahryari, Varahram; Nip, Hannah; Saini, Sharanjot; Dar, Altaf A; Yamamura, Soichiro; Mitsui, Yozo; Colden, Melissa; Bucay, Nathan; Tabatabai, Laura Z; Greene, Kirsten; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir; Majid, Shahana

    2016-08-29

    To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.

  12. Radiobiology of human cancer radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, J.R.

    1978-01-01

    The author has systematically collected and collated the scientific literature correlating the basic and clinical sciences in this field in order to produce a definitive treatise. The book thoroughly reviews the biology and biochemistry relevant to radiobiology and describes the critical locus for the extinction of cell reproductive capacity. Extensive coverage is given to oxygen effect, hyperthermia, high linear energy transfer, cell populations, and similar topics. Separate sections cover time, dose, and fractionation; radiation hematology; cancer chemotherapy; and cancer immunology. The book also contains invaluable discussions of techniques for optimizing radiotherapy alone and in combination with other therapies.

  13. Role of cyclin B1/Cdc2 up-regulation in the development of mitotic prometaphase arrest in human breast cancer cells treated with nocodazole.

    Directory of Open Access Journals (Sweden)

    Hye Joung Choi

    Full Text Available BACKGROUND: During a normal cell cycle, the transition from G₂ phase to mitotic phase is triggered by the activation of the cyclin B1-dependent Cdc2 kinase. Here we report our finding that treatment of MCF-7 human breast cancer cells with nocodazole, a prototypic microtubule inhibitor, results in strong up-regulation of cyclin B1 and Cdc2 levels, and their increases are required for the development of mitotic prometaphase arrest and characteristic phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: It was observed that there was a time-dependent early increase in cyclin B1 and Cdc2 protein levels (peaking between 12 and 24 h post treatment, and their levels started to decline after the initial increase. This early up-regulation of cyclin B1 and Cdc2 closely matched in timing the nocodazole-induced mitotic prometaphase arrest. Selective knockdown of cyclin B1or Cdc2 each abrogated nocodazole-induced accumulation of prometaphase cells. The nocodazole-induced prometaphase arrest was also abrogated by pre-treatment of cells with roscovitine, an inhibitor of cyclin-dependent kinases, or with cycloheximide, a protein synthesis inhibitor that was found to suppress cyclin B1 and Cdc2 up-regulation. In addition, we found that MAD2 knockdown abrogated nocodazole-induced accumulation of cyclin B1 and Cdc2 proteins, which was accompanied by an attenuation of nocodazole-induced prometaphase arrest. CONCLUSIONS/SIGNIFICANCE: These observations demonstrate that the strong early up-regulation of cyclin B1 and Cdc2 contributes critically to the rapid and selective accumulation of prometaphase-arrested cells, a phenomenon associated with exposure to microtubule inhibitors.

  14. Catalog of genetic progression of human cancers: breast cancer.

    Science.gov (United States)

    Desmedt, Christine; Yates, Lucy; Kulka, Janina

    2016-03-01

    With the rapid development of next-generation sequencing, deeper insights are being gained into the molecular evolution that underlies the development and clinical progression of breast cancer. It is apparent that during evolution, breast cancers acquire thousands of mutations including single base pair substitutions, insertions, deletions, copy number aberrations, and structural rearrangements. As a consequence, at the whole genome level, no two cancers are identical and few cancers even share the same complement of "driver" mutations. Indeed, two samples from the same cancer may also exhibit extensive differences due to constant remodeling of the genome over time. In this review, we summarize recent studies that extend our understanding of the genomic basis of cancer progression. Key biological insights include the following: subclonal diversification begins early in cancer evolution, being detectable even in in situ lesions; geographical stratification of subclonal structure is frequent in primary tumors and can include therapeutically targetable alterations; multiple distant metastases typically arise from a common metastatic ancestor following a "metastatic cascade" model; systemic therapy can unmask preexisting resistant subclones or influence further treatment sensitivity and disease progression. We conclude the review by describing novel approaches such as the analysis of circulating DNA and patient-derived xenografts that promise to further our understanding of the genomic changes occurring during cancer evolution and guide treatment decision making.

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

    Science.gov (United States)

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

    2010-08-01

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

  16. Understanding cervical cancer in the context of developing countries

    Directory of Open Access Journals (Sweden)

    Farhad Ali

    2012-01-01

    Full Text Available Cancer is one of the leading causes of deaths worldwide. Among the women, gynecological cancers are most common. Cervical cancer is a main gynecological cancer of the women. The global burden of cervical cancer is disproportionately high among the developing countries where 85 per cent of the estimated 493, 000 new cases and 273, 000 deaths occur worldwide. There are several dimensions of the problem. Cervical cancer is a problem where people are poor, where the socio-economic status of the women is low and sometimes specific ethnicity also posses additional risk to the women to develop cervical cancer. Human papillomavirus infection is a main risk factor for the cervical cancer however there are some other factors which increase the risk. Among them some are number of sexual partners, age of first sexual intercourse, infection of sexually transmitted diseases, use of hormonal contraceptives, parity, age, smoking, food and diet. Apart from these factors, some other issues, such as policy on cancer, capacity of health system, socio-economic and cultural factors and awareness among the women are also associated with the cervical cancer related morbidity and mortality across the developing countries. There some interventions which give promising results in terms of reducing cervical cancer related morbidity and mortality. Among them visual inspection of cervix with acetic acid followed by treatment is one such effective method.

  17. Integration of principles of systems biology and radiation biology: toward development of in silico models to optimize IUdR-mediated radiosensitization of DNA mismatch repair-deficient (damage tolerant human cancers

    Directory of Open Access Journals (Sweden)

    Timothy James Kinsella

    2011-08-01

    Full Text Available Over the last 7 years, we have focused our experimental and computational research efforts on improving our understanding of the biochemical, molecular, and cellular processing of iododeoxyuridine (IUdR and ionizing radiation (IR induced DNA base damage by DNA mismatch repair (MMR. These coordinated research efforts, sponsored by the National Cancer Institute Integrative Cancer Biology Program (ICBP, brought together system scientists with expertise in engineering, mathematics, and complex systems theory and translational cancer researchers with expertise in radiation biology. Our overall goal was to begin to develop computational models of IUdR- and/or IR- induced base damage processing by MMR that may provide new clinical strategies to optimize IUdR-mediated radiosensitiztion in MMR deficient (MMR- damage tolerant human cancers. Using multiple scales of experimental testing, ranging from purified protein systems to in vitro (cellular and to in vivo (human tumor xenografts in athymic mice models, we have begun to integrate and interpolate these experimental data with hybrid stochastic biochemical models of MMR damage processing and probabilistic cell cycle regulation models through a systems biology approach. In this article, we highlight the results and current status of our integration of radiation biology approaches and computational modeling to enhance IUdR-mediated radiosensitization in MMR- damage tolerant cancers.

  18. Identification of cancer risk lncRNAs and cancer risk pathways regulated by cancer risk lncRNAs based on genome sequencing data in human cancers.

    Science.gov (United States)

    Li, Yiran; Li, Wan; Liang, Binhua; Li, Liansheng; Wang, Li; Huang, Hao; Guo, Shanshan; Wang, Yahui; He, Yuehan; Chen, Lina; He, Weiming

    2016-12-19

    Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The complexity of cancer can be reduced to a small number of underlying principles like cancer hallmarks which could govern the transformation of normal cells to cancer. Besides, the growth and metastasis of cancer often relate to combined effects of long non-coding RNAs (lncRNAs). Here, we performed comprehensive analysis for lncRNA expression profiles and clinical data of six types of human cancer patients from The Cancer Genome Atlas (TCGA), and identified six risk pathways and twenty three lncRNAs. In addition, twenty three cancer risk lncRNAs which were closely related to the occurrence or development of cancer had a good classification performance for samples of testing datasets of six cancer datasets. More important, these lncRNAs were able to separate samples in the entire cancer dataset into high-risk group and low-risk group with significantly different overall survival (OS), which was further validated in ten validation datasets. In our study, the robust and effective cancer biomarkers were obtained from cancer datasets which had information of normal-tumor samples. Overall, our research can provide a new perspective for the further study of clinical diagnosis and treatment of cancer.

  19. Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells.

    Science.gov (United States)

    Li, Ruilin; Hu, Siyi; Chang, Yan; Zhang, Zhihui; Zha, Zhao; Huang, Hui; Shen, Guodong; Liu, Jing; Song, Lihua; Wei, Wei

    2016-04-15

    Human epidermal growth factor receptor 2 (HER2) is one of the most studied tumor-associated antigens for cancer immunotherapy. An engineered anti-HER-2 chimeric A21 antibody (chA21) is a chimeric antibody targeted to subdomain I of the HER2 extracellular domain. Here, we report the anti-tumor activity of the novel engineered monoclonal antibody humanized chA21 (HuA21) that targets HER2 on the basis of chA21, and we describe the underlying mechanisms. Our results reveal that HuA21 markedly inhibits the proliferation and migration of HER2-overexpressing breast cancer cells and causes enhanced antibody-dependent cell-mediated cytotoxicity potency against HER2-overexpressing tumor cells. In particular, HuA21, but not trastuzumab (Tra), markedly suppresses growth and enhances the internalization of the antibody in Tra-resistant BT-474 breast cancer cells. These characteristics are highly associated with the intrinsic ability of HuA21 to down-regulate HER2 activation and inhibit the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) signaling pathways. Furthermore, the combination of HuA21 with Tra synergistically enhances the anti-tumor effects in vitro and in vivo and inhibits HER2 activation and the ERK1/2 and Akt signaling pathways. Altogether, our results suggest that HuA21 may represent a unique anti-HER2 antibody with potential as a therapeutic candidate alone or in combination with other anti-HER2 reagents in cancer therapy.

  20. Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruilin Li

    2016-04-01

    Full Text Available Human epidermal growth factor receptor 2 (HER2 is one of the most studied tumor-associated antigens for cancer immunotherapy. An engineered anti-HER-2 chimeric A21 antibody (chA21 is a chimeric antibody targeted to subdomain I of the HER2 extracellular domain. Here, we report the anti-tumor activity of the novel engineered monoclonal antibody humanized chA21 (HuA21 that targets HER2 on the basis of chA21, and we describe the underlying mechanisms. Our results reveal that HuA21 markedly inhibits the proliferation and migration of HER2-overexpressing breast cancer cells and causes enhanced antibody-dependent cell-mediated cytotoxicity potency against HER2-overexpressing tumor cells. In particular, HuA21, but not trastuzumab (Tra, markedly suppresses growth and enhances the internalization of the antibody in Tra-resistant BT-474 breast cancer cells. These characteristics are highly associated with the intrinsic ability of HuA21 to down-regulate HER2 activation and inhibit the extracellular signal-regulated kinase 1/2 (ERK1/2 and protein kinase B (Akt signaling pathways. Furthermore, the combination of HuA21 with Tra synergistically enhances the anti-tumor effects in vitro and in vivo and inhibits HER2 activation and the ERK1/2 and Akt signaling pathways. Altogether, our results suggest that HuA21 may represent a unique anti-HER2 antibody with potential as a therapeutic candidate alone or in combination with other anti-HER2 reagents in cancer therapy.

  1. The oncogenic potential of human cytomegalovirus and breast cancer.

    Directory of Open Access Journals (Sweden)

    Georges eHerbein

    2014-08-01

    Full Text Available Breast cancer is among the leading causes of cancer-related death among women. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. Numerous articles indicate that breast tumors exhibit diverse phenotypes depending on their distinct physiopathological signatures, clinical courses and therapeutic possibilities. The human cytomegalovirus (HCMV is a multifaceted highly host specific betaherpesvirus that is regarded as asymptomatic or mildly pathogenic virus in immunocompetent host. HCMV may cause serious in utero infections as well as acute and chronic complications in immunocompromised individual. The involvement of HCMV in late inflammatory complications underscores its possible role in inflammatory diseases and cancer. HCMV targets a variety of cell types in vivo, including macrophages, epithelial cells, endothelial cells, fibroblasts, stromal cells, neuronal cells, smooth muscle cells, and hepatocytes. HCMV can be detected in the milk after delivery and thereby HCMV could spread to adjacent mammary epithelial cells. HCMV also infects macrophages and induces an atypical M1/M2 phenotype, close to the tumor associated macrophage phenotype, which is associated with the release of cytokines involved in cancer initiation or promotion and breast cancer of poor prognosis. HCMV antigens and DNA have been detected in tissue biopsies of breast cancers and elevation in serum HCMV IgG antibody levels has been reported to precede the development of breast cancer in some women. In this review, we will discuss the potential role of HCMV in the initiation and progression of breast cancer.

  2. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation

    OpenAIRE

    Le Rolle, Anne-France; Chiu, Thang K; ZENG, ZHAOSHI; Shia, Jinru; Weiser, Martin R; Paty, Philip B.; Chiu, Vi K

    2016-01-01

    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut ) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer i...

  3. Lnc2Cancer: a manually curated database of experimentally supported lncRNAs associated with various human cancers.

    Science.gov (United States)

    Ning, Shangwei; Zhang, Jizhou; Wang, Peng; Zhi, Hui; Wang, Jianjian; Liu, Yue; Gao, Yue; Guo, Maoni; Yue, Ming; Wang, Lihua; Li, Xia

    2016-01-04

    Lnc2Cancer (http://www.bio-bigdata.net/lnc2cancer) is a manually curated database of cancer-associated long non-coding RNAs (lncRNAs) with experimental support that aims to provide a high-quality and integrated resource for exploring lncRNA deregulation in various human cancers. LncRNAs represent a large category of functional RNA molecules that play a significant role in human cancers. A curated collection and summary of deregulated lncRNAs in cancer is essential to thoroughly understand the mechanisms and functions of lncRNAs. Here, we developed the Lnc2Cancer database, which contains 1057 manually curated associations between 531 lncRNAs and 86 human cancers. Each association includes lncRNA and cancer name, the lncRNA expression pattern, experimental techniques, a brief functional description, the original reference and additional annotation information. Lnc2Cancer provides a user-friendly interface to conveniently browse, retrieve and download data. Lnc2Cancer also offers a submission page for researchers to submit newly validated lncRNA-cancer associations. With the rapidly increasing interest in lncRNAs, Lnc2Cancer will significantly improve our understanding of lncRNA deregulation in cancer and has the potential to be a timely and valuable resource.

  4. Tissue-engineered models of human tumors for cancer research

    Science.gov (United States)

    Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2015-01-01

    Introduction Drug toxicity often goes undetected until clinical trials, which are the most costly and dangerous phase of drug development. Both the cultures of human cells and animal studies have limitations that cannot be overcome by incremental improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. An area that could greatly benefit from these models is cancer research. Areas covered In this review, the authors first describe the engineered tumor systems, using Ewing's sarcoma as an example of human tumor that cannot be predictably studied in cell culture and animal models. Then, they discuss the importance of the tissue context for cancer progression and outline the biomimetic principles for engineering human tumors. Finally, they discuss the utility of bioengineered tumor models for cancer research and address the challenges in modeling human tumors for use in drug discovery and testing. Expert opinion While tissue models are just emerging as a new tool for cancer drug discovery, they are already demonstrating potential for recapitulating, in vitro, the native behavior of human tumors. Still, numerous challenges need to be addressed before we can have platforms with a predictive power appropriate for the pharmaceutical industry. Some of the key needs include the incorporation of the vascular compartment, immune system components, and mechanical signals that regulate tumor development and function. PMID:25662589

  5. Characterizing metabolic changes in human colorectal cancer.

    Science.gov (United States)

    Williams, Michael D; Zhang, Xing; Park, Jeong-Jin; Siems, William F; Gang, David R; Resar, Linda M S; Reeves, Raymond; Hill, Herbert H

    2015-06-01

    Colorectal cancer (CRC) remains a leading cause of cancer death worldwide, despite the fact that it is a curable disease when diagnosed early. The development of new screening methods to aid in early diagnosis or identify precursor lesions at risk for progressing to CRC will be vital to improving the survival rate of individuals predisposed to CRC. Metabolomics is an advancing area that has recently seen numerous applications to the field of cancer research. Altered metabolism has been studied for many years as a means to understand and characterize cancer. However, further work is required to establish standard procedures and improve our ability to identify distinct metabolomic profiles that can be used to diagnose CRC or predict disease progression. The present study demonstrates the use of direct infusion traveling wave ion mobility mass spectrometry to distinguish metabolic profiles from CRC samples and matched non-neoplastic epithelium as well as metastatic and primary tumors at different stages of disease (T1-T4). By directly infusing our samples, the analysis time was reduced significantly, thus increasing the speed and efficiency of this method compared to traditional metabolomics platforms. Partial least squares discriminant analysis was used to visualize differences between the metabolic profiles of sample types and to identify the specific m/z features that led to this differentiation. Identification of the distinct m/z features was made using the human metabolome database. We discovered alterations in fatty acid biosynthesis and oxidative, glycolytic, and polyamine pathways that distinguish tumors from non-malignant colonic epithelium as well as various stages of CRC. Although further studies are needed, our results indicate that colonic epithelial cells undergo metabolic reprogramming during their evolution to CRC, and the distinct metabolites could serve as diagnostic tools or potential targets in therapy or primary prevention. Graphical Abstract

  6. Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yung-Lin Chu

    2013-07-01

    Full Text Available Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic 大 蒜 Dà Suàn; Allium sativum, is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients.

  7. Expression of Obesity Hormone Leptin in Human Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Jin-chun Cong; Xian-wei Dai; Ming-yang Shen; Jun-jiang Wang; Chun-sheng Chen; Hong Zhang; Lei Qiao

    2009-01-01

    Objective: The obesity hormone, leptin, has been found to participate in the development and proliferation of normal and malignant tissues. The aim of this study was to evaluate the role of leptin in human colorectal cancer.Methods: Serum leptin levels were measured via ABC-ELLSA in 30 colorectal cancers and 24 normal controls. Leptin concentration in colorectal cancer was analyzed in terms of selected clinicopathological features and some oncogenes.Results: The mean concentration of leptin was significantly higher for colorectal cancers(3.54±1.46 ng/ml) than normal controls(2.27±0.99 ng/ml), no gender difference was observed in this study. Leptin expression in poorly differentiated tumors was obviously lower than those in moderately and well differentiated tumors. There were no statistically significant correlations between leptin and the serum CEA and CA199 in colorectal cancers (P>0.05), and between leptin and the expressions of K-RAS, P53, APC, DCC genes in tumor tissues (P>0.05).Conclusion: Leptin is overexpressed in human colorectal cancer, which is related to the differentiation degrees of the tumor. There is no correlation between leptin expression and chages of oncogenes in colorectal cancers.

  8. HAMLET treatment delays bladder cancer development.

    Science.gov (United States)

    Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

    2010-04-01

    HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Isolation of Cancer Stem Cells From Human Prostate Cancer Samples

    Science.gov (United States)

    Vidal, Samuel J.; Quinn, S. Aidan; de la Iglesia-Vicente, Janis; Bonal, Dennis M.; Rodriguez-Bravo, Veronica; Firpo-Betancourt, Adolfo; Cordon-Cardo, Carlos; Domingo-Domenech, Josep

    2014-01-01

    The cancer stem cell (CSC) model has been considerably revisited over the last two decades. During this time CSCs have been identified and directly isolated from human tissues and serially propagated in immunodeficient mice, typically through antibody labeling of subpopulations of cells and fractionation by flow cytometry. However, the unique clinical features of prostate cancer have considerably limited the study of prostate CSCs from fresh human tumor samples. We recently reported the isolation of prostate CSCs directly from human tissues by virtue of their HLA class I (HLAI)-negative phenotype. Prostate cancer cells are harvested from surgical specimens and mechanically dissociated. A cell suspension is generated and labeled with fluorescently conjugated HLAI and stromal antibodies. Subpopulations of HLAI-negative cells are finally isolated using a flow cytometer. The principal limitation of this protocol is the frequently microscopic and multifocal nature of primary cancer in prostatectomy specimens. Nonetheless, isolated live prostate CSCs are suitable for molecular characterization and functional validation by transplantation in immunodeficient mice. PMID:24686446

  10. Combined effects of 5-Fluorouracil, Folinic acid and Oxaliplatin on the expression of carcinoembryonic antigen in human colon cancer cells: pharmacological basis to develop an active antitumor immunochemotherapy

    Directory of Open Access Journals (Sweden)

    De Vecchis Liana

    2008-05-01

    Full Text Available Abstract Background Five-fluorouracil (FU, mainly associated with leucovorin (L, plays an essential role in chemotherapy of colorectal carcinoma. Moreover, FU ± L has been found to increase the expression of tumor-associated carcinoembryonic antigen (CEA, that may be an important target in therapeutic protocols of active specific immunotherapy. FU + L (FUL are frequently combined with oxaliplatin (OXA in advanced colon cancer patients. Thus, we investigated whether FUL in combination with OXA according to 2 different schedules may influence CEA expression in human colon cancer cells in vitro. Methods CEA protein expression was evaluated by cytofluorimetric and western blot analysis. Relative quantification of CEA mRNA was assessed by real time RT-PCR analysis. Results Levels of CEA protein and transcript were found to be higher in FUL-treated cells than in controls. However, when target cells were exposed to OXA before but not after FUL treatment, the up-regulation of CEA was partially inhibited. Conclusion These results suggest that target cells must be exposed to OXA after but not before treatment with the fluoropyrimidine in order to exploit drug-induced up-regulation of CEA. This finding appears to provide useful information to design chemo-immunotherapy protocols based on FUL + OXA, combined with host's immunity against CEA directed cancer vaccines.

  11. Human Potential Development.

    Science.gov (United States)

    Tyree, Edna J.

    This paper describes the organization and implementation of 16 seminars on the subject of developing the potentials inherent in the individuals involved. The stated goals of this group project for teacher corps interns are: (1) identify and use personal strengths and potential in many areas; (2) understand achievement patterns and the way in which…

  12. Emerging of fractal geometry on surface of human cervical epithelial cells during progression towards cancer

    Science.gov (United States)

    Dokukin, M. E.; Guz, N. V.; Woodworth, C.D.; Sokolov, I.

    2015-01-01

    Despite considerable advances in understanding the molecular nature of cancer, many biophysical aspects of malignant development are still unclear. Here we study physical alterations of the surface of human cervical epithelial cells during stepwise in vitro development of cancer (from normal to immortal (premalignant), to malignant). We use atomic force microscopy to demonstrate that development of cancer is associated with emergence of simple fractal geometry on the cell surface. Contrary to the previously expected correlation between cancer and fractals, we find that fractal geometry occurs only at a limited period of development when immortal cells become cancerous; further cancer progression demonstrates deviation from fractal. Because of the connection between fractal behaviour and chaos (or far from equilibrium behaviour), these results suggest that chaotic behaviour coincides with the cancer transformation of the immortalization stage of cancer development, whereas further cancer progression recovers determinism of processes responsible for cell surface formation. PMID:25844044

  13. Developing human resources

    Energy Technology Data Exchange (ETDEWEB)

    Murray, M.B.W.

    1990-02-01

    Over the last eight years, the growth of the market for independent energy facilities in the United States has been spectacular. A combined capacity of about 29,300 MW, from over 2,500 independent energy facilities, has come on line since 1980 and the industry has experienced an annual growth of more than 15 percent per year. This trend is not limited to the United States, however, Governments around the world are recognizing the benefits of privately-owned independent energy plants. The interest is growing as the need for new capacity increases and as more projects are built and operated successfully using private capital. There are several reasons for the trends toward private power around the world. First, in developed countries, a growing need for new power capacity emerged after the 1983-1987 freeze when most utilities in developed countries reaped the benefits of increased energy conservation and halted any further construction. Now the demand is catching up and most large utilities are experiencing the same hesitations as their U.S. counterparts. Second, in less developed countries (LDCs), the increasing demand for new generating capacity stems from high annual growth rates in power demand -generally between four percent and seven percent per year. At the same time, these countries are expanding their power grid, which increases the opportunities for new plants in regions with limited service where delegation of power generation authority to third-parties can be more easily justified. Third, an increasing number of countries worldwide are eying industrial cogeneration and private power facilities favorably. Finally, lending institutions and donor agencies are becoming more interested in promoting cogeneration and private power, often as part of larger privatization schemes.

  14. Differential network analysis in human cancer research.

    Science.gov (United States)

    Gill, Ryan; Datta, Somnath; Datta, Susmita

    2014-01-01

    A complex disease like cancer is hardly caused by one gene or one protein singly. It is usually caused by the perturbation of the network formed by several genes or proteins. In the last decade several research teams have attempted to construct interaction maps of genes and proteins either experimentally or reverse engineer interaction maps using computational techniques. These networks were usually created under a certain condition such as an environmental condition, a particular disease, or a specific tissue type. Lately, however, there has been greater emphasis on finding the differential structure of the existing network topology under a novel condition or disease status to elucidate the perturbation in a biological system. In this review/tutorial article we briefly mention some of the research done in this area; we mainly illustrate the computational/statistical methods developed by our team in recent years for differential network analysis using publicly available gene expression data collected from a well known cancer study. This data includes a group of patients with acute lymphoblastic leukemia and a group with acute myeloid leukemia. In particular, we describe the statistical tests to detect the change in the network topology based on connectivity scores which measure the association or interaction between pairs of genes. The tests under various scores are applied to this data set to perform a differential network analysis on gene expression for human leukemia. We believe that, in the future, differential network analysis will be a standard way to view the changes in gene expression and protein expression data globally and these types of tests could be useful in analyzing the complex differential signatures.

  15. Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

  16. Epigenetic modifications and human pathologies: cancer and CVD.

    Science.gov (United States)

    Duthie, Susan J

    2011-02-01

    Epigenetic changes are inherited alterations in DNA that affect gene expression and function without altering the DNA sequence. DNA methylation is one epigenetic process implicated in human disease that is influenced by diet. DNA methylation involves addition of a 1-C moiety to cytosine groups in DNA. Methylated genes are not transcribed or are transcribed at a reduced rate. Global under-methylation (hypomethylation) and site-specific over-methylation (hypermethylation) are common features of human tumours. DNA hypomethylation, leading to increased expression of specific proto-oncogenes (e.g. genes involved in proliferation or metastasis) can increase the risk of cancer as can hypermethylation and reduced expression of tumour suppressor (TS) genes (e.g. DNA repair genes). DNA methyltransferases (DNMT), together with the methyl donor S-adenosylmethionine (SAM), facilitate DNA methylation. Abnormal DNA methylation is implicated not only in the development of human cancer but also in CVD. Polyphenols, a group of phytochemicals consumed in significant amounts in the human diet, effect risk of cancer. Flavonoids from tea, soft fruits and soya are potent inhibitors of DNMT in vitro, capable of reversing hypermethylation and reactivating TS genes. Folates, a group of water-soluble B vitamins found in high concentration in green leafy vegetables, regulate DNA methylation through their ability to generate SAM. People who habitually consume the lowest level of folate or with the lowest blood folate concentrations have a significantly increased risk of developing several cancers and CVD. This review describes how flavonoids and folates in the human diet alter DNA methylation and may modify the risk of human colon cancer and CVD.

  17. Synchrotron refractive-index microradiography of human liver cancer tissue

    Institute of Scientific and Technical Information of China (English)

    TONG Yongpeng; ZHANG Guilin; LI Yan; HWU Yeukuang; TSAI Wenli; JE Jung Ho; Margaritondo G.; YUAN Dong

    2005-01-01

    Three human liver tissue samples (~5 mm × 40 mm × 20 mm) were excised from a cancer patient's liver during surgery. The microradiology analysis was performed with a non-standard approach on a synchrotron. High-resolution refractive-index edge-enhanced microradiographs that cover a larger volume of the liver tissue sample were obtained. The cancer tissue and normal tissue could be clearly identified and distinguished based on their different textures. Furthermore, new blood vessel hyperplasia was found near the cancer area. Blood vessels with a diameter smaller than 20 μm could be identified. These findings were fully consistent with the histopathological examination of the same area. Microradiographs of the newly formed blood vessels at different angles were also obtained. This result shows that it is possible to further develop this approach into a technique of microradiographic imaging for clinic diagnosis of liver cancer at the early stage.

  18. Silencing human cancer: identification and uses of microRNAs.

    Science.gov (United States)

    Nicolas, Francisco E; Lopez-Gomollon, Sara; Lopez-Martinez, Alfonso F; Dalmay, Tamas

    2011-01-01

    MicroRNAs (miRNAs) are a new class of negative regulators that repress gene expression by pairing with their target messenger RNAs (mRNAs). There are hundreds of miRNAs coded in the human genome and thousands of target mRNAs participating in a wide variety of physiological processes such as development and cell identity. It is therefore not surprising that several recent reports involved deregulated miRNAs in the complex mechanism of human carcinogenesis, and proposed them as new key regulators to correct the unbalanced expression of oncogenes and tumour suppressor genes exhibited in cancer cells. This review summarises most of the recent patents related to the use of miRNA signatures in cancer diagnosis and prognosis, the detection and profiling of miRNAs from tumour samples and the identification of oncogenes and tumour suppressor genes targeted by miRNAs, as well as new cancer therapies based on miRNA modulators.

  19. Lectins in human cancer: both a devil and an angel?

    Science.gov (United States)

    Dan, Xiu Li; Ng, Tzi Bun

    2013-09-01

    Lectins are a group of proteins which could recognize different sugar structures and specifically initiate reversible binding with them. Lectins are universally expressed in different organisms and undertake important biological roles. Understanding of their inherent roles and mechanisms that they employ has inspired researches with new ideas and applications. For example, along with the revelation of their anti-insect function, plant lectins exhibit great potential in agriculture. In human beings, lectins shoulder great missions in cell communication, differentiation and vesicle trafficking etc., aberrant expression of lectins is always associated with diseases. Mannan-binding lectin deficiency leads to immune disorder and liver sinusoidal endothelial cell lectin is involved in colorectal carcinoma liver metastasis. In this review, we present two contradictory roles of lectins in human cancer: the promotive roles of homologous lectins and suppressive roles of heterologous lectins in cancer development. Hopefully, this review will facilitate a better understanding of tumorigenesis and provide references for cancer treatment.

  20. Strategies of functional food for cancer prevention in human beings.

    Science.gov (United States)

    Zeng, Ya-Wen; Yang, Jia-Zheng; Pu, Xiao-Ying; Du, Juan; Yang, Tao; Yang, Shu-Ming; Zhu, Wei-Hua

    2013-01-01

    Functional food for prevention of chronic diseases is one of this century's key global challenges. Cancer is not only the first or second leading cause of death in China and other countries across the world, but also has diet as one of the most important modifiable risk factors. Major dietary factors now known to promote cancer development are polished grain foods and low intake of fresh vegetables, with general importance for an unhealthy lifestyle and obesity. The strategies of cancer prevention in human being are increased consumption of functional foods like whole grains (brown rice, barley, and buckwheat) and by-products, as well some vegetables (bitter melon, garlic, onions, broccoli, and cabbage) and mushrooms (boletes and Tricholoma matsutake). In addition some beverages (green tea and coffee) may be protective. Southwest China (especially Yunnan Province) is a geographical area where functional crop production is closely related to the origins of human evolution with implications for anticancer influence.

  1. Development of a human breast-cancer derived cell line stably expressing a bioluminescence resonance energy transfer (BRET-based phosphatidyl inositol-3 phosphate (PIP3 biosensor.

    Directory of Open Access Journals (Sweden)

    Mei-Shiue Kuo

    Full Text Available Stimulation of tyrosine kinase receptors initiates a signaling cascade that activates PI3K. Activated PI3K uses PIP2 to generate PIP3, which recruit Akt to the plasma membrane through its pleckstrin homology (PH domain, permitting its activation by PDKs. Activated Akt controls important biological functions, including cell metabolism, proliferation and survival. The PI3K pathway is therefore an attractive target for drug discovery. However, current assays for measurement of PIP3 production are technically demanding and not amenable to high-throughput screening. We have established a MCF-7-derived breast cancer cell line, that stably co-expresses the PH domain of Akt fused to Renilla luciferase and YFP fused to a membrane localization signal. This BRET biosensor pair permits to monitor, in real time, in living cells, PIP3 production at the plasma membrane upon stimulation by different ligands, including insulin, the insulin analogue glargine, IGF1, IGF2 and EGF. Moreover, several known inhibitors that target different steps of the PI3K/Akt pathway caused inhibition of ligand-induced BRET. Cetuximab, a humanized anti-EGF receptor monoclonal antibody used for the treatment of cancer, completely inhibited EGF-induced BRET, and the tyrosine kinase inhibitor tyrphostine AG1024 inhibited insulin effect on PIP3 production. Moreover, the effects of insulin and IGF1 were inhibited by molecules that inhibit PI3K catalytic activity or the interaction between PIP3 and the PH domain of Akt. Finally, we showed that human serum induced a dose-dependent increase in BRET signal, suggesting that this stable clone may be used as a prognostic tool to evaluate the PI3K stimulatory activity present in serum of human patients. We have thus established a cell line, suitable for the screening and/or the study of molecules with stimulatory or inhibitory activities on the PI3K/Akt pathway that will constitute a new tool for translational research in diabetes and cancer.

  2. New Humanism and Sustainable Development

    Directory of Open Access Journals (Sweden)

    Han d'Orville

    2015-10-01

    Full Text Available The call for a new humanism in the 21st century roots in the conviction that the moral, intellectual and political foundations of globalization and international cooperation have to be rethought. Whilst the historic humanism was set out to resolve tensions between tradition and modernity and to reconcile individual rights with newly emerging duties of citizenship, the new humanism approach goes beyond the level of the nation state in seeking to unite the process of globalization with its complex and sometimes contradictory manifestations. The new humanism therefore advocates the social inclusion of every human being at all levels of society and underlines the transformative power of education, sciences, culture and communications. Therefore, humanism today needs to be perceived as a collective effort that holds governments, civil society, the private sector and human individuals equally responsible to realize its values and to design creatively and implement a humanist approach to a sustainable society, based on economic, social and environmental development. New humanism describes the only way forward for a world that accounts for the diversity of identities and the heterogeneity of interests and which is based on inclusive, democratic, and, indeed, humanist values. Humanism did evolve into the grand movement of human spiritual and creative liberation, which enabled an unparalleled acceleration of prosperity and transformation of civilizations. In line with humanist ethics, the material growth was understood as a collective good, which was to serve all participants of a community and meant to enable the socio-economic progress of society. The exact definition of humanism has historically fluctuated in accordance with successive and diverse strands of intellectual thought. The underlying concept rests on the universal ideas of human emancipation, independence and social justice. Humanism can hence be understood as a moral inspiration for

  3. Neuroeconomics and Human Resource Development

    DEFF Research Database (Denmark)

    Larsen, Torben

    2009-01-01

      Neuroeconomics and Human Resource Development Objective Neuroeconomic game trials have detected a present-bias in human decision making which represents a serious shortcoming facing the long termed nature of complex problems in a globalized economy i.e. regional residual poverty, ecological...... threats and personal stress. So far, the evidence-based findings on human resource development (HRD) seem not to match these huge challenges. The aim of this study is to identify cost-effective means of mental training to recover sufficiently from the present bias to enable more sustainable decisions...... of Western decision makers to a level of sustainable development. In order to support the dissemination of non-dogmatic medical meditation an international scientific monitoring program for various competing medical meditation settings might be useful. Western psychology rooted in the Western humanities...

  4. Human development, heredity and evolution.

    Science.gov (United States)

    Nishinakamura, Ryuichi; Takasato, Minoru

    2017-06-15

    From March 27-29 2017, the RIKEN Center for Developmental Biology held a symposium entitled 'Towards Understanding Human Development, Heredity, and Evolution' in Kobe, Japan. Recent advances in technologies including stem cell culture, live imaging, single-cell approaches, next-generation sequencing and genome editing have led to an expansion in our knowledge of human development. Organized by Yoshiya Kawaguchi, Mitinori Saitou, Mototsugu Eiraku, Tomoya Kitajima, Fumio Matsuzaki, Takashi Tsuji and Edith Heard, the symposium covered a broad range of topics including human germline development, epigenetics, organogenesis and evolution. This Meeting Review provides a summary of this timely and exciting symposium, which has convinced us that we are moving into the era of science targeted on humans. © 2017. Published by The Company of Biologists Ltd.

  5. Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts

    Directory of Open Access Journals (Sweden)

    Cheng M

    2014-12-01

    Full Text Available Michelle Cheng,1,* Samantha Ho,1,* Jun Hwan Yoo,1,2,* Deanna Hoang-Yen Tran,1,* Kyriaki Bakirtzi,1 Bowei Su,1 Diana Hoang-Ngoc Tran,1 Yuzu Kubota,1 Ryan Ichikawa,1 Hon Wai Koon1 1Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 2Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Republic of Korea *These authors share co-first authorship Background: Cathelicidin (LL-37 in humans and mCRAMP in mice represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. Methods: We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial–mesenchymal transition (EMT of colon cancer cells and fibroblast-supported colon cancer cell proliferation. Results: Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-ß1-induced EMT of colon cancer cells. Media conditioned by the

  6. [Human papillomavirus detection in cervical cancer prevention].

    Science.gov (United States)

    Picconi, María Alejandra

    2013-01-01

    Cervical cancer (CC), which is strongly associated to high-risk human papillomavirus (hr-HPV) infection, continues being a significant health problem in Latin America. The use of conventional cytology to detect precancerous cervical lesions has had no major impact on reducing CC incidence and mortality rates, which are still high in the region. New screening tools to detect precancerous lesions became available, which provide great opportunities for CC prevention, as do highly efficacious HPV vaccines able to prevent nearly all lesions associated with HPV-16 and -18 when applied before viral exposure. Currently, hr-HPV testing represents an invaluable component of clinical guidelines for screening, management and treatment of CC and their precursor lesions. Many testing strategies have been developed that can detect a broad spectrum of hr-HPV types in a single assay; however, only a small subset of them has documented clinical performance for any of the standard HPV testing indications. HPV tests that have not been validated and lack proof of reliability, reproducibility and accuracy should not be used in clinical management. Once incorporated into the lab, it is essential to submit the whole procedure of HPV testing to continuous and rigorous quality assurance to avoid sub-optimal, potentially harmful practices. Recent progress and current status of these methods are discussed in this article.

  7. MicroRNA in human cancer and chronic inflammatory diseases.

    Science.gov (United States)

    Kanwar, Jagat R; Mahidhara, Ganesh; Kanwar, Rupinder K

    2010-06-01

    MicroRNAs (miRNAs) are the non-coding RNAs that act as post-translational regulators to their complimentary messenger RNAs (mRNA). Due to their specific gene silencing property, miRNAs have been implicated in a number of cellular and developmental processes. Also, it has been proposed that a particular set of miRNA spectrum is expressed only in a particular type of tissue. Many interesting findings related to the differential expression of miRNAs in various human diseases including several types of cancers, neurodegenerative diseases and metabolic diseases have been reported. Deregulation of miRNA expression in different types of human diseases and the roles various miRNAs play as tumour suppressors as well as oncogenes, suggest their contribution to cancer and/or in other disease development. These findings have possible implications in the development of diagnostics and/or therapeutics in human malignancies. In this review, we discuss various miRNAs that are differentially expressed in human chronic inflammatory diseases, neurodegenerative diseases, cancer and the further prospective development of miRNA based diagnostics and therapeutics.

  8. Comparative proteomics analysis of human gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Wei Li; Jian-Fang Li; Ying Qu; Xue-Hua Chen; Jian-Min Qin; Qin-Long Gu; Min Yan; Zheng-Gang Zhu; Bing-Ya Liu

    2008-01-01

    AIM: To isolate and identify differentially expressed proteins between cancer and normal tissues of gastric cancer by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).METHODS: Soluble fraction proteins of gastric cancer tissues and paired normal tissues were separated by 2-DE.The differentially expressed proteins were selected and identified by MALDI-TOF-MS and database search.RESULTS: 2-DE profiles with high resolution and reproducibility were obtained.Twenty-three protein spots were excised from sliver staining gel and digested in gel by trypsin,in which fifteen protein spots were identified successfully.Among the identified proteins,there were ten over-expressed and five under-expressed proteins in stomach cancer tissues compared with normal tissues.CONCLUSION: In this study,the well-resolved,reproducible 2-DE patterns of human gastric cancer tissue and paired normal tissue were established and optimized and certain differentially-expressed proteins were identified.The combined use of 2-DE and MS provides an effective approach to screen for potential tumor markers.

  9. Human Colon Cancer Cells Cultivated in Space

    Science.gov (United States)

    1995-01-01

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

  10. Aspartame bioassay findings portend human cancer hazards.

    Science.gov (United States)

    Huff, James; LaDou, Joseph

    2007-01-01

    The U.S. Food and Drug Administration (FDA) should reevaluate its position on aspartame as being safe under all conditions. Animal bioassay results predict human cancer risks, and a recent animal study confirms that there is a potential aspartame risk to humans. Aspartame is produced and packaged in China for domestic use and global distribution. Japan, France, and the United States are also major producers. No study of long-term adverse occupational health effects on aspartame workers have been conducted. The FDA should consider sponsoring a prospective epidemiologic study of aspartame workers.

  11. 1. HUMAN POPULATION MONITORING FOR CANCER PREVENTION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Most of the chemicals classified by the International Agency for Research on Cancer (IARC) as human carcinogens are mutagenic across test systems, cf. [www.epa.gov/gapdb ] and induce tumors at multiple sites in rodent species. They are therefore readity detected in short term tests for gene-tic and related effects (GRE), in animal carcinogenesis bioassays and in human monitoring studies. Carcinogens that are not genotoxic may be studied using new toxicogenomic approaches as will be discussed. A Chemical Effects in Biological Systems (CEBS) database is planned by the National Center for Toxicogenomics to contain information on such compounds. The 1992 Preamble to the IARC Monographs

  12. ANALYSES ON DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    MENG Xu-li; DING Xiao-wen; XU Xiao-hong

    2006-01-01

    Objective: To investigate the molecular etiology of breast cancer by way of studying the differential expression and initial function of the related genes in the occurrence and development of breast cancer. Methods: Two hundred and eighty-eight human tumor related genes were chosen for preparation of the oligochips probe. mRNA was extracted from 16 breast cancer tissues and the corresponding normal breast tissues, and cDNA probe was prepared through reverse-transcription and hybridized with the gene chip. A laser focused fluorescent scanner was used to scan the chip. The different gene expressions were thereafter automatically compared and analyzed between the two sample groups. Cy3/Cy5>3.5 meant significant up-regulation. Cy3/Cy5<0.25 meant significant down-regulation. Results: The comparison between the breast cancer tissues and their corresponding normal tissues showed that 84 genes had differential expression in the Chip. Among the differently expressed genes, there were 4 genes with significant down-regulation and 6 with significant up-regulation. Compared with normal breast tissues, differentially expressed genes did partially exist in the breast cancer tissues. Conclusion: Changes in multi-gene expression regulations take place during the occurrence and development of breast cancer; and the research on related genes can help understanding the mechanism of tumor occurrence.

  13. Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer

    Science.gov (United States)

    Ding, Lin; El Zaatari, Mohamad

    2017-01-01

    Overview Gastric cancer has been traditionally defined by the Correa paradigm as a progression of sequential pathological events that begins with chronic inflammation [1]. Infection with Helicobacter pylori (H. pylori) is the typical explanation for why the stomach becomes chronically inflamed. Acute gastric inflammation then leads to chronic gastritis, atrophy particularly of acid-secreting parietal cells, metaplasia due to mucous neck cell expansion from trans-differentiation of zymogenic cells to dysplasia and eventually carcinoma [2]. The chapter contains an overview of gastric anatomy and physiology to set the stage for signaling pathways that play a role in gastric tumorigenesis. Finally, the major known mouse models of gastric transformation are critiqued in terms of the rationale behind their generation and contribution to our understanding of human cancer subtypes. PMID:27573785

  14. Neoadjuvant breast cancer therapy and drug development.

    Science.gov (United States)

    Cortazar, Patricia; Kluetz, Paul G

    2015-11-01

    Neoadjuvant treatment of breast cancer initially was limited to patients with locally advanced breast cancer in which downstaging was necessary. Now, neoadjuvant trials have become an increasingly common way to facilitate the rapid assessment of new cancer therapies. The appeal of neoadjuvant trials is that they provide the opportunity to study translational science, tumor biomarkers, and intermediate endpoints in response to systemic therapy within a shortened period. This review summarizes the data that contribute to our understanding of the association between pathological complete response and long-term outcomes, describes the implications of drug development and accelerated approval in neoadjuvant treatment of breast cancer, and provides a perspective on future neoadjuvant drug development.

  15. The golden triangle of human dignity: human security, human development and human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2004-01-01

    The success or failure of processes of democratization cannot be detached from processes of development related to the aspirations of people at the grassroots. Human rights, in a more theoretical terminology, require human development in order to enhance human security.

  16. A novel experimental platform for investigating cancer growth and anti-cancer therapy in a human tissue microenvironment derived from human embryonic stem cells.

    Science.gov (United States)

    Tzukerman, Maty; Skorecki, Karl L

    2006-01-01

    There is no available experimental system wherein human cancer cells can be grown in the context of a mixed population of normal differentiated human cells for testing biological aspects of cancer cell growth (tumor cell invasion, angiogenesis) or response to anti-cancer therapies. Human embryonic stem cells when implanted into immunocompromised mice develop teratomas containing complex structures, comprising differentiated cell types representing the major germline-derived lineages. We sought to determine whether human cancer cells would grow within such teratomas and display properties associated with malignancy such as invasiveness and recruitment of blood vessels. Ovarian cancer cells (HEY), stably expressing an H2A-GFP fusion protein, which allows tracking of tumor cells, were injected into mature teratomas and developed into tumors. The growth, proliferation capacity, invasion, and induction of blood vessel formation were examined. We propose using the novel experimental platform we have described, consisting of human tumor cells growing within a human cellular microenvironment derived from human embryonic stem cells, to develop a preclinical model for investigating and manipulating the stromal response in tumor cell growth, as an additional tool in cancer research.

  17. Esophageal cancer developed 13 years after radiotherapy for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Okazaki, Atsushi; Matsuura, Masana; Noda, Masanobu; Katsumata, Yasushi; Maehara, Tadayuki; Tamura, Shizuo; Uzawa, Takeshi; Ishikawa, Toshitaka

    1988-05-01

    This paper reports on an autopsied case manifesting an esophageal cancer that had developed 13 years after radiotherapy for lung cancer. The patient was a 61-year-old man. He was found to have a squamous cell carcinoma of the right lower bronchus with a swelling of the mediastinal and left supraclavicular lymph nodes in July of 1973. He received 60 Gy of irradiation in the right lung, the mediastinum, and the left supraclavicular region. Later, after doing well until August of 1986, a squamous cell carcinoma of the esophagus was found at the upper intrathoracic site. Thus, he also received additional radiotherapy but died of pneumonia after this local recurrence 7 months later. At autopsy, no local recurrence of the primary lung cancer was found. The site of esophageal cancer was far from that of the primary lung cancer thought it was included in the previous treatment ports. This suggests the possibility that the primary esophageal cancer had been induded by therapeutic irradiation. So far as we know, this is the first report of esophageal cancer that may have developed after irradiation for lung cancer.

  18. [Esophageal cancer developing 13 years after radiotherapy of lung cancer].

    Science.gov (United States)

    Okazaki, A; Matsuura, M; Noda, M; Katsumata, Y; Maehara, T; Tamura, S; Uzawa, T; Ishiko, T

    1988-05-01

    This paper reports on an autopsied case manifesting an esophageal cancer that had developed 13 years after radiotherapy for lung cancer. The patient was a 61-year-old man. He was found to have a squamous cell carcinoma of the right lower bronchus with a swelling of the mediastinal and left supraclavicular lymph nodes in July of 1973. He received 60 Gy of irradiation in the right lung, the mediastinum, and the left supraclavicular region. Later, after doing well until August of 1986, a squamous cell carcinoma of the esophagus was found at the upper intrathoracic site. Thus, he also received additional radiotherapy but died of pneumonia after this local recurrence 7 months later. At autopsy, no local recurrence of the primary lung cancer was found. The site of esophageal cancer was far from that of the primary lung cancer though it was included in the previous treatment ports. This suggests the possibility that the primary esophageal cancer had been induced by therapeutic irradiation. So far as we know, this is the first report of esophageal cancer that may have developed after irradiation for lung cancer.

  19. Human development recruiting and selection

    Directory of Open Access Journals (Sweden)

    Maksimović Marijana

    2002-01-01

    Full Text Available Along with the development of trends towards internationalization and globalization, human resource management and, especially, international human resource management, attracted overall theoretical and practical interest. International environment is complex, made of numerous elements like social organization, laws, education, values and attitudes, religion language, politics, material and technological culture. In multicultural environment, strategic activities could be multiplied through economical political, cultural, social and technological spheres of action, making the recruitment, selection and successful resource allocation in the international human resource management a real challenge for top management. In international human resource management practice, several approaches to the recruitment have differentiated, playing the key roles in hiring talented individuals and retaining efficient workforce KW resources, labor force, recruiting, managers, education

  20. Antiangiogenic Steroids in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Richard J. Pietras

    2005-01-01

    Full Text Available Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor-associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activity in vitro, and it significantly disrupts tumor proliferation and progression in laboratory studies. Work on the interactions of squalamine with vascular endothelial cells indicate that it binds with cell membranes, inhibits the membrane Na+/H+ exchanger and may further function as a calmodulin chaperone. These primary actions appear to promote inhibition of several vital steps in angiogenesis, such as blockade of mitogen-induced actin polymerization, cell–cell adhesion and cell migration, leading to suppression of endothelial cell proliferation. Preclinical studies with squalamine have shown additive benefits in tumor growth delay when squalamine is combined with cisplatin, paclitaxel, cyclophosphamide, genistein or radiation therapy. This compound has also been assessed in early phase clinical trials in cancer; squalamine was found to exhibit little systemic toxicity and was generally well tolerated by treated patients with various solid tumor malignancies

  1. Antiangiogenic Steroids in Human Cancer Therapy.

    Science.gov (United States)

    Pietras, Richard J; Weinberg, Olga K

    2005-03-01

    Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor-associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activity in vitro, and it significantly disrupts tumor proliferation and progression in laboratory studies. Work on the interactions of squalamine with vascular endothelial cells indicate that it binds with cell membranes, inhibits the membrane Na(+)/H(+) exchanger and may further function as a calmodulin chaperone. These primary actions appear to promote inhibition of several vital steps in angiogenesis, such as blockade of mitogen-induced actin polymerization, cell-cell adhesion and cell migration, leading to suppression of endothelial cell proliferation. Preclinical studies with squalamine have shown additive benefits in tumor growth delay when squalamine is combined with cisplatin, paclitaxel, cyclophosphamide, genistein or radiation therapy. This compound has also been assessed in early phase clinical trials in cancer; squalamine was found to exhibit little systemic toxicity and was generally well tolerated by treated patients with various solid tumor malignancies, including ovarian, non

  2. Chromatin Repressive Complexes in Stem Cells, Development, and Cancer

    DEFF Research Database (Denmark)

    Laugesen, Anne; Helin, Kristian

    2014-01-01

    of the polycomb repressive complexes, PRC1 and PRC2, and the HDAC1- and HDAC2-containing complexes, NuRD, Sin3, and CoREST, in stem cells, development, and cancer, as well as the ongoing efforts to develop therapies targeting these complexes in human cancer. Furthermore, we discuss the role of repressive......The chromatin environment is essential for the correct specification and preservation of cell identity through modulation and maintenance of transcription patterns. Many chromatin regulators are required for development, stem cell maintenance, and differentiation. Here, we review the roles...... complexes in modulating thresholds for gene activation and their importance for specification and maintenance of cell fate....

  3. Human Papillomavirus 16E6 Oncogene Mutation in Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    Feng Sun; Xiao-qin Ha; Tong-de Lv; Chuan-ping Xing; Bin Liu; Xiao-zhe Cao

    2009-01-01

    Objective: Cervical cancer (CC) is the second most common type of cancer in women worldwide, after breast cancer. High-risk human papillomaviruses (HR-HPVs) are considered to be the major causes of cervical cancer. HPV16 is the most common type of HR-HPVs and HPV16 E6 gene is one of the major oncogenes. Specific mutations are considered as dangerous factors causing CC. This study was designed to find mutations of HPV16 E6 and the relationship between the mutations and the happening of CC.Methods: The tissue DNA was extracted from 15 biopsies of CC. Part of HPV16 E6 gene (nucleotide 201-523) was amplified by polymerase chain reaction (PCR) from the CC tissue DNA. The PCR fragments were sequenced and analyzed.Results: The result of PCR showed that the positive rate of HPV16 E6 was 93.33% (14/15). After sequencing and analyzing, in the 13 out of 14 PCR fragments, 4 maintained prototype (30.77%), 8 had a same 350G mutation (61.54%), and 1 had a 249G mutation (7.69%).Conclusion: This study suggest that there is a high infection rate of HPV in cervical cancer and most of the HPV16 E6 gene has mutations. Those mutations may have an association with the development of cervical cancer.

  4. Strategic Human Resource Development. Symposium.

    Science.gov (United States)

    2002

    This document contains three papers on strategic human resource (HR) development. "Strategic HR Orientation and Firm Performance in India" (Kuldeep Singh) reports findings from a study of Indian business executives that suggests there is a positive link between HR policies and practices and workforce motivation and loyalty and…

  5. Growth charts of human development

    NARCIS (Netherlands)

    Van Buuren, Stef

    2014-01-01

    This article reviews and compares two types of growth charts for tracking human development over age. Both charts assume the existence of a continuous latent variable, but relate to the observed data in different ways. The D-score diagram summarizes developmental indicators into a single aggregate s

  6. Epidemiologic studies of the human microbiome and cancer

    National Research Council Canada - National Science Library

    Vogtmann, Emily; Goedert, James J

    2016-01-01

    .... Previously detected associations of individual bacteria (e.g., Helicobacter pylori), periodontal disease, and inflammation with specific cancers have motivated studies considering the association between the human microbiome and cancer risk...

  7. Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer.

    Directory of Open Access Journals (Sweden)

    Shinya Akatsuka

    Full Text Available Iron overload has been associated with carcinogenesis in humans. Intraperitoneal administration of ferric nitrilotriacetate initiates a Fenton reaction in renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC after repeated treatments. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of this oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletions. Deletions and amplifications were numerous and sometimes fragmented, demonstrating that a Fenton reaction is a cause of such genomic alterations in vivo. Frequency plotting indicated that two of the most commonly altered loci corresponded to a Cdkn2a/2b deletion and a Met amplification. Tumor sizes were proportionally associated with Met expression and/or amplification, and clustering analysis confirmed our results. Furthermore, we developed a procedure to compare whole genomic patterns of the copy number alterations among different species based on chromosomal syntenic relationship. Patterns of the rat RCCs showed the strongest similarity to the human RCCs among five types of human cancers, followed by human malignant mesothelioma, an iron overload-associated cancer. Therefore, an iron-dependent Fenton chemical reaction causes large-scale genomic alterations during carcinogenesis, which may result in distinct genomic profiles. Based on the characteristics of extensive genome alterations in human cancer, our results suggest that this chemical reaction may play a major role during human carcinogenesis.

  8. Galangin induces human colon cancer cell death via the mitochondrial dysfunction and caspase-dependent pathway.

    Science.gov (United States)

    Ha, Tae Kwun; Kim, Mi Eun; Yoon, Ju Hwa; Bae, Sung Jin; Yeom, Jihye; Lee, Jun Sik

    2013-09-01

    Galangin is a member of flavonols and found in Alpinia officinarum, galangal root, and propolis. Previous studies have demonstrated that galangin has anti-cancer effects on several cancers, including melanoma, hepatoma, and leukaemia cells. However, anti-cancer activity of galangin on human colon cancer has not been established yet. In this study, we investigated the anti-cancer effects of galangin on two types of human colon cancer cells (HCT-15 and HT-29). We found that galangin induced apoptosis and DNA condensation of human colon cancer cells in a dose-dependent manner. We also determined that galangin increased the activation of caspase-3 and -9, and release of apoptosis inducing factor from the mitochondria into the cytoplasm by Western blot analysis. In addition, galangin induced human colon cancer cell death through the alteration of mitochondria membrane potential and dysfunction. These results suggest that galangin induces apoptosis of HCT-15 and HT-29 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer.

  9. Differential BCCIP gene expression in primary human ovarian cancer, renal cell carcinoma and colorectal cancer tissues.

    Science.gov (United States)

    Liu, Xiaoxia; Cao, Lingling; Ni, Jinsong; Liu, Ning; Zhao, Xiaoming; Wang, Yanfang; Zhu, Lin; Wang, Lingyao; Wang, Jin; Yue, Ying; Cai, Yong; Jin, Jingji

    2013-12-01

    Human BCCIP, a protein which interacts with BRCA2 and CDKN1A (Cip1, p21), has been implicated in many cellular processes including cell cycle regulation, DNA recombination and damage repair, telomere maintenance, embryonic development and genomic stability. BCCIP gene expression, which is an important BRCA2 cofactor in tumor suppression, has been identified in some primary cancers. Thus, we investigated the role of BCCIP expression in a large sample of clinically diagnosed primary ovarian cancer, renal cell carcinoma (RCC) and colorectal cancer (CRC) tissues. Using clinically diagnosed frozen primary cancer tissues, quantitative PCR (qPCR), western blot analysis (WB) and immunohistochemical staining (IHC) approaches were used to detect and measure gene expression. Reduced BCCIP gene expression in ovarian cancer, RCC and CRC tissues occurred in 74, 89 and 75% of tissue samples, respectively. qPCR analysis of mRNA expression in 54 ovarian cancer, 50 RCC and 44 CRC samples revealed significant (>2-fold decreased) BCCIP downregulation in 56, 70 and 46% of tissue samples, respectively. Although BCCIP expression in three different tumor tissues decreased, the relationship between BCCIP expression and clinicopathological features of each cancer was distinct. Compared to normal tissues, BCCIP expression in ovarian cancers was significantly downregulated in serous, endometrioid and mucinous carcinomas. Downregulation of BCCIP expression was strongly associated with clear cell RCC (ccRCC) and Fuhrman tumor grading, but significant differences in BCCIP expression between CRC and matched normal tissues occurred only in male CRC tissues (ptissue with a T4 tumor stage (ptissue samples (phuman ovarian cancer, RCC and CRC tissues, suggesting a role for the gene in the pathogenesis of these cancers.

  10. Population and human resources development.

    Science.gov (United States)

    Jones, G W

    1992-06-01

    The concern of this discourse on social development planning was that individuals be part of human resources development. Population growth is an obstacle to social development, but so is national expenditures on the military rather than diverting funds for social improvements. There are important benefits for society in social development: a valued consumption good, increased productivity, and reduced fertility. Dissatisfaction with an economic growth model of development occurred during the 1960s, and by the mid-1980s, human resource development was capsuled in Asia and the Pacific Region in the Jakarta Plan of Action on Human Resources Development and adopted in 1988. Earlier approaches favored the supply side. This article emphasizes "human" development which considers people as more than inputs to productivity. The quality of human resources is dependent on the family and society, the educational system, and individual levels of health and nutrition. Differences in income levels between East and South Asia have been attributed by Oshima to full use of the labor force and mechanization and training of workers. Ogawa, Jones, and Williamson contend that huge investment in infrastructure, efficient absorption of advanced technology, a stable political environment, and commitment to human capital formation are key to development. Demographic transition and decline in fertility at one point reflect growth and engagement in the labor force and resource accumulation. Although East Asia had higher levels of literacy and educational attainment than many developing countries, South Asia still has high fertility. Human resource development is dependent on reduced population growth rates, but rapid population growth is not an insurmountable obstacle to achieving higher levels of education. Rapid population growth is a greater obstacle in poorer countries. The impact can be reflected in increased costs of attaining educational targets of universal primary education or in

  11. Prevention of the Angiogenic Switch in Human Breast Cancer

    Science.gov (United States)

    2009-03-01

    chronic myeloid leukaemia | colorectal cancer | Down syndrome | infantile haemangiomas | multiple myeloma | non-small-cell lung cancer | rheumatoid...Human Breast Cancer PRINCIPAL INVESTIGATOR: Donald Ingber, M.D., Ph.D. CONTRACTING ORGANIZATION: Children’s Hospital...From - To) 15 FEB 2004 - 14 FEB 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prevention of the Angiogenic Switch in Human Breast Cancer 5b

  12. [Development of the lung cancer diagnostic system].

    Science.gov (United States)

    Lv, You-Jiang; Yu, Shou-Yi

    2009-07-01

    To develop a lung cancer diagnosis system. A retrospective analysis was conducted in 1883 patients with primary lung cancer or benign pulmonary diseases (pneumonia, tuberculosis, or pneumonia pseudotumor). SPSS11.5 software was used for data processing. For the relevant factors, a non-factor Logistic regression analysis was used followed by establishment of the regression model. Microsoft Visual Studio 2005 system development platform and VB.Net corresponding language were used to develop the lung cancer diagnosis system. The non-factor multi-factor regression model showed a goodness-of-fit (R2) of the model of 0.806, with a diagnostic accuracy for benign lung diseases of 92.8%, a diagnostic accuracy for lung cancer of 89.0%, and an overall accuracy of 90.8%. The model system for early clinical diagnosis of lung cancer has been established.

  13. MicroRNA Regulation of Human Breast Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yohei Shimono

    2015-12-01

    Full Text Available MicroRNAs (miRNAs are involved in virtually all biological processes, including stem cell maintenance, differentiation, and development. The dysregulation of miRNAs is associated with many human diseases including cancer. We have identified a set of miRNAs differentially expressed between human breast cancer stem cells (CSCs and non-tumorigenic cancer cells. In addition, these miRNAs are similarly upregulated or downregulated in normal mammary stem/progenitor cells. In this review, we mainly describe the miRNAs that are dysregulated in human breast CSCs directly isolated from clinical specimens. The miRNAs and their clusters, such as the miR-200 clusters, miR-183 cluster, miR-221-222 cluster, let-7, miR-142 and miR-214, target the genes and pathways important for stem cell maintenance, such as the self-renewal gene BMI1, apoptosis, Wnt signaling, Notch signaling, and epithelial-to-mesenchymal transition. In addition, the current evidence shows that metastatic breast CSCs acquire a phenotype that is different from the CSCs in a primary site. Thus, clarifying the miRNA regulation of the metastatic breast CSCs will further advance our understanding of the roles of human breast CSCs in tumor progression.

  14. Developing phytoestrogens for breast cancer prevention.

    Science.gov (United States)

    Liu, Mandy M; Huang, Ying; Wang, Jeffrey

    2012-12-01

    Breast cancer is one of the most common types of cancer in women, and is the second leading cause of cancer-related deaths in the United States. Chemoprevention using phytoestrogens (PEs) for breast cancer may be a valid strategy. PEs are phytochemicals with estrogen-like structures and can be classified into four types: isoflavones, lignans, stilbenes and coumestans. They are widely distributed in diet and herbs and have shown anti-cancer activity via mechanisms including estrogen receptor modulation, aromatase inhibition, and anti-angiogenesis. Genistein, daidzein and resveratrol are some of the most studied PE examples. Quality control in product manufacturing and clinical study design is a critical issue in developing them as clinically effective chemopreventive agents for breast cancer.

  15. Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer.

    Science.gov (United States)

    Yang, J; Zhang, Y; Cui, X; Yao, W; Yu, X; Cen, P; Hodges, S E; Fisher, W E; Brunicardi, F C; Chen, C; Yao, Q; Li, M

    2013-03-01

    Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

  16. Development of A Mouse Model of Menopausal Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Elizabeth R. Smith

    2014-02-01

    Full Text Available Despite significant understanding of the genetic mutations involved in ovarian epithelial cancer and advances in genomic approaches for expression and mutation profiling of tumor tissues, several key questions in ovarian cancer biology remain enigmatic: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains obscure; questions of the cell of origin of ovarian cancer continue to be debated; and the precursor lesion, sequence, or events in progression remain to be defined. Suitable mouse models should complement the analysis of human tumor tissues and may provide clues to these questions currently perplexing ovarian cancer biology.A potentially useful model is the germ cell-deficient Wv (white spotting variant mutant mouse line, which may be used to study the impact of menopausal physiology on the increased risk of ovarian cancer. The Wv mice harbor a point mutation in c-Kit that reduces the receptor tyrosine kinase activity to about 1-5% (it is not a null mutation. Homozygous Wv mutant females have a reduced ovarian germ cell reservoir at birth and the follicles are rapidly depleted upon reaching reproductive maturity, but other biological phenotypes are minimal and the mice have a normal life span. The loss of ovarian function precipitates changes in hormonal and metabolic activity that model features of menopause in humans. As a consequence of follicle depletion, the Wv ovaries develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis that mark human ovarian aging. Ongoing work will test the possibility of converting the benign epithelial tubular adenomas into neoplastic tumors by addition of an oncogenic mutation, such as of Tp53, to model the genotype and biology of serous ovarian cancer.Model based on the Wv mice may have the potential to gain biological and etiological insights into ovarian cancer development and prevention.

  17. Health, Human Capital, and Development.

    Science.gov (United States)

    Bleakley, Hoyt

    2010-09-01

    How much does disease depress development in human capital and income around the world? I discuss a range of micro evidence, which finds that health is both human capital itself and an input to producing other forms of human capital. I use a standard model to integrate these results, and suggest a re-interpretation of much of the micro literature. I then discuss the aggregate implications of micro estimates, but note the complications in extrapolating to general equilibrium, especially because of health's effect on population size. I also review the macro evidence on this topic, which consists of either cross-country comparisons or measuring responses to health shocks. Micro estimates are 1-2 orders of magnitude smaller than the cross-country relationship, but nevertheless imply high benefit-to-cost ratios from improving certain forms of health.

  18. Health, Human Capital, and Development*

    Science.gov (United States)

    Bleakley, Hoyt

    2013-01-01

    How much does disease depress development in human capital and income around the world? I discuss a range of micro evidence, which finds that health is both human capital itself and an input to producing other forms of human capital. I use a standard model to integrate these results, and suggest a re-interpretation of much of the micro literature. I then discuss the aggregate implications of micro estimates, but note the complications in extrapolating to general equilibrium, especially because of health’s effect on population size. I also review the macro evidence on this topic, which consists of either cross-country comparisons or measuring responses to health shocks. Micro estimates are 1–2 orders of magnitude smaller than the cross-country relationship, but nevertheless imply high benefit-to-cost ratios from improving certain forms of health. PMID:24147187

  19. CERVICAL CANCER AND THE HUMAN IMMUNODEFICIENCY ...

    African Journals Online (AJOL)

    as Mexico, Columbia and many developed nations), the reduction in ..... detection among human immunodeficiency virus-infected pregnant Thai women: implications ... Moscicki A. Impact of HPV infection in adolescent populations. J Adolesc ...

  20. Alterations of 5-Hydroxymethylcytosine in Human Cancers

    Directory of Open Access Journals (Sweden)

    Ali Yesilkanal

    2013-06-01

    Full Text Available Prior to 2009, 5-methylcytosine (5-mC was thought to be the only biologically significant cytosine modification in mammalian DNA. With the discovery of the TET enzymes, which convert 5-methylcytosine (5-mC to 5-hydroxymethylcytosine (5-hmC, however, intense interest has emerged in determining the biological function of 5-hmC. Here, we review the techniques used to study 5-hmC and evidence that alterations to 5-hmC physiology play a functional role in the molecular pathogenesis of human cancers.

  1. Human papillomavirus-associated diseases and cancers

    Institute of Scientific and Technical Information of China (English)

    Lan Yang; Jianbo Zhu Co-first author; Xiaoyue Song; Yan Qi; Xiaobin Cui; Feng Li 

    2015-01-01

    Human papilomaviruses (HPVs) have been detected in cervical cancer cels and skin papiloma cels, which have a variety of types, including low-risk and high-risk types. HPV genome replication requires the host cel’s DNA synthesis machinery, and HPVs encode proteins that maintain diferentiated epithelial cels in a replication-competent state. HPV types are tissue-specific and generaly produce diferent types of le-sions, either benign or malignant. This review examines diferent HPV types and their associated diseases and presents therapeutic options for the treatment of HPV-positive diseases.

  2. Selenium and selenocysteine: roles in cancer, health, and development.

    Science.gov (United States)

    Hatfield, Dolph L; Tsuji, Petra A; Carlson, Bradley A; Gladyshev, Vadim N

    2014-03-01

    The many biological and biomedical effects of selenium are relatively unknown outside the selenium field. This fascinating element, initially described as a toxin, was subsequently shown to be essential for health and development. By the mid-1990s selenium emerged as one of the most promising cancer chemopreventive agents, but subsequent human clinical trials yielded contradictory results. However, basic research on selenium continued to move at a rapid pace, elucidating its many roles in health, development, and in cancer prevention and promotion. Dietary selenium acts principally through selenoproteins, most of which are oxidoreductases involved in diverse cellular functions.

  3. [Development of Nucleic Acid-Based Adjuvant for Cancer Immunotherapy].

    Science.gov (United States)

    Kobiyama, Kouji; Ishii, Ken J

    2015-09-01

    Since the discovery of the human T cell-defined tumor antigen, the cancer immunotherapy field has rapidly progressed, with the research and development of cancer immunotherapy, including cancer vaccines, being conducted actively. However, the disadvantages of most cancer vaccines include relatively weak immunogenicity and immune escape or exhaustion. Adjuvants with innate immunostimulatory activities have been used to overcome these issues, and these agents have been shown to enhance the immunogenicity of cancer vaccines and to act as mono-therapeutic anti-tumor agents. CpG ODN, an agonist for TLR9, is one of the promising nucleic acid-based adjuvants, and it is a potent inducer of innate immune effector functions. CpG ODN suppresses tumor growth in the absence of tumor antigens and peptide administration. Therefore, CpG ODN is expected to be useful as a cancer vaccine adjuvant as well as a cancer immunotherapy agent. In this review, we discuss the potential therapeutic applications and mechanisms of CpG ODN for cancer immunotherapy.

  4. [Expressions and significance of NDRG2 and Bcl-2 in human gastric cancer tissues].

    Science.gov (United States)

    Zhu, Ruixue; Shi, Yongquan; Zhang, Lianfeng

    2015-04-01

    To analyze the expressions of N-myc downstream regulated gene 2 (NDRG2) and B cell lymphoma/leukemia-2 (Bcl-2) in human gastric cancer in an attempt to explore their correlation and clinical significance. Immunohistochemical staining was used to detect the expression of NDRG2 and Bcl-2 in human gastric cancer, para-carcinoma tissues and normal tissues. The correlation between their expressions and clinicopathologic data were analyzed using statistical software in gastric cancer tissues. The tissue microarray consisting of 64 gastric cancer and 10 normal gastric tissues showed NDRG2 expression in gastric cancer tissues was significantly lower than that in normal tissues, whereas Bcl-2 expression in gastric cancer tissues was significantly higher than that in normal tissues. It was also indicated that NDRG2 was negatively correlated with Bcl-2 in gastric cancer tissues. NDRG2 and Bcl-2 were further analyzed in 206 gastric cancer and paired para-carcinoma tissues. It was displayed that the expression levels of NDRG2 and Bcl-2 in human gastric cancer were not associated with age and sex, but significantly associated with tumor differentiation, clinical stage and lymph node metastasis. There is a negative correlation between NDRG2 and Bcl-2 expressions in human gastric cancer, suggesting they might be synergistically involved in the development of gastric cancer.

  5. Generation and characterization of recombinant human antibodies specific for native laminin epitopes. Potential application in cancer therapy. Cancer Immunol. Immunother

    DEFF Research Database (Denmark)

    Sanz, Laura; Kristensen, Peter; Russell, Stephen J.

    2001-01-01

    of human-derived antibody fragments able to modulate laminin-regulated biological functions would allow the development of new strategies to improve treatment of cancer patients. In this report, we explore the use of phage display technology to isolate human anti-laminin antibody fragments. A library...

  6. Educational Solutions for Human Development

    Directory of Open Access Journals (Sweden)

    Inês Kisil Miskalo

    2009-06-01

    Full Text Available The biggest challenge for education in Brazil is not only to popularize school access, but also to provide conditions for students to remain at school successfully. Therefore, it is necessary to invest in teachers qualification and in the adoption of efficient and effective public policies based on managerial patterns designed to cater to human resources articulations, equipment, finance and, mainly, to methodologies focused on results. Quality reorganization of public policy will only be possible through a triplet effort involving political will from public government, cooperation from the private sector and contribution from civil society. These partnerships assure public sphere the development of essential projects to enable the country to grow. They also allow Education to occupy the important place it deserves in the national agenda as a tool to foster human development. It is essential to guarantee to people knowledge and abilities that enable them to make sensible choices, have their health improved and thus, take part in the society actively. This essay intends to provide information on Instituto Ayrton Senna´s mission to boost quality education for new Brazilian generations as a precondition for human development. Its education programs supply managerial praxes to state and municipal public school systems that warrant conceptual changes and alter the school failure vicious cycle.

  7. Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Keita, E-mail: uchino13@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hirano, Gen [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hirahashi, Minako [Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Isobe, Taichi; Shirakawa, Tsuyoshi; Kusaba, Hitoshi; Baba, Eishi [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tsuneyoshi, Masazumi [Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Akashi, Koichi [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2012-09-10

    There is emerging evidence that human solid tumor cells originate from cancer stem cells (CSCs). In cancer cell lines, tumor-initiating CSCs are mainly found in the side population (SP) that has the capacity to extrude dyes such as Hoechst 33342. We found that Nanog is expressed specifically in SP cells of human gastrointestinal (GI) cancer cells. Nucleotide sequencing revealed that NanogP8 but not Nanog was expressed in GI cancer cells. Transfection of NanogP8 into GI cancer cell lines promoted cell proliferation, while its inhibition by anti-Nanog siRNA suppressed the proliferation. Immunohistochemical staining of primary GI cancer tissues revealed NanogP8 protein to be strongly expressed in 3 out of 60 cases. In these cases, NanogP8 was found especially in an infiltrative part of the tumor, in proliferating cells with Ki67 expression. These data suggest that NanogP8 is involved in GI cancer development in a fraction of patients, in whom it presumably acts by supporting CSC proliferation. -- Highlights: Black-Right-Pointing-Pointer Nanog maintains pluripotency by regulating embryonic stem cells differentiation. Black-Right-Pointing-Pointer Nanog is expressed in cancer stem cells of human gastrointestinal cancer cells. Black-Right-Pointing-Pointer Nucleotide sequencing revealed that Nanog pseudogene8 but not Nanog was expressed. Black-Right-Pointing-Pointer Nanog pseudogene8 promotes cancer stem cells proliferation. Black-Right-Pointing-Pointer Nanog pseudogene8 is involved in gastrointestinal cancer development.

  8. Alterations of p63 and p73 in human cancers.

    Science.gov (United States)

    Inoue, Kazushi; Fry, Elizabeth A

    2014-01-01

    p53 and its related genes, p63 and p73 constitute the p53 gene family. While p53 is the most frequently mutated gene in human tumors, p63 and p73 are rarely mutated or deleted in cancers. Many studies have reported p63/p73 overexpression in human cancers while others showed that a loss of p63/p73 is associated with tumor progression and metastasis. Thus, whether p63 or p73 is a tumor suppressor gene or an oncogene has been a matter of debate. This controversy has been attributed to the existence of multiple splicing isoforms with distinct functions; the full-length TA isoform of p63 has structural and functional similarity to wild-type p53, whereas the ΔNp63 acts primarily in dominant-negative fashion against all family members of p53. Differential activities of TA and ΔN isoforms have been shown in vivo by creating isform-specific gene knockout mice. All p53, p63, p73 proteins bind to and activate target genes with p53-response elements; p63 also binds to distinct p63-response elements and regulate expression of specific target genes involved in skin, limb, and craniofacial development. Interestingly, several studies have shown that both p63 and p73 are involved in cellular response to cancer therapy and others have indicated that both of these molecules are required for p53-induced apoptosis, suggesting functional interplay among p53 family proteins. Consistent with these findings, aberrant splicing that result in ΔNp63 or ΔNp73 overexpression are frequently found in human cancers, and is associated with poor clinical outcomes of patients in the latter. Thus immunohistochemical staining of tumor specimen with ΔNp73-specific antibody might have diagnostic values in cancer clinics.

  9. Preclinical and clinical development of DNA vaccines for prostate cancer.

    Science.gov (United States)

    Colluru, V T; Johnson, Laura E; Olson, Brian M; McNeel, Douglas G

    2016-04-01

    Prostate cancer is the most commonly diagnosed cancer in the United States. It is also the second leading cause of cancer-related death in men, making it one of the largest public health concerns today. Prostate cancer is an ideal disease for immunotherapies because of the generally slow progression, the dispensability of the target organ in the patient population, and the availability of several tissue-specific antigens. As such, several therapeutic vaccines have entered clinical trials, with one autologous cellular vaccine (sipuleucel-T) recently gaining Food and Drug Administration approval after demonstrating overall survival benefit in randomized phase III clinical trials. DNA-based vaccines are safe, economical, alternative "off-the-shelf" approaches that have undergone extensive evaluation in preclinical models. In fact, the first vaccine approved in the United States for the treatment of cancer was a DNA vaccine for canine melanoma. Several prostate cancer-specific DNA vaccines have been developed in the last decade and have shown promising results in early phase clinical trials. This review summarizes anticancer human DNA vaccine trials, with a focus on those conducted for prostate cancer. We conclude with an outline of special considerations important for the development and successful translation of DNA vaccines from the laboratory to the clinic.

  10. Endogenous retroviral promoter exaptation in human cancer

    Directory of Open Access Journals (Sweden)

    Artem Babaian

    2016-12-01

    Full Text Available Abstract Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.

  11. FISH CANCER DEVELOPED BY ENVIRONMENTAL POLLUTANTS

    Directory of Open Access Journals (Sweden)

    Madhuri S.

    2012-10-01

    Full Text Available The pollution of rivers and streams with chemical contaminants has become one of the most critical environmental problems. Fish living in a polluted water reservoir use the contaminated water to rinse their gills; this results in the deposition of polycyclic aromatic hydrocarbons (PAHs in the fish body. Contamination of foodstuffs by heavy metals such as arsenic, cadmium, chromium, nickel and lead has poses a potential carcinogenic threat to humans. Arsenic and cadmium appear to be the most harmful to the fish. Several cancers in fish appear to be the result of exposure to different environmental pollutants/chemicals. High frequencies of liver and skin cancers in brown bullheads are associated with high concentrations of PAHs and some metals in the environmental sediments. Taking these facts in view, the present article gives the emphasis on the fish cancer caused by various environmental pollutants, suggesting that fish species are truly suffer from different cancers/tumours.

  12. Human papillomavirus vaccination guideline update: American Cancer Society guideline endorsement.

    Science.gov (United States)

    Saslow, Debbie; Andrews, Kimberly S; Manassaram-Baptiste, Deana; Loomer, Lacey; Lam, Kristina E; Fisher-Borne, Marcie; Smith, Robert A; Fontham, Elizabeth T H

    2016-09-01

    Answer questions and earn CME/CNE The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. CA Cancer J Clin 2016;66:375-385. © 2016 American Cancer Society. © 2016 American Cancer Society.

  13. Modern criteria to establish human cancer etiology.

    Science.gov (United States)

    Carbone, Michele; Klein, George; Gruber, Jack; Wong, May

    2004-08-01

    The Cancer Etiology Branch of the National Cancer Institute hosted a workshop, "Validation of a causal relationship: criteria to establish etiology," to determine whether recent technological advances now make it possible to delineate improved or novel criteria for the rapid establishment for cancer causation. The workshop was held in Washington, D.C., December 11-12, 2003, and participants were among the international leaders in the fields of epidemiology, chemistry, biochemistry, microbiology, virology, environmental and chemical carcinogenesis, immunology, pathology, molecular pathology, genetics, oncology, and surgical oncology. There was a general consensus that the rapid identification of human carcinogens and their removal (when possible) or the establishment of specific preventive and therapeutic measures was the most desirable and effective way to have a rapid and positive impact in the fight against cancer. From a clinical perspective, it may be as important to target initiators, cocarcinogens and promoters, if by removing any one of them tumor growth can be prevented. Future studies should focus on interactions among and between different biological, chemical, and physical agents. Analyses of single agents can at times miss their carcinogenic potential when such agents are carcinogenic only in subgroups of individuals because of their genetic background, diet, exposure to other carcinogens, or microbial infection. Epidemiology, molecular pathology (including chemistry, biochemistry, molecular biology, molecular virology, molecular genetics, epigenetics, genomics, proteomics, and other molecular-based approaches), and animal and tissue culture experiments should all be seen as important integrating evidence in the determination of human carcinogenicity. Concerning the respective roles of epidemiology and molecular pathology, it was noted that epidemiology allows the determination of the overall effect of a given carcinogen in the human population (e

  14. Establishment of a Novel Bladder Cancer Xenograft Model in Humanized Immunodeficient Mice

    Directory of Open Access Journals (Sweden)

    Zhen Gong

    2015-10-01

    Full Text Available Background/Aims: The aim of this study was to develop a novel model by transplanting human bladder cancer xenografts into humanized immunodeficient mice (SCID. Methods: The animals first underwent sublethal irradiation and then were subjected to simultaneous transplantation of human lymphocytes (5 × 107 cells/mouse i.p. and human bladder cancer cells (3 × 106 cells/mouse s.c.. Results: The xenografts developed in all 12 mice that had received bladder cancer BIU-87 cells, and the tumor specimens were evaluated histologically. All 6 model mice expressed human CD3 mRNA and/or protein in the peripheral blood, spleens and xenografts. The mean proportion of human CD3+ cells was 19% with a level of human IgG 532.4µ/ml in the peripheral blood at Week 6 after transplant inoculation. The re-constructed human immune system in these mice was confirmed to be functional by individual in vitro testing of their proliferative, secretory and cytotoxic responses. Conclusion: The successful engraftment of the human bladder cancer xenografts and the establishment of the human immune system in our in vivo model described here may provide a useful tool for the development of novel therapeutic strategies targeting at bladder cancer.

  15. Modelling mutational landscapes of human cancers in vitro

    Science.gov (United States)

    Olivier, Magali; Weninger, Annette; Ardin, Maude; Huskova, Hana; Castells, Xavier; Vallée, Maxime P.; McKay, James; Nedelko, Tatiana; Muehlbauer, Karl-Rudolf; Marusawa, Hiroyuki; Alexander, John; Hazelwood, Lee; Byrnes, Graham; Hollstein, Monica; Zavadil, Jiri

    2014-03-01

    Experimental models that recapitulate mutational landscapes of human cancers are needed to decipher the rapidly expanding data on human somatic mutations. We demonstrate that mutation patterns in immortalised cell lines derived from primary murine embryonic fibroblasts (MEFs) exposed in vitro to carcinogens recapitulate key features of mutational signatures observed in human cancers. In experiments with several cancer-causing agents we obtained high genome-wide concordance between human tumour mutation data and in vitro data with respect to predominant substitution types, strand bias and sequence context. Moreover, we found signature mutations in well-studied human cancer driver genes. To explore endogenous mutagenesis, we used MEFs ectopically expressing activation-induced cytidine deaminase (AID) and observed an excess of AID signature mutations in immortalised cell lines compared to their non-transgenic counterparts. MEF immortalisation is thus a simple and powerful strategy for modelling cancer mutation landscapes that facilitates the interpretation of human tumour genome-wide sequencing data.

  16. Identification of differentially expressed proteins during human urinary bladder cancer progression

    DEFF Research Database (Denmark)

    Memon, Ashfaque Ahmed; chang, Jong. w; Oh, Bong R.

    2005-01-01

    cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may...

  17. Automated whole animal bio-imaging assay for human cancer dissemination

    NARCIS (Netherlands)

    Ghotra, V.P.; He, S.; Bont, de H.J.G.M.; Ent, van der W.; Spaink, H.P.; Water, van de B.; Snaar, B.E.; Danen, E.H.J.

    2012-01-01

    A quantitative bio-imaging platform is developed for analysis of human cancer dissemination in a short-term vertebrate xenotransplantation assay. Six days after implantation of cancer cells in zebrafish embryos, automated imaging in 96 well plates coupled to image analysis algorithms quantifies spre

  18. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation.

    Science.gov (United States)

    Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K

    2016-01-19

    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

  19. Apoptosis of human pancreatic cancer cells induced by Triptolide

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  20. Viral Etiology Relationship between Human Papillomavirus and Human Breast Cancer and Target of Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    YAN Chen; TENG Zhi Ping; CHEN Yun Xin; SHEN Dan Hua; LI Jin Tao; ZENG Yi

    2016-01-01

    ObjectiveTo explore the viral etiology of human breast cancer to determine whether there are novel molecular targets for gene therapy of breast cancer and provide evidence for the research of gene therapy and vaccine development for breast cancer. MethodsPCR was used to screen HPV16 and HPV18 oncogenesE6 andE7 in the SKBR3 cell line andin 76 paraffin embedded breast cancer tissue samples. RNA interference was used to knock down the expression of HPV18E6 andE7 in SKBR3 cells, then the changes in the expression of cell-cycle related proteins, cell viability, colony formation, metastasis, and cell cycle progression were determined. ResultsHPV18 oncogenesE6 andE7 were amplified and sequenced from the SKBR3 cells. Ofthe patient samples, 6.58% and 23.68% were tested to bepositivefor HPV18E6 and HPV18E7. In the cell culture models, the knockdown of HPV18E6 andE7 inhibited the proliferation, metastasis, and cell cycle progression of SKBR3 cell. The knockdown also clearly affected the expression levels of cell cycle related proteins. ConclusionHPV was a contributor to virus causedhuman breast cancer, suggesting that the oncogenes in HPV were potential targets for gene therapy of breast cancer.

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

    Directory of Open Access Journals (Sweden)

    Natália Cristina Ciufa Kobayashi

    2015-02-01

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

  2. Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice.

    Science.gov (United States)

    Wu, Min; Jung, Lina; Cooper, Adrian B; Fleet, Christina; Chen, Lihao; Breault, Lyne; Clark, Kimberly; Cai, Zuhua; Vincent, Sylvie; Bottega, Steve; Shen, Qiong; Richardson, Andrea; Bosenburg, Marcus; Naber, Stephen P; DePinho, Ronald A; Kuperwasser, Charlotte; Robinson, Murray O

    2009-04-28

    Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies.

  3. COMPONENTS OF SUSTAINABLE HUMAN DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Neyda Ibañez

    2017-03-01

    Full Text Available The present research aimed to propose new components of measurement of sustainable human development based on the historical-theoretical trajectory of development. The research assumes a ontoepistemological posture based on positivism, addressing the technique of the survey and the written questionnaire instrument applied to thirty-one (31 experts in the area of knowledge, whose analysis allowed to conclude that the traditional models to measure the Insufficient to demonstrate the reality of nations. Therefore, the proposal of measurement is derived in seven components: ethical, spiritual and cultural, in addition to those formally established by Munasinghe (1993, 2011 and the UN (2012: economic, social, environmental, institutional , In total, by the selection of one hundred and fifty-five (155 variables, whose index is denominated ISIDEHUS.

  4. Bacterial protein toxins in human cancers.

    Science.gov (United States)

    Rosadi, Francesca; Fiorentini, Carla; Fabbri, Alessia

    2016-02-01

    Many bacteria causing persistent infections produce toxins whose mechanisms of action indicate that they could have a role in carcinogenesis. Some toxins, like CDT and colibactin, directly attack the genome by damaging DNA whereas others, as for example CNF1, CagA and BFT, impinge on key eukaryotic processes, such as cellular signalling and cell death. These bacterial toxins, together with other less known toxins, mimic carcinogens and tumour promoters. The aim of this review is to fulfil an up-to-date analysis of toxins with carcinogenic potential that have been already correlated to human cancers. Bacterial toxins-induced carcinogenesis represents an emerging aspect in bacteriology, and its significance is increasingly recognized.

  5. Phase I study of anticolon cancer humanized antibody A33.

    Science.gov (United States)

    Welt, Sydney; Ritter, Gerd; Williams, Clarence; Cohen, Leonard S; John, Mary; Jungbluth, Achim; Richards, Elizabeth A; Old, Lloyd J; Kemeny, Nancy E

    2003-04-01

    Humanized A33 (huA33; IgG1) monoclonal antibody detects a determinant expressed by 95% of colorectal cancers and can activate immune cytolytic mechanisms. The present study was designed to (a) define the toxicities and maximum tolerated dose of huA33 and (b) determine huA33 immunogenicity. Patients (n = 11) with advanced chemotherapy-resistant colorectal cancer received 4-week cycles of huA33 at 10, 25, or 50 mg/m(2)/week. Serum samples were analyzed using biosensor technology for evidence of human antihuman antibody (HAHA) response. Eight of 11 patients developed a HAHA response. Significant toxicity was limited to four patients who developed high HAHA titers. In two of these cases, infusion-related reactions such as fevers, rigors, facial flushing, and changes in blood pressure were observed, whereas in the other two cases, toxicity consisted of skin rash, fever, or myalgia. Of three patients who remained HAHA negative, one achieved a radiographic partial response, with reduction of serum carcinoembryonic antigen from 80 to 3 ng/ml. Four patients had radiographic evidence of stable disease (2, 4, 6, and 12 months), with significant reductions (>25%) in serum carcinoembryonic antigen levels in two cases. The complementarity-determining region-grafted huA33 antibody is immunogenic in the majority of colon cancer patients (73%). HAHA activity can be measured reproducibly and quantitatively by BIACORE analysis. Whereas the huA33 construct tested here may be too immunogenic for further clinical development, the antitumor effects observed in the absence of antibody-mediated toxicity and in this heavily pretreated patient population warrant clinical testing of other IgG1 humanized versions of A33 antibody.

  6. Household human development index in Lakshadweep

    OpenAIRE

    I, Sahadudheen

    2014-01-01

    Since the evolution of the human development index in 1990 there has been a vivacious debate on measurement related issues of quality of human life among the nations. It is a long-established verity that the existing HDI presents averages and thus conceals wide discrepancy and disproportion in distribution of human development in overall population and does not take into account the distribution of human development within a population subgroup. This study is intended to look in to human ...

  7. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

    Science.gov (United States)

    Tanzi, Elisabetta; Bianchi, Silvia; Frati, Elena R; Amicizia, Daniela; Martinelli, Marianna; Bragazzi, Nicola L; Brisigotti, Maria Pia; Colzani, Daniela; Fasoli, Ester; Zehender, Gianguglielmo; Panatto, Donatella; Gasparini, Roberto

    2015-01-01

    Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

  8. Transcriptome Encyclopedia of Early Human Development.

    Science.gov (United States)

    Sahakyan, Anna; Plath, Kathrin

    2016-05-01

    Our understanding of human pre-implantation development is limited by the availability of human embryos and cannot completely rely on mouse studies. Petropoulos et al. now provide an extensive transcriptome analysis of a large number of human pre-implantation embryos at single-cell resolution, revealing previously unrecognized features unique to early human development.

  9. Development of a human epidermal growth factor derivative with EGFR-blocking and depleted biological activities: A comparative in vitro study using EGFR-positive breast cancer cells.

    Science.gov (United States)

    Mehrabi, Masomeh; Mansouri, Kamran; Soleymani, Bijan; Hoseinkhani, Zohreh; Shahlaie, Mohsen; Khodarahmi, Reza

    2017-10-01

    Epidermal growth factor (EGF) is a local growth factor that stimulates cell growth, proliferation, and differentiation by binding to its receptor EGFR. EGF and EGFR are involved in many aspects of the development of carcinomas. Because EGFR has been found to be over-expressed in many tumors of epithelial origin, it is a potential target for antitumor therapy. In this study we designed a mutated form of hEGF (mEGF) with a deletion of four amino acids residues (Gln(43), Tyr(44), Arg(45) and Asp(46)) in order to show importance of Leu spatial location for EGFR binding/activation. Expression vector pET32a(+) and E. Coli, strain Rosetta-gami B (DE3) were used to enhance solubility of the recombinant protein with yielding approximately 10mg/l of cell culture. The purified cleaved hEGF as well as non-cleaved fusion protein were biologically active, which was confirmed by their equal ability to stimulate proliferation of MCF7 cells. The mEGF showed specificity and high affinity for EGFR binding, however binding affinity of mEGF for EGFR was reduced about 11.5 fold compared with that of hEGF. The mEGF effect on the MCF7 cell proliferation had a relatively different outcome; mEGF simulated differential cell growth in a dose dependent manner. On the other hand, in MDA-MB468 cells, hEGF and mEGF induced growth inhibition, which was much more severe for hEGF than that of mEGF. Also, hEGF strongly induced the phosphorylation of EGF receptor in MDA-MB468 cells while mEGF induced poor EGFR phosphorylation. The same observations were also made for migration of cancer cells, especially induction of MDA-MB468 migration by mEGF was significantly lower than that of hEGF, suggesting a connection between tyrosine phosphorylation of EGFR and cell migration. Docking analysis revealed that the binding affinity and the buried surface area of mEGF to EGFR complex are lower than those of hEGF/EGFR. Although theoretical studies confirmed reduction in mEGF-EGFR binding affinity, the data of the

  10. A rising cancer prevention target of RSK2 in human skin cancer

    Directory of Open Access Journals (Sweden)

    Arul eNarayanasamy

    2013-08-01

    Full Text Available RSK2 is a p90 ribosomal S6 kinase family (p90RSK member regulating cell proliferation and transformation induced by tumor promoters such as epithelial growth factor (EGF and 12-O-tetradecanoylphorbol 13-acetate (TPA. This family of p90RSK has classified as a serine/threonine kinase that respond to many growth factors, peptide hormones, neurotransmitters, and environmental stresses such as ultraviolet light (UV. Our recent study demonstrates that RSK2 plays a key role in human skin cancer development. Activation of RSK2 by EGF and UV through ERKs signaling pathway induces cell cycle progression, cell proliferation and anchorage-independent cell transformation. Moreover, knockdown of RSK2 by si-RNA or sh-RNA abrogates cell proliferation and cell transformation of non-malignant human skin keratinocyte, and colony growth of malignant melanoma cells in soft agar. Importantly, activated and total RSK2 protein levels are highly detected in human skin cancer tissues including squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Kaempferol and eriodictyol are natural substances to inhibit kinase activity of the RSK2 N-terminal kinase domain, which is a critical kinase domain to transducer their activation signals to the substrates by phosphorylation. In this review, we discuss the role of RSK2 in skin cancer particularly, in activation of signaling pathways and potent natural substances to target RSK2 as chemopreventive and therapeutic agents.

  11. FOREIGN LANGUAGES AND HUMAN DEVELOPMENT: THE CASE ...

    African Journals Online (AJOL)

    HP

    2017-07-01

    Jul 1, 2017 ... He published the first Human Development report ... The main objective of human development lies on the freedom of its citizens as well as ... scholarship were Professor S. Ade Ojo, the former Director of the French Language.

  12. The effects of human resource flexibility on human resources development

    Directory of Open Access Journals (Sweden)

    SeidMehdi Veise

    2014-08-01

    Full Text Available Human resources are the primary factor for development of competitiveness and innovation and reaching competitive advantage and they try to improve corporate capabilities through various characteristics such as value creation, scarcity and difficulty of imitation. This paper investigates the effect of human resource flexibility and its dimensions on human resource development and its dimensions. The survey was conducted using descriptive-correlation method that intended to describe how human resource flexibility was effective on human resource development. Questionnaire was tool of data collection. The statistical population included one hundred employees of the Electric Company in Ilam province, thus census method was used. Reliability of the questionnaire was measured via Cronbach's alpha equal to 0.96. The findings revealed that flexibility and its dimensions were effective on human resource development and dimensions of it. As a result, human resource flexibility should be considered for development of human resources and employees with the highest flexibility should be selected.

  13. Development of New Treatments for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

    2005-02-01

    The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and

  14. Spatial regulation of receptor tyrosine kinases in development and cancer

    OpenAIRE

    Casaletto, Jessica B.; McClatchey, Andrea I.

    2012-01-01

    During development and tissue homeostasis, patterns of cellular organization, proliferation, and movement are highly choreographed. Receptor tyrosine kinases (RTKs) play a critical role in establishing these patterns. Individual cells and tissues exhibit tight spatial control of the RTKs that they express, enabling tissue morphogenesis and function while preventing unwarranted cell division and migration that can contribute to tumorigenesis. Indeed, RTKs are deregulated in most human cancers ...

  15. Cytogenetics and genetics of human cancer: methods and accomplishments.

    Science.gov (United States)

    Sandberg, Avery A; Meloni-Ehrig, Aurelia M

    2010-12-01

    Cytogenetic and related changes in human cancer constitute part of a constantly developing and enlarging continuum of known genetic alterations associated with cancer development and biology. The cytogenetic component of this continuum has fulfilled much of its pioneering role and now constitutes a small but dynamic segment of the vast literature on cancer genetics, in which it has played an important if not initiating role. The goals of this article are (a) to address historical and methodological aspects of cancer cytogenetics; (b) to present information on diagnostic translocations in leukemias, lymphomas, bone and soft tissue tumors, and carcinomas; (c) to connect some of these chromosomal aberrations with their molecular equivalents; and (d) to describe anomalies in some solid tumors indicative of the complexity of the genomic alterations in cancer. We also look at a few of the more recent genomic developments in cancer and offer an opinion as to what all these findings add up to.

  16. CONSTRUCTION AND EXPRESSION OF A HUMAN-MOUSE CHIMERIC ANTIBODY AGAINST HUMAN BLADDER CANCER

    Institute of Scientific and Technical Information of China (English)

    白银; 王琰; 周丽君; 俞莉章

    2001-01-01

    To construct and express a human-mouse chimeric antibody against human bladder cancer. Method: The variable region genes of anti-human bladder cancer monoclonal antibody BDI-1 were cloned by RT-PCR. A human-mouse chimeric antibody expression vector was constructed and transfected into CHO cells. The chimeric antibody against bladder cancer was expressed and characterized. Result: Eukaryotic expression vector of the chimeric antibody against human bladder carcinoma was successfully constructed, and was expressed in eukaryotic cells; the expressed chimeric antibody ch-BDI showed same specificity as its parent McAb against human bladder cancer cells. Conclusion: The constructed chimeric antibody was expressed successfully in eukaryotic cells, and the chimeric antibody had desired affinity against human bladder cancer cells.

  17. Qualitative analysis of cancer patients' experiences using donated human milk.

    Science.gov (United States)

    Rough, Susanne M; Sakamoto, Pauline; Fee, Caroline H; Hollenbeck, Clarie B

    2009-05-01

    This represents the first published account from the patient's perspective of the use of human milk as cancer therapy. Purposive sampling was used to select a sample of 10 participants. Five were patients and 5 were family proxies. Individual interviews were conducted using confirmatory interviewing technique to obtain individual perspectives on the motivation for cancer patients to take donated human milk. Human milk therapy improved the quality of life (QOL) measures in the physical, psychological, and spiritual domains for most patients interviewed. The patients continued their use of human milk despite cost, taste, and discouragement from the conventional medical community. The study results support the theory that QOL may be more important to cancer patients than cancer outcomes and may improve patient medical care overall. These interviews offer information to cancer patients, their practitioners, and donor milk banks on outcomes and symptom relief from this therapy.

  18. Roles of the Y chromosome genes in human cancers

    Directory of Open Access Journals (Sweden)

    Tatsuo Kido

    2015-06-01

    Full Text Available Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from the same ancestor pair of autosomes, the Y chromosome harbors male-specific genes, which play pivotal roles in male sex determination, germ cell differentiation, and masculinization of various tissues. Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development (previously termed as an intersex condition with dysgenic gonads. Failure of gonadal development results not only in infertility, but also in increased risks of germ cell tumor (GCT, such as gonadoblastoma and various types of testicular GCT. Recent studies demonstrate that either loss of Y chromosome or ectopic expression of Y chromosome genes is closely associated with various male-biased diseases, including selected somatic cancers. These observations suggest that the Y-linked genes are involved in male health and diseases in more frequently than expected. Although only a small number of protein-coding genes are present in the male-specific region of Y chromosome, the impacts of Y chromosome genes on human diseases are still largely unknown, due to lack of in vivo models and differences between the Y chromosomes of human and rodents. In this review, we highlight the involvement of selected Y chromosome genes in cancer development in men.

  19. Macroeconomics and Human Development, by Deepak Nayyar

    Directory of Open Access Journals (Sweden)

    Cristiana Ioana ŞERBĂNEL

    2013-12-01

    Full Text Available Microeconomics and Human Development pursue to tackle both negative and positive effects of macroeconomics on human development and vice-versa through a series of external and internal factors. The book consists in a series of articles published in a prestigious publication: Journal of Human Development and Capabilities. The authors have a perennial echo in the economic field.

  20. Values Reflected in the Human Development Index

    Science.gov (United States)

    Lind, Niels

    2004-01-01

    The Human Development Index (HDI) implicitly defines "human development" and ranks countries accordingly. To elucidate the HDI's meaning of "human development," the paper examines the sensitivity of the HDI to changes in its components, namely social indicators of education, longevity and standard of living. The HDI is next compared with two…

  1. Targeting hedgehog signaling in cancer: research and clinical developments

    Directory of Open Access Journals (Sweden)

    Xie J

    2013-10-01

    Full Text Available Jingwu Xie, Christopher M Bartels, Scott W Barton, Dongsheng GuWells Center for Pediatric Research, Division of Hematology and Oncology, Department of Pediatrics, Indiana University Simon Cancer Center, Indiana University, Indianapolis, IN, USAAbstract: Since its first description in Drosophila by Drs Nusslein-Volhard and Wieschaus in 1980, hedgehog (Hh signaling has been implicated in regulation of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of Gorlin syndrome in 1996 by two independent teams. Later, it was shown that Hh signaling may be involved in many types of cancer, including skin, leukemia, lung, brain, and gastrointestinal cancers. In early 2012, the US Food and Drug Administration approved the clinical use of Hh inhibitor Erivedge/vismodegib for treatment of locally advanced and metastatic basal cell carcinomas. With further investigation, it is possible to see more clinical applications of Hh signaling inhibitors. In this review, we will summarize major advances in the last 3 years in our understanding of Hh signaling activation in human cancer, and recent developments in preclinical and clinical studies using Hh signaling inhibitors.Keywords: hedgehog, smoothened, PTCH1, cancer, signal transduction, clinical trials, animal model

  2. Challenges facing the development of cancer vaccines.

    Science.gov (United States)

    Fishman, Mayer

    2014-01-01

    Just like any other effective immunization in medicine, cancer vaccines need to have antigens with particular specificity and immunostimulatory features, the immune responses to be elicited in the body, and therapeutic effect-regression or prevention of the cancer-must be meaningful and clinically observable. There are many choices for cancer antigens, such as tissue-specific proteins, cancer-specific proteins, class I- or class II-restricted peptides derived from those, or in situ and whole-cell-derived products are some examples. Another translational issue is that cancer patients are heterogeneous with respect to the extent to which the immune system is already activated with potential to impact the tumor growth or, conversely, the extent to which the immune system has been impaired through a prior and ongoing interaction with the tumor. Conventional or immunologic tests have potential to define a subset of patients with better chance or response, so that particular vaccines can be tested. Treatment of cancer patients is expensive, and trials are slow. To meet these challenges in practical terms will require not only careful scientific technical work for product development, coordination with clinicians to define patient subsets with diseases that can show responses, but also a comprehensive, practical implementation so that we can unlock the full potential of anticancer vaccines.

  3. Participation of microbiota in the development of gastric cancer.

    Science.gov (United States)

    Wang, Li-Li; Yu, Xin-Juan; Zhan, Shu-Hui; Jia, Sheng-Jiao; Tian, Zi-Bin; Dong, Quan-Jiang

    2014-05-07

    There are a large number of bacteria inhabiting the human body, which provide benefits for the health. Alterations of microbiota participate in the pathogenesis of diseases. The gastric microbiota consists of bacteria from seven to eleven phyla, predominantly Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria. Intrusion by Helicobacter pylori (H. pylori) does not remarkably interrupt the composition and structure of the gastric microbiota. Absence of bacterial commensal from the stomach delays the onset of H. pylori-induced gastric cancer, while presence of artificial microbiota accelerates the carcinogenesis. Altered gastric microbiota may increase the production of N-nitroso compounds, promoting the development of gastric cancer. Further investigation of the carcinogenic mechanisms of microbiota would benefit for the prevention and management of gastric cancer.

  4. EXPRESSION OF Fas LIGAND IN HUMAN COLON CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    张建军; 丁尔迅; 王强; 陈学云; 付志仁

    2001-01-01

    To investigate the expression of Fas ligand in human colon carcinoma cell lines. Methods: A total of six human colon cancer cell lines were examined for the expression of Fas ligand mRNA and cell surface protein by using RT-PCR and flow cytometry respectively. Results: The results showed that Fas ligand mRNA was expressed in all of the six cancer cell lines and Fas ligand cell surface protein was expressed in part of them. Conclusion: These data suggest that Fas ligand was expressed, at least in part, in human colon cancer cell lines and might facilitate to escape from immune surveillance of the host.

  5. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi

    2016-12-01

    Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

  6. Cancer immunology - development of novel anti-cancer therapies.

    Science.gov (United States)

    Rothschild, Sacha I; Thommen, Daniela S; Moersig, Wolfgang; Müller, Philipp; Zippelius, Alfred

    2015-01-01

    The vast majority of tumours are characterised by high frequencies of genetic and epigenetic alterations resulting in tumour-specific antigens, which may, in principle, be recognised by cytotoxic T cells. Though early clinical immunotherapy trials have yielded mixed results with ambiguous clinical benefit, cancer immunotherapy is now attracting increasing attention as a viable therapeutic option, mainly in melanoma and lung cancer, but increasingly also in other malignancies. In particular, recent therapeutic efforts targeting inhibitory receptors on T cells to overcome tumour-induced immune dysfunction have the potential to reshape current treatment standards in oncology. The clinical development has been pioneered by the antibody ipilimumab, which blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and has demonstrated survival benefit in two randomised landmark trials in melanoma. Capitalising on this success, the research on the clinical implication of T cell checkpoint inhibition has been boosted. Early clinical trials have demonstrated meaningful response rates, sustained clinical benefits with encouraging survival rates and good tolerability of next-generation checkpoint inhibitors, including programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors, across multiple cancer types. Attractive perspectives include the concurrent blockade of immunological (non-redundant) checkpoints, which has recently been demonstrated using combinations of immune checkpoint modulators themselves or with other therapies, such as chemotherapy, targeted therapy or radiotherapy. This article summarises the mechanism of action and subsequent clinical studies of immune checkpoint antibodies in oncology with a particular focus on melanoma and lung cancer.

  7. Notch in mammary gland development and breast cancer.

    Science.gov (United States)

    Politi, Katerina; Feirt, Nikki; Kitajewski, Jan

    2004-10-01

    Notch signaling has been implicated in many processes including cell fate determination and oncogenesis. In mice, the Notch1 and Notch4 genes are both targets for insertion and rearrangement by the mouse mammary tumor virus and these mutations promote epithelial mammary tumorigenesis. Moreover, expression of a constitutively active form of Notch4 in mammary epithelial cells inhibits epithelial differentiation and leads to tumor formation in this organ. These data implicate the Notch pathway in breast tumorigenesis and provide the foundation for future experiments that will aid in our understanding of the role of Notch in human breast cancer development. Here, we review studies of mammary tumorigenesis induced by Notch in mouse and in vitro culture models providing evidence that Notch activation is a causal factor in human breast cancer.

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

    Directory of Open Access Journals (Sweden)

    Klijn Jan GM

    2009-07-01

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

  9. Towards the human colorectal cancer microbiome.

    Directory of Open Access Journals (Sweden)

    Julian R Marchesi

    Full Text Available Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC. To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.

  10. Establishment of a human lung cancer cell line with high metastatic potential to multiple organs: gene expression associated with metastatic potential in human lung cancer.

    Science.gov (United States)

    Nakano, Tetsuhiro; Shimizu, Kimihiro; Kawashima, Osamu; Kamiyoshihara, Mitsuhiro; Kakegawa, Seiichi; Sugano, Masayuki; Ibe, Takashi; Nagashima, Toshiteru; Kaira, Kyoichi; Sunaga, Noriaki; Ohtaki, Youichi; Atsumi, Jun; Takeyoshi, Izumi

    2012-11-01

    Convenient and reliable multiple organ metastasis model systems might contribute to understanding the mechanism(s) of metastasis of lung cancer, which may lead to overcoming metastasis and improvement in the treatment outcome of lung cancer. We isolated a highly metastatic subline, PC14HM, from the human pulmonary adenocarcinoma cell line, PC14, using an in vivo selection method. The expression of 34,580 genes was compared between PC14HM and parental PC14 by cDNA microarray analysis. Among the differentially expressed genes, expression of four genes in human lung cancer tissues and adjacent normal lung tissues were compared using real-time reverse transcription polymerase chain reaction. Although BALB/c nude mice inoculated with parental PC14 cells had few metastases, almost all mice inoculated with PC14HM cells developed metastases in multiple organs, including the lung, bone and adrenal gland, the same progression seen in human lung cancer. cDNA microarray analysis revealed that 981 genes were differentially (more than 3-fold) expressed between the two cell lines. Functional classification revealed that many of those genes were associated with cell growth, cell communication, development and transcription. Expression of three upregulated genes (HRB-2, HS3ST3A1 and RAB7) was higher in human cancer tissue compared to normal lung tissue, while expression of EDG1, which was downregulated, was lower in the cancer tissue compared to the normal lung. These results suggest that the newly established PC14HM cell line may provide a mouse model of widespread metastasis of lung cancer. This model system may provide insights into the key genetic determinants of widespread metastasis of lung cancer.

  11. Early development of the human pelvic diaphragm

    NARCIS (Netherlands)

    Koch, Wijnandus Franciscus Robertus Maria

    2006-01-01

    The last decade an increasing interest in the pelvic floor can be observed in medical sciences. The lack of data on the development of the human pelvic floor is striking. The early development of the human pelvic diaphragm was studied. Materials and methods Use was made of 38 human embryos and fetus

  12. Early development of the human pelvic diaphragm

    NARCIS (Netherlands)

    Koch, Wijnandus Franciscus Robertus Maria

    2006-01-01

    The last decade an increasing interest in the pelvic floor can be observed in medical sciences. The lack of data on the development of the human pelvic floor is striking. The early development of the human pelvic diaphragm was studied. Materials and methodsUse was made of 38 human embryos and

  13. Human Capital Development: A Family Objective.

    Science.gov (United States)

    Hildebrand, Verna

    1995-01-01

    Examines the concept of human capital as an economic construct. Suggests that human capital contributes to economic development, as do physical capital or natural resources, in that its development reinforces individuals' future economic output. Suggests that this perspective may prove useful for human service professionals because funding…

  14. Development of cancer cooperative groups in Japan.

    Science.gov (United States)

    Fukuda, Haruhiko

    2010-09-01

    Investigator-initiated clinical trials are essential for improving the standard of care for cancer patients, because pharmaceutical companies do not conduct trials that evaluate combination chemotherapy using drugs from different companies, surgery, radiotherapy or multimodal treatments. Government-sponsored cooperative groups have played a vital role in developing cancer therapeutics since the 1950s in the USA; however, the establishment of these groups in Japan did not take place until 30 years later. Methodological standards for multicenter cancer clinical trials were established in the 1980s by the National Cancer Institute and cooperative groups. The Japan Clinical Oncology Group, one of the largest cooperative groups in the country, was instituted in 1990. Its data center and operations office, formed during the 1990s, applied the standard methods of US cooperative groups. At present, the Japan Clinical Oncology Group consists of 14 subgroups, a Data Center, an Operations Office, nine standing committees and an Executive Committee represented by the Japan Clinical Oncology Group Chair. Quality control and quality assurance at the Japan Clinical Oncology Group, including regular central monitoring, statistical methods, interim analyses, adverse event reporting and site visit audit, have complied with international standards. Other cooperative groups have also been established in Japan since the 1980s; however, nobody figures out all of them. A project involving the restructuring of US cooperative groups has been ongoing since 2005. Learning from the success of this project will permit further progress of the cancer clinical trials enterprise in Japan.

  15. Role of ARPC2 in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2017-01-01

    Full Text Available Gastric cancer continues to be the second most frequent cause of cancer deaths worldwide. However, the exact molecular mechanisms are still unclear. Further research to find potential targets for therapy is critical and urgent. In this study, we found that ARPC2 promoted cell proliferation and invasion in the human cancer cell line MKN-28 using a cell total number assay, MTT (3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide assay, cell colony formation assay, migration assay, invasion assay, and wound healing assay. For downstream pathways, CTNND1, EZH2, BCL2L2, CDH2, VIM, and EGFR were upregulated by ARPC2, whereas PTEN, BAK, and CDH1 were downregulated by ARPC2. In a clinical study, we examined the expression of ARPC2 in 110 cases of normal human gastric tissues and 110 cases of human gastric cancer tissues. ARPC2 showed higher expression in gastric cancer tissues than in normal gastric tissues. In the association analysis of 110 gastric cancer tissues, ARPC2 showed significant associations with large tumor size, lymph node invasion, and high tumor stage. In addition, ARPC2-positive patients exhibited lower RFS and OS rates compared with ARPC2-negative patients. We thus identify that ARPC2 plays an aneretic role in human gastric cancer and provided a new target for gastric cancer therapy.

  16. Calorimetric signatures of human cancer cells and their nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Todinova, S. [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, Sofia 1113 (Bulgaria); Stoyanova, E. [Department of Molecular Immunology, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Tzarigradsko shose Blvd. 73, Sofia 1113 (Bulgaria); Krumova, S., E-mail: sakrumo@gmail.com [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, Sofia 1113 (Bulgaria); Iliev, I. [Institute of Experimental Morphology, Pathology and Anthropology with Museum, Acad. G. Bonchev Str., Bl. 25, Sofia 1113 (Bulgaria); Taneva, S.G. [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, Sofia 1113 (Bulgaria)

    2016-01-10

    Graphical abstract: - Highlights: • Two temperature ranges are distinguished in the thermograms of cells/nuclei. • Different thermodynamic properties of cancer and normal human cells/nuclei. • Dramatic reduction of the enthalpy of the low-temperature range in cancer cells. • Oxaliplatin and 5-FU affect the nuclear matrix proteins and the DNA stability. - Abstract: The human cancer cell lines HeLa, JEG-3, Hep G2, SSC-9, PC-3, HT-29, MCF7 and their isolated nuclei were characterized by differential scanning calorimetry. The calorimetric profiles differed from normal human fibroblast (BJ) cells in the two well distinguished temperature ranges—the high-temperature range (H{sub T}, due to DNA-containing structures) and the low-temperature range (L{sub T}, assigned to the nuclear matrix and cellular proteins). The enthalpy of the L{sub T} range, and, respectively the ratio of the enthalpies of the L{sub T}- vs. H{sub T}-range, ΔH{sub L}/ΔH{sub H}, is strongly reduced for all cancer cells compared to normal fibroblasts. On the contrary, for most of the cancer nuclei this ratio is higher compared to normal nuclei. The HT-29 human colorectal cancer cells/nuclei differed most drastically from normal human fibroblast cells/nuclei. Our data also reveal that the treatment of HT-29 cancer cells with cytostatic drugs affects not only the DNA replication but also the cellular proteome.

  17. Proteasome inhibition as a novel therapeutic target in human cancer.

    Science.gov (United States)

    Rajkumar, S Vincent; Richardson, Paul G; Hideshima, Teru; Anderson, Kenneth C

    2005-01-20

    The 26S proteasome is a large intracellular adenosine 5'-triphosphate-dependent protease that identifies and degrades proteins tagged for destruction by the ubiquitin system. The orderly degradation of cellular proteins is critical for normal cell cycling and function, and inhibition of the proteasome pathway results in cell-cycle arrest and apoptosis. Dysregulation of this enzymatic system may also play a role in tumor progression, drug resistance, and altered immune surveillance, making the proteasome an appropriate and novel therapeutic target in cancer. Bortezomib (formerly known as PS-341) is the first proteasome inhibitor to enter clinical practice. It is a boronic aid dipeptide that binds directly with and inhibits the enzymatic complex. Bortezomib has recently shown significant preclinical and clinical activity in several cancers, confirming the therapeutic value of proteasome inhibition in human malignancy. It was approved in 2003 for the treatment of advanced multiple myeloma (MM), with approximately one third of patients with relapsed and refractory MM showing significant clinical benefit in a large clinical trial. Its mechanism of action is partly mediated through nuclear factor-kappa B inhibition, resulting in apoptosis, decreased angiogenic cytokine expression, and inhibition of tumor cell adhesion to stroma. Additional mechanisms include c-Jun N-terminal kinase activation and effects on growth factor expression. Several clinical trials are currently ongoing in MM as well as several other malignancies. This article discusses proteasome inhibition as a novel therapeutic target in cancer and focuses on the development, mechanism of action, and current clinical experience with bortezomib.

  18. Development of Humane Interpersonal Relationships

    Science.gov (United States)

    Kleptsova, Elena Yuryevna; Balabanov, Anton Anatolyevich

    2016-01-01

    The article reflects some theoretical aspects of humanization of interpersonal relationships in the sphere of education. The notion "humanization of interpersonal relationships" is being analyzed. The authors offer a characterization of some parameters of relationships: orientation, modality, valence, intensity, awareness,…

  19. Review of colorectal cancer and its metastases in rodent models: comparative aspects with those in humans

    DEFF Research Database (Denmark)

    Kobaek-Larsen, M; Thorup, I; Diederichsen, Axel Cosmus Pyndt;

    2000-01-01

    that human trials become more directed, with greater chances of success. The orthotopic transplantation of colon cancer cells into the cecum of syngeneic animals or intraportal inoculation appears to resemble the human metastatic disease most closely, providing a model for study of the treatment......BACKGROUND AND PURPOSE: Colorectal cancer (CRC) remains one of the most common cancer forms developing in industrialized countries, and its incidence appears to be rising. Studies of human population groups provide insufficient information about carcinogenesis, pathogenesis, and treatment of CRC...... models approximate many of the characteristics of human colonic carcinogenesis and metastasis. So far few comparative evaluations of the various animal models of CRC have been made. CONCLUSION: Animal studies cannot replace human clinical trials, but they can be used as a pre-screening tool, so...

  20. Telmisartan inhibits human urological cancer cell growth through early apoptosis

    Science.gov (United States)

    MATSUYAMA, MASAHIDE; FUNAO, KIYOAKI; KURATSUKURI, KATSUYUKI; TANAKA, TOMOAKI; KAWAHITO, YUTAKA; SANO, HAJIME; CHARGUI, JAMEL; TOURAINE, JEAN-LOUIS; YOSHIMURA, NORIO; YOSHIMURA, RIKIO

    2010-01-01

    Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agents. In addition, studies have provided evidence that ARBs have the potential to inhibit the growth of several types of cancer cells. It was reported that telmisartan (a type of ARB) has peroxisome proliferator-activated receptor (PPAR)-γ activation activity. We previously reported that the PPAR-γ ligand induces growth arrest in human urological cancer cells through apoptosis. In this study, we evaluated the effects of telmisartan and other ARBs on cell proliferation in renal cell carcinoma (RCC), bladder cancer (BC), prostate cancer (PC) and testicular cancer (TC) cell lines. The inhibitory effects of telmisartan and other ARBs (candesartan, valsartan, irbesartan and losartan) on the growth of the RCC, BC, PC and TC cell lines was investigated using an MTT assay. Flow cytometry and Hoechst staining were used to determine whether the ARBs induced apoptosis. Telmisartan caused marked growth inhibition in the urological cancer cells in a dose- and time-dependent manner. Urological cancer cells treated with 100 μM telmisartan underwent early apoptosis and DNA fragmentation. However, the other ARBs had no effect on cell proliferation in any of the urological cancer cell lines. Telmisartan may mediate potent anti-proliferative effects in urological cancer cells through PPAR-γ. Thus, telmisartan is a potent target for the prevention and treatment of human urological cancer. PMID:22993542

  1. The relationship between Human Papillomavirus and Epstein-Barr virus infections with breast cancer of Iranian patients

    OpenAIRE

    Zahra Tahmasebi fard

    2013-01-01

    Background: Breast cancer is the malignancy in humans and other mammals. Several risk factors are involved in their appearance such as higher hormone levels and obesity. Identification of a mouse mammary tumor virus supports a viral etiology for breast tumors in animals. Viruses have been implicated in the development of various cancers, but viral induction for formation breast cancer is controversial. The purpose of this study was investigation of the presence of human papillomavirus (HPV) &...

  2. Comparative oncology: what dogs and other species can teach us about humans with cancer.

    Science.gov (United States)

    Schiffman, Joshua D; Breen, Matthew

    2015-07-19

    Over 1.66 million humans (approx. 500/100,000 population rate) and over 4.2 million dogs (approx. 5300/100,000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us.

  3. Comparative oncology: what dogs and other species can teach us about humans with cancer

    Science.gov (United States)

    Schiffman, Joshua D.; Breen, Matthew

    2015-01-01

    Over 1.66 million humans (approx. 500/100 000 population rate) and over 4.2 million dogs (approx. 5300/100 000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us. PMID:26056372

  4. Development of a next generation Semliki Forest virus-based DNA vaccine against cervical cancer

    NARCIS (Netherlands)

    Van De Wall, Stephanie; Ljungberg, Karl; Peng IP, Peng; Boerma, Annemarie; Nijman, Hans W.; Liljeström, Peter; Daemen, Toos

    2014-01-01

    Cervical cancer is the second most prevalent cancer among women worldwide. The disease develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7 with transforming capacities in cervical epithelial cells. Our group pioneered

  5. Development of a next generation Semliki Forest virus-based DNA vaccine against cervical cancer

    NARCIS (Netherlands)

    Van De Wall, Stephanie; Ljungberg, Karl; Peng IP, Peng; Boerma, Annemarie; Nijman, Hans W.; Liljeström, Peter; Daemen, Toos

    2014-01-01

    Cervical cancer is the second most prevalent cancer among women worldwide. The disease develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7 with transforming capacities in cervical epithelial cells. Our group pioneered

  6. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue.

    Science.gov (United States)

    Teraoka, S; Kyoizumi, S; Seyama, T; Yamakido, M; Akiyama, M

    1995-05-01

    We established a novel severe combined immunodeficient (SCID) mouse model for the study of human lung cancer metastasis to human lung. Implantation of both human fetal and adult lung tissue into mammary fat pads of SCID mice showed a 100% rate of engraftment, but only fetal lung implants revealed normal morphology of human lung tissue. Using these chimeric mice, we analyzed human lung cancer metastasis to both mouse and human lungs by subcutaneous inoculation of human squamous cell carcinoma and adenocarcinoma cell lines into the mice. In 60 to 70% of SCID mice injected with human-lung squamous-cell carcinoma, RERF-LC-AI, cancer cells were found to have metastasized to both mouse lungs and human fetal lung implants but not to human adult lung implants 80 days after cancer inoculation. Furthermore, human-lung adenocarcinoma cells, RERF-LC-KJ, metastasized to the human lung implants within 90 days in about 40% of SCID mice, whereas there were no metastases to the lungs of the mice. These results demonstrate the potential of this model for the in vivo study of human lung cancer metastasis.

  7. Highlights of Human Resource Development Conferences 1979.

    Science.gov (United States)

    Bunker, Barbara Benedict; And Others

    1979-01-01

    The articles focus on building interpersonal skills utilizing experiential training to socialize new employees and develop leadership. They also focus on training decision makers, performance appraisal, career development, mobilizing human resources and ego stages in organizational development. (CMG)

  8. Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.

    Science.gov (United States)

    Jiang, Guosong; Wu, Amy D; Huang, Chao; Gu, Jiayan; Zhang, Liping; Huang, Haishan; Liao, Xin; Li, Jingxia; Zhang, Dongyun; Zeng, Xingruo; Jin, Honglei; Huang, Haojie; Huang, Chuanshu

    2016-07-01

    Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR.

  9. Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia.

    Science.gov (United States)

    Al-Zoughbi, Wael; Pichler, Martin; Gorkiewicz, Gregor; Guertl-Lackner, Barbara; Haybaeck, Johannes; Jahn, Stephan W; Lackner, Carolin; Liegl-Atzwanger, Bernadette; Popper, Helmut; Schauer, Silvia; Nusshold, Elisa; Kindt, Alida S D; Trajanoski, Zlatko; Speicher, Michael R; Haemmerle, Guenther; Zimmermann, Robert; Zechner, Rudolf; Vesely, Paul W; Hoefler, Gerald

    2016-06-01

    Metabolic reprogramming is a hallmark of cancer. Understanding cancer metabolism is instrumental to devise innovative therapeutic approaches. Anabolic metabolism, including the induction of lipogenic enzymes, is a key feature of proliferating cells. Here, we report a novel tumor suppressive function for adipose triglyceride lipase (ATGL), the rate limiting enzyme in the triglyceride hydrolysis cascade.In immunohistochemical analysis, non-small cell lung cancers, pancreatic adenocarcinoma as well as leiomyosarcoma showed significantly reduced levels of ATGL protein compared to corresponding normal tissues. The ATGL gene was frequently deleted in various forms of cancers. Low levels of ATGL mRNA correlated with significantly reduced survival in patients with ovarian, breast, gastric and non-small cell lung cancers. Remarkably, pulmonary neoplasia including invasive adenocarcinoma developed spontaneously in mice lacking ATGL pointing to an important role for this lipase in controlling tumor development.Loss of ATGL, as detected in several forms of human cancer, induces spontaneous development of pulmonary neoplasia in a mouse model. Our results, therefore, suggest a novel tumor suppressor function for ATGL and contribute to the understanding of cancer metabolism. We propose to evaluate loss of ATGL protein expression for the diagnosis of malignant tumors. Finally, modulation of the lipolytic pathway may represent a novel therapeutic approach in the treatment of human cancer.

  10. Evolution of animal models in cancer vaccine development.

    Science.gov (United States)

    Wei, Wei-Zen; Jones, Richard F; Juhasz, Csaba; Gibson, Heather; Veenstra, Jesse

    2015-12-16

    Advances in cancer vaccine development are facilitated by animal models reflecting key features of human cancer and its interface with host immunity. Several series of transplantable preneoplastic and neoplastic mouse mammary lesions have been used to delineate mechanisms of anti-tumor immunity. Mimicking immune tolerance to tumor-associated antigens (TAA) such as HER2/neu, transgenic mice developing spontaneous mammary tumors are strong model systems for pre-clinical vaccine testing. In these models, HER2 DNA vaccines are easily administered, well-tolerated, and induce both humoral and cellular immunity. Although engineered mouse strains have advanced cancer immunotherapy, basic shortcomings remain. For example, multiple mouse strains have to be tested to recapitulate genetic regulation of immune tolerance in humans. Outbred domestic felines more closely parallel humans in the natural development of HER2 positive breast cancer and their varying genetic background. Electrovaccination with heterologous HER2 DNA induces robust adaptive immune responses in cats. Importantly, homologous feline HER2 DNA with a single amino acid substitution elicits unique antibodies to feline mammary tumor cells, unlocking a new vaccine principle. As an alternative approach to targeted vaccination, non-surgical tumor ablation such as cryoablation induces anti-tumor immunity via in situ immunization, particularly when combined with toll-like receptor (TLR) agonist. As strategies for vaccination advance, non-invasive monitoring of host response becomes imperative. As an example, magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning following administration of tryptophan metabolism tracer [11C]-alpha-methyl-tryptophan (AMT) provides non-invasive imaging of both tumor growth and metabolic activities. Because AMT is a substrate of indoleamine-pyrrole 2,3-dioxygenase (IDO), an enzyme that produces the immune regulatory molecule kynurenine, AMT imaging can provide

  11. Effect of sulindac sulfide on metallohydrolases in the human colon cancer cell line HT-29.

    Science.gov (United States)

    Guillen-Ahlers, Hector; Tan, Jiangning; Castellino, Francis J; Ploplis, Victoria A

    2011-01-01

    Matrix metalloproteinase 7 (MMP7), a metallohydrolase involved in the development of several cancers, is downregulated in the Apc(Min/+) colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.

  12. Role of papillomavirus oncogenes in human cervical cancer: Transgenic animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Griep, A.E.; Lambert, P.F. [Univ. of Wisconsin School of Medicine, Madison, WI (United States)

    1994-05-01

    Human papillomaviruses are believed to be etiologic agents for the majority of human cervical carcinoma, a common cancer that is a leading cause of death by cancer among women worldwide. In cervical carcinoma, a subset of papillomaviral genes, namely E6 and E7, are expressed. In vitro tissue culture studies indicate that HPV E6 and E7 are oncogenes, and that their oncogenicity is due in part to their capacity to inactivate cellular tumor suppressor genes. The behavior of E6 and E7 in vitro and the genetic evidence from analysis of human cancers suggest that the E6 and E7 genes play a significant role in the development of cervical cancer. This hypothesis is now being tested using animal models. In this review, we summarize our current knowledge of the oncogenicity of papillomavirus genes that has been generated through their study in transgenic mice. 82 refs., 4 figs., 1 tab.

  13. Effect of sulindac sulfide on metallohydrolases in the human colon cancer cell line HT-29.

    Directory of Open Access Journals (Sweden)

    Hector Guillen-Ahlers

    Full Text Available Matrix metalloproteinase 7 (MMP7, a metallohydrolase involved in the development of several cancers, is downregulated in the Apc(Min/+ colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.

  14. A Calibrated Index of Human Development

    Science.gov (United States)

    Lind, Niels

    2010-01-01

    The weightings of the four component indicators of the UNDP's Human Development Index HDI appear to be arbitrary and have not been given justification. This paper develops a variant of the HDI, calculated to reflect peoples' revealed evaluations of education and the productivity of work. The resulting Calibrated human Development Index CDI has a…

  15. A Calibrated Index of Human Development

    Science.gov (United States)

    Lind, Niels

    2010-01-01

    The weightings of the four component indicators of the UNDP's Human Development Index HDI appear to be arbitrary and have not been given justification. This paper develops a variant of the HDI, calculated to reflect peoples' revealed evaluations of education and the productivity of work. The resulting Calibrated human Development Index CDI has a…

  16. Human Development, Inequality and Poverty: empirical findings

    OpenAIRE

    Suman Seth; Antonio Villar

    2014-01-01

    This paper provides a discussion on the empirical findings surrounding the design of human development, inequality and poverty measures. We focus on the United Nations Development Program approach to those issues, in particular regarding the human development index and the multidimensional poverty index.

  17. Integrated Human Development Programme in Angola

    OpenAIRE

    UNDP - UNOPS EDINFODEC Project - Cooperazione italiana,

    2004-01-01

    This report is an excerpt from the sixth UNDP-UNOPS-Cooperazione Italiana Report on Multilateral Human Development Programmes (2004). The Integrated Human Development Programme in Angola began in 1999 and ended in 2003. It focused on the maintenance and consolidation of the Local Economic Development Agencies (LEDAs). The PDHI helped set up the LEDAs in the Provinces of Bengo, Benguela and Kwanza Sul.

  18. A taxonomy of epithelial human cancer and their metastases

    Directory of Open Access Journals (Sweden)

    De Moor Bart

    2009-12-01

    . Moreover, a signature was developed based on our unsupervised clustering of breast tumors and this was predictive for disease-specific survival in three independent studies. Next, the metastases from ovarian, breast, lung and vulva cluster with their tissue of origin while metastases from colon showed a bimodal distribution. A significant part clusters with tissue of origin while the remaining tumors cluster with the tissue of destination. Conclusion Our molecular taxonomy of epithelial human cancer indicates surprising correlations over tissues. This may have a significant impact on the classification of many cancer sites and may guide pathologists, both in research and daily practice. Moreover, these results based on unsupervised analysis yielded a signature predictive of clinical outcome in breast cancer. Additionally, we hypothesize that metastases from gastrointestinal origin either remember their tissue of origin or adapt to the tissue of destination. More specifically, colon metastases in the liver show strong evidence for such a bimodal tissue specific profile.

  19. Immune therapy for human papillomaviruses-related cancers.

    Science.gov (United States)

    Rosales, Ricardo; Rosales, Carlos

    2014-12-10

    Human papillomaviruses (HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered low-risk such as HPV 6 and 11, produce warts; while high-risk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of pre-cancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cells by the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virus-host interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested.

  20. Human papilloma viruses and cancer in the post-vaccine era.

    Science.gov (United States)

    Galani, E; Christodoulou, C

    2009-11-01

    Human papilloma viruses (HPV) are strong human carcinogens, in fact today they are considered as the second most frequent carcinogen. In the middle of the 1970s the hypothesis that cervical cancer may arise from viruses was established and in the 1990s the relationship between HPV and cervical neoplasia was confirmed. HPV infections are the most common sexually transmitted infections. Specific subtypes of human papilomaviruses are now considered as the etiological agents in nearly all cases of cervical cancer and cervical epithelial neoplasia. Approximately 470,000 new cases and 23,000 deaths of cervical cancer occur each year, with the majority taking place in developing countries. Cervical cancer remains among the three leading causes of cancer deaths among women below the age of 45. Human papilomaviruses are classified into two groups: high-risk (oncogenic) types and low risk types. HPV types 16, 18, 45 and 31 are considered to be the most important oncogenic types. Subtypes 16 and 18 are the causative agents of more than 50% of cervical pre-cancerous lesions, and more than 70% of cervical cancer cases. High risk subtypes are also implicated with anal, perianal and oropharyngeal carcinomas. Recently, the prophylactic bivalent HPV 16/18 and the quadrivalent HPV 6/11/16/18/ vaccines have been approved. The development of prophylactic vaccines against human papilomavirus has been hailed as one of the most significant advances of recent years and it is expected to reduce dramatically the mortality of human papilomavirus associated cancers, but has also given rise to some of the most intense scientific debates.

  1. Fat accumulation in adipose tissues as a risk factor for the development of endometrial cancer.

    Science.gov (United States)

    Nakamura, Keiichiro; Hongo, Atsushi; Kodama, Junichi; Hiramatsu, Yuji

    2011-07-01

    Fat accumulation in adipose tissues is a risk factor for the development of human cancers. However, there are no studies describing the fat accumulation in adipose tissue or its distribution in human endometrial cancer. We first examined fat accumulation in adipose tissues separately on CT images of 122 patients with endometrial cancer, and investigated the correlation of these findings with various histological types of endometrial cancers. Fat accumulation in adipose tissues [subcutaneous fat area (SFA) and/or visceral fat areas (VFA)] was strongly correlated with the group of obesity-related biological parameters (weight, body mass index (BMI), waist and body surface area (BSA)) in endometrial cancer. The incidence of type I endometrial cancer was more closely correlated with an increase in obesity-related parameters such as weight (p=0.011), BMI (p=0.006), waist circumference (p=0.038), BSA (p=0.016), SFA (p=0.005), total fat area (TFA) (p=0.006) and total cholesterol (T.Cho) (P=0.010) than type II endometrial cancer. In particular, the SFA was most strongly correlated with obesity-related biological parameters of type I endometrial cancer. The present findings indicate that type I endometrial cancer has a statistically significant increase in obesity-related biological parameters than type II endometrial cancer. We propose that the subcutaneous fat accumulation in adipose tissue is a strong risk factor for developing type I endometrial cancer.

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

    Science.gov (United States)

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

    2013-01-01

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

  3. Mouse Tumor Biology (MTB): a database of mouse models for human cancer.

    Science.gov (United States)

    Bult, Carol J; Krupke, Debra M; Begley, Dale A; Richardson, Joel E; Neuhauser, Steven B; Sundberg, John P; Eppig, Janan T

    2015-01-01

    The Mouse Tumor Biology (MTB; http://tumor.informatics.jax.org) database is a unique online compendium of mouse models for human cancer. MTB provides online access to expertly curated information on diverse mouse models for human cancer and interfaces for searching and visualizing data associated with these models. The information in MTB is designed to facilitate the selection of strains for cancer research and is a platform for mining data on tumor development and patterns of metastases. MTB curators acquire data through manual curation of peer-reviewed scientific literature and from direct submissions by researchers. Data in MTB are also obtained from other bioinformatics resources including PathBase, the Gene Expression Omnibus and ArrayExpress. Recent enhancements to MTB improve the association between mouse models and human genes commonly mutated in a variety of cancers as identified in large-scale cancer genomics studies, provide new interfaces for exploring regions of the mouse genome associated with cancer phenotypes and incorporate data and information related to Patient-Derived Xenograft models of human cancers.

  4. Frequent mutations in EGFR, KRAS and TP53 genes in human lung cancer tumors detected by ion torrent DNA sequencing.

    Directory of Open Access Journals (Sweden)

    Xin Cai

    Full Text Available Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.

  5. PIK3CA and TP53 gene mutations in human breast cancer tumors frequently detected by ion torrent DNA sequencing.

    Directory of Open Access Journals (Sweden)

    Xusheng Bai

    Full Text Available Breast cancer is the most common malignancy and the leading cause of cancer deaths in women worldwide. While specific genetic mutations have been linked to 5-10% of breast cancer cases, other environmental and epigenetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive breast cancer molecular profile is needed to develop more effective target therapies. Until recently, identifying genetic cancer mutations via personalized DNA sequencing was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 105 human breast cancer samples. The sequencing analysis revealed missense mutations in PIK3CA, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.

  6. Tea and cancer prevention: studies in animals and humans.

    Science.gov (United States)

    Chung, Fung-Lung; Schwartz, Joel; Herzog, Christopher R; Yang, Yang-Ming

    2003-10-01

    The role of tea in protection against cancer has been supported by ample evidence from studies in cell culture and animal models. However, epidemiological studies have generated inconsistent results, some of which associated tea with reduced risk of cancer, whereas others found that tea lacks protective activity against certain human cancers. These results raise questions about the actual role of tea in human cancer that needs to be addressed. This article is intended to provide a better perspective on this controversy by summarizing the laboratory studies in animals and humans with emphasis on animal tumor bioassays on skin, lung, mammary glands and colon, and the molecular and cellular mechanisms affected by tea. Finally, a recent small pilot intervention study with green tea in smokers is presented.

  7. Preclinical Remodeling of Human Prostate Cancer through the PTEN/AKT Pathway

    Directory of Open Access Journals (Sweden)

    Marco A. De Velasco

    2012-01-01

    Full Text Available Knowledge gained from the identification of genetic and epigenetic alterations that contribute to the progression of prostate cancer in humans is now being implemented in the development of functionally relevant translational models. GEM (genetically modified mouse models are being developed to incorporate the same molecular defects associated with human prostate cancer. Haploinsufficiency is common in prostate cancer and homozygous loss of PTEN is strongly correlated with advanced disease. In this paper, we discuss the evolution of the PTEN knockout mouse and the cooperation between PTEN and other genetic alterations in tumor development and progression. Additionally, we will outline key points that make these models key players in the development of personalized medicine, as potential tools for target and biomarker development and validation as well as models for drug discovery.

  8. Human Resource Development in Construction Industry

    OpenAIRE

    Behnam Neyerstani

    2014-01-01

    Human Resource Development (HRD) is the domain that performs core function in an organization for the advancement of personal and professional skills, knowledge and abilities of employees. Human resource development includes such opportunities as employee training, employee career development, performance management and development, coaching, mentoring, succession planning, key employee identification and organization development. HRD has the key role in improving knowledge and skills on huma...

  9. Milk fermented by Propionibacterium freudenreichii induces apoptosis of HGT-1 human gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Fabien J Cousin

    Full Text Available BACKGROUND: Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate. METHODOLOGY/PRINCIPAL FINDINGS: A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy. CONCLUSIONS/SIGNIFICANCE: Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.

  10. Expression of Axl and its prognostic significance in human breast cancer

    Science.gov (United States)

    Jin, Gaoyuan; Wang, Zhenzhen; Wang, Jianguang; Zhang, Like; Chen, Yanbin; Yuan, Pengfei; Liu, Dechun

    2017-01-01

    Breast cancer is the most common malignant cancer and second leading cause of cancer-related death among women, and its prevalence continues to increase. Axl overexpression has been identified in the many types of human cancer, and it has been demonstrated to participate in signaling pathways related to carcinogenesis and cancer development. In the present study, Axl expression was examined by performing immunohistochemical staining in 60 breast cancer tumors and 40 benign breast lesions (25 mammary dysplasia and 15 breast fibroadenoma). In total, 34 (56.67%) cancer tissues and 13 (32.5%) benign breast lesions were classified as exhibiting high levels of Axl expression, indicating a significant association between malignancy and high Axl expression. High Axl expression was also associated with estrogen receptor (ER) positivity (P=0.028), progesterone receptor (PR) positivity (P=0.007), and poor tumor differentiation (P=0.033). No significant associations were observed between Axl expression and age, tumor size, lymph node metastasis, tumor node metastasis staging, human epidermal growth factor receptor 2 and Ki67 antigen. The Kaplan-Meier survival analysis and Cox proportional hazard model both demonstrated that there was no statistical difference between Axl expression and breast cancer prognosis. However, it remains unclear whether the expression of Axl is correlated with the prognosis of luminal type breast cancer patients. PMID:28356938

  11. Zinc finger protein 278, a potential oncogene in human colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoqing Tian; Danfeng Sun; Yanjie Zhang; Shuliang Zhao; Hua Xiong; Jingyuan Fang

    2008-01-01

    Zinc finger protein 278 (ZNF278) is a novel Krueppel Cys2-His2-type zinc finger protein that is ubiquitously distributed in human tissues. Whether ZNF278 is related to the development of colorectal cancer is still unclear. The transcriptional level of ZNF278 was studied in colorectal cancer by real-time polymerase chain reaction. The results showed that ZNF278 expression was increased in 53% of colorectal cancer tissues compared to corresponding non-cancerous tissues. The transcriptional down-regulation of ZNF278 was detected in only three (6%) human colorectal cancer tissues compared to corresponding non-cancer tissues. No significant difference was detected in 19 (41%) pairs of samples.However, we failed to find a significant association between the up-regulation of ZNF278 transcription and age, sex, the degree of infiltration, or the tumor size of colorectal cancer.To study the function of ZNF278 in colorectal carcinogenesis,the colon cancer cell line SW1116 was stably transfected with a wild-type ZNF278 plasmid to construct an overexpression system, and was transiently transfected with the small interfering RNA of ZNF278 to construct a ZNF278 knockdown system. Cell proliferation was assessed with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide dye and a cell counter. The results show that ZNF278 promotes cell growth, and its knockdown suppresses cell proliferation. ZNF278 could be a potential proto-oncogene in colorectal cancer.

  12. Developing a nanoparticle test for prostate cancer scoring

    Directory of Open Access Journals (Sweden)

    Huo Qun

    2012-03-01

    Full Text Available Abstract Background Over-diagnosis and treatment of prostate cancer has been a major problem in prostate cancer care and management. Currently the most relevant prognostic factor to predict a patient's risk of death due to prostate cancer is the Gleason score of the biopsied tissue samples. However, pathological analysis is subjective, and the Gleason score is only a qualitative estimate of the cancer malignancy. Molecular biomarkers and diagnostic tests that can accurately predict prostate tumor aggressiveness are rather limited. Method We report here for the first time the development of a nanoparticle test that not only can distinguish prostate cancer from normal and benign conditions, but also has the potential to predict the aggressiveness of prostate cancer quantitatively. To conduct the test, a prostate tissue lysate sample is spiked into a blood serum or human IgG solution and the spiked sample is incubated with a citrate-protected gold nanoparticle solution. IgG is known to adsorb to citrate-protected gold nanoparticles to form a "protein corona" on the nanoparticle surface. From this study, we discovered that certain tumor-specific molecules can interact with IgG and change the adsorption behavior of IgG to the gold nanoparticles. This change is reflected in the nanoparticle size of the assay solution and detected by a dynamic light scattering technique. Assay data were analyzed by one-way ANOVA for multiple variant analysis, and using the Student t-test or nonparametric Mann-Whitney U-tests for pairwise analyses. Results An inverse, quantitative correlation of the average nanoparticle size of the assay solution with tumor status and histological diagnostic grading was observed from the nanoparticle test. IgG solutions spiked with prostate tumor tissue exhibit significantly smaller nanoparticle size than the solutions spiked with normal and benign tissues. The higher grade the tumor is, the smaller the nanoparticle size is. The test

  13. Human mammaglobin: a superior marker for reverse-transcriptase PCR in detecting circulating tumor cells in breast cancer patients.

    Science.gov (United States)

    Li, GuangLiang; Zhang, Jing; Jin, KeTao; He, KuiFeng; Wang, HaoHao; Lu, HaiQi; Teng, LiSong

    2011-04-01

    Breast cancer is the most frequent cancer in women in the USA and the second most common cause of death in females who develop cancer. Recently, the detection of circulating tumor cells has emerged as a promising tool for monitoring the progression of clinically occult micrometastases in breast cancer patients. Sensitive molecular techniques, primarily based upon the reverse-transcriptase PCR, using various molecules as markers, have been developed to detect circulating tumor cells. Among those molecules, human mammaglobin mRNA has been found to be the most specific marker for the hematogenous spread of breast cancer cells. In this article, we review the current knowledge regarding the use of reverse-transcriptase PCR for detecting human mammaglobin mRNA as a biomarker for circulating tumor cells in breast cancer patients, and evaluate the clinical implications of human mammaglobin since it was first isolated in 1996.

  14. Hypoxia-regulated microRNAs in human cancer

    Institute of Scientific and Technical Information of China (English)

    Guomin SHEN; Xiaobo LI; Yong-feng JIA; Gary A PIAZZA; Yaguang XI

    2013-01-01

    Hypoxia plays an important role in the tumor microenvironment by allowing the development and maintenance of cancer cells,but the regulatory mechanisms by which tumor cells adapt to hypoxic conditions are not yet well understood.MicroRNAs are recognized as a new class of master regulators that control gene expression and are responsible for many normal and pathological cellular processes.Studies have shown that hypoxia inducible factor 1 (HIF1) regulates a panel of microRNAs,whereas some of microRNAs target HIF1.The interaction between microRNAs and HIF1 can account for many vital events relevant to tumorigenesis,such as angiogenesis,metabolism,apoptosis,cell cycle regulation,proliferation,metastasis,and resistance to anticancer therapy.This review will summarize recent findings on the roles of hypoxia and microRNAs in human cancer and illustrate the machinery by which microRNAs interact with hypoxia in tumor cells,It is expected to update our knowledge about the regulatory roles of microRNAs in regulating tumor microenvironments and thus benefit the development of new anticancer drugs.

  15. Endocrine therapy of human breast cancer grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Osborne, C K; Spang-Thomsen, M

    1987-01-01

    mice bearing transplanted human breast tumors have been proposed as such a model. This review therefore discusses the use of the athymic nude mouse model of the study of human breast cancer biology, and focuses on four subjects: 1. biological characteristics of heterotransplanted breast tumors; 2...

  16. Orthomolecular enhancement of human development

    Science.gov (United States)

    Pauling, L.

    1978-01-01

    The importance of molecules introduced into the human body by the way of foods is emphasized. Examples of orthomolecular therapy are given that range from the control of epileptic seizures, the therapy of mental illness, to the prevention of the common cold.

  17. Human cancer long non-coding RNA transcriptomes.

    Directory of Open Access Journals (Sweden)

    Ewan A Gibb

    Full Text Available Once thought to be a part of the 'dark matter' of the genome, long non-coding RNAs (lncRNAs are emerging as an integral functional component of the mammalian transcriptome. LncRNAs are a novel class of mRNA-like transcripts which, despite no known protein-coding potential, demonstrate a wide range of structural and functional roles in cellular biology. However, the magnitude of the contribution of lncRNA expression to normal human tissues and cancers has not been investigated in a comprehensive manner. In this study, we compiled 272 human serial analysis of gene expression (SAGE libraries to delineate lncRNA transcription patterns across a broad spectrum of normal human tissues and cancers. Using a novel lncRNA discovery pipeline we parsed over 24 million SAGE tags and report lncRNA expression profiles across a panel of 26 different normal human tissues and 19 human cancers. Our findings show extensive, tissue-specific lncRNA expression in normal tissues and highly aberrant lncRNA expression in human cancers. Here, we present a first generation atlas for lncRNA profiling in cancer.

  18. The Importance of Autophagy in Breast Cancer Development and Treatment

    Science.gov (United States)

    2010-09-01

    21:177-84. 12. Arteaga CL. The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. J...factor receptor in malignant gliomas. Cancer Res 2003; 63:7443-50. 16. Rexer BN, Engelman JA, Arteaga CL. Overcoming resistance to tyrosine kinase...12. Arteaga CL (2001) The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. J Clin

  19. Development of terahertz endoscopic system for cancer detection

    Science.gov (United States)

    Doradla, Pallavi; Alavi, Karim; Joseph, Cecil S.; Giles, Robert H.

    2016-02-01

    Terahertz (THz) imaging is emerging as a robust platform for a myriad of applications in the fields of security, health, astronomy and material science. The terahertz regime with wavelengths spanning from microns to millimeters is a potentially safe and noninvasive medical imaging modality for detecting cancers. Endoscopic imaging systems provide high flexibility in examining the interior surfaces of an organ or tissue. Researchers have been working on the development of THz endoscopes with photoconductive antennas, which necessarily operate under high voltage, and require at least two channels to measure the reflected signal from the specimen. This manuscript provides the design and imperative steps involved in the development of a single-channel terahertz endoscopic system. The continuous-wave terahertz imaging system utilizes a single flexible terahertz waveguide channel to transmit and collect the back reflected intrinsic terahertz signal from the sample and is capable of operation in both transmission and reflection modalities. To determine the feasibility of using a terahertz endoscope for cancer detection, the co- and cross-polarized terahertz remittance from human colonic tissue specimens were collected at 584 GHz frequency. The two dimensional terahertz images obtained using polarization specific detection exhibited intrinsic contrast between cancerous and normal regions of fresh colorectal tissue. The level of contrast observed using endoscopic imaging correlates well with the contrast levels observed in the free space ex vivo terahertz reflectance studies of human colonic tissue. The prototype device developed in this study represents a significant step towards clinical endoscopic application of THz technology for in vivo colon cancer screening.

  20. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudio Pulito

    Full Text Available Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR. It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954 human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative. These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  1. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    Science.gov (United States)

    Pulito, Claudio; Terrenato, Irene; Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  2. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    Science.gov (United States)

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  3. Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer

    Science.gov (United States)

    2016-10-01

    AWARD NUMBERS: W81XWH-14-1-0554 TITLE: Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer PRINCIPAL INVESTIGATOR...Dr. Nora M. Navone (Initiating PI) RECIPIENT: The University of Texas MD Anderson Cancer Center Houston, TX 77030 REPORT DATE: TYPE OF...21Sep2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER N/A Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer 5b. GRANT

  4. Human Papillomavirus (HPV) and Oropharyngeal Cancer

    Science.gov (United States)

    ... HPV? People get HPV from another person during intimate sexual contact. Most of the time, people get ... 17, 2017 Page last updated: July 17, 2017 Content source: Division of Cancer Prevention and Control, Centers ...

  5. Study of apoptosis in human liver cancers

    Institute of Scientific and Technical Information of China (English)

    Chang-Min Shan; Juan Li

    2002-01-01

    AIM: To investigate the action of apoptosis in occurrence ofliver cacinornas in vivo and the biological effect of Solanumlyratum Thumb on BEL-7404 cell line inducing apoptosis invitro.METHODS: The apoptosis in the liver carcinoma wasdetected with terminal deoxynucl neotidyl transferasemediated dUTP nick end labelling (TUNEL); the cancer cellscultured in DMED medium were treated with extract ofSolanum lyratum Thumb and observed under microscope,and their DNA was assayed by gel electrophoresis.RESULTS: In vivo apoptotic cells in the cancer adjacenttissues inceased; in vitro treatment of liver cancers withextract of Solanum lyratum Thumb could induce the cells tomanifest a typical apoptotic morphology. Their DNA wasfractured and a characteristic ladder pattem could be foundusing electrophoresis.CONCLUSION: In vivo the apoptosis of carcinomas waslower; maybe the cells divided quickly and then the cancersoccurred. In the cancer adjacent tissues, the apoptosispricked up, and in vitro Solarium lyratum Thumb couldinduce the apoptosis of BEL-7404 cells.

  6. Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer

    NARCIS (Netherlands)

    Garcia, M.B.; Blankenstein, M.A.; Wall, E. van der; Nortier, J.W.R.; Schornagel, J.H.; Thijssen, J.H.H.

    1990-01-01

    The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15-3, another member of the human mammary epithelial antigen

  7. Development and characterization of a novel human Waldenström macroglobulinemia cell line: RPCI-WM1, Roswell Park Cancer Institute - Waldenström Macroglobulinemia 1.

    Science.gov (United States)

    Chitta, Kasyapa S; Paulus, Aneel; Ailawadhi, Sikander; Foster, Barbara A; Moser, Michael T; Starostik, Petr; Masood, Aisha; Sher, Taimur; Miller, Kena C; Iancu, Dan M; Conroy, Jeffrey; Nowak, Norma J; Sait, Sheila N; Personett, David A; Coleman, Morton; Furman, Richard R; Martin, Peter; Ansell, Stephen M; Lee, Kelvin; Chanan-Khan, Asher A

    2013-02-01

    Understanding the biology of Waldenström macroglobulinemia is hindered by a lack of preclinical models. We report a novel cell line, RPCI-WM1, from a patient treated for WM. The cell line secretes human immunoglobulin M (h-IgM) with κ-light chain restriction identical to the primary tumor. The cell line has a modal chromosomal number of 46 and harbors chromosomal changes such as deletion of 6q21, monoallelic deletion of 9p21 (CDKN2A), 13q14 (RB1) and 18q21 (BCL-2), with a consistent amplification of 14q32 (immunoglobulin heavy chain; IgH) identical to its founding tumor sample. The clonal relationship is confirmed by identical CDR3 length and single nucleotide polymorphisms as well as a matching IgH sequence of the cell line and founding tumor. Both also harbor a heterozygous, non-synonymous mutation at amino acid 265 in the MYD88 gene (L265P). The cell line expresses most of the cell surface markers present on the parent cells. Overall, RPCI-WM1 represents a valuable model to study Waldenström macroglobulinemia.

  8. Distribution of trace metal concentrations in paired cancerous and non-cancerous human stomach tissues

    Institute of Scientific and Technical Information of China (English)

    Mehmet Yaman; Gokce Kaya; Hayrettin Yekeler

    2007-01-01

    AIM: To assess whether trace metal concentrations (which influence metabolism as both essential and non-essential elements) are increased or decreased in cancerous tissues and to understand the precise role of these metals in carcinogenesis.METHODS: Concentrations of trace metals including Cd,Ni, Cu, Zn, Fe, Mg and Ca in both cancerous and noncancerous stomach tissue samples were determined by atomic absorption spectrometry (AAS). Tissue samples were digested using microwave energy. Slotted tube atom trap was used to improve the sensitivity of copper and cadmium in flame AAS determinations.RESULTS: From the obtained data in this study,the concentrations of nickel, copper and iron in the cancerous human stomach were found to be significantly higher than those in the non-cancerous tissues, by using t-test for the paired samples. Furthermore, the average calcium concentrations in the cancerous stomach tissue samples were found to be significantly lower than those in the non-cancerous stomach tissue samples by using t-test. Exceedingly high Zn concentrations (207-826 mg/kg) were found in two paired stomach tissue samples from both cancerous and non-cancerous parts.CONCLUSION: In contrast to the literature data for Cu and Fe, the concentrations of copper, iron and nickel in cancerous tissue samples are higher than those in the non-cancerous samples. Furthermore, the Ca levels are lower in cancerous tissue samples than in non-cancerous tissue samples.

  9. Chestnut extract induces apoptosis in AGS human gastric cancer cells.

    Science.gov (United States)

    Lee, Hyun Sook; Kim, Eun Ji; Kim, Sun Hyo

    2011-06-01

    In Korea, chestnut production is increasing each year, but consumption is far below production. We investigated the effect of chestnut extracts on antioxidant activity and anticancer effects. Ethanol extracts of raw chestnut (RCE) or chestnut powder (CPE) had dose-dependent superoxide scavenging activity. Viable numbers of MDA-MD-231 human breast cancer cells, DU145 human prostate cancer cells, and AGS human gastric cancer cells decreased by 18, 31, and 69%, respectively, following treatment with 200 µg/mL CPE for 24 hr. CPE at various concentrations (0-200 µg/mL) markedly decreased AGS cell viability and increased apoptotic cell death dose and time dependently. CPE increased the levels of cleaved caspase-8, -7, -3, and poly (ADP-ribose) polymerase in a dose-dependent manner but not cleaved caspase-9. CPE exerted no effects on Bcl-2 and Bax levels. The level of X-linked inhibitor of apoptosis protein decreased within a narrow range following CPE treatment. The levels of Trail, DR4, and Fas-L increased dose-dependently in CPE-treated AGS cells. These results show that CPE decreases growth and induces apoptosis in AGS gastric cancer cells and that activation of the death receptor pathway contributes to CPE-induced apoptosis in AGS cells. In conclusion, CPE had more of an effect on gastric cancer cells than breast or prostate cancer cells, suggesting that chestnuts would have a positive effect against gastric cancer.

  10. Dietary Acrylamide and Human Cancer: A Systematic Review of Literature

    Science.gov (United States)

    Nagy, Tim R.; Barnes, Stephen; Groopman, John

    2014-01-01

    Cancer remains the second leading cause of death in the United States, and the numbers of cases are expected to continue to rise worldwide. Cancer prevention strategies are crucial for reducing the cancer burden. The carcinogenic potential of dietary acrylamide exposure from cooked foods is unknown. Acrylamide is a by-product of the common Maillard reaction where reducing sugars (i.e., fructose and glucose) react with the amino acid, asparagine. Based on the evidence of acrylamide carcinogenicity in animals, the International Agency for Research on Cancer has classified acrylamide as a group 2A carcinogen for humans. Since the discovery of acrylamide in foods in 2002, a number of studies have explored its potential as a human carcinogen. This paper outlines a systematic review of dietary acrylamide and human cancer, acrylamide exposure and internal dose, exposure assessment methods in the epidemiologic studies, existing data gaps, and future directions. A majority of the studies reported no statistically significant association between dietary acrylamide intake and various cancers, and few studies reported increased risk for renal, endometrial, and ovarian cancers; however, the exposure assessment has been inadequate leading to potential misclassification or underestimation of exposure. Future studies with improved dietary acrylamide exposure assessment are encouraged. PMID:24875401

  11. Deoxyribonucleic-binding homeobox proteins are augmented in human cancer

    DEFF Research Database (Denmark)

    Wewer, U M; Mercurio, A M; Chung, S Y;

    1990-01-01

    the highly conserved 60 amino acid homeodomain. This peptide antiserum recognized a protein species of molecular weight 63,000 in immunoblots of nuclear extracts obtained from several tumor cell lines. The predominant molecular weight 63,000 nuclear protein recognized by the peptide antiserum...... the same patients exhibited little immunoreactivity. Both the peptide antiserum and the polyclonal antiserum against the native protein immunoblotted a molecular weight 63,000 protein in nuclear extracts of tumor tissue, but not significantly in extracts of normal tissue. At the molecular level......Homeobox genes encode sequence-specific DNA-binding proteins that are involved in the regulation of gene expression during embryonic development. In this study, we examined the expression of homeobox proteins in human cancer. Antiserum was obtained against a synthetic peptide derived from...

  12. The utility of Apc-mutant rats in modeling human colon cancer

    Directory of Open Access Journals (Sweden)

    Amy A. Irving

    2014-11-01

    Full Text Available Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc and Kyoto Apc Delta (KAD strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer.

  13. The utility of Apc-mutant rats in modeling human colon cancer

    Science.gov (United States)

    Irving, Amy A.; Yoshimi, Kazuto; Hart, Marcia L.; Parker, Taybor; Clipson, Linda; Ford, Madeline R.; Kuramoto, Takashi; Dove, William F.; Amos-Landgraf, James M.

    2014-01-01

    Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer. PMID:25288683

  14. Economics and Human Resource Development: A Rejoinder

    Science.gov (United States)

    Wang, Greg G.; Swanson, Richard A.

    2008-01-01

    This article focuses on the areas agreement between two recent and seemingly disparate Human Resource Development Review articles by Wang and Swanson (2008) and McLean, Lynham, Azevedo, Lawrence, and Nafukho (2008). The foundational roles of economics in human resource development theory and practice are highlighted as well as the need for…

  15. Learning Human Aspects of Collaborative Software Development

    Science.gov (United States)

    Hadar, Irit; Sherman, Sofia; Hazzan, Orit

    2008-01-01

    Collaboration has become increasingly widespread in the software industry as systems have become larger and more complex, adding human complexity to the technological complexity already involved in developing software systems. To deal with this complexity, human-centric software development methods, such as Extreme Programming and other agile…

  16. Economics and Human Resource Development: A Rejoinder

    Science.gov (United States)

    Wang, Greg G.; Swanson, Richard A.

    2008-01-01

    This article focuses on the areas agreement between two recent and seemingly disparate Human Resource Development Review articles by Wang and Swanson (2008) and McLean, Lynham, Azevedo, Lawrence, and Nafukho (2008). The foundational roles of economics in human resource development theory and practice are highlighted as well as the need for…

  17. Linking Career Development and Human Resource Planning.

    Science.gov (United States)

    Gutteridge, Thomas G.

    When organizations integrate their career development and human resources planning activities into a comprehensive whole, it is the exception rather than the rule. One reason for the frequent dichotomy between career development and human resource planning is the failure to recognize that they are complements rather than synonyms or substitutes.…

  18. Learning Human Aspects of Collaborative Software Development

    Science.gov (United States)

    Hadar, Irit; Sherman, Sofia; Hazzan, Orit

    2008-01-01

    Collaboration has become increasingly widespread in the software industry as systems have become larger and more complex, adding human complexity to the technological complexity already involved in developing software systems. To deal with this complexity, human-centric software development methods, such as Extreme Programming and other agile…

  19. Human Papillomavirus Induced Transformation in Cervical and Head and Neck Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Allie K. [Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229 (United States); Wise-Draper, Trisha M. [Division of Hematology/Oncology, University of Cincinnati Medical Center, University of Cincinnati, Cincinnati, OH 45229 (United States); Wells, Susanne I., E-mail: Susanne.Wells@cchmc.org [Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229 (United States)

    2014-09-15

    Human papillomavirus (HPV) is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervical cancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervical cancer, and preventive vaccines, cervical cancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervical cancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed.

  20. CE: Human Papillomavirus-Related Oropharyngeal Cancer: A Review of Nursing Considerations.

    Science.gov (United States)

    McKiernan, Janet; Thom, Bridgette

    2016-08-01

    : The overall incidence of head and neck cancer-which includes laryngeal, hypopharyngeal, nasal cavity, paranasal sinus, nasopharyngeal, oral, oropharyngeal, and salivary gland cancers-has declined in the United States over the past 30 years with the concomitant reduction in tobacco use. Over that same period, however, the worldwide incidence of oropharyngeal cancer has escalated significantly, most notably among men and women under age 60 who live in developed countries. This epidemic rise in oropharyngeal cancer is largely attributed to certain genotypes of the human papillomavirus (HPV). In the United States, HPV prevalence in oropharyngeal tumors increased dramatically, from roughly 16% between 1984 and 1989 to nearly 73% between 2000 and 2004, and the annual incidence of HPV-positive oropharyngeal cancer is expected to surpass that of HPV-related cervical cancer by 2020.This article provides an overview of head and neck cancer-its incidence, risk factors, treatment, and posttreatment sequelae-with a focus on HPV-related oropharyngeal cancer. Unlike other forms of head and neck cancer, HPV-related oropharyngeal cancer tends to affect younger patients with few or none of the traditional risk factors and has a distinctive presentation, histology, and natural course. In order to provide appropriate patient education and to help these patients monitor and manage late and long-term treatment effects, it is important for nurses to be aware of this disease and its treatment, and of the unique survivorship issues that arise for affected patients.

  1. Human Papillomavirus Induced Transformation in Cervical and Head and Neck Cancers

    Directory of Open Access Journals (Sweden)

    Allie K. Adams

    2014-09-01

    Full Text Available Human papillomavirus (HPV is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervical cancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervical cancer, and preventive vaccines, cervical cancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervical cancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed.

  2. Therapeutic Prostate Cancer Vaccines: A Review of the Latest Developments

    OpenAIRE

    Mohebtash, Mahsa; Madan, Ravi A.; Gulley, James L.; Arlen, Philip M.

    2008-01-01

    Therapeutic cancer vaccines are well-tolerated immunotherapy modalities designed to activate the immune system to kill cancer cells without a significant effect on normal cells. Better understanding of tumor immunology has led to improved strategies in vaccine development, which have resulted in improved outcomes. This review discusses different types of cancer vaccines, focusing predominantly on prostate cancer vaccines because of the high prevalence of prostate cancer and the wide variety o...

  3. DESIGN METHODS OF HUMAN DEVELOPMENT MANAGEMENT SYSTEM

    Directory of Open Access Journals (Sweden)

    Stanislav E. Elkin

    2017-09-01

    Full Text Available The article discusses the concept of "human development" and the schematic diagram of the organizational design of regional management systems in relation to human development. Management as an organizational process in the study is considered as part of all social subsystems, specifies regularities of development and formation of new structures and functions. In the study applied the following methods: allocation of levels of models, techniques of domination, the allocation phases of the operation, the construction of generalized indicators, etc. As a result of research design problems of systems management human development revealed that the primary means of successful adaptation of organizations to changing conditions is an effective mechanism for management of human capacity, which will provide the best in current economic terms the end results that allows you to apply the concept of "innovation potential" in relation to the process of human development.

  4. Human papilloma virus identification in breast cancer patients with previous cervical neoplasia

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2016-01-01

    Full Text Available Purpose: Women with human papilloma virus (HPV associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i identify high risk for cancer HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii determine if these HPVs were biologically active.Methods: A range of polymerase chain reaction (PCR and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients. Results: The same high risk HPV types were identified in both the cervical and breast specimens in 13 (46% of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001. Conclusions: These findings indicate that high risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of 2 similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.

  5. Interactive effects of selenium and cadmium on mammary tumor development and growth in MMTV-infected female mice. A model study on the roles of cadmium and selenium in human breast cancer.

    Science.gov (United States)

    Schrauzer, G N

    2008-01-01

    Previous studies demonstrated that the age-corrected breast cancer mortalities in different countries are inversely correlated with the per-capita dietary intakes of selenium and directly with the estimated intakes of cadmium, zinc, and chromium, suggesting that the anticarcinogenic properties of selenium are counteracted by these elements. The tumor-preventative effects of selenium and the converse effects zinc and chromium have already been confirmed experimentally in studies with female inbred C3H mice carrying murine mammary tumor virus (MMTV). Using the same model of human breast cancer, it is now demonstrated that cadmium abolishes the cancer-protecting effects of selenium. In addition, cadmium was also found to interact with zinc, copper, and chromium. At 1.4 ppm in the drinking water, cadmium caused a significant depletion of zinc in vital organs such as the liver, which is held responsible for a delay of the appearance of the mammary tumors by 4 months and their slower growth rates relative to the Cd-unexposed controls. The results of the present study are relevant to human breast cancer prevention as selenium counteracts the effects of cadmium.

  6. Human Resources in Geothermal Development

    Energy Technology Data Exchange (ETDEWEB)

    Fridleifsson, I.B.

    1995-01-01

    Some 80 countries are potentially interested in geothermal energy development, and about 50 have quantifiable geothermal utilization at present. Electricity is produced from geothermal in 21 countries (total 38 TWh/a) and direct application is recorded in 35 countries (34 TWh/a). Geothermal electricity production is equally common in industrialized and developing countries, but plays a more important role in the developing countries. Apart from China, direct use is mainly in the industrialized countries and Central and East Europe. There is a surplus of trained geothermal manpower in many industrialized countries. Most of the developing countries as well as Central and East Europe countries still lack trained manpower. The Philippines (PNOC) have demonstrated how a nation can build up a strong geothermal workforce in an exemplary way. Data from Iceland shows how the geothermal manpower needs of a country gradually change from the exploration and field development to monitoring and operations.

  7. Frequency of TERT promoter mutations in human cancers.

    Science.gov (United States)

    Vinagre, João; Almeida, Ana; Pópulo, Helena; Batista, Rui; Lyra, Joana; Pinto, Vasco; Coelho, Ricardo; Celestino, Ricardo; Prazeres, Hugo; Lima, Luis; Melo, Miguel; da Rocha, Adriana Gaspar; Preto, Ana; Castro, Patrícia; Castro, Ligia; Pardal, Fernando; Lopes, José Manuel; Santos, Lúcio Lara; Reis, Rui Manuel; Cameselle-Teijeiro, José; Sobrinho-Simões, Manuel; Lima, Jorge; Máximo, Valdemar; Soares, Paula

    2013-01-01

    Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase.

  8. [Use of human recombinant erythropoietin in children with cancer].

    Science.gov (United States)

    Guyot, D; Margueritte, G

    2005-09-01

    Eighty percent of children with cancer suffer from anemia at the time of diagnosis. The physiopathology of anemia is complex. Although anemia can be life threatening, its consequences on the physical, psychological and social state of the child are often minimized. Blood transfusion is the main treatment of anemia: its efficacy is immediate but shortlasting, and it involves infectious and hemolytic risks. The human recombinant erythropoietin has been used for more than 25-years, and is often prescribed to adults with cancer and anemia. The human recombinant erythropoietin rHuEPO is nowadays used when blood transfusion is contra-indicated because of religious or cultural considerations, although several promising studies have been conducted about rHuEPO and children with cancer since 1996: it might be soon the preferential alternative treatment to anemia in children with cancer.

  9. Siah1 proteins enhance radiosensitivity of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Engenhart-Cabillic Rita

    2010-08-01

    Full Text Available Abstract Background Siah proteins play an important role in cancer progression. We evaluated the effect of Siah1, its splice variants Siah1L and the Siah1 mutant with the RING finger deleted (Siah1ΔR on radiosensitization of human breast cancer cells. Methods The status of Siah1 and Siah1L was analysed in five breast cancer cell lines. To establish stable cells, SKBR3 cells were transfected with Siah1, Siah-1L and Siah1ΔR. Siah1 function was suppressed by siRNA in MCF-7 cells. The impact of Siah1 overexpression and silencing on apoptosis, proliferation, survival, invasion ability and DNA repair was assessed in SKBR3 and MCF-7 cells, also in regards to radiation. Results Siah1 and Siah1L mRNA expression was absent in four of five breast cancer cells lines analysed. Overexpression of Siah1 and Siah1L enhanced radiation-induced apoptosis in stable transfected SKBR3 cells, while Siah1ΔR failed to show this effect. In addition, Siah1 and Siah1L significantly reduced cell clonogenic survival and proliferation. Siah1L sensitization enhancement ratio values were over 1.5 and 4.0 for clonogenic survival and proliferation, respectively, pointing to a highly cooperative and potentially synergistic fashion with radiation. Siah1 or Siah1L significantly reduced invasion ability of SKBR3 and suppressed Tcf/Lef factor activity. Importantly, Siah1 siRNA demonstrated opposite effects in MCF-7 cells. Siah1 and Siah1L overexpression resulted in inhibition of DNA repair as inferred by increased levels of DNA double-strand breaks in irradiated SKBR3 cells. Conclusion Our results reveal for the first time how overexpression of Siah1L and Siah1 can determine radiosensitivity of breast cancer cells. These findings suggest that development of drugs augmenting Siah1 and Siah1L activity could be a novel approach in improving tumor cell kill.

  10. Development of an Integrated Human Factors Toolkit

    Science.gov (United States)

    Resnick, Marc L.

    2003-01-01

    An effective integration of human abilities and limitations is crucial to the success of all NASA missions. The Integrated Human Factors Toolkit facilitates this integration by assisting system designers and analysts to select the human factors tools that are most appropriate for the needs of each project. The HF Toolkit contains information about a broad variety of human factors tools addressing human requirements in the physical, information processing and human reliability domains. Analysis of each tool includes consideration of the most appropriate design stage, the amount of expertise in human factors that is required, the amount of experience with the tool and the target job tasks that are needed, and other factors that are critical for successful use of the tool. The benefits of the Toolkit include improved safety, reliability and effectiveness of NASA systems throughout the agency. This report outlines the initial stages of development for the Integrated Human Factors Toolkit.

  11. Human intestinal microbiota: cross-talk with the host and its potential role in colorectal cancer.

    Science.gov (United States)

    Candela, Marco; Guidotti, Marco; Fabbri, Alessia; Brigidi, Patrizia; Franceschi, Claudio; Fiorentini, Carla

    2011-02-01

    In this review, we discuss the multifactorial role of intestinal microbiota in colorectal cancer. The peculiar metabolism of dietary compounds of the individual microbiota complement, its overall immunostimulation and immunomodulatory activity, and eventually the production of toxins that perturb the regulation of cell growth, define the balance of positive and negative risk factors for colorectal cancer development. Moreover, shaping the composition of the human intestinal microbiota, diet has an indirect impact in determining the balance between health and disease. The integration of diet, microbial, and host factors in a system approach is mandatory to determine the overall balance of risk and protective factors for colorectal cancer onset.

  12. An In Vivo Mouse Model for Human Prostate Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Aaron M. Havens

    2008-04-01

    Full Text Available We developed a sensitive real-time polymerase chain reaction (QPCR assay that allows us to track early lodging/homing events in vivo. We used this technology to develop a metastasis assay of human prostate cancer (PCa growth in severe combined immunodeficient mice. For this purpose, marked human PCa cell lines were implanted subcutaneously or in the prostate (orthotopically of severe combined immunodeficient mice as models of primary tumors. Mice were then sacrificed at various time points, and distant tissues were investigated for the presence of metastatic cells. At 3 weeks, a number of tissues were recovered and evaluated by QPCR for the presence of metastatic cells. The data demonstrate that several PCa cell lines are able to spread from the primary lesion and take up residence in distant sites. If the primary tumors were resected at 3 weeks, in several cases, metastastic lesions were identified over the course of 9 months. We propose that this new model may be particularly useful in exploring the molecular events in early metastasis, identifying the metastatic niche, and studying issues pertaining to dormancy.

  13. Anticancer Properties of Capsaicin Against Human Cancer.

    Science.gov (United States)

    Clark, Ruth; Lee, Seong-Ho

    2016-03-01

    There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities.

  14. Development of novel radiosensitizers for cancer therapy

    CERN Document Server

    Akamatsu, K

    2002-01-01

    The novel radiosensitizers for cancer therapy, which have some atoms with large X-ray absorption cross sections, were synthesized. The chemical and radiation (X-rays, W target, 100kVp) toxicities and the radiosensitivities to LS-180 human colon adenocarcinoma cells were also evaluated. 2,3,4,5,6-pentabromobenzylalcohol (PBBA) derivatives were not radiosensitive even around the maximum concentration. On the other hand, the hydrophilic sodium 2,4,6-triiodobenzoate (STIB) indicated meaningful radiosensitivity to the cells. Moreover, the membrane-specific radiosensitizers, cetyl fluorescein isthiocyanate (cetyl FITC), cetyl eosin isothiocyanate (cetyl br-FITC), cetyl erythrosin isothiocyanate (cetyl I-FITC), which aim for the membrane damage by X-ray photoabsorption on the target atoms, were localized in the plasma membrane. As the results of the colony formation assay, it was found that both cetyl FITC are similarly radiosensitive. In this report, we demonstrate the synthetic methods of the radiosensitizers, the...

  15. Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, prespiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues. PMID:24073224

  16. Comparing the DNA hypermethylome with gene mutations in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Kornel E Schuebel

    2007-09-01

    Full Text Available We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island DNA hypermethylation and transcriptional silencing in colorectal cancer. By screening cell lines and validating tumor-specific hypermethylation in a panel of primary human colorectal cancer samples, we estimate that nearly 5% or more of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find larger numbers of genes hypermethylated in individual tumors, and a higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and to facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken.

  17. Paraneoplasia, cancer development and immunity: what are the connections?

    Science.gov (United States)

    Chesler, Louis

    2014-07-01

    Paraneoplasia literally means conditions adjacent to, or associated with, abnormal cancerous tissue growth. In this Comment article, I discuss what the immune-mediated paraneoplasias teach us about the immune response and cancer development.

  18. A model of study for human cancer: Spontaneous occurring tumors in dogs. Biological features and translation for new anticancer therapies.

    Science.gov (United States)

    Ranieri, G; Gadaleta, C D; Patruno, R; Zizzo, N; Daidone, M G; Hansson, M G; Paradiso, A; Ribatti, D

    2013-10-01

    Murine cancer models have been extremely useful for analyzing the biology of pathways involved in cancer initiation, promotion, and progression. Interestingly, several murine cancer models also exhibit heterogeneity, genomic instability and an intact immune system. However, they do not adequately represent several features that define cancer in humans, including long periods of latency, the complex biology of cancer recurrence and metastasis and outcomes to novel therapies. Therefore, additional models that better investigate the human disease are needed. In the pet population, with special references to the dog, cancer is a spontaneous disease and dogs naturally develop cancers that share many characteristics with human malignancies. More than 40 years ago, optimization of bone marrow transplantation protocols was undertaken in dogs and recently novel targeted therapies such as liposomal muramyl tripeptide phosphatidylethanolamine and several tyrosine kinase inhibitors, namely masitinib (AB1010) and toceranib phosphate (SU11654), have been developed to treat dog tumors which have then been translated to human clinical trials. In this review article, we will analyze biological data from dog tumors and comparative features with human tumors, and new therapeutic approaches translated from dog to human cancer.

  19. Role of ARPC2 in Human Gastric Cancer

    OpenAIRE

    Jun Zhang; Yi Liu; Chang-Jun Yu; Fu Dai; Jie Xiong; Hong-Jun Li; Zheng-Sheng Wu; Rui Ding; Hong Wang

    2017-01-01

    Gastric cancer continues to be the second most frequent cause of cancer deaths worldwide. However, the exact molecular mechanisms are still unclear. Further research to find potential targets for therapy is critical and urgent. In this study, we found that ARPC2 promoted cell proliferation and invasion in the human cancer cell line MKN-28 using a cell total number assay, MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, cell colony formation assay, migration assay...

  20. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

    Directory of Open Access Journals (Sweden)

    G-Andre Banat

    Full Text Available Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+, cytotoxic-T cells (CD8+, T-helper cells (CD4+, B cells (CD20+, macrophages (CD68+, mast cells (CD117+, mononuclear cells (CD11c+, plasma cells, activated-T cells (MUM1+, B cells, myeloid cells (PD1+ and neutrophilic granulocytes (myeloperoxidase+ compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

  1. Current status of cancer immunodetection with radiolabeled human monoclonal antibodies.

    Science.gov (United States)

    De Jager, R; Abdel-Nabi, H; Serafini, A; Pecking, A; Klein, J L; Hanna, M G

    1993-04-01

    The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting

  2. A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development

    OpenAIRE

    Faca, Vitor M; Song, Kenneth S; Hong Wang; Qing Zhang; Krasnoselsky, Alexei L.; Newcomb, Lisa F; Plentz, Ruben R.; Sushma Gurumurthy; Redston, Mark S.; Pitteri, Sharon J.; Pereira-Faca, Sandra R.; Ireton, Renee C.; Hiroyuki Katayama; Veronika Glukhova; Douglas Phanstiel

    2008-01-01

    Editors' Summary Background. Cancers are life-threatening, disorganized masses of cells that can occur anywhere in the human body. They develop when cells acquire genetic changes that allow them to grow uncontrollably and to spread around the body (metastasize). If a cancer is detected when it is still small and has not metastasized, surgery can often provide a cure. Unfortunately, many cancers are detected only when they are large enough to press against surrounding tissues and cause pain or...

  3. BRB-ArrayTools Data Archive for Human Cancer Gene Expression: A Unique and Efficient Data Sharing Resource

    Directory of Open Access Journals (Sweden)

    Richard Simon

    2008-01-01

    Full Text Available The explosion of available microarray data on human cancer increases the urgency for developing methods for effectively sharing this data among clinical cancer investigators. Lack of a smooth interface between the databases and statistical analysis tools limits the potential benefits of sharing the publicly available microarray data. To facilitate the efficient sharing and use of publicly available microarray data among cancer investigators, we have built a BRB-ArrayTools Data Archive including over one hundred human cancer microarray projects for 28 cancer types. Expression array data and clinical descriptors have been imported into BRB-ArrayTools and are stored as BRB-ArrayTools project folders on the archive. The data archive can be accessed from: http://linus.nci.nih.gov/~brb/DataArchive.html Our BRB-ArrayTools data archive and GEO importer represent ongoing efforts to provide effective tools for efficiently sharing and utilizing human cancer microarray data.

  4. Fibroblast TGF-Beta Signaling in Breast Development and Cancer

    Science.gov (United States)

    2012-09-01

    breast cancer [46]. In this study, Gli1 expression was primarily noted in cancer cells and correlated with another Hedgehog ligand, Sonic Hedge- hog. This...44]. The Hedgehog pathway, which is essential for normal mammary gland development, is also essential for mainte- nance of the CD44+/CD24low...and those active in cancer. Future studies should focus on the pathways, such as TGF-, Hedgehog and chemokines, in breast cancer development and

  5. Development of the asymmetric human

    Science.gov (United States)

    Wolpert, Lewis

    2005-10-01

    Symmetry across the midline is present in many animals, together with the left/right asymmetry of several organs, such as the heart in vertebrates. The development of such asymmetries during embryonic development requires first the specification of the midline and then specification of left/right. One model proposes the transfer of molecular asymmetry to the multicellular level. Nodal expression on the left side in mammals and chicks is a key event, and is due to the release of calcium on the left possibly involving an ion pump and the Notch pathway

  6. Human adipocytes stimulate invasion of breast cancer MCF-7 cells by secreting IGFBP-2.

    Directory of Open Access Journals (Sweden)

    Chen Wang

    Full Text Available A better understanding of the effects of human adipocytes on breast cancer cells may lead to the development of new treatment strategies. We explored the effects of adipocytes on the migration and invasion of breast cancer cells both in vitro and in vivo.To study the reciprocal effects of adipocytes and cancer cells, we co-cultured human mature adipocytes and breast cancer cells in a system devoid of heterogeneous cell-cell contact. To analyze the factors that were secreted from adipocytes and that affected the invasive abilities of breast cancer cells, we detected different cytokines in various co-culture media. To study the communication of mature adipocytes and breast cancer cells in vivo, we chose 10 metastatic pathologic samples and 10 non-metastatic pathologic samples to do immunostaining.The co-culture media of human MCF-7 breast cancer cells and human mature adipocytes increased motility of MCF-7 cells. In addition, MMP-2 was remarkably up-regulated, whereas E-cadherin was down-regulated in these MCF-7 cells. Based on our co-culture medium chip results, we chose four candidate cytokines and tested their influence on metastasis individually. We found that IGFBP-2 enhanced the invasion ability of MCF-7 cells in vitro more prominently than did the other factors. In vivo, metastatic human breast tumors had higher levels of MMP-2 than did non-metastatic tumor tissue, whereas adipocytes around metastatic breast tumors had higher levels of IGFBP-2 than did adipocytes surrounding non-metastatic breast tumors.IGFBP-2 secreted by mature adipocytes plays a key role in promoting the metastatic ability of MCF-7 breast cancer cells.

  7. Expression profile of saccharide epitope CaMBr1 in normal and neoplastic tissue from dogs, cats, and rats: implication for the development of human-derived cancer vaccines.

    Science.gov (United States)

    Adobati, E; Zacchetti, A; Perico, M E; Cremonesi, F; Rasi, G; Vallebona, P S; Hagenaars, M; Kuppen, P J; Pastan, I; Panza, L; Russo, G; Colnaghi, M I; Canevari, S

    1999-11-01

    CaMBr1 is a blood group-related tumour-associated antigen, whose pattern of expression provides a therapeutic window for passive or active immunotherapy and points to the promise of a vaccine against carcinomas overexpressing this antigen. In this context, an animal model that closely mimics the human situation would be extremely useful. We, therefore, utilised the murine monoclonal antibody MBr1, which defines CaMBr1, as a useful probe to detect the molecule targeted for vaccine development on canine and feline spontaneous breast and uterus tumours and on their normal counterparts, and on rat normal tissues and carcinoma cell lines. Immunoperoxidase staining of cryostat sections revealed homogeneous CaMBr1 expression only in normal feline uterus and a uterus papilloma, whereas MBr1 reactivity was very weak and heterogeneous in normal (1/3 and 1/3) and tumour (1/10 and 1/6) breast tissues from dogs and cats, respectively. In contrast, the data obtained in rat tissues were reproducible in the strains tested and showed that CaMBr1 was expressed in all epithelial tissues of the digestive tract, although with variable intensities. Monoclonal antibody staining appeared to correspond to membrane-bound structures as well as mucinous secretions. Similarly, secretion products of lactating mammary glands expressed CaMBr1. The spectrum of expression on rat digestive tract was broader than that in humans but the specificity of MBr1 reactivity was confirmed by competition assay with a synthetic tetrasaccharide that mimics the CaMBr1 antigen. On FACS analysis, only one of two clonal derivatives of the rat breast carcinoma line RAMA 25 expressed CaMBr1, and a negative cell subset was evident in repeated experiments. By contrast, both colon carcinoma lines, DHD/K12 and CC531, showed staining with MBr1, albeit at different levels of intensity, and no evidence of a negative subset. The cell line CC531 maintained or even increased CaMBr1 expression levels following transplantation in

  8. Automated whole animal bio-imaging assay for human cancer dissemination.

    Directory of Open Access Journals (Sweden)

    Veerander P S Ghotra

    Full Text Available A quantitative bio-imaging platform is developed for analysis of human cancer dissemination in a short-term vertebrate xenotransplantation assay. Six days after implantation of cancer cells in zebrafish embryos, automated imaging in 96 well plates coupled to image analysis algorithms quantifies spreading throughout the host. Findings in this model correlate with behavior in long-term rodent xenograft models for panels of poorly- versus highly malignant cell lines derived from breast, colorectal, and prostate cancer. In addition, cancer cells with scattered mesenchymal characteristics show higher dissemination capacity than cell types with epithelial appearance. Moreover, RNA interference establishes the metastasis-suppressor role for E-cadherin in this model. This automated quantitative whole animal bio-imaging assay can serve as a first-line in vivo screening step in the anti-cancer drug target discovery pipeline.

  9. Analysis of human papillomavirus E7 protein status in C-33A cervical cancer cells.

    Science.gov (United States)

    Kaiser, Andreas; Jenewein, Brigitte; Pircher, Haymo; Rostek, Ursula; Jansen-Dürr, Pidder; Zwerschke, Werner

    2015-02-01

    High-risk human papillomaviruses (HPV) are the main etiologic factor for the development of cervical cancer. Infections by these viruses have been detected in virtually all cervical cancers. C-33A is one of the rare cervical cancer derived cell lines considered as HPV-negative. Employing monoclonal antibodies raised against a conformational epitope of the HPV-16 E7 oncoprotein, we present evidence suggesting that E7-positive cells can be sporadically and transiently detected in C-33A cell cultures. Immunoblotting with affinity-purified rabbit polyclonal anti-HPV 16 E7 antisera and q-RT-PCR analysis suggest that these cells do probably not express HPV-16 E7. Moreover, we show that the HPV E7 protein level differs considerably between individual cells in cultures of several established cervical cancer cell lines. Our data suggest that expression of the E7 protein is variable in established cervical cancer cell lines including C-33A cells.

  10. The landscape of isoform switches in human cancers

    DEFF Research Database (Denmark)

    Vitting-Seerup, Kristoffer; Sandelin, Albin Gustav

    2017-01-01

    developed methods for identification and visualization of isoform switches with predicted functional consequences. Using these methods, we characterized isoform switching in RNA-seq data from >5,500 cancer patients covering 12 solid cancer types. Isoform switches with potential functional consequences were...... highly predictive of patient survival independent of cancer types. Our data constitute an important resource for cancer researchers, available through interactive web tools. Moreover, our methods, available as an R package, enable systematic analysis of isoform switches from other RNA-seq datasets...

  11. Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Huang Wen-bin

    2009-09-01

    Full Text Available Abstract Background Most deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17 in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance. Methods Immunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910. Results We found that HSp17 was aberrantly expressed in 43% (30/70 of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin. Conclusion HSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy.

  12. Bionutrition and oral cancer in humans.

    Science.gov (United States)

    Enwonwu, C O; Meeks, V I

    1995-01-01

    Tobacco (smoking and smokeless) use and excessive consumption of alcohol are considered the main risk factors for oral cancer (ICD9 140-149). Conspicuous national and international variations in oral cancer incidence and mortality rates, as well as observations in migrant populations, raise the possibility that diet and nutritional status could be an important etiologic factor in oral carcinogenesis. As shown in this report, abuse of alcohol and tobacco has serious nutritional implications for the host, and generates increased production of reactive free radicals as well as eliciting immunosuppression. Maintenance of optimal competence of the immune system is critical for cancer surveillance. Active oxygen species and other reactive free radicals mediate phenotypic and genotypic alterations that lead from mutation to neoplasia. Consequently, the most widely used chemopreventive agents against oral cancer (e.g., vitamins A, E, C, and beta-carotene) are anti-oxidants/free radical scavengers. These anti-oxidants, both natural and synthetic, neutralize metabolic products (including reactive oxygen species), interfere with activation of procarcinogens, prevent binding of carcinogens to DNA, inhibit chromosome aberrations, restrain replication of the transformed cell, suppress actions of cancer promoters, and may even induce regression of precancerous oral lesions such as leukoplakia and erythroplakia. Malnutrition is characterized by marked tissue depletion of anti-oxidant nutrients, including GSH (gamma-glutamyl-cysteinyl-glycine), a key cellular anti-oxidant as well as a modulator of T-cell activation. GSH or its precursor cysteine inhibits activation of the nuclear transcription factor kB(NFkB), and has been shown to be protective against chemically induced oral cancer and leukoplakia. Alcohol-, tobacco-, and/or malnutrition-induced immunosuppression promotes impaired salivary gland function and oral mucosal immunity, a prominent reduction in the number of helper CD4

  13. Making Human Beings Human: Bioecological Perspectives on Human Development. The SAGE Program on Applied Developmental Science

    Science.gov (United States)

    Bronfenbrenner, Urie, Ed.

    2004-01-01

    To a greater extent than any other species, human beings create the environments that, in turn, shape their own development. This book endeavors to demonstrate that human beings can also develop those environments to optimize their most constructive genetic potentials. What makes human beings human, therefore, is both the potential to shape their…

  14. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    Science.gov (United States)

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  15. Gene expression profiling predicts the development of oral cancer.

    Science.gov (United States)

    Saintigny, Pierre; Zhang, Li; Fan, You-Hong; El-Naggar, Adel K; Papadimitrakopoulou, Vassiliki A; Feng, Lei; Lee, J Jack; Kim, Edward S; Ki Hong, Waun; Mao, Li

    2011-02-01

    Patients with oral premalignant lesion (OPL) have a high risk of developing oral cancer. Although certain risk factors, such as smoking status and histology, are known, our ability to predict oral cancer risk remains poor. The study objective was to determine the value of gene expression profiling in predicting oral cancer development. Gene expression profile was measured in 86 of 162 OPL patients who were enrolled in a clinical chemoprevention trial that used the incidence of oral cancer development as a prespecified endpoint. The median follow-up time was 6.08 years and 35 of the 86 patients developed oral cancer over the course. Gene expression profiles were associated with oral cancer-free survival and used to develop multivariate predictive models for oral cancer prediction. We developed a 29-transcript predictive model which showed marked improvement in terms of prediction accuracy (with 8% predicting error rate) over the models using previously known clinicopathologic risk factors. On the basis of the gene expression profile data, we also identified 2,182 transcripts significantly associated with oral cancer risk-associated genes (P value oral cancer risk. In multiple independent data sets, the expression profiles of the genes can differentiate head and neck cancer from normal mucosa. Our results show that gene expression profiles may improve the prediction of oral cancer risk in OPL patients and the significant genes identified may serve as potential targets for oral cancer chemoprevention. ©2011 AACR.

  16. Cervical cancer and human papillomavirus: Epidemiological evidence and perspectives for prevention

    Directory of Open Access Journals (Sweden)

    MUÑOZ NUBIA

    1997-01-01

    Full Text Available Cervical cancer is a major public health problem, as it is the second most common cancer in women world-wide after breast cancer. About 80% of the half a million cases estimated to occur annually in the world, occur in developing countries. The epidemiological evidence linking human papillomavirus (HPV to cervical cancer is reviewed. It is concluded that over 90% of cervical cancers can be attributed to certain HPV types. HPV 16 accounts for the highest proportion (50% followed by HPV 18 (12%, HPV 45 (8% and HPV 31 (5%. The associations with these HPV types are very b and consistent with odds ratios over 15 in all case-control studies in high- and low-risk countries for cervical cancer. However, HPV is not a sufficient cause of this malignancy; certain cofactors are necessary for a proportion of HPV persistent infections to eventually progress to cancer. These include host factors such as histocompatibilidad types and immunological response, hormonal influences and infections with other sexually transmitted agents such as Chlamydia trachomatis. In addition, results from our studies carried out in Spain and Colombia support the hypothesis that male carriers of HPV play an important role in the development of cervical cancer in their wives. The recognition of the central role of HPV in cervical cancer has far-reaching implications for the primary and secondary prevention of this malignancy. Prophylactic and therapeutic HPV vaccines are now under development and HPV typing is being integrated into screening programmes in pilot studies in a few developed countries. In developing countries, well conducted conventional screening programmes remain the best approach for the control of cervical cancer until a safe and efficient HPV vaccine can be used in the general population.

  17. Breast cancer in intraductal carcinogen-treated non-human primates.

    Science.gov (United States)

    Lillie, Madeline A; Ambrus, Clara M; Pickren, John W; Akhter, Selina; Islam, Abul; Ambrus, Julian L

    2004-01-01

    Eight female Macaca arctoides monkeys were given dimethylbenzanthracene (DMBA) directly into the milk ducts. During a 4-year observation period, ending with euthanasia and autopsy, no mammary cancers were noticed. However, one animal developed a superficial localized squamous cell carcinoma. DMBA is highly carcinogenic in rodents, e.g. producing a high incidence of breast cancer in C3H mice. It was concluded that carcinogenicity testing should be extended beyond testing in rodents to non-human primates in order to distinguish "primary rodent carcinogens" from those highly active in primates as well. Studies are in progress to study carcinogens in human cell lines transplanted into nu/nu mice.

  18. Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

    Energy Technology Data Exchange (ETDEWEB)

    Furuya, Mitsuko [Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004 (Japan)

    2012-07-18

    Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers.

  19. Strategies to support human oocyte development in vitro.

    Science.gov (United States)

    Telfer, Evelyn E; McLaughlin, Marie

    2012-01-01

    Many young cancer patients are now being given the option to store ovarian cortical biopsies before undergoing potentially damaging chemo- or radiotherapy. This tissue mainly contains large numbers of immature primordial follicles. Currently the only option to restore fertility using this tissue is by transplantation which may not be a viable option for all patients. Greater options to realise the potential of this tissue to restore fertility could be achieved by the development of in vitro systems that support oocyte development. The ability to develop human oocytes from the most immature stages of follicles (primordial) through to maturation and fertilisation in vitro would revolutionise fertility preservation practice. This has been achieved in mouse where in vitro grown (IVG) oocytes from primordial follicles have resulted in the production of live offspring. However, developing IVG systems to support complete development of human oocytes has been more difficult because of differences in scale of timing and size. Our lab has been working on a multi-step culture system to support growth and development of bo-vine and human oocytes from primordial through to fully grown, using fresh and cryopreserved ovarian cortical tissue. This review outlines the approaches being taken to obtain complete in vitro development of human oocytes and strategies for assessing the health and viability of IVG oocytes.

  20. Cytotoxicity of dietary flavonoids on different human cancer types

    Directory of Open Access Journals (Sweden)

    Katrin Sak

    2014-01-01

    Full Text Available Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. While luteolin and kaempferol can be considered as promising candidate agents for treatment of gastric and ovarian cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as potent antitumor agents for cervical cancer; cells from main sites of flavonoid metabolism (colon and liver reveal rather large fluctuations in anticancer activity probably due to exposure to various metabolites with different activities. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue-specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment.

  1. Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

    Science.gov (United States)

    Chitose, Shun-ichi; Sakazaki, T; Ono, T; Kurita, T; Mihashi, H; Nakashima, T

    2010-06-01

    This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-09

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

  3. The histone demethylase PHF8 is an oncogenic protein in human non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Yuzhou; Pan, Xufeng; Zhao, Heng, E-mail: hengzhao1966@sina.com

    2014-08-15

    Highlights: • PHF8 overexpresses in human NSCLC and predicts poor survival. • PHF8 regulates lung cancer cell growth and transformation. • PHF8 regulates apoptosis in human lung cancer cells. • PHF8 promotes miR-21 expression in human lung cancer. • MiR-21 is critically essential for PHF8 function in human lung cancer cells. - Abstract: PHF8 is a JmjC domain-containing protein and erases repressive histone marks including H4K20me1 and H3K9me1/2. It binds to H3K4me3, an active histone mark usually located at transcription start sites (TSSs), through its plant homeo-domain, and is thus recruited and enriched in gene promoters. PHF8 is involved in the development of several types of cancer, including leukemia, prostate cancer, and esophageal squamous cell carcinoma. Herein we report that PHF8 is an oncogenic protein in human non-small cell lung cancer (NSCLC). PHF8 is up-regulated in human NSCLC tissues, and high PHF8 expression predicts poor survival. Our in vitro and in vivo evidence demonstrate that PHF8 regulates lung cancer cell proliferation and cellular transformation. We found that PHF8 knockdown induces DNA damage and apoptosis in lung cancer cells. PHF8 promotes miR-21 expression in human lung cancer, and miR-21 knockdown blocks the effects of PHF8 on proliferation and apoptosis of lung cancer cells. In summary, PHF8 promotes lung cancer cell growth and survival by regulating miR-21.

  4. Role of Nuclear Matrix in Estrogen Regulated Gene Expression in Human Breast Cancer Cells

    Science.gov (United States)

    1998-08-01

    form of endocrine manipulative therapy, e.g., antiestrogen therapy. However, most human breast cancers originate as hormonally dependent tumors as...development. 49 "Proprietary Data - Distribution to Government Agencies Only" ACKNOWLEDGMENTS Pierre Chambon (Institut de Genetique et de Biologie

  5. The role of miRNAs in human papilloma virus (HPV)-associated cancers

    DEFF Research Database (Denmark)

    Lajer, C.B.; Garnæs, E.; Friis-Hansen, Lennart Jan

    2012-01-01

    Although the role of human papilloma virus (HPV) in cervical squamous cell carcinoma (CSCC) is well established, the role in head and neck SCC (HNSCC) is less clear. MicroRNAs (miRNAs) have a role in the cancer development, and HPV status may affect the miRNA expression pattern in HNSCC. To explore...

  6. Educating the Human Brain. Human Brain Development Series

    Science.gov (United States)

    Posner, Michael I.; Rothbart, Mary K.

    2006-01-01

    "Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

  7. Educating the Human Brain. Human Brain Development Series

    Science.gov (United States)

    Posner, Michael I.; Rothbart, Mary K.

    2006-01-01

    "Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

  8. Human Capital Development: Comparative Analysis of BRICs

    Science.gov (United States)

    Ardichvili, Alexandre; Zavyalova, Elena; Minina, Vera

    2012-01-01

    Purpose: The goal of this article is to conduct macro-level analysis of human capital (HC) development strategies, pursued by four countries commonly referred to as BRICs (Brazil, Russia, India, and China). Design/methodology/approach: This analysis is based on comparisons of macro indices of human capital and innovativeness of the economy and a…

  9. Human Resource Development in Changing Organizations.

    Science.gov (United States)

    London, Manuel; Wueste, Richard A.

    This book is intended to help managers and human resource professionals understand organizational change and manage its effects on their own development and that of their subordinates. The following topics are covered in 11 chapters: organizational change, employee motivation, new managerial roles, human performance systems, upward and peer…

  10. Pakistan's Water Challenges: A Human Development Perspective

    NARCIS (Netherlands)

    S. Shezad (Shafqat); K.A. Siegmann (Karin Astrid)

    2006-01-01

    textabstractAbstract This paper gives an overview of the human and social dimensions of Pakistan’s water policies to provide the basis for water-related policy interventions that contribute to the country’s human development, with special attention being given to the concerns of women and the poor.

  11. Human Capital Development: Comparative Analysis of BRICs

    Science.gov (United States)

    Ardichvili, Alexandre; Zavyalova, Elena; Minina, Vera

    2012-01-01

    Purpose: The goal of this article is to conduct macro-level analysis of human capital (HC) development strategies, pursued by four countries commonly referred to as BRICs (Brazil, Russia, India, and China). Design/methodology/approach: This analysis is based on comparisons of macro indices of human capital and innovativeness of the economy and a…

  12. Incidence and Mortality of Testicular Cancer and Relationships with Development in Asia.

    Science.gov (United States)

    Sadeghi, Mostafa; Ghoncheh, Mahshid; Mohammadian-Hafshejani, Abdollah; Gandomani, Hamidreza Sadeghi; Rafiemanesh, Hosein; Salehiniya, Hamid

    2016-01-01

    Testicular cancer is one of the most common cancers among young men between ages 20-34 in countries with high or very high levels of the Human Development Index (HDI). This study investigated the incidence and mortality of prostate cancer and the relationship with the HDI and its dimensions in Asia in 2012. The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Standardized incidence and mortality rates of testicular cancer were calculated for Asian countries. Correlations between incidence and/ormortality rates, and the HDI and its components were assessed with the use of the correlation test, using SPSS software. There was a total of 14902 incidences and 5832 death were recorded in Asian countries in 2012. Among the Asian countries, the five countries with the highest standardized incidence rates of testicular cancer were Israel, Georgia, Turkey, Lebanon and Kazakhstan and the five countries with the highest standardized mortality rates were Turkey, Georgia, Jordan, Cambodia and the Syrian Arab Republic. A positive correlation of 0.382 was observed between the standardized incidence rates of testicular cancer and the HDI (p=0.009). Also a negative correlation of 0.298 between the standardized mortality rate of testicular cancer and the Human Development Index was noted although this relation was statistically non-significant (p=0.052). There is a positive correlation between HDI and the standardized incidence rate of testicular cancer and negative correlation with standardized mortality rate.

  13. Cervical Cancer Screening after Perimenopause: How Is Human Papillomavirus Test Performed?

    Science.gov (United States)

    Chung, Soo-Ho

    2016-08-01

    Cervical cancer is the third most prevalent cancer in women around the world. Recently in Korea, the incidence of cervical cancer has decreased, but in all stages of cervical intraepithelial neoplasia (CIN), CIN has shown a 91% increase from 1999 to 2008. Persistent human papillomavirus (HPV) infection has been found to be the main cause of cervical cancer. HPV types 16 and 18 have been found in 70% of cervical cancer patients around the world. Cervical cancer screening such as cytology has limitations in terms of sensitivity and specificity. A discussion about the need for the HPV test is becoming active in order to compensate for the limitation of cytology. After the role of HPV in cervical cancer was identified, the importance of HPV detection test as a screening was emphasized. Several tests have been developed and each test has its own advantages and disadvantages, and new test method to overcome the disadvantages is still being developed. Today's guidelines and tests are those you would choose from among the large number of cervical cancer screening guidelines and tests, based on the consideration that the selected guidelines and the test are effective.

  14. Hegel's Hold on Conceptions of Human Development

    Science.gov (United States)

    Mulryan, Seamus

    2008-01-01

    The use of "development" is ubiquitous in everyday language, and theories regarding it can be found in the social sciences and humanities. Although much work has been done to examine the meaning of development and its history, little attention has been paid to Hegel's role as the philosophical anchor for the modern life of "development". By…

  15. Hegel's Hold on Conceptions of Human Development

    Science.gov (United States)

    Mulryan, Seamus

    2008-01-01

    The use of "development" is ubiquitous in everyday language, and theories regarding it can be found in the social sciences and humanities. Although much work has been done to examine the meaning of development and its history, little attention has been paid to Hegel's role as the philosophical anchor for the modern life of "development". By…

  16. Cultural Development through Human Resource Systems Integration.

    Science.gov (United States)

    Albert, Michael

    1985-01-01

    Discusses the framework for developing a cultural human resources management (HRM) perspective. Central to this framework is modifying HRM programs to reinforce the organization's preferred practices. Modification occurs through selection, orientation, training and development, performance appraisal, career development, and compensation and…

  17. Cultural Development through Human Resource Systems Integration.

    Science.gov (United States)

    Albert, Michael

    1985-01-01

    Discusses the framework for developing a cultural human resources management (HRM) perspective. Central to this framework is modifying HRM programs to reinforce the organization's preferred practices. Modification occurs through selection, orientation, training and development, performance appraisal, career development, and compensation and…

  18. FXR silencing in human colon cancer by DNA methylation and KRAS signaling.

    Science.gov (United States)

    Bailey, Ann M; Zhan, Le; Maru, Dipen; Shureiqi, Imad; Pickering, Curtis R; Kiriakova, Galina; Izzo, Julie; He, Nan; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Liang, Han; Kopetz, Scott; Powis, Garth; Guo, Grace L

    2014-01-01

    Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue (n = 238), polyps (n = 32), and adenocarcinomas, staged I-IV (n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol-4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ~12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer.

  19. [The development process of colon cancer centres].

    Science.gov (United States)

    Sahm, M; Wesselmann, S; Kube, R; Schöffel, N; Pross, M; Lippert, H; Kahl, S

    2013-02-01

    Colon carcinomas are the most common malignant tumours in the Western world. Important findings about the overall quality of medical care have been reported in multi-centre observational studies. A quality enhancement of therapeutic care can be achieved by an additional increase in diagnostic and therapeutic measures in the interdisciplinary setting. The development of colon cancer centres improves the chance to objectively observe the results of medical care induced by the development of an interdisciplinary and cross-sectoral unit that includes a comprehensive medical care for patients. The implementation of the current medical findings based on evidence in clinical routine, the inspection of the usage of guidelines by external specialists as part of an audit and the continuous correction of analysed deficits in the course of treatment guarantee a continuous improvement of service.

  20. Development of the human hypothalamus.

    Science.gov (United States)

    Swaab, D F

    1995-05-01

    The hypothalamus has been claimed to be involved in a great number of physiological functions in development, such as sexual differentiation (gender, sexual orientation) and birth, as well as in various developmental disorders including mental retardation, sudden infant death syndrome (SIDS), Kallman's syndrome and Prader-Willi syndrome. In this review a number of hypothalamic nuclei have therefore been discussed with respect to their development in health and disease. The suprachiasmatic nucleus (SCN) is the clock of the brain and shows circadian and seasonal fluctuations in vasopressin-expressing cell numbers. The SCN also seems to be involved in reproduction, adding interest to the sex differences in shape of the vasopressin-containing SCN subnucleus and in its VIP cell number. In addition, differences in relation to sexual orientation can be seen in this perspective. The vasopressin and VIP neurons of the SCN develop mainly postnatally, but as premature children may have circadian temperature rhythms, a different SCN cell type is probably more mature at birth. The sexually dimorphic nucleus (SDN, intermediate nucleus, INAH-1) is twice as large in young male adults as in young females. At the moment of birth only 20% of the SDN cell number is present. From birth until two to four years of age cell numbers increase equally rapidly in both sexes. After this age cell numbers start to decrease in girls, creating the sex difference. The size of the SDN does not show any relationship to sexual orientation in men. The large neurosecretory cells of the supraoptic (SON) and paraventricular nucleus (PVN) project to the neurohypophysis, where they release vasopressin and oxytocin into the blood circulation. In the fetus these hormones play an active role in the birth process. Fetal oxytocin may initiate or accelerate the course of labor. Fetal vasopressin plays a role in the adaptation to stress--caused by the birth process--by redistribution of the fetal blood flow

  1. FOREIGN LANGUAGES AND HUMAN DEVELOPMENT: THE CASE ...

    African Journals Online (AJOL)

    HP

    2017-07-01

    Jul 1, 2017 ... Key words: human development, foreign language, French. Introduction ..... to communicate with each other and exchange ideas. Not only ... This will enable learners have an early exposure to the language which will in turn.

  2. Human Resource Development Strategies: The Malaysian Scenario

    Directory of Open Access Journals (Sweden)

    Haslinda Abdullah

    2007-01-01

    Full Text Available The socio-economic development of Malaysia is greatly influenced by human resources activities in both the private and public sectors. But the private sector, particularly the industrial sector is the key player for the country’s economic growth. In acknowledging human resources importance in this sector, the country’s developmental plans developed thrusts that support the development of human resources to become skilled, creative and innovative. This article examines the concepts and nature of human resource development (HRD at the national level in Malaysia. In examining HRD from the national perspective, a review of documentary evidence from relevant Governmental reports and documents was utilised. The plans, policies, strategies, roles and responsibilities in HRD at the national level were discussed.

  3. Human Resources Development in the 70s

    Science.gov (United States)

    Ludeman, Bart L.

    1977-01-01

    Discusses five major objectives (put forth by the behavioral scientist, Dr. Gordon Lippitt) for human resource development which focus on the need for teamwork among future leaders, company management, and top educators. (LAS)

  4. Ecological Factors in Human Development.

    Science.gov (United States)

    Cross, William E

    2017-03-09

    Urie Bronfenbrenner (1992) helped developmental psychologists comprehend and define "context" as a rich, thick multidimensional construct. His ecological systems theory consists of five layers, and within each layer are developmental processes unique to each layer. The four articles in this section limit the exploration of context to the three innermost systems: the individual plus micro- and macrolayers. Rather than examine both the physical features and processes, the articles tend to focus solely on processes associated with a niche. Processes explored include social identity development, social network dynamics, peer influences, and school-based friendship patterns. The works tend to extend the generalization of extant theory to the developmental experience of various minority group experiences.

  5. Entrepreneurship and human development: A capability approach

    OpenAIRE

    Gries, Thomas; Naudé, Wim

    2010-01-01

    We provide a formal model of entrepreneurship in human development. The framework is provided by the capabilities approach (CA). Hence we extend not only the conceptualisation of entrepreneurship in development, but the reach of the CA into entrepreneurship. From a CA view, entrepreneurship is not only a production factor, or a means to an end, as is often taken to be the case by economists, but also an end in itself. Entrepreneurship can be a human functioning and can contribute towards expa...

  6. Use of a Novel Embryonic Mammary Stem Cell Gene Signature to Improve Human Breast Cancer Diagnostics and Therapeutic Decision Making

    Science.gov (United States)

    2014-10-01

    SUBTITLE Use of a Novel Embryonic Mammary Stem Cell Gene Signature to Improve Human Breast Cancer Diagnostics and Therapeutic Decision Making Improve...to determine whether Fetal Mammary Stem Cell (fMaSC) signatures correlate with response to chemotherapy and metastasis in different breast cancer...positioned to achieve its aims. 15. SUBJECT TERMS Breast Cancer Prognosis, Mammary Stem Cells, Embryonic Development, Single Cell Transcriptomics 16

  7. PXRF characterization of gold nanoparticles in human cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, Fabio; Estevam, Marcelo; Appoloni, Carlos R.; Panis, Carolina; Galvao, Tiago Dutra [Universidade Estadual de Londrina (UEL), PR (Brazil); Zucolotto, Valtencir [Universidade de Sao Paulo (USP), Sao Carlos, SP (Brazil). Inst. de Fisica

    2011-07-01

    Full Text: Nanomaterials, including nanoparticles and nanotubes, have been widely used in biotechnology and medicine. Applications include systems for controlled release of drugs, biomarkers, biosensors and devices for diagnosis of various diseases like cancer, tuberculosis and Chagas. In the case of cancer, the success of current anti-cancer therapy depends on the speed of diagnosis. Gold nanoparticles can be used to visualize lesions or to destroy cancer cells. In this study, was developed a methodology for identification and quantification of gold nanoparticles (AuNPs) deposited on polymer films and matrices that simulate the human skin with pH 7.4, as well as determining the radiation dose of the measures. The nanoparticles were chemically synthesized at the Laboratory of Nanomedicine and nanotoxicology the IFSC/USP and used in concentrations from 1 ppm to 1000 ppm. The measurements were performed with the portable system of the Laboratory of Applied Nuclear Physics (LFNA-UEL), composed of X-ray detector type S-PIN with a resolution of 149 eV for the line at 5.9 keV Mn (AMPTEK) and an X-ray detector type Si-Drift with a resolution of 139 eV for 5.9 keV line of Fe (AMPTEK) and standard electronics, the excitation of samples was performed with a mini X-ray tube with target Silver operated at 28 kV and 10{mu} A (MOXTEK). Filters were used for silver and aluminum in the output of X-ray tube. The positioner for the set of excitation-detection allows degrees of freedom of translation and rotation. The lower limit of quantification was 5 ppm of gold, using measurement times of 300 s to 1000 s, with R2 ranging from 0.92 to 0.96. X-ray fluorescence lines of gold were analyzed by 8.5 keV, 9.7 keV and 11.4 keV showing a statistical deviation of 0.24. (author)

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

    Science.gov (United States)

    Horrobin, D F; Trosko, J E

    1981-01-01

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

  9. IMMUNORESPONSES OF HUMANIZED SCID MICE TO HUMAN LUNG CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    陈力真; 王树蕙; 张云; 王世真

    1996-01-01

    HuPBL-SCID mice were used to explore how they would response to human ttmoor cells of 801/MLC.Living 801/MLC cells appeared to be fetal to the the mice due to the production of human TNF. The huP-BL-SCID rniee did not generate any noticeable amotmt of specific human immunoglobttlin either by single immunization with living 801/MLC cells or by repeated immunization with irradiated 801/MLC cells. Our preliminary experiments with huPBL-SCID mice showed that such chimeras would he a very useful models for tumor immunological researches.

  10. Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

    Institute of Scientific and Technical Information of China (English)

    Jun Hui Cui; Uwe Krueger; Doris Henne-Bruns; Bernd Kremer; Holger Kalthoff

    2001-01-01

    AIM To establish a relevant animal model ofhuman gastrointestinal cancer, which can beused for repetitive investigations, so as toimprove our understanding and management ofcarcinogenesis and cancer metastasis.METHODS Intact tissues of human colorectaland pancreatic cancers were transplanted innude mice. The biological characteristics of theoriginal and the corresponding transplantedtumors were investigated by HE staining, PASstaining and immunostaining. The metastases inthe livers and lungs of nude mice wereinvestigated by immunostaining withbiotinylated mab KL-1 and by RT-PCR using CK20specific primers.RESULTS There were totally 9 of 16 surgicalspecimens growing in nude mice subcutaneouslyand/.or orthotopically (4 of 6 colorectal and 5 of10 pancreatic cancer). Tumor cell content of thespecimens and freezing of tissue specimens areimportant factors influencing the growth oftransplanted tumor. In the group of fresh tumortissues with greater than 50% tumor cellcontent, the success rate of the transplantationwas 100% (3 cases of pancreatic cancer and 3cases of colorectal cancer). The orthotopicallytransplanted tumors resemble the original tumormorphologically and biologically, including TAAexpression such as CEA byimmunohistochemistry, and CEA level in theserum of mice. Ki-67 labeling index and theexpression of TAA especially K-ras, 17-lA andRA-96, are associated with the potential of tumorgrowth in nude mice. Micrometastases in thelungs and livers of tumor bearing mice can bedetected by immunostaining with biotinylatedmab KL-1 and CK20-specific RT-PCR.CONCLUSION An orthotopic transplantationmodel for human colon and pancreatic cancer innude mice has been set up. We have alsoestablished sensitive detection methods withCK-immunohistochemistry and CK20-RT-PCR tostudy xenotransplanted human cancer and itsmetastatic cancer cells in the liver and lung ofnude mice. This study may be helpful inunderstanding the mechanism of cancermetastasis and in developing new

  11. Mutated human androgen receptor gene detected in a prostatic cancer patient is also activated by estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Elo, J.P.; Kvist, L.; Leinonen, K.; Isomaa, V. [Univ. of Oulu (Finland)] [and others

    1995-12-01

    Androgens are necessary for the development of prostatic cancer. The mechanisms by which the originally androgen-dependent prostatic cancer cells are relieved of the requirement to use androgen for their growth are largely unknown. The human prostatic cancer cell line LNCaP has been shown to contain a point mutation in the human androgen receptor gene (hAR), suggesting that changes in the hAR may contribute to the abnormal hormone response of prostatic cells. To search for point mutations in the hAR, we used single strand conformation polymorphism analysis and a polymerase chain reaction direct sequencing method to screen 23 prostatic cancer specimens from untreated patients, 6 prostatic cancer specimens from treated patients, and 11 benign prostatic hyperplasia specimens. One mutation was identified in DNA isolated from prostatic cancer tissue, and the mutation was also detected in the leukocyte DNA of the patient and his offspring. The mutation changed codon 726 in exon E from arginine to leucine and was a germ line mutation. The mutation we found in exon E of the hAR gene does not alter the ligand binding specificity of the AR, but the mutated receptor was activated by estradiol to a significantly greater extent than the wild-type receptor. The AR gene mutation described in this study might be one explanation for the altered biological activity of prostatic cancer. 36 refs., 4 figs.

  12. Requirement for estrogen receptor alpha in a mouse model for human papillomavirus-associated cervical cancer.

    Science.gov (United States)

    Chung, Sang-Hyuk; Wiedmeyer, Kerri; Shai, Anny; Korach, Kenneth S; Lambert, Paul F

    2008-12-01

    The majority of human cervical cancers are associated with the high-risk human papillomaviruses (HPV), which encode the potent E6 and E7 oncogenes. On prolonged treatment with physiologic levels of exogenous estrogen, K14E7 transgenic mice expressing HPV-16 E7 oncoprotein in their squamous epithelia succumb to uterine cervical cancer. Furthermore, prolonged withdrawal of exogenous estrogen results in complete or partial regression of tumors in this mouse model. In the current study, we investigated whether estrogen receptor alpha (ERalpha) is required for the development of cervical cancer in K14E7 transgenic mice. We show that exogenous estrogen fails to promote either dysplasia or cervical cancer in K14E7/ERalpha-/- mice despite the continued presence of the presumed cervical cancer precursor cell type, reserve cells, and evidence for E7 expression therein. We also observed that cervical cancers in our mouse models are strictly associated with atypical squamous metaplasia (ASM), which is believed to be the precursor for cervical cancer in women. Consistently, E7 and exogenous estrogen failed to promote ASM in the absence of ERalpha. We conclude that ERalpha plays a crucial role at an early stage of cervical carcinogenesis in this mouse model.

  13. Effect of S1P5 on proliferation and migration of human esophageal cancer cells

    OpenAIRE

    Hu, Wei-Min; Li, Li; Jing, Bao-Qian; Zhao, Yong-Sheng; Wang, Chao-Li; Feng, Li; Xie, Yong-En

    2010-01-01

    AIM: To investigate the sphingosine 1-phosphate (S1P) receptor expression profile in human esophageal cancer cells and the effects of S1P5 on proliferation and migration of human esophageal cancer cells.

  14. Microbial dysbiosis is associated with human breast cancer.

    Directory of Open Access Journals (Sweden)

    Caiyun Xuan

    Full Text Available Breast cancer affects one in eight women in their lifetime. Though diet, age and genetic predisposition are established risk factors, the majority of breast cancers have unknown etiology. The human microbiota refers to the collection of microbes inhabiting the human body. Imbalance in microbial communities, or microbial dysbiosis, has been implicated in various human diseases including obesity, diabetes, and colon cancer. Therefore, we investigated the potential role of microbiota in breast cancer by next-generation sequencing using breast tumor tissue and paired normal adjacent tissue from the same patient. In a qualitative survey of the breast microbiota DNA, we found that the bacterium Methylobacterium radiotolerans is relatively enriched in tumor tissue, while the bacterium Sphingomonas yanoikuyae is relatively enriched in paired normal tissue. The relative abundances of these two bacterial species were inversely correlated in paired normal breast tissue but not in tumor tissue, indicating that dysbiosis is associated with breast cancer. Furthermore, the total bacterial DNA load was reduced in tumor versus paired normal and healthy breast tissue as determined by quantitative PCR. Interestingly, bacterial DNA load correlated inversely with advanced disease, a finding that could have broad implications in diagnosis and staging of breast cancer. Lastly, we observed lower basal levels of antibacterial response gene expression in tumor versus healthy breast tissue. Taken together, these data indicate that microbial DNA is present in the breast and that bacteria or their components may influence the local immune microenvironment. Our findings suggest a previously unrecognized link between dysbiosis and breast cancer which has potential diagnostic and therapeutic implications.

  15. Human Papillomavirus Testing in the Prevention of Cervical Cancer

    Science.gov (United States)

    Wentzensen, Nicolas; Wacholder, Sholom; Kinney, Walter; Gage, Julia C.; Castle, Philip E.

    2011-01-01

    Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment. PMID:21282563

  16. Differentially Expressed Genes and Signature Pathways of Human Prostate Cancer.

    Directory of Open Access Journals (Sweden)

    Jennifer S Myers

    Full Text Available Genomic technologies including microarrays and next-generation sequencing have enabled the generation of molecular signatures of prostate cancer. Lists of differentially expressed genes between malignant and non-malignant states are thought to be fertile sources of putative prostate cancer biomarkers. However such lists of differentially expressed genes can be highly variable for multiple reasons. As such, looking at differential expression in the context of gene sets and pathways has been more robust. Using next-generation genome sequencing data from The Cancer Genome Atlas, differential gene expression between age- and stage- matched human prostate tumors and non-malignant samples was assessed and used to craft a pathway signature of prostate cancer. Up- and down-regulated genes were assigned to pathways composed of curated groups of related genes from multiple databases. The significance of these pathways was then evaluated according to the number of differentially expressed genes found in the pathway and their position within the pathway using Gene Set Enrichment Analysis and Signaling Pathway Impact Analysis. The "transforming growth factor-beta signaling" and "Ran regulation of mitotic spindle formation" pathways were strongly associated with prostate cancer. Several other significant pathways confirm reported findings from microarray data that suggest actin cytoskeleton regulation, cell cycle, mitogen-activated protein kinase signaling, and calcium signaling are also altered in prostate cancer. Thus we have demonstrated feasibility of pathway analysis and identified an underexplored area (Ran for investigation in prostate cancer pathogenesis.

  17. The natural immunity to evolutionary atavistic endotoxin for human cancer.

    Science.gov (United States)

    Moncevičiūtė-Eringienė, Elena; Rotkevič, Kristina; Grikienis, Ruta Grikienyte

    2015-11-01

    We propose a new theory of the immunological control of cancer corresponding to the hypothesis that the specific natural immunity to evolutionary atavistic endotoxin has a potential role in human cancer prevention. The results of our studies have shown that IgMNAE, i.e. endogenous or spontaneous IgM class antibodies to enterobacterial lipopolysaccharide molecules (lipid A), control the immune mechanisms responsible for the internal medium stability not only against the damaging impact of the carcinogenic factors, but also against the malignant transformation of its own degenerated cells. Among people who in 1979 and 1982 had IgMNAE in their blood serum, after 15-30years fell ill with cancer 10%, versus 15% among people who had no IgMNAE (pimmunity to endotoxin it is possible to see the formation of the respective evolutionary protective reactions which protect the damaged cells from acquiring resistance to damaging factors and thus from becoming an independent new parasitic population. Thereby the presented theory of the immunological control of cancer has a causal connection with our evolutionary resistance theory of the origin of cancer. Collectively, these data suggest that activation of natural immunity to endotoxin and production of vaccines against evolutionary atavistic endotoxin or gram-negative bacterial endotoxin can be helpful when applied in cancer prophylaxis for persons with a low level of natural immunity to endotoxin and perhaps in creating immunotherapeutic methods for stopping the endogenous parasitism of tumour cells by binding IgMNAE to atavistic endotoxin in cancer patients.

  18. [Apropos of the studies of Lewis, Nusslein-Volhard and Wieschaus, 1995 Nobel prize winners, on the genetic mechanisms of embryonic development of drosophila. A model for human cancer progression].

    Science.gov (United States)

    Cillo, C

    1996-07-01

    EB Lewis, C Nusslein-Volhard and E Wieschaus were the winners of the Nobel prize in 1995 for the discovery of genes controling the embryonic development in drosophila. Drosophila development is dependent on sequential activities of three types of genes: the maternal genes, the segmentation genes, and the homeotic genes which are responsible for the segment identity and finally for the building of the body. Mutations of these genes are spectacular because they affect the body structure formed from individual segments. Therefore, the molecular processes regulating the development of inferior organisms such as yeast or more complex as the vertebrates were elucidated by these three researchers. These early biological mechanisms regulate the cell life through interactions with neighbouring cells. We speculate that any alteration of these processes might be implicated in cancer. Understanding of these molecular mechanisms which control cell interactions in cancer constitutes a basis for definition of new prognostic markers and putatively novel therapeutic approaches.

  19. Endothelium specific matrilysin (MMP-7) expression in human cancers

    NARCIS (Netherlands)

    Sier, C.F.M.; Hawinkels, L.J.A.C.; Zijlmans, H.J.M.A.A.; Zuidwijk, K.; Jonge de; Muller, E.S.M.; Ferreira, V.; Hanemaaijer, R.; Mulder-Stapel, A.A.; Kenter, G.G.; Verspaget, H.W.; Gorter, A.

    2008-01-01

    Over-expression of matrilysin (MMP-7) is predominantly associated with epithelial (pre)malignant cells. In the present study MMP-7 expression is also found in endothelial cells in various human cancer types. Endothelial MMP-7 was associated with CD34 and/or CD105 expression. These immunohistochemica

  20. Hanging drop cultures of human testis and testis cancer samples

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Young, J; Nielsen, J E

    2014-01-01

    limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. METHODS: Human testis and testis cancer specimens from orchidectomies were...

  1. Development of human factors design review guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea)

    1997-10-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: 25. Human Factors Engineering Program Review Model and 26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation, which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994. (author). 12 refs., 5 figs., 2 tabs.

  2. Trefoil factor-3 expression in human colon cancer liver metastasis.

    Science.gov (United States)

    Babyatsky, Mark; Lin, Jing; Yio, Xianyang; Chen, Anli; Zhang, Jie-yu; Zheng, Yan; Twyman, Christina; Bao, Xiuliang; Schwartz, Myron; Thung, Swan; Lawrence Werther, J; Itzkowitz, Steven

    2009-01-01

    Deaths from colorectal cancer are often due to liver metastasis. Trefoil factor-3 (TFF3) is expressed by normal intestinal epithelial cells and its expression is maintained throughout the colon adenoma-carcinoma sequence. Our previous work demonstrated a correlation between TFF3 expression and metastatic potential in an animal model of colon cancer. The aim of this study was to determine whether TFF3 is expressed in human colon cancer liver metastasis (CCLM) and whether inhibiting TFF3 expression in colon cancer cells would alter their invasive potential in vitro. Human CCLMs were analyzed at the mRNA and protein level for TFF3 expression. Two highly metastatic rat colon cancer cell lines that either natively express TFF3 (LN cells) or were transfected with TFF3 (LPCRI-2 cells), were treated with two rat TFF3 siRNA constructs (si78 and si365), and analyzed in an in vitro invasion assay. At the mRNA and protein level, TFF3 was expressed in 17/17 (100%) CCLMs and 10/11 (91%) primary colon cancers, but not in normal liver tissue. By real time PCR, TFF3 expression was markedly inhibited by both siRNA constructs in LN and LPCRI-2 cells. The si365 and si78 constructs inhibited invasion by 44% and 53%, respectively, in LN cells, and by 74% and 50%, respectively, in LPCRI-2 cells. These results provide further evidence that TFF3 contributes to the malignant behavior of colon cancer cells. These observations may have relevance for designing new diagnostic and treatment approaches to colorectal cancer.

  3. Cancer Prevention and Control Research Manpower Development

    Science.gov (United States)

    1998-09-01

    is conclusive evidence that screening will decrease morality . The methods used to screen for breast cancer include Self Breast Examination, Clinical...Raciathnic Pattern of Cancer in United States. MMWR. 1991;40:754-757. the United States, 1973-1993. Rockville, Md: National Cancer 11. Escobedo LG

  4. Molecular medicine and the development of cancer chemopreventive agents.

    Science.gov (United States)

    Izzotti, Alberto

    2012-07-01

    Chemoprevention is effective in inhibiting the onset of cancer in experimental animal models, but the transferability of similar results to humans is questionable. Therefore, reliable intermediate molecular biomarkers are needed to evaluate the efficacy of chemopreventive agents before the onset of cancer. The use of genomic biomarkers is limited by their poor predictive value. Although post-genomic biomarkers (i.e., gene-expression analyses) are useful for evaluating the safety, efficacy, and mechanistic basis of chemopreventive agents, the biomarkers are often poorly related to the phenotype, due to posttranscriptional regulation. Proteome analyses can evaluate preclinical phenotype alterations, but only at low protein counts. MicroRNA alterations, which are essential for the development of cancer, may be modulated by chemopreventive agents. Furthermore, microRNA delivery may be used to counteract carcinogenesis. Exposure to cigarette smoke induces microRNA let-7 downregulation and cell proliferation that can be converted to cell growth arrest and apoptosis upon let-7a transfection. Therefore, microRNAs are reliable biomarkers for evaluating chemoprevention efficacy and may be used to counteract carcinogenesis. © 2012 New York Academy of Sciences.

  5. ANTI-TUMOR ACTIVITY AND IMMUNE RESPONSES INDUCED BY HUMAN CANCER-ASSOCIATED MUCIN CORE PEPTIDE

    Institute of Scientific and Technical Information of China (English)

    Ma Yunguo; Yuan Mei; Fei Lihua; Li Li

    1998-01-01

    Objective: To investigate the immune responses induced by apomucin which is a mixture of mucin core peptide, in mice for elucidating the role of mucin core peptide in the modulation of cancers. Methods:Apomucin was isolated from human pancreatic cancer cell line SW1990. The mice were immunized with this apomucin (10μg/time×6) plus DETOX. Results: When immunized, all mice developed delayed-type hypersensitivity (DTH) after challenged with apomucin or synthetic peptide MUC-2 or MUC-3, while the mice immunized with apomucin alone did not develop DTH.No antibodies were detected by ELISA after immunization. When the spleen cells of vaccinated mice were cocultured with this apomucin (10-50μg/ml) and rhIL-2(50U/ml) in vitro, the proliferated lymphocytes showed cytotoxicity against human cancer cells, including colon cancer, gastric cancer, pancreatic cancer and leukemia as measured by Cr-51 release assay. Antibodies against MUC-2 and MUC-3 could block the cytotoxicity. Conclusion: It was identified that a vaccine combined of apomucin and immune adjuvant DETOX can induce cellular immune response and anti-tumor cytotoxicity in mice.

  6. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Christopher M. Fulkerson

    2017-01-01

    Full Text Available Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  7. A snapshot of cancer in Chile: analytical frameworks for developing a cancer policy.

    Science.gov (United States)

    Jimenez de la Jara, Jorge; Bastias, Gabriel; Ferreccio, Catterina; Moscoso, Cristian; Sagues, Sofia; Cid, Camilo; Bronstein, Eduardo; Herrera, Cristian; Nervi, Bruno; Corvalan, Alejandro; Velasquez, Ethel V; Gonzalez, Pamela; Castellon, Enrique; Bustamante, Eva; Oñate, Sergio; McNerney, Eileen; Sullivan, Richard; Owen, Gareth I

    2015-01-26

    The South American country Chile now boasts a life expectancy of over 80 years. As a consequence, Chile now faces the increasing social and economic burden of cancer and must implement political policy to deliver equitable cancer care. Hindering the development of a national cancer policy is the lack of comprehensive analysis of cancer infrastructure and economic impact. Evaluate existing cancer policy, the extent of national investigation and the socio-economic impact of cancer to deliver guidelines for the framing of an equitable national cancer policy. Burden, research and care-policy systems were assessed by triangulating objective system metrics--epidemiological, economic, etc.--with political and policy analysis. Analysis of the literature and governmental databases was performed. The oncology community was interviewed and surveyed. Chile utilizes 1% of its gross domestic product on cancer care and treatment. We estimate that the economic impact as measured in Disability Adjusted Life Years to be US$ 3.5 billion. Persistent inequalities still occur in cancer distribution and treatment. A high quality cancer research community is expanding, however, insufficient funding is directed towards disproportionally prevalent stomach, lung and gallbladder cancers. Chile has a rapidly ageing population wherein 40% smoke, 67% are overweight and 18% abuse alcohol, and thus the corresponding burden of cancer will have a negative impact on an affordable health care system. We conclude that the Chilean government must develop a national cancer strategy, which the authors outline herein and believe is essential to permit equitable cancer care for the country.

  8. Establishing of the Transplanted Animal Models for Human Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Xingli Zhang; Jinchang Wu

    2009-01-01

    Lung cancer is the leading cause of cancer mortality worldwide.Even with the applications of excision,radiotherapy,chemotherapy,and gene therapy,the 5 year survival rate is only 15% in the USA.Clinically relevant laboratory animal models of the disease could greatly facilitate understanding of the pathogenesis of lung cancer,its progression,invasion and metastasis.Transplanted lung cancer models are of special interest and are widely used today.Such models are essential tools in accelerating development of new therapies for lung cancer.In this communication we will present a brief overview of the hosts,sites and pathways used to establish transplanted animal lung tumor models.

  9. New drug development in metastatic prostate cancer.

    Science.gov (United States)

    Armstrong, Andrew J; George, Daniel J

    2008-01-01

    In 2007, drug development in castration-resistant metastatic prostate cancer (CRPC) remains challenging, due to the number of potentially viable molecular targets and clinical trials available, the lack of established surrogates for overall survival, and competing causes of mortality. This review will highlight the highest impact phase II and phase III trials of novel agents in the current CRPC landscape, and focus on both molecular targets and clinical trial designs that are more likely to demonstrate clinical benefit. The need for tissue correlative studies for target evaluation and drug mechanism is stressed to continue to advance the field and to define biomarkers that may identify patient populations that may derive a greater benefit from these molecular agents.

  10. Avasimibe encapsulated in human serum albumin blocks cholesterol esterification for selective cancer treatment.

    Science.gov (United States)

    Lee, Steve Seung-Young; Li, Junjie; Tai, Jien Nee; Ratliff, Timothy L; Park, Kinam; Cheng, Ji-Xin

    2015-03-24

    Undesirable side effects remain a significant challenge in cancer chemotherapy. Here we report a strategy for cancer-selective chemotherapy by blocking acyl-CoA cholesterol acyltransferase-1 (ACAT-1)-mediated cholesterol esterification. To efficiently block cholesterol esterification in cancer in vivo, we developed a systemically injectable nanoformulation of avasimibe (a potent ACAT-1 inhibitor), called avasimin. In cell lines of human prostate, pancreatic, lung, and colon cancer, avasimin significantly reduced cholesteryl ester storage in lipid droplets and elevated intracellular free cholesterol levels, which led to apoptosis and suppression of proliferation. In xenograft models of prostate cancer and colon cancer, intravenous administration of avasimin caused the concentration of avasimibe in tumors to be 4-fold higher than the IC50 value. Systemic treatment of avasimin notably suppressed tumor growth in mice and extended the length of survival time. No adverse effects of avasimin to normal cells and organs were observed. Together, this study provides an effective approach for selective cancer chemotherapy by targeting altered cholesterol metabolism of cancer cells.

  11. DETECTION OF OXIDATIVE STRESS, APOPTOSIS AND MOLECULAR LESIONS IN HUMAN OVARIAN CANCER CELLS

    Directory of Open Access Journals (Sweden)

    H. I. Falfushynska

    2016-05-01

    Full Text Available Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development. Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones. Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage in blood as the consequence of overexpression of oxyradicals (by 300%. Higher level of glutathione (by 366%, lower level of metallothioneins (by 65% as well as higher level of lipid peroxidation (by 174% and protein carbonyls (by 186% in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control level of DNA fragmentation (by 160%, choline esterase (up to twice, higher rate of both caspase dependent and caspase independent lysosomal mediated apoptosis. Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of human ovarian cancer.

  12. Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research.

    Science.gov (United States)

    Lee, Sung Jong; Yang, Andrew; Wu, T C; Hung, Chien Fu

    2016-09-01

    Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.

  13. Human papillomavirus DNA in plasma of patients with cervical cancer

    Directory of Open Access Journals (Sweden)

    Voravud Narin

    2001-03-01

    Full Text Available Abstract Background Human papillomavirus (HPV is a crucial etiological factor for cervical cancer (CC development. From a diagnostic view-point, the consistent presence of HPV in CC allows the viral DNA to be used as a genetic marker. The aims of this study were to evaluate the presence, physical status and clinical significant of HPV DNA in circulation of CC patients. Results Whereas 6 out of 50 (12% HPV positive CC patients revealed plasma HPV DNA, it was detected in none of 20 normal controls or 13 HPV negative CC cases. The plasma DNA exhibited an HPV type identical to the HPV in the primary tumors and the DNA from both sources was integrated into host genome. Interestingly, several findings suggested an association between plasma HPV DNA and metastasis. First, three of the HPV DNA positive cases were CC patients with clinical stage IVB or recurrence with distance metastases (P = 0.001, RR = 15.67. Second, the amount of plasma HPV DNA from metastatic patients to be three times more than three other patients without metastases. Finally, the later cases had tendency to develop recurrence distant metastases within one year after complete treatment when compared with other HPV associated CC patients with the same stage but without the present of plasma HPV DNA. Conclusions The plasma HPV DNA originated from the CC, was associated with metastasis and could be used as a marker representing the circulating free CC DNA.

  14. The role of intestinal microflora and probiotic bacteria in prophylactic and development of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ewa Wasilewska

    2013-08-01

    Full Text Available The gut microbiota comprises a large and diverse range of microorganisms whose activities have a significant impact on health. It interacts with its host at both the local and systemic level, resulting in a broad range of beneficial or detrimental outcomes for nutrition, infections, xenobiotic metabolism, and cancer. The current paper reviews research on the role of intestinal microflora in colorectal cancer development. Especially a protective effect of beneficial bacteria and probiotics on the risk of cancer development is highly discussed. There is substantial experimental evidence that the beneficial gut bacteria and their metabolism have the potential to inhibit the development and progression of neoplasia in the large intestine. Most of the data derive, however, from experimental and animal trials. Over a dozen well-documented animal studies have been published, wherein it has been clearly revealed that some lactic acid bacteria, especially lactobacilli and bifidobacteria, inhibit initiation and progression of colorectal cancer. Studies on cancer suppression in humans as a result of the consumption of probiotics are still sparse. Nevertheless, some epidemiological and interventional studies seem to confirm the bacterial anticancerogenic activity also in human gut. The mechanism by which probiotics may inhibit cancer development is unknown. Probiotics increase the amount of beneficial bacteria and decrease the pathogen level in the gut, consequently altering metabolic, enzymatic and carcinogenic activity in the intestine, decreasing inflammation and enhancing immune function, which may contribute to cancer defense.

  15. Preclinical development of HIvax: Human survivin highly immunogenic vaccines.

    Science.gov (United States)

    Hoffmann, Peter R; Panigada, Maddalena; Soprana, Elisa; Terry, Frances; Bandar, Ivo Sah; Napolitano, Andrea; Rose, Aaron H; Hoffmann, Fukun W; Ndhlovu, Lishomwa C; Belcaid, Mahdi; Moise, Lenny; De Groot, Anne S; Carbone, Michele; Gaudino, Giovanni; Matsui, Takashi; Siccardi, Antonio; Bertino, Pietro

    2015-01-01

    Our previous work involved the development of a recombinant fowlpox virus encoding survivin (FP-surv) vaccine that was evaluated for efficacy in mesothelioma mouse models. Results showed that FP-surv vaccination generated significant immune responses, which led to delayed tumor growth and improved animal survival. We have extended those previous findings in the current study, which involves the pre-clinical development of an optimized version of FP-surv designed for human immunization (HIvax). Survivin-derived peptides for the most common haplotypes in the human population were identified and their immunogenicity confirmed in co-culture experiments using dendritic cells and T cells isolated from healthy donors. Peptides confirmed to induce CD8(+) and CD4(+) T cells activation in humans were then included in 2 transgenes optimized for presentation of processed peptides on MHC-I (HIvax1) and MHC-II (HIvax2). Fowlpox vectors expressing the HIvax transgenes were then generated and their efficacy was evaluated with subsequent co-culture experiments to measure interferon-γ and granzyme B secretion. In these experiments, both antigen specific CD4(+) and CD8(+) T cells were activated by HIvax vaccines with resultant cytotoxic activity against survivin-overexpressing mesothelioma cancer cells. These results provide a rationale for clinical testing of HIvax1 and HIvax2 vaccines in patients with survivin-expressing cancers.

  16. Development Tendencies of Sciences of Human Settlements

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In reviewing the scientific explorations in human settlements in the past century, as well as the new accomplishments in the study on Chinese human settlements, the author proposes that the Sciences of Human Settlements should respond to a series of new situations and chal-lenges of world development, such as global climate change and development mode transformation, in order to embody the ideal of "a Greater Science, a Greater Humanism, and a Greater Art". It is argued that the development tendencies of Sciences of Human Settlements in China should include: the concern for people’s livelihood based on the principle of people-oriented, the enhancement of strategic spatial planning for the new modes of spatial growth, the rising of ecological awareness for the Green Revolution, the balance of urban and rural development for rational urbanization, the exploration for the Third System from the perspectives of both Eastern and Western cultures, the innovations on the education of human settlements and the creation of both a better environment and a harmonious society.

  17. Human Resource Development in the Knowledge Economy

    DEFF Research Database (Denmark)

    Jørgensen, Sanne Lehmann

    . In this line of thinking, the aim is to propose a model for analysing the progress of knowledge improvements in developing countries as an outcome of the management of human, social and organisational capital. In this regard, the paper considers relevant practices and strategies in the context of developing...

  18. DNA Methylation Landscapes of Human Fetal Development

    NARCIS (Netherlands)

    Slieker, Roderick C.; Roost, Matthias S.; van Iperen, Liesbeth; Suchiman, H. Eka D; Tobi, Elmar W.; Carlotti, Françoise; de Koning, Eelco J P; Slagboom, P. Eline; Heijmans, Bastiaan T.; Chuva de Sousa Lopes, Susana M.

    2015-01-01

    Remodelling the methylome is a hallmark of mammalian development and cell differentiation. However, current knowledge of DNA methylation dynamics in human tissue specification and organ development largely stems from the extrapolation of studies in vitro and animal models. Here, we report on the DNA

  19. Human Resources Management & Development Handbook. Second Edition.

    Science.gov (United States)

    Tracey, William R., Ed.

    This revised handbook on the theory and practice of human resources management and development (HRM/D) focuses on people management and the personnel development processes. The book's 18 parts and 102 chapters by 107 contributors provide authoritative and comprehensive information on every aspect of modern HRM/D. Part 1 provides an overview of…

  20. Clinicopathological significance of PTPN12 expression in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Xunyi [Breast Disease Diagnosis and Treatment Centre, Affiliated Hospital of Medical College, Qingdao University, Qingdao Shandong Province (China); Yuan, Zhentao [Department of Anesthesiology, Shengli Oilfield Central Hospital, Dongying Shandong Province (China); Jiang, Dandan; Li, Funian [Breast Disease Diagnosis and Treatment Centre, Affiliated Hospital of Medical College, Qingdao University, Qingdao Shandong Province (China)

    2012-10-15

    Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a recently identified tumor suppressor gene (TSG) that is frequently compromised in human triple-negative breast cancer. In the present study, we investigated the expression of PTPN12 protein by patients with breast cancer in a Chinese population and the relationship between PTPN12 expression levels and patient clinicopathological features and prognosis. Additionally, we explored the underlying down-regulation mechanism from the perspective of an epigenetic alteration. We examined PTPN12 mRNA expression in five breast cancer cell lines using semi-quantitative reverse-transcription PCR, and detected PTPN12 protein expression using immunohistochemistry in 150 primary invasive breast cancer cases and paired adjacent non-tumor tissues. Methylation-specific PCR was performed to analyze the promoter CpG island methylation status of PTPN12. PTPN12 was significantly down-regulated in breast cancer cases (48/150) compared to adjacent noncancerous tissues (17/150; P < 0.05). Furthermore, low expression of PTPN12 showed a significant positive correlation with tumor size (P = 0.047), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), histological grade (P = 0.012), and survival time (P = 0.019). Additionally, promoter CpG island hypermethylation occurs more frequently in breast cancer cases and breast cancer cell lines with low PTPN12 expression. Our findings suggest that PTPN12 is potentially a methylation-silenced TSG for breast cancer that may play an important role in breast carcinogenesis and could potentially serve as an independent prognostic factor for invasive breast cancer patients.

  1. National Cultures and Human Development Index

    Directory of Open Access Journals (Sweden)

    Edvard Konrad

    2012-12-01

    Full Text Available This paper explores the relationships between basic cultural characteristics of countries and some economic indexes. As cultural characteristics, the data from The Global Leadership and Organizational Behavior Effectiveness Research Program (GLOBE about the 9 cultural dimensions for 60 countries were used. Two facets of cultural dimensions were measured: the perceptions of actual practices and the perceptions of preferred values. On the other hand, the data about different economic indexes were taken from archival sources such as Human Development Report. Results show that some cultural practices and preferences are related to the development of countries as measured by Human Development Index (HDI. The implications of these results are discussed.

  2. Another Approach to Measuring Human Development: The Composite Dynamic Human Development Index

    Science.gov (United States)

    Bilbao-Ubillos, Javier

    2013-01-01

    This paper seeks mainly to contribute to the debate on how the relative degree of development of a country should be measured by proposing an indicator to build on the valuable starting point provided by the Human Development Index (HDI). The indicator proposed is called the "Composite, Dynamic Human Development Index". It incorporates in a simple…

  3. Another Approach to Measuring Human Development: The Composite Dynamic Human Development Index

    Science.gov (United States)

    Bilbao-Ubillos, Javier

    2013-01-01

    This paper seeks mainly to contribute to the debate on how the relative degree of development of a country should be measured by proposing an indicator to build on the valuable starting point provided by the Human Development Index (HDI). The indicator proposed is called the "Composite, Dynamic Human Development Index". It incorporates in a simple…

  4. The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer

    Science.gov (United States)

    Fernandez, Agustin F.; Rosales, Cecilia; Lopez-Nieva, Pilar; Graña, Osvaldo; Ballestar, Esteban; Ropero, Santiago; Espada, Jesus; Melo, Sonia A.; Lujambio, Amaia; Fraga, Mario F.; Pino, Irene; Javierre, Biola; Carmona, Francisco J.; Acquadro, Francesco; Steenbergen, Renske D.M.; Snijders, Peter J.F.; Meijer, Chris J.; Pineau, Pascal; Dejean, Anne; Lloveras, Belen; Capella, Gabriel; Quer, Josep; Buti, Maria; Esteban, Juan-Ignacio; Allende, Helena; Rodriguez-Frias, Francisco; Castellsague, Xavier; Minarovits, Janos; Ponce, Jordi; Capello, Daniela; Gaidano, Gianluca; Cigudosa, Juan Cruz; Gomez-Lopez, Gonzalo; Pisano, David G.; Valencia, Alfonso; Piris, Miguel Angel; Bosch, Francesc X.; Cahir-McFarland, Ellen; Kieff, Elliott; Esteller, Manel

    2009-01-01

    The natural history of cancers associated with virus exposure is intriguing, since only a minority of human tissues infected with these viruses inevitably progress to cancer. However, the molecular reasons why the infection is controlled or instead progresses to subsequent stages of tumorigenesis are largely unknown. In this article, we provide the first complete DNA methylomes of double-stranded DNA viruses associated with human cancer that might provide important clues to help us understand the described process. Using bisulfite genomic sequencing of multiple clones, we have obtained the DNA methylation status of every CpG dinucleotide in the genome of the Human Papilloma Viruses 16 and 18 and Human Hepatitis B Virus, and in all the transcription start sites of the Epstein-Barr Virus. These viruses are associated with infectious diseases (such as hepatitis B and infectious mononucleosis) and the development of human tumors (cervical, hepatic, and nasopharyngeal cancers, and lymphoma), and are responsible for 1 million deaths worldwide every year. The DNA methylomes presented provide evidence of the dynamic nature of the epigenome in contrast to the genome. We observed that the DNA methylome of these viruses evolves from an unmethylated to a highly methylated genome in association with the progression of the disease, from asymptomatic healthy carriers, through chronically infected tissues and pre-malignant lesions, to the full-blown invasive tumor. The observed DNA methylation changes have a major functional impact on the biological behavior of the viruses. PMID:19208682

  5. Laparoscopic optical coherence tomographic imaging of human ovarian cancer

    Science.gov (United States)

    Hariri, Lida P.; Bonnema, Garret T.; Schmidt, Kathy; Korde, Vrushali; Winkler, Amy M.; Hatch, Kenneth; Brewer, Molly; Barton, Jennifer K.

    2009-02-01

    Ovarian cancer is the fourth leading cause of cancer-related death among women. If diagnosed at early stages, 5-year survival rate is 94%, but drops to 68% for regional disease and 29% for distant metastasis; only 19% of cases are diagnosed at early, localized stages. Optical coherence tomography is a recently emerging non-destructive imaging technology, achieving high axial resolutions (10-20 µm) at imaging depths up to 2 mm. Previously, we studied OCT in normal and diseased human ovary ex vivo. Changes in collagen were suggested with several images that correlated with changes in collagen seen in malignancy. Areas of necrosis and blood vessels were also visualized using OCT, indicative of an underlying tissue abnormality. We recently developed a custom side-firing laparoscopic OCT (LOCT) probe fabricated for in vivo imaging. The LOCT probe, consisting of a 38 mm diameter handpiece terminated in a 280 mm long, 4.6 mm diameter tip for insertion into the laparoscopic trocar, is capable of obtaining up to 9.5 mm image lengths at 10 µm axial resolution. In this pilot study, we utilize the LOCT probe to image one or both ovaries of 17 patients undergoing laparotomy or transabdominal endoscopy and oophorectomy to determine if OCT is capable of differentiating normal and neoplastic ovary. We have laparoscopically imaged the ovaries of seventeen patients with no known complications. Initial data evaluation reveals qualitative distinguishability between the features of undiseased post-menopausal ovary and the cystic, non-homogenous appearance of neoplastic ovary such as serous cystadenoma and endometroid adenocarcinoma.

  6. Salinomycin as a Drug for Targeting Human Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Cord Naujokat

    2012-01-01

    Full Text Available Cancer stem cells (CSCs represent a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of malignant cells that comprise a tumor. CSCs possess multiple intrinsic mechanisms of resistance to chemotherapeutic drugs, novel tumor-targeted drugs, and radiation therapy, allowing them to survive standard cancer therapies and to initiate tumor recurrence and metastasis. Various molecular complexes and pathways that confer resistance and survival of CSCs, including expression of ATP-binding cassette (ABC drug transporters, activation of the Wnt/β-catenin, Hedgehog, Notch and PI3K/Akt/mTOR signaling pathways, and acquisition of epithelial-mesenchymal transition (EMT, have been identified recently. Salinomycin, a polyether ionophore antibiotic isolated from Streptomyces albus, has been shown to kill CSCs in different types of human cancers, most likely by interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, and other CSC pathways. Promising results from preclinical trials in human xenograft mice and a few clinical pilote studies reveal that salinomycin is able to effectively eliminate CSCs and to induce partial clinical regression of heavily pretreated and therapy-resistant cancers. The ability of salinomycin to kill both CSCs and therapy-resistant cancer cells may define the compound as a novel and an effective anticancer drug.

  7. The development of human nature in childhood

    Directory of Open Access Journals (Sweden)

    Gordana Simonovski

    2001-12-01

    Full Text Available The article deals with the development of human nature in children from 4 to 12 years of age. The concept of human nature is described by Oerter (Oerter, 1991, 1994; Oerter, Oerter, Agostiani, Kim, in Wibowo, 1996 in his theory of development of implicit anthropology. Two procedures were applied in the research: an interview on adulthood and a social dilemma story, which was followed by a guided interview. The distribution of the developmental stages of the concept of human nature in children of different age is presented, along with the frequency of higher-stage answers that progressively rises with subject's age. The frequency of the answers on the first, the second and the third developmental stage is compared between sexes. Higher level of conceptualisation of human nature in girls was found when compared with boys. The intering in personality, social and action theory are explained.

  8. Development of Technologies for Early Detection and Stratification of Breast Cancer

    Science.gov (United States)

    2013-10-01

    fluid phase from fine needle aspirate (FNA) samples from murine tumors in HIM model (Months 1-12). 4b. Develop and submit proposal to IRB for...working to characterize breast cancer biopsy samples with single cell resolution to discover the nature of the underlying heterogeneity in complex...Confirm presence of the single cells in human breast cancer biopsy samples obtained from Buchsbaum (Months 48-60). These studies have not been

  9. Human Papilloma Virus Vaccine: Future of Cervical Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Jannatul Fardows

    2016-09-01

    Full Text Available Cervical cancer is a deadly cancer that clutches lives of the women in most of the cases due to lack of consciousness about the disease in the developing countries. It remains a threat which is second only to breast cancer in overall disease burden for women throughout the world. Cervical cancer is almost a preventable disease by prophylactic vaccine and routine screening. Both Cervarix and Gardasil vaccines have been effective in preventing persistent infection with targeted HPV types and in preventing cervical intraepithelial lesions. It is safe and nearly 100% effective if given before onset of sexual activity. This review article is aimed to explore different aspects of this vaccine as well as to develop awareness among health professionals of different disciplines.

  10. Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development.

    Science.gov (United States)

    Chung, Min-Yu; Lim, Tae Gyu; Lee, Ki Won

    2013-02-21

    Cancer is one of the leading causes of death worldwide. Commonly used cancer treatments, including chemotherapy and radiation therapy, often have side effects and a complete cure is sometimes impossible. Therefore, prevention, suppression, and/or delaying the onset of the disease are important. The onset of gastroenterological cancers is closely associated with an individual's lifestyle. Thus, changing lifestyle, specifically the consumption of fruits and vegetables, can help to protect against the development of gastroenterological cancers. In particular, naturally occurring bioactive compounds, including curcumin, resveratrol, isothiocyanates, (-)-epigallocatechin gallate and sulforaphane, are regarded as promising chemopreventive agents. Hence, regular consumption of these natural bioactive compounds found in foods can contribute to prevention, suppression, and/or delay of gastroenterological cancer development. In this review, we will summarize natural phytochemicals possessing potential antioxidant and/or anti-inflammatory and anti-carcinogenic activities, which are exerted by regulating or targeting specific molecules against gastroenterological cancers, including esophageal, gastric and colon cancers.

  11. Human prefrontal cortex: evolution, development, and pathology.

    Science.gov (United States)

    Teffer, Kate; Semendeferi, Katerina

    2012-01-01

    The prefrontal cortex is critical to many cognitive abilities that are considered particularly human, and forms a large part of a neural system crucial for normal socio-emotional and executive functioning in humans and other primates. In this chapter, we survey the literature regarding prefrontal development and pathology in humans as well as comparative studies of the region in humans and closely related primate species. The prefrontal cortex matures later in development than more caudal regions, and some of its neuronal subpopulations exhibit more complex dendritic arborizations. Comparative work suggests that the human prefrontal cortex differs from that of closely related primate species less in relative size than it does in organization. Specific reorganizational events in neural circuitry may have taken place either as a consequence of adjusting to increases in size or as adaptive responses to specific selection pressures. Living in complex environments has been recognized as a considerable factor in the evolution of primate cognition. Normal frontal lobe development and function are also compromised in several neurological and psychiatric disorders. A phylogenetically recent reorganization of frontal cortical circuitry may have been critical to the emergence of human-specific executive and social-emotional functions, and developmental pathology in these same systems underlies many psychiatric and neurological disorders, including autism and schizophrenia.

  12. [HPV (Human Papilloma Virus) implication in other cancers than gynaecological].

    Science.gov (United States)

    Badoual, C; Tartour, E; Roussel, H; Bats, A S; Pavie, J; Pernot, S; Weiss, L; Mohamed, A Si; Thariat, J; Hoffmann, C; Péré, H

    2015-08-01

    Worldwide, approximately 5 to 10% of the population is infected by a Human Papilloma Virus (HPV). Some of these viruses, with a high oncogenic risk (HPV HR), are responsible for about 5% of cancer. It is now accepted that almost all carcinomas of the cervix and the vulva are due to an HPV HR (HPV16 and 18) infection. However, these viruses are known to be involved in the carcinogenesis of many other cancers (head and neck [SCCHN], penis, anus). For head and neck cancer, HPV infection is considered as a good prognostic factor. The role of HPV HR in anal cancer is also extensively studied in high-risk patient's population. The role of HPV infection in the carcinogenesis of esophageal, bladder, lung, breast or skin cancers is still debated. Given the multiple possible locations of HPV HR infection, the question of optimizing the management of patients with a HPV+ cancer arises in the implementation of a comprehensive clinical and biological monitoring. It is the same in therapeutics with the existence of a preventive vaccination, for example.

  13. Marker evaluation of human breast and bladder cancers

    Energy Technology Data Exchange (ETDEWEB)

    Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. (California Univ., San Francisco, CA (USA))

    1990-11-02

    We are investigating multiple markers in human breast and bladder cancers. Our aim is to identify markers that are clinically relevant and that contribute to our understanding of the disease process in individual patients. Good markers accurately assess the malignant potential of a cancer in an individual patient. Thus, they help identify those cancers that will recur, and they may be used to predict more accurately time to recurrence, response to treatment, and overall prognosis. Therapy and patient management may then be optimized to the individual patient. Relevant markers reflect the underlying pathobiology of individual tumors. As a tissue undergoes transformation from benign to malignant, the cells lose their differentiated phenotype. As a generalization, the more the cellular phenotype, cellular proliferation and cellular genotype depart from normal, the more advanced is the tumor in its biological evolution and the more likely it is that the patient has a poor prognosis. We use three studies to illustrate our investigation of potential tumor markers. Breast cancers are labeled in vivo with 5-bromodeoxyuridine (BrdUrd) to give a direct measure of the tumor labeling index. Bladder cancers are analyzed immunocytochemically using an antibody against proliferation. Finally, the techniques of molecular genetics are used to detect allelic loss in breast cancers. 6 refs., 3 figs.

  14. The inhibition of Wnt/β-catenin signaling pathway in human colon cancer cells by sulindac.

    Science.gov (United States)

    Tai, Wei-Ping; Hu, Pin-Jin; Wu, Jing; Lin, Xiang-Chun

    2014-01-01

    The aberrant activation of Wnt/β-catenin signaling plays important roles in the initial development of colon cancer. Sulindac is a commonly used non-steroidal anti-inflammatory drug. We demonstrated the effects of sulindac on growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. Sulindac significantly inhibited proliferation of HT-29 colon cancer cells in a dose- and time-dependent manner. Sulindac was found to induce the apoptosis of HT-29 cells and inhibit the Wnt/β-catenin pathway. The inhibition was further confirmed by the decreased protein levels of β-catenin. The results indicate that sulindac may play a beneficial role in the comprehensive treatment of colon cancer.

  15. Characterization of the Usage of the Serine Metabolic Network in Human Cancer

    Directory of Open Access Journals (Sweden)

    Mahya Mehrmohamadi

    2014-11-01

    Full Text Available The serine, glycine, one-carbon (SGOC metabolic network is implicated in cancer pathogenesis, but its general functions are unknown. We carried out a computational reconstruction of the SGOC network and then characterized its expression across thousands of cancer tissues. Pathways including methylation and redox metabolism exhibited heterogeneous expression indicating a strong context dependency of their usage in tumors. From an analysis of coexpression, simultaneous up- or downregulation of nucleotide synthesis, NADPH, and glutathione synthesis was found to be a common occurrence in all cancers. Finally, we developed a method to trace the metabolic fate of serine using stable isotopes, high-resolution mass spectrometry, and a mathematical model. Although the expression of single genes didn’t appear indicative of flux, the collective expression of several genes in a given pathway allowed for successful flux prediction. Altogether, these findings identify expansive and heterogeneous functions for the SGOC metabolic network in human cancer.

  16. KiSS-1 expression in human breast cancer.

    Science.gov (United States)

    Martin, Tracey A; Watkins, Gareth; Jiang, Wen G

    2005-01-01

    The KiSS-1 gene encodes a 145 amino acid residue peptide that is further processed to a final peptide, metastin, a ligand to a G-coupled orphan receptor (OT7T175/AXOR12). KiSS-1 has been identified as a putative human metastasis suppressor gene in melanomas and in breast cancer cell lines. This study aimed to determine the expression and distribution of KiSS-1 and its receptor in human breast cancer tissues and to identify a possible link between expression levels and patient prognosis. Frozen sections from breast cancer primary tumours (matched tumour 124 and background 33) were immuno-stained with KiSS-1 antibody. RNA was reverse transcribed and analyzed by Q-PCR (standardized using beta-actin, and normalized with cytokeratin-19 levels). Levels of expression of KiSS-1 were higher in tumour compared to background tissues (3,124+/-1,262 vs 2,397+/-1,181) and significantly increased in node positive tumours compared to node negative (3,637+/-1,719 vs 2,653+/-1,994, P = 0.02). KiSS-1 expression was also increased with increasing grade and TNM status. There were no such trends with the KiSS-1 receptor. Expression of KiSS-1 was higher in patients who had died from breast cancer than those who had remained healthy (4,631+/-3,024 vs 2,280+/-1,403) whereas expression of the receptor was reduced (480+/-162 vs 195+/-134). Immunohistochemical staining showed increased expression of KiSS-1 in tumour sections. Insertion of the KiSS-1 gene into the human breast cancer cell line MDA-MB-231, resulted in cells that were significantly more motile and invasive in behaviour, with reduced adhesion to matrix, using respective assays. In conclusion, KiSS-1 expression is increased in human breast cancer, particularly in patients with aggressive tumours and with mortality. Over-expression of KiSS-1 in breast cancer cells result in more aggressive phenotype. Together, it suggests that KiSS-1 plays a role beyond the initial metastasis repressor in this cancer type.

  17. Are 20 human papillomavirus types causing cervical cancer?

    OpenAIRE

    Arbyn, Marc; Tommasino, Massimo; Depuydt, Christophe; Dillner, Joakim

    2014-01-01

    Abstract: In 2012, the International Agency for Research on Cancer concluded that there was consistent and sufficient epidemiological, experimental and mechanistic evidence of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer. Therefore, these types were considered as 1A carcinogens. They all belong to the family of the -Papillomaviridae, in particular to the species 5 (HPV51), 6 (HPV56), 7 (H...

  18. Aurora-A Oncogene in Human Ovarian Cancer

    Science.gov (United States)

    2006-11-01

    in Human Ovarian Cancer 5b. GRANT NUMBER W81XWH-05-1-0021 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Jin Q. Cheng, M.D...this project : 1) examine the clinicalpathological significance and the mechanism of Aurora-A overexpression/activation in ovarian cancer; 2) determine...kinase is required to localize D-TACC to centro- somes and to regulate astral microtubules. J Cell Biol 2002;156:437–51. 33. Castro A, Mandart E, Lorca T

  19. Moving Forward in Human Cancer Risk Assessment

    OpenAIRE

    Paules, Richard S.; Aubrecht, Jiri; Corvi, Raffaella; Garthoff, Bernward; Kleinjans, Jos C.

    2010-01-01

    Background The current safety paradigm for assessing carcinogenic properties of drugs, cosmetics, industrial chemicals, and environmental exposures relies mainly on in vitro genotoxicity testing followed by 2-year rodent bioassays. This testing battery is extremely sensitive but has low specificity. Furthermore, rodent bioassays are associated with high costs, high animal burden, and limited predictive value for human risks. Objectives We provide a response to a growing appeal for a paradigm ...

  20. Human endogenous retroviruses and cancer prevention: evidence and prospects

    Directory of Open Access Journals (Sweden)

    Cegolon Luca

    2013-01-01

    Full Text Available Abstract Background Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity, hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Discussion Human endogenous retroviruses (HERVs are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well

  1. Discovery and development of sulforaphane as a cancer chemopreventive phytochemical

    Institute of Scientific and Technical Information of China (English)

    Yuesheng ZHANG; Li TANG

    2007-01-01

    Sulforaphane (SF) is a phytochemical that displays both anticarcinogenic and anticancer activity. SF modulates many cancer-related events, including suscep-tibility to carcinogens, cell death, cell cycle, angiogenesis, invasion and metastasis.We review its discovery and development as a cancer chemopreventive agent with the intention of encouraging further research on this important compound and facilitating the identification and development of new phytochemicals for cancer prevention.

  2. Hippo pathway in mammary gland development and breast cancer.

    Science.gov (United States)

    Shi, Peiguo; Feng, Jing; Chen, Ceshi

    2015-01-01

    Accumulated evidence suggests that the Hippo signaling pathway plays crucial roles in mammary gland development and breast cancer. Key components of the Hippo pathway regulate breast epithelial cell proliferation, migration, invasion, and stemness. Additionally, the Hippo pathway regulates breast tumor growth, metastasis, and drug resistance. It is expected that the Hippo pathway will provide novel therapeutic targets for breast cancer. This review will discuss and summarize the roles of several core components of the Hippo pathway in mammary gland development and breast cancer.

  3. Transduction motif analysis of gastric cancer based on a human signaling network

    Energy Technology Data Exchange (ETDEWEB)

    Liu, G.; Li, D.Z.; Jiang, C.S.; Wang, W. [Fuzhou General Hospital of Nanjing Command, Department of Gastroenterology, Fuzhou, China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou (China)

    2014-04-04

    To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

  4. Transduction motif analysis of gastric cancer based on a human signaling network

    Directory of Open Access Journals (Sweden)

    G. Liu

    2014-05-01

    Full Text Available To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

  5. Diabetes: energetics, development and human evolution.

    Science.gov (United States)

    Campbell, B C; Cajigal, A

    2001-07-01

    The recent emergence of the thrifty phenotype as an explanation for metabolic efficiency has brought evolutionary perspectives on diabetes, as represented by the thrifty genotype, under scrutiny. However, the logic of natural selection along with evidence from non-human primates supports the role for energetic constraints in the evolution of metabolic efficiency, particularly in skeletal muscle physiology. Environmental fluctuation during human evolution would have provided selective pressures for the development of efficient skeletal muscle starting prenatally and continuing throughout the lifespan. Such mechanisms including, glucose transporters, mitochondrial gene expression, leptin receptors and uncoupling proteins, should be present in all humans, though some living populations may exhibit particular 'thriftier' alleles. A focus on physical activity and the factors underlying efficient muscle physiology has implications for prevention of diabetes in both developing and developed societies. Copyright 2001 Harcourt Publishers Ltd.

  6. Elevated connexin 43 expression in arsenite-and cadmium-transformed human bladder cancer cells, tumor transplants and selected high grade human bladder cancers.

    Science.gov (United States)

    Zhang, Ruowen; Wang, Liping; Garrett, Scott H; Sens, Donald A; Dunlevy, Jane R; Zhou, Xu Dong; Somji, Seema

    2016-10-01

    Connexin 43 has been shown to play a role in cell migration and invasion; however, its role in bladder cancer is not well defined. Previous studies from our laboratory have shown that the environmental pollutants arsenite and cadmium can cause malignant transformation of the immortalized urothelial cell line UROtsa. These transformed cells can form tumors in immune-compromised mice. The goal of the present study was to determine if connexin 43 is expressed in the normal human bladder, the arsenite and cadmiun-transformed UROtsa cells as well as human urothelial cancer. The results obtained showed that connexin 43 is not expressed in the epithelial cells of the human bladder but is expressed in immortalized cultures of human urothelial cells and the expression is variable in the arsenite and cadmium- transformed urothelial cell lines derived from these immortalized cells. Tumor heterotransplants generated from the transformed cells expressed connexin 43 and the expression was localized to areas of squamous differentiation. Immuno-histochemical analysis of human bladder cancers also showed that the expression of connexin 43 was localized to areas of the tumor that showed early features of squamous differentiation. Treatment of UROtsa cells with various concentrations of arsenite or cadmium did not significantly alter the expression level of connexin 43. In conclusion, our results show that the expression of connexin 43 is localized to the areas of the tumor that show squamous differentiation, which may be an indicator of poor prognosis. This suggests that connexin 43 has the potential to be developed as a biomarker for bladder cancer that may have the ability to invade and metastasize.

  7. Apoptosis mechanisms of human gastric cancer cell line MKN-45 infected with human mutant p27

    Institute of Scientific and Technical Information of China (English)

    Jin-Shui Zhu; Long Wang; Guo-Qiang Cheng; Qin Li; Zu-Ming Zhu; Li Zhu

    2005-01-01

    AIM: To explore the inducing effect of human mutant p27 gene on the apoptosis of the human gastric cancer cell line MKN-45 and its associated mechanisms. METHODS: The recombinant adenovirus Ad-p27mt was constructed to infect the human gastric cancer cell line MKN-45. Using flow cytometry, TUNEL assay and DNA fragment analysis, we measured the apoptotic effect of Ad-p27mt on the human gastric cancer cells. RESULTS: Ad-p27mt was successfully constructed and the infection efficiency reached 100%. After 18 h of infection, we observed an apoptotic hypodiploid peak on the flow cytometer before G1-S and apoptotic characteristic bands in the DNA electrophoresis. The apoptotic rate detected by TUNEL method was significantly higher in the Ad-p27mt group (89.4±3.12%)compared to the control group (3.12±0.13%, P < 0.01).CONCLUSION: Human mutant p27 can induce apoptosis of the human gastric cancer cells in vitro.

  8. The development of human behavior analysis techniques

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Lee, Yong Hee; Park, Geun Ok; Cheon, Se Woo; Suh, Sang Moon; Oh, In Suk; Lee, Hyun Chul; Park, Jae Chang

    1997-07-01

    In this project, which is to study on man-machine interaction in Korean nuclear power plants, we developed SACOM (Simulation Analyzer with a Cognitive Operator Model), a tool for the assessment of task performance in the control rooms using software simulation, and also develop human error analysis and application techniques. SACOM was developed to assess operator`s physical workload, workload in information navigation at VDU workstations, and cognitive workload in procedural tasks. We developed trip analysis system including a procedure based on man-machine interaction analysis system including a procedure based on man-machine interaction analysis and a classification system. We analyzed a total of 277 trips occurred from 1978 to 1994 to produce trip summary information, and for 79 cases induced by human errors time-lined man-machine interactions. The INSTEC, a database system of our analysis results, was developed. The MARSTEC, a multimedia authoring and representation system for trip information, was also developed, and techniques for human error detection in human factors experiments were established. (author). 121 refs., 38 tabs., 52 figs.

  9. Cancer proteomics: developments in technology, clinical use and commercialization.

    Science.gov (United States)

    Yeat, Nai Chien; Lin, Charlotte; Sager, Monica; Lin, Jimmy

    2015-08-01

    In the last two decades, advances in genomic, transcriptomic and proteomic methods have enabled us to identify and classify cancers by their molecular profiles. Many anticipate that a molecular taxonomy of cancer will not only lead to more effective subtyping of cancers but also earlier diagnoses, more informative prognoses and more targeted treatments. This article reviews recent technological developments in the field of proteomics, recent discoveries in proteomic cancer biomarker research and trends in clinical use. Readers are also informed of examples of successful commercialization, and the future of proteomics in cancer diagnostics.

  10. Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

    Directory of Open Access Journals (Sweden)

    Assunta Catalano

    2011-05-01

    Full Text Available Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk.

  11. Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

    Energy Technology Data Exchange (ETDEWEB)

    Palozza, Paola, E-mail: p.palozza@rm.unicatt.it; Simone, Rossella E.; Catalano, Assunta [Institute of General Pathology, School of Medicine, Catholic University, L. Go F. Vito, Rome 1 00168 (Italy); Mele, Maria Cristina [Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, L. Go F. Vito, Rome 1 00168 (Italy)

    2011-05-11

    Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk.

  12. LpMab-23: A Cancer-Specific Monoclonal Antibody Against Human Podoplanin.

    Science.gov (United States)

    Yamada, Shinji; Ogasawara, Satoshi; Kaneko, Mika K; Kato, Yukinari

    2017-04-07

    Human podoplanin (hPDPN), the ligand of C-type lectin-like receptor-2, is involved in cancer metastasis. Until now, many monoclonal antibodies (mAbs) have been established against hPDPN. However, it is still difficult to develop a cancer-specific mAb (CasMab) against hPDPN because the protein sequence of hPDPN expressed in cancer cells is the same as that in normal cells. Herein, we report LpMab-23 of the mouse IgG1 subclass, a novel CasMab against hPDPN. In an immunohistochemical analysis, LpMab-23 reacted with tumor cells of human oral cancer, but did not react with normal cells such as lymphatic endothelial cells (LECs). In contrast, LpMab-17, another anti-hPDPN mAb, reacted with both tumor cells and LECs. Furthermore, flow cytometric analysis revealed that LpMab-23 reacted with hPDPN-expressing cancer cell lines (LN319, RERF-LC-AI/hPDPN, Y-MESO-14/hPDPN, and HSC3/hPDPN) but showed little reaction with normal cells (LECs and HEK-293T), although another anti-hPDPN mAb, LpMab-7, reacted with both hPDPN-expressing cancer cells and normal cells, indicating that LpMab-23 is a CasMab against hPDPN.

  13. A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs

    Directory of Open Access Journals (Sweden)

    Maria Isabel Carvalho

    2016-01-01

    Full Text Available Infiltrating cells of the immune system are widely accepted to be generic constituents of tumor microenvironment. It has been well established that the development of mammary cancer, both in humans and in dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cells seem to exhibit exclusive phenotypic and functional characteristics and mammary cancer cells can take advantage of signaling molecules released by them. Cancer related inflammation has an important role in mammary carcinogenesis, contributing to the acquisition of core hallmark capabilities that allow cancer cells to survive, proliferate, and disseminate. Indeed, recent studies in human breast cancer and in canine mammary tumors have identified a growing list of signaling molecules released by inflammatory cells that serve as effectors of their tumor-promoting actions. These include the COX-2, the tumor EGF, the angiogenic VEGF, other proangiogenic factors, and a large variety of chemokines and cytokines that amplify the inflammatory state. This review describes the intertwined signaling pathways shared by T-lymphocytic/macrophage infiltrates and important tissue biomarkers in both human and dog mammary carcinogenesis.

  14. A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs.

    Science.gov (United States)

    Carvalho, Maria Isabel; Silva-Carvalho, Ricardo; Pires, Isabel; Prada, Justina; Bianchini, Rodolfo; Jensen-Jarolim, Erika; Queiroga, Felisbina L

    2016-01-01

    Infiltrating cells of the immune system are widely accepted to be generic constituents of tumor microenvironment. It has been well established that the development of mammary cancer, both in humans and in dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cells seem to exhibit exclusive phenotypic and functional characteristics and mammary cancer cells can take advantage of signaling molecules released by them. Cancer related inflammation has an important role in mammary carcinogenesis, contributing to the acquisition of core hallmark capabilities that allow cancer cells to survive, proliferate, and disseminate. Indeed, recent studies in human breast cancer and in canine mammary tumors have identified a growing list of signaling molecules released by inflammatory cells that serve as effectors of their tumor-promoting actions. These include the COX-2, the tumor EGF, the angiogenic VEGF, other proangiogenic factors, and a large variety of chemokines and cytokines that amplify the inflammatory state. This review describes the intertwined signaling pathways shared by T-lymphocytic/macrophage infiltrates and important tissue biomarkers in both human and dog mammary carcinogenesis.

  15. Serological proteome analysis of dogs with breast cancer unveils common serum biomarkers with human counterparts.

    Science.gov (United States)

    Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi; Rahbarghazi, Reza

    2014-03-01

    Canine mammary tumor is being touted as a model for investigating the human breast cancer. Breast cancer of the both species has similar biological behavior, histopathologic characteristics, and metastatic pattern. In this study, we used the serological proteome analysis to detect autoantigens that elicit a humoral response in dogs with mammary tumor in order to identify serum biomarkers with potential usefulness as diagnostic markers and to better understand molecular mechanisms underlying canine breast cancer development. Protein extract from a cell line was subject to 2DE followed by Western blotting using sera from 15 dogs with mammary tumor and sera from 15 healthy control dogs. Immunoreactive autoantigens were subsequently identified by the MALDI-TOF MS. Four autoantigens, including manganese-superoxide dismutase, triose phosphate isomerase, alpha-enolase, and phosphoglycerate mutase1, with significantly higher immunoreactivity in the tumor samples than in the normal samples were identified as biomarker candidates. Immunohistochemistry and Western blotting revealed higher expression of these biomarkers in the malignant tumors than in the normal or benign tumors. The autoantigens found in this study have been reported to elicit autoantibody response in the human breast cancer, indicating the similarity of breast cancer proteome profile in dogs with that in human beings.

  16. The human brain. Prenatal development and structure

    Energy Technology Data Exchange (ETDEWEB)

    Marin-Padilla, Miguel

    2011-07-01

    This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

  17. Anti-cancer effects of Kochia scoparia fruit in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Hye-Yeon Han

    2014-01-01

    Full Text Available Background: The fruit of Kochia scoparia Scharder is widely used as a medicinal ingredient for the treatment of dysuria and skin diseases in China, Japan and Korea. Especially, K. scoparia had been used for breast masses and chest and flank pain. Objective: To investigate the anti-cancer effect of K. scoparia on breast cancer. Materials and Methods: We investigated the anti-cancer effects of K. scoparia, methanol extract (MEKS in vitro. We examined the effects of MEKS on the proliferation rate, cell cycle arrest, reactive oxygen species (ROS generation and activation of apoptosis-associated proteins in MDA-MB-231, human breast cancer cells. Results: MTT assay results demonstrated that MEKS decreased the proliferation rates of MDA-MB-231 cells in a dose-dependent manner with an IC 50 value of 36.2 μg/ml. MEKS at 25 μg/ml significantly increased the sub-G1 DNA contents of MDA-MB-231 cells to 44.7%, versus untreated cells. In addition, MEKS induced apoptosis by increasing the levels of apoptosis-associated proteins such as cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and cleaved Poly (ADP-ribose polymerase (PARP. Conclusion: These results suggest that MEKS inhibits cell proliferation and induces apoptosis in breast cancer cells and that MEKS may have potential chemotherapeutic value for the treatment of human breast cancer.

  18. Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

    Directory of Open Access Journals (Sweden)

    Richa Tripathi

    Full Text Available BACKGROUND: Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis. METHODS: This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98, precancer (n = 30 and non-neoplastic cervical tissues (n = 40 were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting. RESULTS: 80% (24/30 were found to be positive for HPV in precancer and 86.7% (85/98 in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001 and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001 obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; p<0.001; p<0.001. However, Notch-3 expression of above cases was significantly up-regulated with severity of disease and showed intense nuclear (4.17±0.39; 4.74±0.18, p = 0.0001, p = 0.0001 and cytoplasm (3.67±0.36; 4.48±0.18, p = 0.0001, p = 0.0001 of different stages as compared to normal cervix tissue (0.95±0.20, 0.70±0.20; p<0.001; p<0.001 respectively. CONCLUSIONS: These findings suggest that Notch-1 and Notch-3 may play an important role with synergistic effect of HPV in regulating development and proliferation of cervical cancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide

  19. Impact of mycotoxins on human health in developing countries.

    Science.gov (United States)

    Shephard, G S

    2008-02-01

    Adverse human health effects from the consumption of mycotoxins have occurred for many centuries. Although mycotoxin contamination of agricultural products still occurs in the developed world, the application of modern agricultural practices and the presence of a legislatively regulated food processing and marketing system have greatly reduced mycotoxin exposure in these populations. At the mycotoxin contamination levels generally found in food products traded in these market economies, adverse human health effects have largely been overcome. However, in the developing world, where climatic and crop storage conditions are frequently conducive to fungal growth and mycotoxin production, much of the population relies on subsistence farming or on unregulated local markets. The extent to which mycotoxins affect human health is difficult to investigate in countries whose health systems lack capacity and in which resources are limited. Aflatoxin B(1), the toxin on which major resources have been expended, has long been linked to liver cancer, yet its other effects, such as immune suppression and growth faltering previously observed in veterinary studies, are only now being investigated and characterized in human populations. The extent to which factors such as immune suppression contribute to the overall burden of infectious disease is difficult to quantify, but is undoubtedly significant. Thus, food safety remains an important opportunity for addressing current health problems in developing countries.

  20. Bioengineered models of solid human tumors for cancer research

    Science.gov (United States)

    Marturano-Kruik, Alessandro; Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2016-01-01

    Summary The lack of controllable in vitro models that can recapitulate the features of solid tumors such as Ewing’s sarcoma limits our understanding of the tumor initiation and progression and impedes the development of new therapies. Cancer research still relies of the use of simple cell culture, tumor spheroids, and small animals. Tissue-engineered tumor models are now being grown in vitro to mimic the actual tumors in patients. Recently, we have established a new protocol for bioengineering the Ewing’s sarcoma, by infusing tumor cell aggregates into the human bone engineered from the patient’s mesenchymal stem cells. The bone niche allows crosstalk between the tumor cells, osteoblasts and supporting cells of the bone, extracellular matrix and the tissue microenvironment. The bioreactor platform used in these experiments also allows the implementation of physiologically relevant mechanical signals. Here, we describe a method to build an in vitro model of Ewing’s sarcoma that mimics the key properties of the native tumor and provides the tissue context and physical regulatory signals. PMID:27115504

  1. Puzzling and ambivalent roles of malarial infections in cancer development and progression.

    Science.gov (United States)

    Faure, Eric

    2016-12-01

    Scientific evidence strongly suggests that parasites are directly or indirectly associated with carcinogenesis in humans. However, studies have also indicated that parasites or their products might confer resistance to tumour growth. Plasmodium protozoa, the causative agents of malaria, exemplify the ambivalent link between parasites and cancer. Positive relationships between malaria and virus-associated cancers are relatively well-documented; for example, malaria can reactivate the Epstein-Barr Virus, which is the known cause of endemic Burkitt lymphoma. Nevertheless, possible anti-tumour properties of malaria have also been reported and, interestingly, this disease has long been thought to be beneficial to patients suffering from cancers. Current knowledge of the potential pro- and anti-cancer roles of malaria suggests that, contrary to other eukaryotic parasites affecting humans, Plasmodium-related cancers are principally lymphoproliferative disorders and attributable to virus reactivation, whereas, similar to other eukaryotic parasites, the anti-tumour effects of malaria are primarily associated with carcinomas and certain sarcomas. Moreover, malarial infection significantly suppresses murine cancer growth by inducing both innate and specific adaptive anti-tumour responses. This review aims to present an update regarding the ambivalent association between malaria and cancer, and further studies may open future pathways to develop novel strategies for anti-cancer therapies.

  2. Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development.

    Science.gov (United States)

    Takeda, Haruna; Rust, Alistair G; Ward, Jerrold M; Yew, Christopher Chin Kuan; Jenkins, Nancy A; Copeland, Neal G

    2016-04-05

    Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4(+/-) mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers. Similar to human GC, pathway analyses identified WNT, TGF-β, and PI3K-PTEN signaling, ubiquitin-mediated proteolysis, adherens junctions, and RNA degradation in addition to genes involved in chromatin modification and organization as highly deregulated pathways in GC. Comparative oncogenomic filtering of the complete list of SB-identified genes showed that they are highly enriched for genes mutated in human GC and identified many candidate human GC genes. Finally, by comparing our complete list of SB-identified genes against the list of mutated genes identified in five large-scale human GC sequencing studies, we identified LDL receptor-related protein 1B (LRP1B) as a previously unidentified human candidate GC tumor suppressor gene. In LRP1B, 129 mutations were found in 462 human GC samples sequenced, and LRP1B is one of the top 10 most deleted genes identified in a panel of 3,312 human cancers. SB mutagenesis has, thus, helped to catalog the cooperative molecular mechanisms driving SMAD4-induced GC growth and discover genes with potential clinical importance in human GC.

  3. Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells.

    Science.gov (United States)

    Charles, Amelia K; Darbre, Philippa D

    2013-05-01

    The alkyl esters of p-hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF-7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no-observed-effect concentrations (NOEC), lowest-observed-effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF-7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF-7 cells could be increased by combining all five parabens at concentrations down to the 50(th) percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF-7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF-7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually. Copyright © 2013 John Wiley & Sons, Ltd.

  4. Mutations of p53 gene exons 4-8 in human esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Li-Ya Li; Jin-Tian Tang; Li-Qun Jia; Pei-Wen Li

    2005-01-01

    AIM: To characterize the tumor suppressor gene p53 mutations in exon 4, esophageal cancer and adjacent noncancerous tissues.METHODS: We performed p53 (exons 4-8) gene mutation analysis on 24 surgically resected human esophageal cancer specimens by PCR, single-strand conformation polymorphism, and DNA sequencing. RESULTS: p53 gene mutations were detected in 9 of 22 (40.9%) esophageal cancer specimens and 10 of 17 (58.8%) adjacent non-cancerous tissues. Eight of sixteen (50.0%) point mutations detected were G-A transitions and 9 of 18 (50.0%) p53 gene mutations occurred in exon 4 in esophageal cancer specimens. Only 1 of 11 mutations detected was G-A transition and 4 of 11 (36.4%) p53 gene mutations occurred in exon 4 in adjacent non-cancerous tissues.CONCLUSION: Mutation of p53 gene in exon 4 may play an important role in development of esophageal cancer. The observation of p53 gene mutation in adjacent noncancerous tissues suggests that p53 gene mutation may be an early event in esophageal carcinogenesis. Some clinical factors, including age, sex, pre-operation therapy and location of tumors, do not influence p53 gene mutation rates.

  5. A comprehensive review on host genetic susceptibility to human papillomavirus infection and progression to cervical cancer

    Directory of Open Access Journals (Sweden)

    Koushik Chattopadhyay

    2011-01-01

    Full Text Available Cervical cancer is the second most common cancer in women worldwide. This is caused by oncogenic types of human papillomavirus (HPV infection. Although large numbers of young sexually active women get HPV-infected, only a small fraction develop cervical cancer. This points to different co-factors for regression of HPV infection or progression to cervical cancer. Host genetic factors play an important role in the outcome of such complex or multifactor diseases such as cervical cancer and are also known to regulate the rate of disease progression. The aim of this review is to compile the advances in the field of host genetics of cervical cancer. MEDLINE database was searched using the terms, ′HPV′, ′cervical′, ′CIN′, ′polymorphism(s′, ′cervical′ + FNx01the name of the geneFNx01 and ′HPV′ + FNx01the name of the geneFNx01. This review focuses on the major host genes reported to affect the progression to cervical cancer in HPV infected individuals.

  6. Activation of miR-9 by human papillomavirus in cervical cancer.

    Science.gov (United States)

    Liu, Weijun; Gao, Ge; Hu, Xiaoxia; Wang, Yuhui; Schwarz, Julie K; Chen, Jason J; Grigsby, Perry W; Wang, Xiaowei

    2014-11-30

    Cervical cancer is the third most common cancer in women worldwide, leading to about 300,000 deaths each year. Most cervical cancers are caused by human papillomavirus (HPV) infection. However, persistent transcriptional activity of HPV oncogenes, which indicates active roles of HPV in cervical cancer maintenance and progression, has not been well characterized. Using our recently developed assays for comprehensive profiling of HPV E6/E7 transcripts, we have detected transcriptional activities of 10 high-risk HPV strains from 87 of the 101 cervical tumors included in the analysis. These HPV-positive patients had significantly better survival outcome compared with HPV-negative patients, indicating HPV transcriptional activity as a favorable prognostic marker for cervical cancer. Furthermore, we have determined microRNA (miRNA) expression changes that were correlated with tumor HPV status. Our profiling and functional analyses identified miR-9 as the most activated miRNA by HPV E6 in a p53-independent manner. Further target validation and functional studies showed that HPV-induced miR-9 activation led to significantly increased cell motility by downregulating multiple gene targets involved in cell migration. Thus, our work helps to understand the molecular mechanisms as well as identify potential therapeutic targets for cervical cancer and other HPV-induced cancers.

  7. Establishment of a drug sensitivity panel using human lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Matsushita A

    1999-04-01

    Full Text Available We established a drug sensitivity panel consisting of 24 human lung cancer cell lines. Using this panel, we evaluated 26 anti-cancer agents: three alkylators, three platinum compounds, four antimetabolites, one topoisomerase I inhibitor, five topoisomerase II inhibitors, seven antimitotic agents and three tyrosine kinase inhibitors. This panel showed the following: a Drug sensitivity patterns reflected their clinically-established patterns of action. For example, doxorubicin and etoposide were shown to be active against small cell lung cancer cell lines and mitomycin-C and 5-fluorouracil were active against non-small cell lung cancer cell lines, in agreement with clinical data. b Correlation analysis of the mean graphs derived from the logarithm of IC50 values of the drugs gave insight into the mechanism of each drug's action. Thus, two drug combinations with reverse or no correlation, such as the combination of cisplatin and vinorelbine, might be good candidates for the ideal two drug combination in the treatment of lung cancer, as is being confirmed in clinical trials. c Using cluster analysis of the cell lines in the panel with their drug sensitivity patterns, we could classify the cell lines into four groups depending on the drug sensitivity similarity. This classification will be useful to elucidate the cellular mechanism of action and drug resistance. Thus, our drug sensitivity panel will be helpful to explore new drugs or to develop a new combination of anti-cancer agents for the treatment of lung cancer.

  8. EVOLUTION OF KNOWLEDGE DEVELOPMENT IN HUMAN RESUSCITATION

    Directory of Open Access Journals (Sweden)

    O. Zabolotina

    2010-01-01

    Full Text Available Study of human resuscitation development history is the first step in understanding modern approaches to cardiopulmonary resuscitation. A significant increase in survival parameters is driven by accumulation of knowledge, expertise, improvement in resuscitation technologies. Development of cardiopulmonary resuscitation structure, development of recommendations approved for study and practical use, addressing these issues at the state level are accompanied with a significant reduction in mortality both at the hospital and pre-hospital levels. Key words: children, cardiopulmonary resuscitation, development stages, training of pediatricians. (Pediatric Pharmacology. – 2010; 7(3:25-27

  9. Development of Small Molecules Targeting the Wnt Signaling Pathway in Cancer Stem Cells for the Treatment of Colorectal Cancer.

    Science.gov (United States)

    Song, Lele; Li, Yuemin; He, Baoming; Gong, Yuan

    2015-09-01

    Colorectal cancer (CRC) was ranked third in morbidity and mortality in the United States in 2013. Although substantial progress has been made in surgical techniques and postoperative chemotherapy in recent years, the prognosis for colon cancer is still not satisfactory, mainly because of cancer recurrence and metastasis. The latest studies have shown that cancer stem cells (CSCs) play important roles in cancer recurrence and metastasis. Drugs that target CSCs might therefore have great therapeutic potential in prevention of cancer recurrence and metastasis. The wingless-int (Wnt) signaling pathway in CSCs has been suggested to play crucial roles in colorectal carcinogenesis, and has become a popular target for anti-CRC therapy. Dysregulation of the Wnt signaling pathway, mostly by inactivating mutations of the adenomatous polyposis coli tumor suppressor or oncogenic mutations of β-catenin, has been implicated as a key factor in colorectal tumorigenesis. Abnormal increases of β-catenin levels represents a common pathway in Wnt signaling activation and is also observed in other human malignancies. These findings highlight the importance of developing small-molecule drugs that target the Wnt pathway. Herein we provide an overview on the current development of small molecules that target the Wnt pathway in colorectal CSCs and discuss future research directions.

  10. Cadmium-induced cancers in animals and in humans.

    Science.gov (United States)

    Huff, James; Lunn, Ruth M; Waalkes, Michael P; Tomatis, Lorenzo; Infante, Peter F

    2007-01-01

    Discovered in the early 1800s, the use of cadmium and various cadmium salts started to become industrially important near the close of the 19th century, rapidly thereafter began to flourish, yet has diminished more recently. Most cadmium used in the United States is a byproduct from the smelting of zinc, lead, or copper ores, and is used to manufacture batteries. Carcinogenic activity of cadmium was discovered first in animals and only subsequently in humans. Cadmium and cadmium compounds have been classified as known human carcinogens by the International Agency for Research on Cancer and the National Toxicology Program based on epidemiologic studies showing a causal association with lung cancer, and possibly prostate cancer, and studies in experimental animals, demonstrating that cadmium causes tumors at multiple tissue sites, by various routes of exposure, and in several species and strains. Epidemiologic studies published since these evaluations suggest that cadmium is also associated with cancers of the breast, kidney, pancreas, and urinary bladder. The basic metal cationic portion of cadmium is responsible for both toxic and carcinogenic activity, and the mechanism of carcinogenicity appears to be multifactorial. Available information about the carcinogenicity of cadmium and cadmium compounds is reviewed, evaluated, and discussed.

  11. The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

    Directory of Open Access Journals (Sweden)

    F. Xavier Bosch

    2007-01-01

    Full Text Available Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI. The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs. The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC, the adenocarcinomas and the vast majority (i.e. > 95% of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL/Cervical Intraepithelial Neoplasia 3 (CIN3/Carcinoma in situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC for five or more years, smoking, high parity (five or more full term pregnancies and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT and Herpes Simplex Virus type 2 (HSV-2. Women exposed to the Human Immunodeficiency Virus (HIV are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.

  12. Cancer genes hypermethylated in human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Vincenzo Calvanese

    Full Text Available Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation.

  13. How to Find Out in: Human Development.

    Science.gov (United States)

    Kaplan, Doris F.

    This library handbook was designed to aid the student in human development. It lists reference materials basic to general research and gives their location in the Fogler Library at the University of Maine. Materials are listed in five categories: (1) bibliographies; (2) handbooks and guides; (3) yearbooks; (4) congresses; and (5) documents. Some…

  14. The Dictionary for Human Resource Development.

    Science.gov (United States)

    Smith, Douglas H., Comp.

    This dictionary lists and defines approximately 360 words and phrases used in the field of human resource development (HRD). It reflects the opinions and collective expertise of a diverse range of HRD practitioners and faculty. The words and phrases selected were drawn from a search of more than 300 current and recent texts and 10 periodicals in…

  15. Human rights and sustainable spatial development

    NARCIS (Netherlands)

    Pallemaerts, M.

    2009-01-01

    What is the relationship between spatial planning and human rights? Though this question may seem highly theoretical at first glance, closer analysis will reveal that there are in fact a number of ways in which public policies in the area of territorial planning and development and the imperative of

  16. Human Capital Development Policies: Enhancing Employees Satisfaction

    Science.gov (United States)

    Wan, Hooi Lan

    2007-01-01

    Purpose--The aim of this article is to gain insight into some of the human capital development (HCD) policies that enhance employee satisfaction. A salient focus of the study is to assess whether employees in globalised foreign-owned MNCs are likely to be more satisfied with the HCD policies than with the practices employed by locally owned MNCs.…

  17. Human Resource Development and Organizational Values

    Science.gov (United States)

    Hassan, Arif

    2007-01-01

    Purpose: Organizations create mission statements and emphasize core values. Inculcating those values depends on the way employees are treated and nurtured. Therefore, there seems to be a strong relationship between human resource development (HRD) practices and organizational values. The paper aims to empirically examine this relationship.…

  18. How to Find Out in: Human Development.

    Science.gov (United States)

    Kaplan, Doris F.

    This library handbook was designed to aid the student in human development. It lists reference materials basic to general research and gives their location in the Fogler Library at the University of Maine. Materials are listed in five categories: (1) bibliographies; (2) handbooks and guides; (3) yearbooks; (4) congresses; and (5) documents. Some…

  19. A novel human ex vivo model for the analysis of molecular events during lung cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Lang Dagmar S

    2007-06-01

    Full Text Available Abstract Background Non-small cell lung cancer (NSCLC causes most of cancer related deaths in humans and is characterized by poor prognosis regarding efficiency of chemotherapeutical treatment and long-term survival of the patients. The purpose of the present study was the development of a human ex vivo tissue culture model and the analysis of the effects of conventional chemotherapy, which then can serve as a tool to test new chemotherapeutical regimens in NSCLC. Methods In a short-term tissue culture model designated STST (Short-Term Stimulation of Tissues in combination with the novel *HOPE-fixation and paraffin embedding method we examined the responsiveness of 41 human NSCLC tissue specimens to the individual cytotoxic drugs carboplatin, vinorelbine or gemcitabine. Viability was analyzed by LIFE/DEAD assay, TUNEL-staining and colorimetric MTT assay. Expression of Ki-67 protein and of BrdU (bromodeoxyuridine uptake as markers for proliferation and of cleaved (activated effector caspase-3 as indicator of late phase apoptosis were assessed by immunohistochemistry. Transcription of caspase-3 was analyzed by RT-PCR. Flow cytometry was utilized to determine caspase-3 in human cancer cell lines. Results Viability, proliferation and apoptosis of the tissues were moderately affected by cultivation. In human breast cancer, small-cell lung cancer (SCLC and human cell lines (CPC-N, HEK proliferative capacity was clearly reduced by all 3 chemotherapeutic agents in a very similar manner. Cleavage of caspase-3 was induced in the chemo-sensitive types of cancer (breast cancer, SCLC. Drug-induced effects in human NSCLC tissues were less evident than in the chemo-sensitive tumors with more pronounced effects in adenocarcinomas as compared to squamous cell carcinomas. Conclusion Although there was high heterogeneity among the individual tumor tissue responses as expected, we clearly demonstrate specific multiple drug-induced effects simultaneously. Thus, STST

  20. Oncogenic potential of Human Papillomavirus (HPV) and its relation with cervical cancer

    OpenAIRE

    Idrees Muhammad; Khan Khalida; Zahra Amreen; Faridi Rabia

    2011-01-01

    Abstract Human Papillomavirus (HPV) is the most common cause of cervical cancer. Cervical cancer being the second most common cancer after lung cancer, affecting women of different age groups; has a prevalence of about 20% in young sexually active women. Among different types of HPV, HPV16 the major strain causing this cancer and is sexually transmitted had been unnoticed for decades. Keeping in mind the multiple risk factors related with cervical cancer such as early age sexual activities, t...

  1. A multi-scale model for describing cancer-therapeutic transport in the human lung

    OpenAIRE

    Erbertseder, Karin Maria

    2012-01-01

    This thesis proposes a multi-scale model for describing cancer-therapeutic transport in the human lung. The developed multi-scale model represents flow, transport and reaction processes: in the pulmonary macrocirculation on the organ scale, in the capillary bed around an alveolus, in the surrounding pulmonary tissue and in the tumor on the tissue scale, and in the tumor cell population and in the single cancer cells on the cells scale. The model concept is specialized for an alveolar cell car...

  2. Nanoparticle Albumin Bound Paclitaxel in the Treatment of Human Cancer: Nanodelivery Reaches Prime-Time?

    Directory of Open Access Journals (Sweden)

    Iole Cucinotto

    2013-01-01

    Full Text Available Nanoparticle albumin bound paclitaxel (nab-paclitaxel represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment. This is the first clinical demonstration of major activity of nanotechnologically modified drugs in the treatment of human neoplasms.

  3. Nanoparticle Albumin Bound Paclitaxel in the Treatment of Human Cancer: Nanodelivery Reaches Prime-Time?

    Science.gov (United States)

    Cucinotto, Iole; Fiorillo, Lucia; Gualtieri, Simona; Arbitrio, Mariamena; Ciliberto, Domenico; Staropoli, Nicoletta; Grimaldi, Anna; Luce, Amalia; Tassone, Pierfrancesco; Caraglia, Michele; Tagliaferri, Pierosandro

    2013-01-01

    Nanoparticle albumin bound paclitaxel (nab-paclitaxel) represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment. This is the first clinical demonstration of major activity of nanotechnologically modified drugs in the treatment of human neoplasms. PMID:23738077

  4. Development of Human System Integration at NASA

    Science.gov (United States)

    Whitmore, Mihriban; McGuire, Kerry; Thompson, Shelby; Vos, Gordon

    2012-01-01

    Human Systems Integration seeks to design systems around the capabilities and limitations of the humans which use and interact with the system, ensuring greater efficiency of use, reduced error rates, and less rework in the design, manufacturing and operational deployment of hardware and software. One of the primary goals of HSI is to get the human factors practitioner involved early in the design process. In doing so, the aim is to reduce future budget costs and resources in redesign and training. By the preliminary design phase of a project nearly 80% of the total cost of the project is locked in. Potential design changes recommended by evaluations past this point will have little effect due to lack of funding or a huge cost in terms of resources to make changes. Three key concepts define an effective HSI program. First, systems are comprised of hardware, software, and the human, all of which operate within an environment. Too often, engineers and developers fail to consider the human capacity or requirements as part of the system. This leads to poor task allocation within the system. To promote ideal task allocation, it is critical that the human element be considered early in system development. Poor design, or designs that do not adequately consider the human component, could negatively affect physical or mental performance, as well as, social behavior. Second, successful HSI depends upon integration and collaboration of all the domains that represent acquisition efforts. Too often, these domains exist as independent disciplines due to the location of expertise within the service structure. Proper implementation of HSI through participation would help to integrate these domains and disciplines to leverage and apply their interdependencies to attain an optimal design. Via this process domain interests can be integrated to perform effective HSI through trade-offs and collaboration. This provides a common basis upon which to make knowledgeable decisions. Finally

  5. INTERDEPENDENCE BETWEEN SUSTAINABLE DEVELOPMENT AND HUMAN HEALTH

    Directory of Open Access Journals (Sweden)

    Dorina MOCUTA

    2013-01-01

    Full Text Available Sustainable development in Romania can be achieved only through consensus orchestrated prioritizing people's attitudes and values. In order to achieve a maximum performance, cultural change must precede structural and functional changes, such an approach leading to a lasting transformation. Cultural change is not about social traditions, history, language, art, etc.., But those on the behavior, mentality, attitude towards work, economy and society. Sustainable development have to mean quality and achieve only limited natural capital, social and anthropogenic own or attracted. A drawing resources must be addressed by cost and their global rarity. Sustainable development for Romania, represents the effective management of resources in the national competitiveness and national foreign goods and services. Human health suppliers, health organizations that offer health services and those who need these services, meet on a market, called health services market, whose mechanism has features different from the other markets, not only from the point of view of the two forces, demand and supply, but also from the third party who pays. In the context of globalization, human development, defined as a process of people’s expanding possibilities to choose, cannot exist without an appropriate health. People often make choices in the economic, social and political fields, situated in the centre of development policies. From the human health perspective, attention is aimed at quality of the economic development, and not quantity, in three critical domains: expectation and quality of life, educational level and access to all the necessary economic resources in order to lead a decent life.

  6. Occurrence of BK Virus and Human Papilloma Virus in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Adrian Jarzyński

    2017-09-01

    Developing colorectal cancer can show no symptoms, even for many years. This is why it is so important to become familiar with as many etiological factors as possible. The development of many human neoplasms is often initiated by exposure to infectious agents – such as bacterial or viral infections. Similar to the human papillomavirus, the BK virus was detected in clinical specimens. It seems that HPV and BKV infections can contribute to the neoplastic process, which requires detailed studies on a larger group of patients.

  7. EMT is the dominant program in human colon cancer

    Directory of Open Access Journals (Sweden)

    Tollenaar Rob AEM

    2011-01-01

    Full Text Available Abstract Background Colon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging. Methods We performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1 of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence. Results Here we report that the most dominant pattern of intrinsic gene expression in colon cancer (PC1 was tightly correlated (Pearson R = 0.92, P -135 with the EMT signature-- both in gene identity and directionality. In a global micro-RNA screen, we further identified the most anti-correlated microRNA with PC1 as MiR200, known to regulate EMT. Conclusions These data demonstrate that the biology underpinning the native, molecular classification of human colon cancer--previously thought to be highly heterogeneous-- was clarified through the lens of comprehensive transcriptome analysis.

  8. Analyzing the regulation of metabolic pathways in human breast cancer

    Directory of Open Access Journals (Sweden)

    Schramm Gunnar

    2010-09-01

    Full Text Available Abstract Background Tumor therapy mainly attacks the metabolism to interfere the tumor's anabolism and signaling of proliferative second messengers. However, the metabolic demands of different cancers are very heterogeneous and depend on their origin of tissue, age, gender and other clinical parameters. We investigated tumor specific regulation in the metabolism of breast cancer. Methods For this, we mapped gene expression data from microarrays onto the corresponding enzymes and their metabolic reaction network. We used Haar Wavelet transforms on optimally arranged grid representations of metabolic pathways as a pattern recognition method to detect orchestrated regulation of neighboring enzymes in the network. Significant combined expression patterns were used to select metabolic pathways showing shifted regulation of the aggressive tumors. Results Besides up-regulation for energy production and nucleotide anabolism, we found an interesting cellular switch in the interplay of biosynthesis of steroids and bile acids. The biosynthesis of steroids was up-regulated for estrogen synthesis which is needed for proliferative signaling in breast cancer. In turn, the decomposition of steroid precursors was blocked by down-regulation of the bile acid pathway. Conclusion We applied an intelligent pattern recognition method for analyzing the regulation of metabolism and elucidated substantial regulation of human breast cancer at the interplay of cholesterol biosynthesis and bile acid metabolism pointing to specific breast cancer treatment.

  9. Identification of differentially expressed circular RNAs in human colorectal cancer.

    Science.gov (United States)

    Zhang, Peili; Zuo, Zhigui; Shang, Wenjing; Wu, Aihua; Bi, Ruichun; Wu, Jianbo; Li, Shaotang; Sun, Xuecheng; Jiang, Lei

    2017-03-01

    Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.

  10. Integrated proteomic analysis of human cancer cells and plasma from tumor bearing mice for ovarian cancer biomarker discovery.

    Directory of Open Access Journals (Sweden)

    Sharon J Pitteri

    Full Text Available The complexity of the human plasma proteome represents a substantial challenge for biomarker discovery. Proteomic analysis of genetically engineered mouse models of cancer and isolated cancer cells and cell lines provide alternative methods for identification of potential cancer markers that would be detectable in human blood using sensitive assays. The goal of this work is to evaluate the utility of an integrative strategy using these two approaches for biomarker discovery.We investigated a strategy that combined quantitative plasma proteomics of an ovarian cancer mouse model with analysis of proteins secreted or shed by human ovarian cancer cells. Of 106 plasma proteins identified with increased levels in tumor bearing mice, 58 were also secreted or shed from ovarian cancer cells. The remainder consisted primarily of host-response proteins. Of 25 proteins identified in the study that were assayed, 8 mostly secreted proteins common to mouse plasma and human cancer cells were significantly upregulated in a set of plasmas from ovarian cancer patients. Five of the eight proteins were confirmed to be upregulated in a second independent set of ovarian cancer plasmas, including in early stage disease.Integrated proteomic analysis of cancer mouse models and human cancer cell populations provides an effective approach to identify potential circulating protein biomarkers.

  11. Left behind: cancer disparities in the developed world.

    Science.gov (United States)

    Dixit, Niharika; Crawford, Gregory B; Lemonde, Manon; Rittenberg, Cynthia N; Fernández-Ortega, Paz

    2016-08-01

    Huge advances have been made in cancer treatments over recent decades; however, significant disparities still exist in the developed world on the basis of race, socioeconomic status, education level, geographical location, and immigration status and in the United States, insurance status. Cancer disparities persist in the continuum of cancer care from risk factors, screening, diagnosis, treatment, survivorship, and end-of-life care. The causes of disparities are complex and multifactorial. The MASCC (Multinational Association of Supportive Care in Cancer) Education Study Group would like to propose a framework of cancer disparities from a social perspective utilizing "social determinants of health" as delineated by the World Health Organization and highlight an unmet need for research and policy innovations to address cancer disparities in developed world.

  12. Molecular Recognition of Human Liver Cancer Cells Using DNA Aptamers Generated via Cell-SELEX.

    Directory of Open Access Journals (Sweden)

    Jiehua Xu

    Full Text Available Most clinical cases of liver cancer cannot be diagnosed until they have evolved to an advanced stage, thus resulting in high mortality. It is well recognized that the implementation of early detection methods and the development of targeted therapies for liver cancer are essential to reducing the high mortality rates associated with this disease. To achieve these goals, molecular probes capable of recognizing liver cancer cell-specific targets are needed. Here we describe a panel of aptamers able to distinguish hepatocarcinoma from normal liver cells. The aptamers, which were selected by cell-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment, have Kd values in the range of 64-349 nM toward the target human hepatoma cell HepG2, and also recognize ovarian cancer cells and lung adenocarcinoma. The proteinase treatment experiment indicated that all aptamers could recognize target HepG2 cells through surface proteins. This outcome suggested that these aptamers could be used as potential probes for further research in cancer studies, such as developing early detection assays, targeted therapies, and imaging agents, as well as for the investigation of common membrane proteins in these distinguishable cancers.

  13. Echinacoside Induces Apoptosis in Human SW480 Colorectal Cancer Cells by Induction of Oxidative DNA Damages

    Directory of Open Access Journals (Sweden)

    Liwei Dong

    2015-06-01

    Full Text Available Echinacoside is a natural compound with potent reactive oxygen species (ROS-scavenging and anti-oxidative bioactivities, which protect cells from oxidative damages. As cancer cells are often under intense oxidative stress, we therefore tested if Echinacoside treatment would promote cancer development. Surprisingly, we found that Echinacoside significantly inhibited the growth and proliferation of a panel of cancer cell lines. Treatment of the human SW480 cancer cells with Echinacoside resulted in marked apoptosis and cell cycle arrest, together with a significant increase in active caspase 3 and cleaved PARP, and upregulation of the G1/S-CDK blocker CDKN1B (p21. Interestingly, immunocytochemistry examination of drug-treated cancer cells revealed that Echinacoside caused a significant increase of intracellular oxidized guanine, 8-oxoG, and dramatic upregulation of the double-strand DNA break (DSB-binding protein 53BP1, suggesting that Echinacoside induced cell cycle arrest and apoptosis in SW480 cancer cells via induction of oxidative DNA damages. These results establish Echinacoside as a novel chemical scaffold for development of anticancer drugs.

  14. Molecular Recognition of Human Liver Cancer Cells Using DNA Aptamers Generated via Cell-SELEX.

    Science.gov (United States)

    Xu, Jiehua; Teng, I-Ting; Zhang, Liqin; Delgado, Stefanie; Champanhac, Carole; Cansiz, Sena; Wu, Cuichen; Shan, Hong; Tan, Weihong

    2015-01-01

    Most clinical cases of liver cancer cannot be diagnosed until they have evolved to an advanced stage, thus resulting in high mortality. It is well recognized that the implementation of early detection methods and the development of targeted therapies for liver cancer are essential to reducing the high mortality rates associated with this disease. To achieve these goals, molecular probes capable of recognizing liver cancer cell-specific targets are needed. Here we describe a panel of aptamers able to distinguish hepatocarcinoma from normal liver cells. The aptamers, which were selected by cell-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment), have Kd values in the range of 64-349 nM toward the target human hepatoma cell HepG2, and also recognize ovarian cancer cells and lung adenocarcinoma. The proteinase treatment experiment indicated that all aptamers could recognize target HepG2 cells through surface proteins. This outcome suggested that these aptamers could be used as potential probes for further research in cancer studies, such as developing early detection assays, targeted therapies, and imaging agents, as well as for the investigation of common membrane proteins in these distinguishable cancers.

  15. Imaging Proteolysis by Living Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mansoureh Sameni

    2000-01-01

    Full Text Available Malignant progression is accompanied by degradation of extracellular matrix proteins. Here we describe a novel confocal assay in which we can observe proteolysis by living human breast cancer cells (BT20 and BT549 through the use of quenchedfluorescent protein substrates. Degradation thus was imaged, by confocal optical sectioning, as an accumulation of fluorescent products. With the BT20 cells, fluorescence was localized to pericellular focal areas that coincide with pits in the underlying matrix. In contrast, fluorescence was localized to intracellular vesicles in the BT549 cells, vesicles that also label for lysosomal markers. Neither intracellular nor pericellular fluorescence was observed in the BT549 cells in the presence of cytochalasin B, suggesting that degradation occurred intracellularly and was dependent on endocytic uptake of substrate. In the presence of a cathepsin 13-selective cysteine protease inhibitor, intracellular fluorescence was decreased ~90% and pericellular fluorescence decreased 67% to 96%, depending on the protein substrate. Matrix metallo protease inhibitors reduced pericellular fluorescence ~50%, i.e., comparably to a serine and a broad spectrum cysteine protease inhibitor. Our results suggest that: 1 a proteolytic cascade participates in pericellular digestion of matrix proteins by living human breast cancer cells, and 2 the cysteine protease cathepsin B participates in both pericellular and intracellular digestion of matrix proteins by living human breast cancer cells.

  16. Exosomes in development, metastasis and drug resistance of breast cancer.

    Science.gov (United States)

    Yu, Dan-dan; Wu, Ying; Shen, Hong-yu; Lv, Meng-meng; Chen, Wei-xian; Zhang, Xiao-hui; Zhong, Shan-liang; Tang, Jin-hai; Zhao, Jian-hua

    2015-08-01

    Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system.

  17. Myricetin Induces Apoptosis of Human Anaplastic Thyroid Cancer Cells via Mitochondria Dysfunction.

    Science.gov (United States)

    Jo, Sunhyo; Ha, Tae Kwun; Han, Sang-Hun; Kim, Mi Eun; Jung, Inae; Lee, Hee-Woo; Bae, Sung Kwon; Lee, Jun Sik

    2017-04-01

    Thyroid cancer is the most common endocrine malignancy, with an increasing incidence worldwide. Most thyroid cancers are well differentiated and have a favorable outcome. However, undifferentiated thyroid cancers are one of the most lethal human malignancies. Anaplastic thyroid cancer (ATC) accounts for 2% of all thyroid cancers, and its median survival rate is low. ATC is responsible for more than one-third of thyroid cancer-related deaths. Myricetin is a flavonol compound found in walnuts, herbs, and various berries and is known to induce apoptotic death of various types of cancer cells. However, an anticancer effect of myricetin against human anaplastic thyroid cancer (HATCs) cells has not been demonstrated. In the present study, the anticancer effects and mechanism of action of myricetin were examined using SNU-80 HATC cells. SNU-80 HATC cells were treated with various concentrations of myricetin and compared with untreated controls. Myricetin significantly reduced HATC cell proliferation, by approximately 70%. A substantial proportion of dead cells exhibited arrest in the sub-G1 phase. Myricetin also exhibited cytotoxicity and induced DNA condensation in SNU-80 HATC cells in a dose-dependent manner. The mechanism of myricetin-induced cell death involved an increase in the activation of caspase cascades and the Bax:Bcl-2 ratio at a concentration of 100 μM. Myricetin also induced the release of apoptosis-inducing factor (AIF) from mitochondria into the cytosol and altered the mitochondrial membrane potential. Our results indicate that myricetin is a potent inducer of HATC cell death and may thus prove useful in the development of therapeutic agents for HATC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Circulating interleukin-8 levels explain breast cancer osteolysis in mice and humans.

    Science.gov (United States)

    Kamalakar, Archana; Bendre, Manali S; Washam, Charity L; Fowler, Tristan W; Carver, Adam; Dilley, Joshua D; Bracey, John W; Akel, Nisreen S; Margulies, Aaron G; Skinner, Robert A; Swain, Frances L; Hogue, William R; Montgomery, Corey O; Lahiji, Parshawn; Maher, Jacqueline J; Leitzel, Kim E; Ali, Suhail M; Lipton, Alan; Nicholas, Richard W; Gaddy, Dana; Suva, Larry J

    2014-04-01

    Skeletal metastases of breast cancer and subsequent osteolysis connote a dramatic change in the prognosis for the patient and significantly increase the morbidity associated with disease. The cytokine interleukin 8 (IL-8/CXCL8) is able to directly stimulate osteoclastogenesis and bone resorption in mouse models of breast cancer bone metastasis. In this study, we determined whether circulating levels of IL-8 were associated with increased bone resorption and breast cancer bone metastasis in patients and investigated IL-8 action in vitro and in vivo in mice. Using breast cancer patient plasma (36 patients), we identified significantly elevated IL-8 levels in bone metastasis patients compared with patients lacking bone metastasis (pIL-8 and increased bone resorption (pIL-8 expression. In vitro, human MDA-MB-231 and MDA-MET breast cancer cell lines secrete two distinct IL-8 isoforms, both of which were found to stimulate osteoclastogenesis. However, the more osteolytic MDA-MET-derived full length IL-8(1-77) had significantly higher potency than the non-osteolytic MDA-MB-231-derived IL-8(6-77), via the CXCR1 receptor. MDA-MET breast cancer cells were injected into the tibia of nude mice and 7days later treated daily with a neutralizing IL-8 monoclonal antibody. All tumor-injected mice receiving no antibody developed large osteolytic bone tumors, whereas 83% of the IL-8 antibody-treated mice had no evidence of tumor at the end of 28days and had significantly increased survival. The pro-osteoclastogenic activity of IL-8 in vivo was confirmed when transgenic mice expressing human IL-8 were examined and found to have a profound osteopenic phenotype, with elevated bone resorption and inherently low bone mass. Collectively, these data suggest that IL-8 plays an important role in breast cancer osteolysis and that anti-IL-8 therapy may be useful in the treatment of the skeletal related events associated with breast cancer.

  19. BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Liu Jun

    2004-07-01

    Full Text Available Abstract Background BAK (Bcl-2 homologous antagonist/killer is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in