Sample records for human cancer estimation

  1. Human Viruses and Cancer

    Directory of Open Access Journals (Sweden)

    Abigail Morales-Sánchez


    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.

  2. Estimation of Nickel in Different Smokeless Tobacco Products and Their Impact on Human Health of Oral Cancer Patients. (United States)

    Arain, Sadaf S; Kazi, Tasneem G; Afridi, Hassan I; Talpur, Farah N; Kazi, Atif G; Brahman, Kapil D; Naeemullah; Arain, Mariam S; Sahito, Oan M


    It has been extensively investigated that the chewing of smokeless tobacco (SLT) products may enhance the inflammation of the oral cavity. The aim of the present study is to evaluate the relationship between nickel (Ni) exposure via different SLT products with oral cancer (different sites) incidence in the population of Sindh, Pakistan. The different brands of SLT products (mainpuri, gutkha, and moist snuff) commonly consumed by the studied population were analyzed for Ni contents. The biological samples of oral cancer patients and noncancerous control subjects of both genders, who have or have not consumed SLT products, were collected. The concentration of Ni in biological samples and SLT products were measured by electrothermal atomic absorption spectrophotometer after microwave-assisted acid digestion. The validity and accuracy of the methodology were checked by using certified reference materials. The results of this study showed that the Ni level was significantly higher in scalp hair and blood samples of oral cancer patients compared to controls (P < 0.01). The study suggested that exposure of Ni as a result of chewing different SLT products may be synergistic with risk factors associated with oral cancer.

  3. Human papillomaviruses and cancer. (United States)

    Haedicke, Juliane; Iftner, Thomas


    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.

  4. Serglycin in human cancers

    Institute of Scientific and Technical Information of China (English)

    Xin-Jian Li; Chao-Nan Qian


    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.

  5. Early estimates of SEER cancer incidence, 2014. (United States)

    Lewis, Denise Riedel; Chen, Huann-Sheng; Cockburn, Myles G; Wu, Xiao-Cheng; Stroup, Antoinette M; Midthune, Douglas N; Zou, Zhaohui; Krapcho, Martin F; Miller, Daniel G; Feuer, Eric J


    Cancer incidence rates and trends for cases diagnosed through 2014 using data reported to the Surveillance, Epidemiology, and End Results (SEER) program in February 2016 and a validation of rates and trends for cases diagnosed through 2013 and submitted in February 2015 using the November 2015 submission are reported. New cancer sites include the pancreas, kidney and renal pelvis, corpus and uterus, and childhood cancer sites for ages birth to 19 years inclusive. A new reporting delay model is presented for these estimates for more consistent results with the model used for the usual November SEER submissions, adjusting for the large case undercount in the February submission. Joinpoint regression methodology was used to assess trends. Delay-adjusted rates and trends were checked for validity between the February 2016 and November 2016 submissions. Validation revealed that the delay model provides similar estimates of eventual counts using either February or November submission data. Trends declined through 2014 for prostate and colon and rectum cancer for males and females, male and female lung cancer, and cervical cancer. Thyroid cancer and liver and intrahepatic bile duct cancer increased. Pancreas (male and female) and corpus and uterus cancer demonstrated a modest increase. Slight increases occurred for male kidney and renal pelvis, and for all childhood cancer sites for ages birth to 19 years. Evaluating early cancer data submissions, adjusted for reporting delay, produces timely and valid incidence rates and trends. The results of the current study support using delay-adjusted February submission data for valid incidence rate and trend estimates over several data cycles. Cancer 2017;123:2524-34. © 2017 American Cancer Society. © 2017 American Cancer Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

  6. Estimating the Risks of Breast Cancer Radiotherapy

    DEFF Research Database (Denmark)

    Taylor, Carolyn; Correa, Candace; Duane, Frances K


    and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality.......06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers. Conclusion For long-term smokers......Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature...

  7. Colon cancer associated transcripts in human cancers. (United States)

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


    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.

  8. Report: Human cancer genetics

    Institute of Scientific and Technical Information of China (English)

    LI Marilyn; ALBERTSON Donna


    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.

  9. Human cancer genetics*



    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.

  10. Human walking estimation with radar

    NARCIS (Netherlands)

    Dorp, Ph. van; Groen, F.C.A.


    Radar can be used to observe humans that are obscured by objects such as walls. These humans cannot be visually observed. The radar measurements are used to animate an obscured human in virtual reality. This requires detailed information about the motion. The radar measurements give detailed informa

  11. Human walking estimation with radar

    NARCIS (Netherlands)

    Dorp, Ph. van; Groen, F.C.A.


    Radar can be used to observe humans that are obscured by objects such as walls. These humans cannot be visually observed. The radar measurements are used to animate an obscured human in virtual reality. This requires detailed information about the motion. The radar measurements give detailed

  12. Estimation of Cancer Burden Attributable to Infection in Asia

    Directory of Open Access Journals (Sweden)

    He Huang


    Full Text Available Background: Some infectious agents have been shown to be human carcinogens. The current study focused on estimation of cancer burden attributable to infection in different regions of Asia. Methods: By systematically reviewing previous studies of the infection prevalence data of 13 countries in Asia and relative risks of specific cancers, we calculated the population attributable fraction of carcinogenic infections. Using data from GLOBOCAN 2012, the overall country-specific and gender-specific number of new cancer cases and deaths resulting from infection were estimated. Results: Across 13 principal Asian countries, the average prevalence and range was 6.6% (0.5% in Japanese women to 15.0% in Vietnamese men for hepatitis B virus (HBV, 2.6% (0.3% in Iran to 5.1% in Saudi Arabia for hepatitis C virus (HCV, 7.9% (2.8% in Pakistan to 17.7% in China for human papillomavirus (HPV, and 61.8% (12.8% in Indonesia to 91.7% in Bangladesh for Helicobacter pylori (HP. The estimated total number of cancer cases and deaths caused by infection in these 13 countries were 1 212 026 (19.6% of all new cancer cases and 908 549 (22.0% of all deaths from cancer. The fractions of cancer incidence attributable to infection were 19.7% and 19.5% in men and women, respectively. The percentages of cancer deaths attributable to infection were 21.9% and 22.1% in men and women, respectively. Among the main infectious agents, HP was responsible for 31.5% of infection-related cancer cases and 32.8% of infection-related cancer deaths, followed by HBV (28.6% of new cases and 23.8% of deaths, HPV (22.0% of new cases and 27.3% of deaths, and HCV (12.2% of new cases and 10.6% of deaths. Conclusions: Approximately one quarter of all cancer cases and deaths were infection-associated in Asia, which could be effectively prevented if appropriate long-term controls of infectious agents were applied.


    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...

  14. Interactive inverse kinematics for human motion estimation

    DEFF Research Database (Denmark)

    Engell-Nørregård, Morten Pol; Hauberg, Søren; Lapuyade, Jerome


    We present an application of a fast interactive inverse kinematics method as a dimensionality reduction for monocular human motion estimation. The inverse kinematics solver deals efficiently and robustly with box constraints and does not suffer from shaking artifacts. The presented motion...... estimation system uses a single camera to estimate the motion of a human. The results show that inverse kinematics can significantly speed up the estimation process, while retaining a quality comparable to a full pose motion estimation system. Our novelty lies primarily in use of inverse kinematics...... to significantly speed up the particle filtering. It should be stressed that the observation part of the system has not been our focus, and as such is described only from a sense of completeness. With our approach it is possible to construct a robust and computationally efficient system for human motion estimation....

  15. Oncogenes and human cancer

    NARCIS (Netherlands)

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


    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.

  16. Assessing global transitions in human development and colorectal cancer incidence. (United States)

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


    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.

  17. Human Posture Estimation using Visual Information

    Institute of Scientific and Technical Information of China (English)

    Jiayu XU


    Human-robot cooperation is one of the central research issues in robotics.Al kinds of sensors wil be used since the robot should understand human’s intention.This article wil focus on the human posture estimation by using Microsoft Kinect.The visual Information from Kinect can be acquired and used to extract the human skeletal information and further,calcu-late the human posture.The experiment results have been compared with a Qualisys system,which has been proved quite precisely.

  18. Human papillomavirus and gastrointestinal cancer: A review (United States)

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


    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

  19. Viruses and human cancer

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  20. National estimates of cancer prevalence in China, 2011. (United States)

    Zheng, Rongshou; Zeng, Hongmei; Zhang, Siwei; Chen, Tianhui; Chen, Wanqing


    Little is known about the nationwide cancer prevalence in China. This paper aimed at assessing the 5-year cancer prevalence in China for 25 major cancers. Incidence data were estimated using data from 177 cancer registries and covering 175 million populations. Survival data were from 17 cancer registries diagnosed during 2003-2005 and followed up until 31 December 2010. Standardized protocols for data collection and validation were adopted. Cancer prevalence for 25 major sites was estimated from year-specific incidence rates and survival probabilities according to standardized formula. The estimated 5-year prevalence for all cancers combined in 2011 in China was 7.49 million (3.68 million for men and 3.81 million for women). Cancer prevalence estimates for 5 years varied by cancer sites, ranging from 11,900 for testicular cancer to 1.02 million for women breast cancer. Those most prevalent five cancers (breast, colorectal, lung, stomach and esophageal cancers) covered 56.1% of cancer burden in China. The proportion for the 5-year prevalence was higher in urban areas compared to rural areas (666 per 100,000 versus 440 per 100,000), while cancer prevalence estimates were higher for women compared to men, with the men/women ratio of 5-year cancer prevalence reaching 0.96. This paper provides the first systematic analysis on 5-year cancer prevalence for 25 major cancers in China in 2011, which may serve as a baseline for assessment of the overall effectiveness of cancer health care. The huge number of cancer survivors requires resource allocation to improve health care programs and primary prevention, especially in rural areas. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Human papillomavirus and cervical cancer. (United States)

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


    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.

  2. Estimating 3D Human Shapes from Measurements

    CERN Document Server

    Wuhrer, Stefanie


    We describe a solution to the problem of estimating 3D human shapes (either faces or full body shapes) based on a set of anthropometric measurements. We use statistical learning to model the relationship between the shape and a set of measurements. We learn the relationship using a database of human shapes. When predicting a shape, our approach finds an initial solution using a variant of feature analysis and refines the solution to fit the measurements using non-linear optimization. This way, we can predict likely human shapes with local variations that are outside the shape space spanned by the database used for learning.

  3. Septin mutations in human cancers

    Directory of Open Access Journals (Sweden)

    Elias T Spiliotis


    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.

  4. DBGC: A Database of Human Gastric Cancer. (United States)

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


    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

  5. Prevalence of human papillomavirus in epithelial ovarian cancer tissue. A meta-analysis of observational studies

    DEFF Research Database (Denmark)

    Svahn, Malene F; Faber, Mette Tuxen; Christensen, Jane


    The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue.......The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue....

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

    Directory of Open Access Journals (Sweden)

    Nyariaro Kelvin Momanyi


    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

  7. Human motion estimation from a single view (United States)

    Sun, Yi; An, Hongjie; Cui, Chengyi


    Human motion analysis is receiving increasing attention from biomedical image processing researchers. In order to reflect the human motion in reality, the body's structure is recovered using its 2D model. This paper proposes a practical system which tracks human motion automatically. The major processing units are as follows: 1) coarse matching between real image and 2D model, 2) fine matching between real image and 2D model, 3) the formation of body structure from 2D model sequence. We first segment a human body from stationary background. Then prior posture database is established, and the primary posture in image sequence can be estimated coarsely by comparing posture in database and real image series. After this, in the precise adjustment stage, precise matching can be obtained by the criterion of region overlay between image sequence and 2D model. Finally, structure of human body is recovered by adjusting parameters of 2D model series, in the above process, the sizes of the body parts are measured manually from one of the picture of real images. Finally, 2D model can be established, and skeleton or frame representation of human body movement is given. In the end of this paper, future directions are suggested for further improvement.

  8. The global cancer burden and human development: A review. (United States)

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


    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.

  9. Correlation dimension estimates of human postural sway. (United States)

    Gurses, Senih; Celik, Huseyin


    Human postural sway during quiet standing demonstrates a complex structured dynamics, which has been studied by applying numerous methods, such as linear system identification methods, stochastic analysis, and nonlinear system dynamics tools. Although each of the methods applied revealed some particular features of the sway data none of them have succeeded to present a global picture of the quiet stance dynamics, which probably has both stochastic and deterministic properties. In this study we have started applying ergodic theory of dynamical systems to explore statistical characteristic of the sway dynamics observed in successive trials of a subject, different subjects in an age group, and finally different age groups constituted by children, adults, and elderly subjects. Five successive 180-s long trials were performed by each of 28 subjects in four age groups at quiet stance with eyes open. Stationary and ergodic signal characteristics of five successive center of pressure time series collected from a subject in antero-posterior direction (CoPx) were examined. 97% of the trials were found to be stationary by applying Run Test while children and elderly groups demonstrated significant nonstationary behavior. On the other hand 13 out of 24 subjects were found to be nonergodic. We expected to observe differences in complexity of CoPx dynamics due to aging (Farmer, Ott, & Yorke, 1983). However linear metrics such as standard deviation and Fourier spectra of CoPx signals did not show differences due to the age groups. Correlation dimension (Dk) estimates of stationary CoPx signals being an invariant measure of nonlinear system dynamics were computed by using the average displacement method (Eckmann & Ruelle, 1985). Postural dynamics was expanded in m-dimensional space through CoPx signal by introducing optimum time delays, τcritical. 112 out of 136 stationary CoPx signals for 24 stationary subjects converged to Dk estimates. Average of Dk estimates for children and

  10. HCSD: the human cancer secretome database (United States)

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


    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: PMID:26078477

  11. Cancer estimation of incidence and survival in Algeria 2014

    Directory of Open Access Journals (Sweden)

    Hamdi Cherif M


    Full Text Available Cancer is one of the major public health problems in Algeria. In the last 25 years, a significant increase in the incidence of the major types of cancers has been observed in both sexes. Moreover, the 5-year survival rate is low for the severe tumors due to a difficulty in access to cancer care and an incomplete health care framework. Cancer Registry of Setif, Algeria, has been recording cancer incidence, mortality, and survival since 1986 in collaboration with International Agency for Research on Cancer (IARC of Lyon. Cancer Registry of Setif is being a source of information for cancer planning and corresponding surveillance in the National Cancer Plan 2015-2019, starting in January 2015. Data is recorded by means of CanReg 5 software. This software is developed and provided by the International Agency for Research on Cancer (IARC of Lyon. It is designed specifically for cancer registration, and standardized to capture, control, and process the data. Estimation of cancer incidence in Algeria and survival rates are very important for surveillance, control, and planning of care. In men the incidence of lung, colorectal, bladder, prostate, and laryngeal cancers has significantly and steadily increased in the last decade. In women, the incidence of breast, colorectal, thyroid, and lung cancers has also increased significantly in the same period. Five-year survival rates for cancer of the stomach, colon, rectum, liver, lung, breast, cervix, ovary, and prostate in adults, and childhood leukemia are relatively low compared with other countries. The aim of our study was to estimate incidence and survival by means of Setif cancer registry data.

  12. Human Cancer Models Initiative | Office of Cancer Genomics (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.

  13. Estimation of Cachexia among Cancer Patients Based on Four Definitions



    Objectives. Estimate and compare the proportion of cancer patients with cachexia using different definitions from available clinical data. Methods. Electronic medical records were examined to estimate the proportion of cancer patients with cachexia using 4 definitions: (1) ICD-9 diagnostic code of 799.4 (cachexia), (2) ICD-9 diagnosis of cachexia, anorexia, abnormal weight loss, or feeding difficulties, (3) prescription for megestrol acetate, oxandrolone, somatropin, or dronabinol, and (4) ≥ ...

  14. Human Body Orientation Estimation using a Committee based Approach

    NARCIS (Netherlands)

    Ichim, M; Tan, R.T.; van der Aa, N.P.; Veltkamp, R.C.


    Human body orientation estimation is useful for analyzing the activities of a single person or a group of people. Estimating body orientation can be subdivided in two tasks: human tracking and orientation estimation. In this paper, the second task of orientation estimation is accomplished by using H

  15. Telomerase activity in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, J.


    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.

  16. [Obesity and cancer in Chile: estimation of population attributable fractions]. (United States)

    Garmendia, María Luisa; Ruiz, Pablo; Uauy, Ricardo


    Obesity is a risk factor for the development of certain types of cancer. To estimate the proportion of cancers potentially attributable to obesity in men and women in Chile based on the calculation of population attributable fractions (PAF %). Cancer sites studied were those where obesity is a known risk factor based on the updated World Cancer Research Fund (WCRF) analysis. Namely, colorectal, endometrium, esophagus, breast, pancreas, kidney and gallbladder cancers were analyzed. Overall and specific PAFs% were calculated for cancer sites and sex from known estimates of relative risk and national prevalence of overweight and obesity. The overall estimates of cancer PAF% for obesity were approximately 20%, without differences between men and women. Highest cancer PAFs% were for endometrial (47%) in women, and esophageal (35%) and pancreatic (31%) in men. The largest sex differences in PAFs% were for gallbladder (higher in women) and colorectal (higher in men). Results are closer to those reported from developed countries (USA and United Kingdom) than those from developing countries (Brasil, China). In Chile about 20% of all cancers could be prevented by obesity prevention and control strategies.

  17. Estimating the Proportion of Childhood Cancer Cases and Costs Attributable to the Environment in California. (United States)

    Nelson, Lauren; Valle, Jhaqueline; King, Galatea; Mills, Paul K; Richardson, Maxwell J; Roberts, Eric M; Smith, Daniel; English, Paul


    To estimate the proportion of cases and costs of the most common cancers among children aged 0 to 14 years (leukemia, lymphoma, and brain or central nervous system tumors) that were attributable to preventable environmental pollution in California in 2013. We conducted a literature review to identify preventable environmental hazards associated with childhood cancer. We combined risk estimates with California-specific exposure prevalence estimates to calculate hazard-specific environmental attributable fractions (EAFs). We combined hazard-specific EAFs to estimate EAFs for each cancer and calculated an overall EAF. Estimated economic costs included annual (indirect and direct medical) and lifetime costs. Hazards associated with childhood cancer risks included tobacco smoke, residential exposures, and parental occupational exposures. Estimated EAFs for leukemia, lymphoma, and brain or central nervous system cancer were 21.3% (range = 11.7%-30.9%), 16.1% (range = 15.0%-17.2%), and 2.0% (range = 1.7%-2.2%), respectively. The combined EAF was 15.1% (range = 9.4%-20.7%), representing $18.6 million (range = $11.6 to $25.5 million) in annual costs and $31 million in lifetime costs. Reducing environmental hazards and exposures in California could substantially reduce the human burden of childhood cancer and result in significant annual and lifetime savings.

  18. Estimated generic prices of cancer medicines deemed cost-ineffective in England: a cost estimation analysis (United States)

    Hill, Andrew; Redd, Christopher; Gotham, Dzintars; Erbacher, Isabelle; Meldrum, Jonathan; Harada, Ryo


    Objectives The aim of this study was to estimate lowest possible treatment costs for four novel cancer drugs, hypothesising that generic manufacturing could significantly reduce treatment costs. Setting This research was carried out in a non-clinical research setting using secondary data. Participants There were no human participants in the study. Four drugs were selected for the study: bortezomib, dasatinib, everolimus and gefitinib. These medications were selected according to their clinical importance, novel pharmaceutical actions and the availability of generic price data. Primary and secondary outcome measures Target costs for treatment were to be generated for each indication for each treatment. The primary outcome measure was the target cost according to a production cost calculation algorithm. The secondary outcome measure was the target cost as the lowest available generic price; this was necessary where export data were not available to generate an estimate from our cost calculation algorithm. Other outcomes included patent expiry dates and total eligible treatment populations. Results Target prices were £411 per cycle for bortezomib, £9 per month for dasatinib, £852 per month for everolimus and £10 per month for gefitinib. Compared with current list prices in England, these target prices would represent reductions of 74–99.6%. Patent expiry dates were bortezomib 2014–22, dasatinib 2020–26, everolimus 2019–25 and gefitinib 2017. The total global eligible treatment population in 1 year is 769 736. Conclusions Our findings demonstrate that affordable drug treatment costs are possible for novel cancer drugs, suggesting that new therapeutic options can be made available to patients and doctors worldwide. Assessing treatment cost estimations alongside cost-effectiveness evaluations is an important area of future research. PMID:28110283

  19. Attributing death to cancer: cause-specific survival estimation.

    Directory of Open Access Journals (Sweden)

    Mathew A


    Full Text Available Cancer survival estimation is an important part of assessing the overall strength of cancer care in a region. Generally, the death of a patient is taken as the end point in estimation of overall survival. When calculating the overall survival, the cause of death is not taken into account. With increasing demand for better survival of cancer patients it is important for clinicians and researchers to know about survival statistics due to disease of interest, i.e. net survival. It is also important to choose the best method for estimating net survival. Increase in the use of computer programmes has made it possible to carry out statistical analysis without guidance from a bio-statistician. This is of prime importance in third- world countries as there are a few trained bio-statisticians to guide clinicians and researchers. The present communication describes current methods used to estimate net survival such as cause-specific survival and relative survival. The limitation of estimation of cause-specific survival particularly in India and the usefulness of relative survival are discussed. The various sources for estimating cancer survival are also discussed. As survival-estimates are to be projected on to the population at large, it becomes important to measure the variation of the estimates, and thus confidence intervals are used. Rothman′s confidence interval gives the most satisfactory result for survival estimate.

  20. Cancer stem cells in human gastrointestinal cancer. (United States)

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


    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 papillomaviruses and skin cancer. (United States)

    Smola, Sigrun


    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.

  2. Cancer Related-Knowledge - Small Area Estimates (United States)

    These model-based estimates are produced using statistical models that combine data from the Health Information National Trends Survey, and auxiliary variables obtained from relevant sources and borrow strength from other areas with similar characteristics.

  3. Optimization of human cancer radiotherapy

    CERN Document Server

    Swan, George W


    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...

  4. Prevalence of Human Papillomavirus in endometrial cancer

    DEFF Research Database (Denmark)

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


    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....

  5. HCSD: the human cancer secretome database

    DEFF Research Database (Denmark)

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


    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...

  6. Estimation of National Colorectal-Cancer Incidence Using Claims Databases

    Directory of Open Access Journals (Sweden)

    C. Quantin


    Full Text Available Background. The aim of the study was to assess the accuracy of the colorectal-cancer incidence estimated from administrative data. Methods. We selected potential incident colorectal-cancer cases in 2004-2005 French administrative data, using two alternative algorithms. The first was based only on diagnostic and procedure codes, whereas the second considered the past history of the patient. Results of both methods were assessed against two corresponding local cancer registries, acting as “gold standards.” We then constructed a multivariable regression model to estimate the corrected total number of incident colorectal-cancer cases from the whole national administrative database. Results. The first algorithm provided an estimated local incidence very close to that given by the regional registries (646 versus 645 incident cases and had good sensitivity and positive predictive values (about 75% for both. The second algorithm overestimated the incidence by about 50% and had a poor positive predictive value of about 60%. The estimation of national incidence obtained by the first algorithm differed from that observed in 14 registries by only 2.34%. Conclusion. This study shows the usefulness of administrative databases for countries with no national cancer registry and suggests a method for correcting the estimates provided by these data.

  7. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model. (United States)

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


    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.

  8. Estimating the economic costs of skin cancer in New South Wales, Australia. (United States)

    Doran, Christopher M; Ling, Rod; Byrnes, Joshua; Crane, Melanie; Searles, Andrew; Perez, Donna; Shakeshaft, Anthony


    Skin cancer is one of the most common cancers in the world. The increased incidence of skin cancer, combined with limited health care resources and tight budgetary conditions, has increased the importance of understanding the economic impact of skin cancer. This research estimates the economic cost of skin cancer in the Australian state of New South Wales. An incidence based approach is used to estimate lifetime costs of skin cancer. Both direct and indirect costs are considered - direct costs include resources associated with the management of skin cancer and indirect costs refer to productivity costs associated with morbidity and premature mortality. Diagnosis of skin cancer was determined according to ICD-10 codes using principal diagnosis. Linked administrative data and regression modelling are used to calculate costs; presented as Australian dollars for the year 2010. The human capital approach is used to value present and future productivity losses. The lifetime cost of the 150,000 incident cases of skin cancer diagnosed in NSW in 2010 is estimated at $536 million ($44,796 per melanoma and $2459 per non-melanoma). Direct costs accounted for 72 % of costs ($10,230 per melanoma and $2336 per non-melanoma) and indirect costs accounted for 28 % of costs ($34,567 per melanoma and $123 per non-melanoma). Direct costs are, on average, higher for females than males with indirect costs, on average, higher for males than females. This research provides new evidence on the economic cost of skin cancer and provides policy makers with information of the potential monetary savings that may arise from efforts to reduce the incidence of skin cancer.

  9. Trends in all-cause five-year mortality after head and neck cancers diagnosed over a period of 33 years. Focus on estimated degree of association with human papillomavirus. (United States)

    Svahn, Malene F; Munk, Christian; Nielsen, Thor S S; von Buchwald, Christian; Frederiksen, Kirsten; Kjaer, Susanne K

    Factors influencing survival after head and neck cancer (HNC) include among others stage, age, and sex. More recently, human papillomavirus (HPV) positivity has been described as a favorable prognostic factor in relation to some HNCs. In this nationwide register-based cohort study of all 20 925 individuals diagnosed with squamous cell carcinoma of the head and neck (HNSCC) in Denmark 1978-2010, we investigate secular trends in all-cause five-year mortality after HNSCC according to the anticipated degree of association with HPV using a Cox proportional hazards model. Furthermore, we examine whether any trend over time differed according to sex, stage, and age at diagnosis. All-cause five-year mortality after HNSCC has decreased over time. The greatest decrease was seen in the last decade (2000-2010) among patients with HNSCC at sites estimated to be strongly associated with HPV, i.e. the base of the tongue and the tonsils, where a 28% decrease per five years (e.g. HRbase of tongue/tonsils=0.72; 95% CI 0.64-0.81) was observed. When examining sex- and age-specific time trends, the decrease in mortality was most pronounced among male patients and patients below 60 years at diagnosis. In contrast, no clear pattern was observed when examining five-year all-cause mortality trends according to stage. All-cause five-year mortality after HNSCC has decreased significantly in Denmark from 1978 to 2010, especially for HNSCCs at sites anticipated to be strongly associated with HPV, possibly due to an increasing proportion of HPV-positive HNSCCs.

  10. Expression of polarity genes in human cancer. (United States)

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


    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.

  11. Antiangiogenic Steroids in Human Cancer Therapy



    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 ...


    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 revie


    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 revie

  14. 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.


    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

  15. 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.


    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


    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

  17. Potential Prognostic Markers for Human Prostate Cancer (United States)


    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

  18. Estimating Human Predictability From Mobile Sensor Data

    DEFF Research Database (Denmark)

    Jensen, Bjørn Sand; Larsen, Jakob Eg; Jensen, Kristian


    Quantification of human behavior is of prime interest in many applications ranging from behavioral science to practical applications like GSM resource planning and context-aware services. As proxies for humans, we apply multiple mobile phone sensors all conveying information about human behavior...

  19. Estimation of health state utilities in breast cancer

    Directory of Open Access Journals (Sweden)

    Kim SH


    Full Text Available Seon-Ha Kim,1 Min-Woo Jo,2 Minsu Ock,2 Hyeon-Jeong Lee,2 Jong-Won Lee3,4 1Department of Nursing, College of Nursing, Dankook University, Cheonan, 2Department of Preventive Medicine, University of Ulsan College of Medicine, Seoul, 3Department of Breast and Endocrine Surgery, Asan Medical Center, Seoul, 4Department of Surgery, University of Ulsan College of Medicine, Seoul, South Korea Purpose: The aim of this study is to determine the utility of breast cancer health states using the standard gamble (SG and visual analog scale (VAS methods in the Korean general population.Materials and methods: Eight hypothetical breast cancer health states were developed based on patient education material and previous publications. Data from 509 individuals from the Korean general population were used to evaluate breast cancer health states using the VAS and the SG methods, which were obtained via computer-assisted personal interviews. Mean utility values were calculated for each human papillomavirus (HPV-related health state.Results: The rank of health states was identical between two valuation methods. SG values were higher than VAS values in all health states. The utility values derived from SG were 0.801 (noninvasive breast cancer with mastectomy and followed by reconstruction, 0.790 (noninvasive breast cancer with mastectomy only, 0.779 (noninvasive breast cancer with breast-conserving surgery and radiation therapy, 0.731 (invasive breast cancer with surgery, radiation therapy, and/or chemotherapy, 0.610 (locally advanced breast cancer with radical mastectomy with radiation therapy, 0.587 (inoperable locally advanced breast cancer, 0.496 (loco-regional recurrent breast cancer, and 0.352 (metastatic breast cancer.Conclusion: Our findings might be useful for economic evaluation of breast cancer screening and interventions in general populations. Keywords: breast neoplasm, Korea, quality-adjusted life years, quality of life

  20. 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

  1. Novel innate cancer killing activity in humans

    Directory of Open Access Journals (Sweden)

    Lovato James


    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.

  2. Estimating Skin Cancer Risk: Evaluating Mobile Computer-Adaptive Testing. (United States)

    Djaja, Ngadiman; Janda, Monika; Olsen, Catherine M; Whiteman, David C; Chien, Tsair-Wei


    Response burden is a major detriment to questionnaire completion rates. Computer adaptive testing may offer advantages over non-adaptive testing, including reduction of numbers of items required for precise measurement. Our aim was to compare the efficiency of non-adaptive (NAT) and computer adaptive testing (CAT) facilitated by Partial Credit Model (PCM)-derived calibration to estimate skin cancer risk. We used a random sample from a population-based Australian cohort study of skin cancer risk (N=43,794). All 30 items of the skin cancer risk scale were calibrated with the Rasch PCM. A total of 1000 cases generated following a normal distribution (mean [SD] 0 [1]) were simulated using three Rasch models with three fixed-item (dichotomous, rating scale, and partial credit) scenarios, respectively. We calculated the comparative efficiency and precision of CAT and NAT (shortening of questionnaire length and the count difference number ratio less than 5% using independent t tests). We found that use of CAT led to smaller person standard error of the estimated measure than NAT, with substantially higher efficiency but no loss of precision, reducing response burden by 48%, 66%, and 66% for dichotomous, Rating Scale Model, and PCM models, respectively. CAT-based administrations of the skin cancer risk scale could substantially reduce participant burden without compromising measurement precision. A mobile computer adaptive test was developed to help people efficiently assess their skin cancer risk.

  3. Estimating cancer risks to adults undergoing body CT examinations. (United States)

    Huda, Walter; He, Wenjun


    The purpose of the study is to estimate cancer risks from the amount of radiation used to perform body computed tomography (CT) examination. The ImPACT CT Patient Dosimetry Calculator was used to compute values of organ doses for adult body CT examinations. The radiation used to perform each examination was quantified by the dose-length product (DLP). Patient organ doses were converted into corresponding age and sex dependent cancer risks using data from BEIR VII. Results are presented for cancer risks per unit DLP and unit effective dose for 11 sensitive organs, as well as estimates of the contribution from 'other organs'. For patients who differ from a standard sized adult, correction factors based on the patient weight and antero-posterior dimension are provided to adjust organ doses and the corresponding risks. At constant incident radiation intensity, for CT examinations that include the chest, risks for females are markedly higher than those for males, whereas for examinations that include the pelvis, risks in males were slightly higher than those in females. In abdominal CT scans, risks for males and female patients are very similar. For abdominal CT scans, increasing the patient age from 20 to 80 resulted in a reduction in patient risks of nearly a factor of 5. The average cancer risk for chest/abdomen/pelvis CT examinations was ∼26 % higher than the cancer risk caused by 'sensitive organs'. Doses and radiation risks in 80 kg adults were ∼10 % lower than those in 70 kg patients. Cancer risks in body CT can be estimated from the examination DLP by accounting for sex, age, as well as patient physical characteristics.

  4. Global and regional estimates of cancer mortality and incidence by site: I. Application of regional cancer survival model to estimate cancer mortality distribution by site

    Directory of Open Access Journals (Sweden)

    Lopez Alan D


    Full Text Available Abstract Background The Global Burden of Disease 2000 (GBD 2000 study starts from an analysis of the overall mortality envelope in order to ensure that the cause-specific estimates add to the total all cause mortality by age and sex. For regions where information on the distribution of cancer deaths is not available, a site-specific survival model was developed to estimate the distribution of cancer deaths by site. Methods An age-period-cohort model of cancer survival was developed based on data from the Surveillance, Epidemiology, and End Results (SEER. The model was further adjusted for the level of economic development in each region. Combined with the available incidence data, cancer death distributions were estimated and the model estimates were validated against vital registration data from regions other than the United States. Results Comparison with cancer mortality distribution from vital registration confirmed the validity of this approach. The model also yielded the cancer mortality distribution which is consistent with the estimates based on regional cancer registries. There was a significant variation in relative interval survival across regions, in particular for cancers of bladder, breast, melanoma of the skin, prostate and haematological malignancies. Moderate variations were observed among cancers of colon, rectum, and uterus. Cancers with very poor prognosis such as liver, lung, and pancreas cancers showed very small variations across the regions. Conclusions The survival model presented here offers a new approach to the calculation of the distribution of deaths for areas where mortality data are either scarce or unavailable.

  5. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson


    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

  6. Chronomics, human time estimation, and aging

    Directory of Open Access Journals (Sweden)

    Franz Halberg


    Full Text Available Franz Halberg, Robert B Sothern, Germaine Cornélissen, Jerzy Czaplicki1Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA; 1Institut de Pharmacologie et de Biologie Structurale CNRS, Université Paul Sabatier, Toulouse, FranceBackground: Circadian rhythm stage affects many outcomes, including those of mental aging.Methods: Estimations of 1 minute ∼5 times/day for a year, 25 years apart, by a healthy male biomedical scientist (RBS, are analyzed by the extended cosinor.Results: Cycles of a half-week, a week, ∼30 days, a half-year and a year, in self-assessed 1-minute estimation by RBS between 25 and 60 years of age in health, are mapped for the first time, compared and opposite effects are found. For RBS at 60 vs at 25 years of age, it takes less time in the morning around 10:30 (P < 0.001, but not in the evening around 19:30 (P = 0.956, to estimate 1 minute.Discussion: During the intervening decades, the time of estimating 1 minute differed greatly, dependent on circadian stage, being a linear decrease in the morning and increase in the evening, the latter modulated by a ∼33.6-year cycle.Conclusion: Circadian and infradian rhythm mapping is essential for a scrutiny of effects of aging. A ∼30-day and a circannual component apparent at 25 years of age are not found later; cycles longer than a year are detected. Rhythm stages await tests as markers for timing therapy in disease.Keywords: circadian rhythm, mental function, time estimation

  7. Prevalence of Telomerase Activity in Human Cancer

    Directory of Open Access Journals (Sweden)

    Chi-Hau Chen


    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.

  8. Cancer Metabolomics and the Human Metabolome Database

    Directory of Open Access Journals (Sweden)

    David S. Wishart


    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.

  9. Radiation-Induced Second Cancer Risk Estimates From Radionuclide Therapy (United States)

    Bednarz, Bryan; Besemer, Abigail


    The use of radionuclide therapy in the clinical setting is expected to increase significantly over the next decade. There is an important need to understand the radiation-induced second cancer risk associated with these procedures. In this study the radiation-induced cancer risk in five radionuclide therapy patients was investigated. These patients underwent serial SPECT imaging scans following injection as part of a clinical trial testing the efficacy of a 131Iodine-labeled radiopharmaceutical. Using these datasets the committed absorbed doses to multiple sensitive structures were calculated using RAPID, which is a novel Monte Carlo-based 3D dosimetry platform developed for personalized dosimetry. The excess relative risk (ERR) for radiation-induced cancer in these structures was then derived from these dose estimates following the recommendations set forth in the BEIR VII report. The radiation-induced leukemia ERR was highest among all sites considered reaching a maximum value of approximately 4.5. The radiation-induced cancer risk in the kidneys, liver and spleen ranged between 0.3 and 1.3. The lifetime attributable risks (LARs) were also calculated, which ranged from 30 to 1700 cancers per 100,000 persons and were highest for leukemia and the liver for both males and females followed by radiation-induced spleen and kidney cancer. The risks associated with radionuclide therapy are similar to the risk associated with external beam radiation therapy.

  10. Human Papillomavirus in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Anna Rosa Garbuglia


    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.

  11. Oral contraceptives, human papillomavirus and cervical cancer. (United States)

    La Vecchia, Carlo; Boccia, Stefania


    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.

  12. Radiobiology of human cancer radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, J.R.


    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. Water pipe smoking and human oral cancers. (United States)

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


    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.

  14. Estimation of human dose to radon progeny

    Energy Technology Data Exchange (ETDEWEB)

    Shimo, Michikuni [Gifu Coll. of Medical Technology, Sekiichi, Gifu (Japan)


    The aim of the paper is the estimation of the effective dose due to radon progeny for Japanese population. The estimation was performed by a modified UNSCEAR equation. The equation was needed the radon concentration annual occupancy time and the tidal volume on Japanese people and the dose conversion coefficient are needed. Furthermore, not only these figures but also unattached fraction and aerosol distribution data obtained in Japan and the factor related to the Japanese living style were used in the calculation. We used following figures as representative value in Japan; radon concentration: 13(6 - 25) Bq/m{sup 3} indoors and 6.7(3.5 - 13) Bq/m{sup 3} outdoors; the equilibrium factor: 0.45(0.35 - 0.57) indoors and 0.70(0.50 - 0.90) outdoors; the occupancy factor: 0.87 indoors, 0.09 outdoors and 0.04 in vehicle for male and 0.91 indoors, 0.06 outdoors and 0.03 in vehicle for female; the tidal volume: 7,000 (4,000 - 8,000) m{sup 3} for male, 6,200 (3,500 - 7,500) m{sup 3} for female. The effective doses due to radon progeny were estimated to be 0.45 mSv/y for male and 0.40 mSv/y for female, and the variance was -80 - +130%. These values were 1/2 - 1/3 as small as values shown by UNSCEAR 1993 Report and estimated by ICRP Publication 65. (author)

  15. Pose estimation based on human detection and segmentation

    Institute of Scientific and Technical Information of China (English)

    CHEN Qiang; ZHENG EnLiang; LIU YunCai


    We address the problem of 3D human pose estimation in a single real scene image. Normally, 3D pose estimation from real Image needs background subtraction to extract the appropriate features. We do not make such assumption. In this paper, a two-step approach is proposed, first, Instead of applying background subtraction to get the segmentation of human, we combine the segmentation with human detection using an ISM-based detector. Then, silhouette feature can be extracted and 3D pose estimation Is solved as a regression problem. RVMs and ridge regression method are applied to solve this problem. The results show the robustness and accuracy of our method.

  16. Estimation of Hospital Costs for Colorectal Cancer Care for Nova Scotia

    Directory of Open Access Journals (Sweden)

    Brian D O'Brien


    Full Text Available BACKGROUND: Colorectal cancer (CRC is the second most common invasive cancer in Canada. Estimates of the costs of care allow estimation of the cost effectiveness of screening for premalignant and early disease.

  17. Estimation of Cachexia among Cancer Patients Based on Four Definitions

    Directory of Open Access Journals (Sweden)

    Kathleen M. Fox


    Full Text Available Objectives. Estimate and compare the proportion of cancer patients with cachexia using different definitions from available clinical data. Methods. Electronic medical records were examined to estimate the proportion of cancer patients with cachexia using 4 definitions: (1 ICD-9 diagnostic code of 799.4 (cachexia, (2 ICD-9 diagnosis of cachexia, anorexia, abnormal weight loss, or feeding difficulties, (3 prescription for megestrol acetate, oxandrolone, somatropin, or dronabinol, and (4 ≥5% weight loss. Patients with cancer of the stomach, pancreas, lung, colon/rectum, head/neck, esophagus, prostate, breast, or liver diagnosed between 1999 and 2004 were followed for cachexia. Results. Of 8541 cancer patients (60% men and 55% Caucasian, cachexia was observed in 2.4% of patients using the cachexia diagnostic code, 5.5% expanded diagnoses, 6.4% prescription medication definition, and 14.7% with ≥5% weight loss. Conclusions. The proportion of patients with cachexia varied considerably depending upon the definition employed, indicating that a standard operational definition is needed.

  18. Estimation of volumetric breast density for breast cancer risk prediction (United States)

    Pawluczyk, Olga; Yaffe, Martin J.; Boyd, Norman F.; Jong, Roberta A.


    Mammographic density (MD) has been shown to be a strong risk predictor for breast cancer. Compared to subjective assessment by a radiologist, computer-aided analysis of digitized mammograms provides a quantitative and more reproducible method for assessing breast density. However, the current methods of estimating breast density based on the area of bright signal in a mammogram do not reflect the true, volumetric quantity of dense tissue in the breast. A computerized method to estimate the amount of radiographically dense tissue in the overall volume of the breast has been developed to provide an automatic, user-independent tool for breast cancer risk assessment. The procedure for volumetric density estimation consists of first correcting the image for inhomogeneity, then performing a volume density calculation. First, optical sensitometry is used to convert all images to the logarithm of relative exposure (LRE), in order to simplify the image correction operations. The field non-uniformity correction, which takes into account heel effect, inverse square law, path obliquity and intrinsic field and grid non- uniformity is obtained by imaging a spherical section PMMA phantom. The processed LRE image of the phantom is then used as a correction offset for actual mammograms. From information about the thickness and placement of the breast, as well as the parameters of a breast-like calibration step wedge placed in the mammogram, MD of the breast is calculated. Post processing and a simple calibration phantom enable user- independent, reliable and repeatable volumetric estimation of density in breast-equivalent phantoms. Initial results obtained on known density phantoms show the estimation to vary less than 5% in MD from the actual value. This can be compared to estimated mammographic density differences of 30% between the true and non-corrected values. Since a more simplistic breast density measurement based on the projected area has been shown to be a strong indicator

  19. Human Pose Estimation from Monocular Images: A Comprehensive Survey

    Directory of Open Access Journals (Sweden)

    Wenjuan Gong


    Full Text Available Human pose estimation refers to the estimation of the location of body parts and how they are connected in an image. Human pose estimation from monocular images has wide applications (e.g., image indexing. Several surveys on human pose estimation can be found in the literature, but they focus on a certain category; for example, model-based approaches or human motion analysis, etc. As far as we know, an overall review of this problem domain has yet to be provided. Furthermore, recent advancements based on deep learning have brought novel algorithms for this problem. In this paper, a comprehensive survey of human pose estimation from monocular images is carried out including milestone works and recent advancements. Based on one standard pipeline for the solution of computer vision problems, this survey splits the problem into several modules: feature extraction and description, human body models, and modeling methods. Problem modeling methods are approached based on two means of categorization in this survey. One way to categorize includes top-down and bottom-up methods, and another way includes generative and discriminative methods. Considering the fact that one direct application of human pose estimation is to provide initialization for automatic video surveillance, there are additional sections for motion-related methods in all modules: motion features, motion models, and motion-based methods. Finally, the paper also collects 26 publicly available data sets for validation and provides error measurement methods that are frequently used.

  20. Use of claims data to estimate annual cervical cancer screening percentages in Portland metropolitan area, Oregon. (United States)

    Abdullah, Nasreen; Laing, Robert S; Hariri, Susan; Young, Collette M; Schafer, Sean


    Human papillomavirus (HPV) vaccine should reduce cervical dysplasia before cervical cancer. However, dysplasia diagnosis is screening-dependent. Accurate screening estimates are needed. To estimate the percentage of women in a geographic population that has had cervical cancer screening. We analyzed claims data for (Papanicolau) Pap tests from 2008-2012 to estimate the percentage of insured women aged 18-39 years screened. We estimated screening in uninsured women by dividing the percentage of insured Behavioral Risk Factor Surveillance Survey respondents reporting previous-year testing by the percentage of uninsured respondents reporting previous-year testing, and multiplying this ratio by claims-based estimates of insured women with previous-year screening. We calculated a simple weighted average of the two estimates to estimate overall screening percentage. We estimated credible intervals using Monte-Carlo simulations. During 2008-2012, an annual average of 29.6% of women aged 18-39 years were screened. Screening increased from 2008 to 2009 in all age groups. During 2009-2012, the screening percentages decreased for all groups, but declined most in women aged 18-20 years, from 21.5% to 5.4%. Within age groups, compared to 2009, credible intervals did not overlap during 2011 (except age group 21-29 years) and 2012, and credible intervals in the 18-20 year group did not overlap with older groups in any year. This introduces a novel method to estimate population-level cervical cancer screening. Overall, percentage of women screened in Portland, Oregon fell following changes in screening recommendations released in 2009 and later modified in 2012. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Markov chain for estimating human mitochondrial DNA mutation pattern (United States)

    Vantika, Sandy; Pasaribu, Udjianna S.


    The Markov chain was proposed to estimate the human mitochondrial DNA mutation pattern. One DNA sequence was taken randomly from 100 sequences in Genbank. The nucleotide transition matrix and mutation transition matrix were estimated from this sequence. We determined whether the states (mutation/normal) are recurrent or transient. The results showed that both of them are recurrent.

  2. Isolation of Cancer Stem Cells From Human Prostate Cancer Samples (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


    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

  3. Human motion estimation with multiple frequency modulated continuous wave radars

    NARCIS (Netherlands)

    Dorp, Ph. van; Groen, F.C.A.


    Human motion estimation is an important issue in automotive, security or home automation applications. Radar systems are well suited for this because they are robust, are independent of day or night conditions and have accurate range and speed domain. The human response in a radar range-speed-time m

  4. Human motion estimation with multiple frequency modulated continuous wave radars

    NARCIS (Netherlands)

    Dorp, Ph. van; Groen, F.C.A.


    Human motion estimation is an important issue in automotive, security or home automation applications. Radar systems are well suited for this because they are robust, are independent of day or night conditions and have accurate range and speed domain. The human response in a radar range-speed-time

  5. Estimation of radiation cancer risk in CT-KUB (United States)

    Karim, M. K. A.; Hashim, S.; Bakar, K. A.; Bradley, D. A.; Ang, W. C.; Bahrudin, N. A.; Mhareb, M. H. A.


    The increased demand for computed tomography (CT) in radiological scanning examinations raises the question of a potential health impact from the associated radiation exposures. Focusing on CT kidney-ureter-bladder (CT-KUB) procedures, this work was aimed at determining organ equivalent dose using a commercial CT dose calculator and providing an estimate of cancer risks. The study, which included 64 patients (32 males and 32 females, mean age 55.5 years and age range 30-80 years), involved use of a calibrated CT scanner (Siemens-Somatom Emotion 16-slice). The CT exposures parameter including tube potential, pitch factor, tube current, volume CT dose index (CTDIvol) and dose-length product (DLP) were recorded and analyzed using CT-EXPO (Version 2.3.1, Germany). Patient organ doses, including for stomach, liver, colon, bladder, red bone marrow, prostate and ovaries were calculated and converted into cancer risks using age- and sex-specific data published in the Biological Effects of Ionizing Radiation (BEIR) VII report. With a median value scan range of 36.1 cm, the CTDIvol, DLP, and effective dose were found to be 10.7 mGy, 390.3 mGy cm and 6.2 mSv, respectively. The mean cancer risks for males and females were estimated to be respectively 25 and 46 out of 100,000 procedures with effective doses between 4.2 mSv and 10.1 mSv. Given the increased cancer risks from current CT-KUB procedures compared to conventional examinations, we propose that the low dose protocols for unenhanced CT procedures be taken into consideration before establishing imaging protocols for CT-KUB.

  6. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng


    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.

  7. Temporal evolution of risk estimates for presumed human teratogens. (United States)

    Koebert, M K; Haun, J M; Pauli, R M


    We present preliminary data assessing a previously untried method of deriving estimates of risk from case reports on presumed human teratogens. We postulated that we could take advantage of biases inherent to case reports in order to generate one or more families of temporal curves that could be used to estimate the "true" risk of teratogenic exposure. Using this method (which we refer to as the "case-cumulative method") we found that two agents (parvovirus B19 and isotretinoin) demonstrated a logarithmic decrease in the estimated risk over time, as intuitively expected, while trimethadione and the coumarin derivatives showed a more complex pattern over time. Analysis of estimated risks quoted by reviews and large studies for these four agents showed large variability from estimate to estimate and no discernible temporal pattern. With further analysis of other agents, the case-cumulative method might eventually prove to be useful in teratogen counseling.

  8. Financial impact estimate for radioinduced cancer treatment following RDD scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Gabriel F.Q. da; Andrade, Edson R. de; Rebello, Wilson F.; Araujo, Olga M.O., E-mail:, E-mail:, E-mail:, E-mail: [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Secao de Engenharia Nuclear


    This study aims to propose a methodology to estimate the possible financial impact of cancer development and treatment over general public as consequence of a radiological event. Asymmetric threats involving radioactive materials and its consequences are being studied by some groups worldwide but without using the concept of methodology of convergence. This concept is based on combining single platforms into a package in order to effectively support the decision-making process during an emergency. A Radiological Dispersive Device (RDD) can be built of small amounts of explosive and radioactive material which are packed together. A fictional scenario was modeled using cesium-137. The venue is the Athletes Park, located in the city of Rio de Janeiro which will host large events such as Olympics .The RDD explosion was modeled using the HotSpot Health Physics Codes 3.0, which provided radioactive isodoses over the affected location with thresholds in agreement with those recommended by Brazilian National Nuclear Energy Commission (CNEN). Also included in the results, Hotspot simulated the contaminated area and, the total effective dose for individuals. Estimative about excess relative risk (ERR) were performed by using Biological Effects of Ionizing Radiation V (BEIR V) report and TECDOC-870 (IAEA - Methods for Estimating the Probability of Cancer from Occupation Radiation Exposure). Leukemia was considered as morbidity for this study due to its short period of latency. The Total Body Irradiation was considered as a treatment and the financial impact was roughly estimated about coasts excluding logistical issues which should be calculated for each specific demand in further studies. (author)

  9. Cancer Risk Estimates from Space Flight Estimated Using Yields of Chromosome Damage in Astronaut's Blood Lymphocytes (United States)

    George, Kerry A.; Rhone, J.; Chappell, L. J.; Cucinotta, F. A.


    To date, cytogenetic damage has been assessed in blood lymphocytes from more than 30 astronauts before and after they participated in long-duration space missions of three months or more on board the International Space Station. Chromosome damage was assessed using fluorescence in situ hybridization whole chromosome analysis techniques. For all individuals, the frequency of chromosome damage measured within a month of return from space was higher than their preflight yield, and biodosimetry estimates were within the range expected from physical dosimetry. Follow up analyses have been performed on most of the astronauts at intervals ranging from around 6 months to many years after flight, and the cytogenetic effects of repeat long-duration missions have so far been assessed in four individuals. Chromosomal aberrations in peripheral blood lymphocytes have been validated as biomarkers of cancer risk and cytogenetic damage can therefore be used to characterize excess health risk incurred by individual crewmembers after their respective missions. Traditional risk assessment models are based on epidemiological data obtained on Earth in cohorts exposed predominantly to acute doses of gamma-rays, and the extrapolation to the space environment is highly problematic, involving very large uncertainties. Cytogenetic damage could play a key role in reducing uncertainty in risk estimation because it is incurred directly in the space environment, using specimens from the astronauts themselves. Relative cancer risks were estimated from the biodosimetry data using the quantitative approach derived from the European Study Group on Cytogenetic Biomarkers and Health database. Astronauts were categorized into low, medium, or high tertiles according to their yield of chromosome damage. Age adjusted tertile rankings were used to estimate cancer risk and results were compared with values obtained using traditional modeling approaches. Individual tertile rankings increased after space

  10. Carrying-over toxicokinetic model uncertainty into cancer risk estimates. The TCDD example

    Energy Technology Data Exchange (ETDEWEB)

    Edler, L. [Division of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Heinzl, H.; Mittlboeck, M. [Medical Univ. of Vienna (Austria). Dept. of Medical Computer Sciences


    Estimation of human cancer risks depends on the assessment of exposure to the investigated hazardous compound as well as on its toxicokinetic and toxicodynamic in the body. Modeling these processes constitutes a basic prerequisite for any quantitative risk assessment including assessment of the uncertainty of risk estimates. Obviously, the modeling process itself is part of the risk assessment task, and it affects the development of valid risk estimates. Due to the wealth of information available on exposure and effects in humans and animals 2,3,7,8 tetrachlorodibenzo-pdioxin (TCDD) provides an excellent example to elaborate methods which allow a quantitative analysis of the uncertainty of TCDD risk estimates, and which show how toxicokinetic model uncertainty carries over to risk estimate uncertainty and uncertainty of the dose-response relationship. Cancer is usually considered as a slowly evolving disease. An increase in TCDD dose may result in an increase of the observable cancer response not until some latency time period has elapsed. This fact needs careful consideration when a dose-response relationship is to be established. Toxicokinetic models are capable to reconstruct TCDD exposure concentrations during a lifetime such that time-dependent TCDD dose metrics like the area under the concentration-time curve (AUC) can be constructed for each individual cohort member. Two potentially crucial model assumptions for estimating the exposure of a person are the assumption of lifetime constancy of total lipid volume (TLV) of the human body and the assumption of a simple linear kinetic of TCDD elimination. In 1995 a modified Michaelis-Menten kinetic (also known as Carrier kinetic) has been suggested to link the TCDD elimination rate to the available TCDD amount in the body. That is, TCDD elimination would be faster, of nearly the same rate, or slower under this kinetic than under a simple linear kinetic when the individual would be highly, moderately, or slightly

  11. 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


    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.

  12. Human Colon Cancer Cells Cultivated in Space (United States)


    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.

  13. Estimation of Human Body Shape and Posture Under Clothing


    Wuhrer, Stefanie; Pishchulin, Leonid; Brunton, Alan; Shu, Chang; Lang, Jochen


    Estimating the body shape and posture of a dressed human subject in motion represented as a sequence of (possibly incomplete) 3D meshes is important for virtual change rooms and security. To solve this problem, statistical shape spaces encoding human body shape and posture variations are commonly used to constrain the search space for the shape estimate. In this work, we propose a novel method that uses a posture-invariant shape space to model body shape variation combined with a skeleton-bas...

  14. Aspartame bioassay findings portend human cancer hazards. (United States)

    Huff, James; LaDou, Joseph


    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.


    Institute of Scientific and Technical Information of China (English)


    @@Most of the chemicals classified by the International Agency for Research on Cancer (IARC) as human carcinogens are mutagenic across test systems, cf. [ ] 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

  16. Human age estimation framework using different facial parts


    Mohamed Y. El Dib; Hoda M. Onsi


    Human age estimation from facial images has a wide range of real-world applications in human computer interaction (HCI). In this paper, we use the bio-inspired features (BIF) to analyze different facial parts: (a) eye wrinkles, (b) whole internal face (without forehead area) and (c) whole face (with forehead area) using different feature shape points. The analysis shows that eye wrinkles which cover 30% of the facial area contain the most important aging features compared to internal face and...

  17. Human endogenous retroviruses and cancer prevention: evidence and prospects

    Directory of Open Access Journals (Sweden)

    Cegolon Luca


    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

  18. Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer (United States)

    Ding, Lin; El Zaatari, Mohamad


    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


    Directory of Open Access Journals (Sweden)

    Sergey N. Rumyantsev


    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.

  20. Methodology for the Model-based Small Area Estimates of Cancer-Related Knowledge - Small Area Estimates (United States)

    The HINTS is designed to produce reliable estimates at the national and regional levels. GIS maps using HINTS data have been used to provide a visual representation of possible geographic relationships in HINTS cancer-related variables.

  1. Data Sources for the Model-based Small Area Estimates of Cancer-Related Knowledge - Small Area Estimates (United States)

    The model-based estimates of important cancer risk factors and screening behaviors are obtained by combining the responses to the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS).

  2. Data Sources for the Model-based Small Area Estimates of Cancer Risk Factors and Screening Behaviors - Small Area Estimates (United States)

    The model-based estimates of important cancer risk factors and screening behaviors are obtained by combining the responses to the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS).

  3. Estimating Preferences for Treatments in Patients With Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ávila, Mónica [Health Services Research Unit, IMIM (Hospital del Mar Medical Research Institute), Barcelona (Spain); CIBER en Epidemiología y Salud Pública (CIBERESP) (Spain); Universitat Pompeu Fabra, Barcelona (Spain); Becerra, Virginia [Health Services Research Unit, IMIM (Hospital del Mar Medical Research Institute), Barcelona (Spain); Guedea, Ferran [Servicio de Oncología Radioterápica, Institut Català d' Oncologia, L' Hospitalet de Llobregat (Spain); Suárez, José Francisco [Servicio de Urología, Hospital Universitari de Bellvitge, L' Hospitalet de Llobregat (Spain); Fernandez, Pablo [Servicio de Oncología Radioterápica, Instituto Oncológico de Guipúzcoa, San Sebastián (Spain); Macías, Víctor [Servicio de Oncología Radioterápica, Hospital Clínico Universitario de Salamanca, Salamanca (Spain); Servicio de Oncología Radioterápica, Institut Oncologic del Valles-Hospital General de Catalunya, Sant Cugat del Vallès (Spain); Mariño, Alfonso [Servicio de Oncología Radioterápica, Centro Oncológico de Galicia, A Coruña (Spain); and others


    Purpose: Studies of patients' preferences for localized prostate cancer treatments have assessed radical prostatectomy and external radiation therapy, but none of them has evaluated brachytherapy. The aim of our study was to assess the preferences and willingness to pay of patients with localized prostate cancer who had been treated with radical prostatectomy, external radiation therapy, or brachytherapy, and their related urinary, sexual, and bowel side effects. Methods and Materials: This was an observational, prospective cohort study with follow-up until 5 years after treatment. A total of 704 patients with low or intermediate risk localized prostate cancer were consecutively recruited from 2003 to 2005. The estimation of preferences was conducted using time trade-off, standard gamble, and willingness-to-pay methods. Side effects were measured with the Expanded Prostate Index Composite (EPIC), a prostate cancer-specific questionnaire. Tobit models were constructed to assess the impact of treatment and side effects on patients' preferences. Propensity score was applied to adjust for treatment selection bias. Results: Of the 580 patients reporting preferences, 165 were treated with radical prostatectomy, 152 with external radiation therapy, and 263 with brachytherapy. Both time trade-off and standard gamble results indicated that the preferences of patients treated with brachytherapy were 0.06 utilities higher than those treated with radical prostatectomy (P=.01). Similarly, willingness-to-pay responses showed a difference of €57/month (P=.004) between these 2 treatments. Severe urinary incontinence presented an independent impact on the preferences elicited (P<.05), whereas no significant differences were found by bowel and sexual side effects. Conclusions: Our findings indicate that urinary incontinence is the side effect with the highest impact on preferences and that brachytherapy and external radiation therapy are more valued than radical

  4. Blood pressure estimation in the human fetal descending aorta.

    NARCIS (Netherlands)

    Struijk, P.C.; Mathews, V.J.; Loupas, T.; Stewart, P.A.; Clark, E.B.; Steegers, E.A.P.; Wladimiroff, J.W.


    OBJECTIVES: The objectives of this study were to estimate fetal blood pressure non-invasively from two-dimensional color Doppler-derived aortic blood flow and diameter waveforms, and to compare the results with invasively derived human fetal blood pressures available from the literature. METHODS:

  5. Blood pressure estimation in the human fetal descending aorta

    NARCIS (Netherlands)

    P.C. Struijk (Pieter); V.J. Mathews; T. Loupas; P.A. Stewart (Patricia); E.B. Clark; R.P.M. Steegers-Theunissen (Régine); J.W. Wladimiroff (Juriy)


    textabstractObjectives: The objectives of this study were to estimate fetal blood pressure non-invasively from two-dimensional color Doppler-derived aortic blood flow and diameter waveforms, and to compare the results with invasively derived human fetal blood pressures available from the literature.

  6. Demographic Estimation from Face Images: Human vs. Machine Performance. (United States)

    Han, Hu; Otto, Charles; Liu, Xiaoming; Jain, Anil K


    Demographic estimation entails automatic estimation of age, gender and race of a person from his face image, which has many potential applications ranging from forensics to social media. Automatic demographic estimation, particularly age estimation, remains a challenging problem because persons belonging to the same demographic group can be vastly different in their facial appearances due to intrinsic and extrinsic factors. In this paper, we present a generic framework for automatic demographic (age, gender and race) estimation. Given a face image, we first extract demographic informative features via a boosting algorithm, and then employ a hierarchical approach consisting of between-group classification, and within-group regression. Quality assessment is also developed to identify low-quality face images that are difficult to obtain reliable demographic estimates. Experimental results on a diverse set of face image databases, FG-NET (1K images), FERET (3K images), MORPH II (75K images), PCSO (100K images), and a subset of LFW (4K images), show that the proposed approach has superior performance compared to the state of the art. Finally, we use crowdsourcing to study the human perception ability of estimating demographics from face images. A side-by-side comparison of the demographic estimates from crowdsourced data and the proposed algorithm provides a number of insights into this challenging problem.

  7. Age estimation based on aspartic acid racemization in human sclera. (United States)

    Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie


    Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.

  8. Antiangiogenic Steroids in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Richard J. Pietras


    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

  9. Antiangiogenic Steroids in Human Cancer Therapy. (United States)

    Pietras, Richard J; Weinberg, Olga K


    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

  10. Ubiquitous human upper-limb motion estimation using wearable sensors. (United States)

    Zhang, Zhi-Qiang; Wong, Wai-Choong; Wu, Jian-Kang


    Human motion capture technologies have been widely used in a wide spectrum of applications, including interactive game and learning, animation, film special effects, health care, navigation, and so on. The existing human motion capture techniques, which use structured multiple high-resolution cameras in a dedicated studio, are complicated and expensive. With the rapid development of microsensors-on-chip, human motion capture using wearable microsensors has become an active research topic. Because of the agility in movement, upper-limb motion estimation has been regarded as the most difficult problem in human motion capture. In this paper, we take the upper limb as our research subject and propose a novel ubiquitous upper-limb motion estimation algorithm, which concentrates on modeling the relationship between upper-arm movement and forearm movement. A link structure with 5 degrees of freedom (DOF) is proposed to model the human upper-limb skeleton structure. Parameters are defined according to Denavit-Hartenberg convention, forward kinematics equations are derived, and an unscented Kalman filter is deployed to estimate the defined parameters. The experimental results have shown that the proposed upper-limb motion capture and analysis algorithm outperforms other fusion methods and provides accurate results in comparison to the BTS optical motion tracker.

  11. Estimating the indirect costs associated with the expected number of cancer cases in Mexico by 2020


    Cristina Gutiérrez-Delgado; Daniel Armas-Texta; Nancy Reynoso-Noverón; Abelardo Meneses-García; Alejandro Mohar-Betancourt


    Objective. To estimate the indirect costs generated by adults with cancer in Mexico from 2002-2020. Materials and methods. Using information from national sources and the national cancer incidence from GLOBOCAN, we estimated income lost due to premature death (ILPD), short-term benefits (STBs), disability pensions (DPs), and opportunity costs for the carer (OCCs) generated by patients with cancer. Amounts were reported in Mexican pesos. Results. We estimated 23 359 deaths and 216 679 new case...

  12. Epidemiologic studies of the human microbiome and cancer

    National Research Council Canada - National Science Library

    Vogtmann, Emily; Goedert, James J


    .... 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...

  13. Systemic estimation of the effect of photodynamic therapy of cancer (United States)

    Kogan, Eugenia A.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Loschenov, Victor B.; Volkova, Anna I.; Posypanova, Anna M.


    The effects of photodynamic therapy (PDT) of cancer needs objective estimation and its unification in experimental as well as in clinical studies. They must include not only macroscopical changes but also the complex of following morphological criteria: (1) the level of direct tumor damage (direct necrosis and apoptosis); (2) the level of indirect tumor damage (ischemic necrosis); (3) the signs of vascular alterations; (4) the local and systemic antiblastome resistance; (5) the proliferative activity and malignant potential of survival tumor tissue. We have performed different regimes PDT using phthalocyanine derivatives. The complex of morphological methods (Ki-67, p53, c-myc, bcl-2) was used. Obtained results showed the connection of the tilted morphological criteria with tumor regression.

  14. Predicting human genetic interactions from cancer genome evolution.

    Directory of Open Access Journals (Sweden)

    Xiaowen Lu

    Full Text Available Synthetic Lethal (SL genetic interactions play a key role in various types of biological research, ranging from understanding genotype-phenotype relationships to identifying drug-targets against cancer. Despite recent advances in empirical measuring SL interactions in human cells, the human genetic interaction map is far from complete. Here, we present a novel approach to predict this map by exploiting patterns in cancer genome evolution. First, we show that empirically determined SL interactions are reflected in various gene presence, absence, and duplication patterns in hundreds of cancer genomes. The most evident pattern that we discovered is that when one member of an SL interaction gene pair is lost, the other gene tends not to be lost, i.e. the absence of co-loss. This observation is in line with expectation, because the loss of an SL interacting pair will be lethal to the cancer cell. SL interactions are also reflected in gene expression profiles, such as an under representation of cases where the genes in an SL pair are both under expressed, and an over representation of cases where one gene of an SL pair is under expressed, while the other one is over expressed. We integrated the various previously unknown cancer genome patterns and the gene expression patterns into a computational model to identify SL pairs. This simple, genome-wide model achieves a high prediction power (AUC = 0.75 for known genetic interactions. It allows us to present for the first time a comprehensive genome-wide list of SL interactions with a high estimated prediction precision, covering up to 591,000 gene pairs. This unique list can potentially be used in various application areas ranging from biotechnology to medical genetics.

  15. Estimation of the Human Absorption Cross Section Via Reverberation Models

    DEFF Research Database (Denmark)

    Steinböck, Gerhard; Pedersen, Troels; Fleury, Bernard Henri;


    Since the presence of persons affects the reverberation time observed for in-room channels, the absorption cross section of a person can be estimated from measurements via Sabine's and Eyring's models for the reverberation time. We propose an estimator relying on the more accurate model by Eyring...... and compare the obtained results to those of Sabine's model. We find that the absorption by persons is large enough to be measured with a wideband channel sounder and that estimates of the human absorption cross section differ for the two models. The obtained values are comparable to values reported...... in the literature. We also suggest the use of controlled environments with low average absorption coefficients to obtain more reliable estimates. The obtained values can be used to predict the change of reverberation time with persons in the propagation environment. This allows prediction of channel characteristics...

  16. Prevention of the Angiogenic Switch in Human Breast Cancer (United States)


    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

  17. An SV-GMR Needle Sensor-Based Estimation of Volume Density of Magnetic Fluid inside Human Body

    Directory of Open Access Journals (Sweden)

    C. P. Gooneratne


    Full Text Available A spin-valve giant magneto-resistive (SV-GMR sensor of needle-type configuration is reported to estimate the volume density of magnetic fluid inside human body. The magnetic fluid is usually injected into human body to kill cancerous cell using hyperthermia-based treatment. To control the heat treatment, a good knowledge of temperature is very much essential. The SV-GMR-based needle-type sensor is used to measure the magnetic flux density of the magnetic fluid inside the human body from which the temperature is estimated. The needle-type sensor provides a semi-invasive approach of temperature determination.

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


    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.

  19. Theoretical and Experimental Estimations of Volumetric Inductive Phase Shift in Breast Cancer Tissue (United States)

    González, C. A.; Lozano, L. M.; Uscanga, M. C.; Silva, J. G.; Polo, S. M.


    Impedance measurements based on magnetic induction for breast cancer detection has been proposed in some studies. This study evaluates theoretical and experimentally the use of a non-invasive technique based on magnetic induction for detection of patho-physiological conditions in breast cancer tissue associated to its volumetric electrical conductivity changes through inductive phase shift measurements. An induction coils-breast 3D pixel model was designed and tested. The model involves two circular coils coaxially centered and a human breast volume centrally placed with respect to the coils. A time-harmonic numerical simulation study addressed the effects of frequency-dependent electrical properties of tumoral tissue on the volumetric inductive phase shift of the breast model measured with the circular coils as inductor and sensor elements. Experimentally; five female volunteer patients with infiltrating ductal carcinoma previously diagnosed by the radiology and oncology departments of the Specialty Clinic for Women of the Mexican Army were measured by an experimental inductive spectrometer and the use of an ergonomic inductor-sensor coil designed to estimate the volumetric inductive phase shift in human breast tissue. Theoretical and experimental inductive phase shift estimations were developed at four frequencies: 0.01, 0.1, 1 and 10 MHz. The theoretical estimations were qualitatively in agreement with the experimental findings. Important increments in volumetric inductive phase shift measurements were evident at 0.01MHz in theoretical and experimental observations. The results suggest that the tested technique has the potential to detect pathological conditions in breast tissue associated to cancer by non-invasive monitoring. Further complementary studies are warranted to confirm the observations.

  20. Alterations of 5-Hydroxymethylcytosine in Human Cancers

    Directory of Open Access Journals (Sweden)

    Ali Yesilkanal


    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 


    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. Meta-basic estimates the size of druggable human genome. (United States)

    Plewczynski, Dariusz; Rychlewski, Leszek


    We present here the estimation of the upper limit of the number of molecular targets in the human genome that represent an opportunity for further therapeutic treatment. We select around approximately 6300 human proteins that are similar to sequences of known protein targets collected from DrugBank database. Our bioinformatics study estimates the size of 'druggable' human genome to be around 20% of human proteome, i.e. the number of the possible protein targets for small-molecule drug design in medicinal chemistry. We do not take into account any toxicity prediction, the three-dimensional characteristics of the active site in the predicted 'druggable' protein families, or detailed chemical analysis of known inhibitors/drugs. Instead we rely on remote homology detection method Meta-BASIC, which is based on sequence and structural similarity. The prepared dataset of all predicted protein targets from human genome presents the unique opportunity for developing and benchmarking various in silico chemo/bio-informatics methods in the context of the virtual high throughput screening.

  3. Stereological estimation of total brain numbers in humans


    Solveig eWalloe; Bente ePakkenberg; Katrine eFabricius


    Our knowledge of the relationship between brain structure and cognitive function is still limited. Human brains and individual cortical areas vary considerably in size and shape. Studies of brain cell numbers have historically been based on biased methods, which did not always result in correct estimates and were often very time-consuming. Within the last 20–30 years, it has become possible to rely on more advanced and unbiased methods. These methods have provided us with information about fe...

  4. Human ECG signal parameters estimation during controlled physical activity (United States)

    Maciejewski, Marcin; Surtel, Wojciech; Dzida, Grzegorz


    ECG signal parameters are commonly used indicators of human health condition. In most cases the patient should remain stationary during the examination to decrease the influence of muscle artifacts. During physical activity, the noise level increases significantly. The ECG signals were acquired during controlled physical activity on a stationary bicycle and during rest. Afterwards, the signals were processed using a method based on Pan-Tompkins algorithms to estimate their parameters and to test the method.

  5. Type-specific human papillomavirus biological features: validated model-based estimates.

    Directory of Open Access Journals (Sweden)

    Iacopo Baussano

    Full Text Available Infection with high-risk (hr human papillomavirus (HPV is considered the necessary cause of cervical cancer. Vaccination against HPV16 and 18 types, which are responsible of about 75% of cervical cancer worldwide, is expected to have a major global impact on cervical cancer occurrence. Valid estimates of the parameters that regulate the natural history of hrHPV infections are crucial to draw reliable projections of the impact of vaccination. We devised a mathematical model to estimate the probability of infection transmission, the rate of clearance, and the patterns of immune response following the clearance of infection of 13 hrHPV types. To test the validity of our estimates, we fitted the same transmission model to two large independent datasets from Italy and Sweden and assessed finding consistency. The two populations, both unvaccinated, differed substantially by sexual behaviour, age distribution, and study setting (screening for cervical cancer or Chlamydia trachomatis infection. Estimated transmission probability of hrHPV types (80% for HPV16, 73%-82% for HPV18, and above 50% for most other types; clearance rates decreasing as a function of time since infection; and partial protection against re-infection with the same hrHPV type (approximately 20% for HPV16 and 50% for the other types were similar in the two countries. The model could accurately predict the HPV16 prevalence observed in Italy among women who were not infected three years before. In conclusion, our models inform on biological parameters that cannot at the moment be measured directly from any empirical data but are essential to forecast the impact of HPV vaccination programmes.

  6. In vivo Estimation of Human Forearm and Wrist Dynamic Properties. (United States)

    Park, Kyungbin; Chang, Pyung-Hun; Kang, Sang


    It is important to estimate the 3 degree-of-freedom (DOF) impedance of human forearm and wrist (i.e., forearm prono-supination, and wrist flexion-extension and radial-ulnar deviation) in motor control and in the diagnosis of altered mechanical resistance following stroke. There is, however, a lack of methods to characterize 3 DOF impedance. Thus, we developed a reliable and accurate impedance estimation method, the distal internal model based impedance control (dIMBIC)-based method, to characterize the 3 DOF impedance, including cross-coupled terms between DOFs, for the first time. Its accuracy and reliability were experimentally validated using a robot with substantial nonlinear joint friction. The 3 DOF human forearm and wrist impedance of 8 healthy subjects was reliably characterized, and its linear behavior was verified. Thus, the dIMBIC-based method can provide us with 3 DOF forearm and wrist impedance regardless of nonlinear robot joint friction. It is expected that, with the proposed method, the 3 DOF impedance estimation can promote motor control studies and complement the diagnosis of altered wrist and forearm resistance post stroke by providing objective impedance estimates, including cross-coupled terms.

  7. Estimating successive cancer risks in Lynch Syndrome families using a progressive three-state model. (United States)

    Choi, Yun-Hee; Briollais, Laurent; Green, Jane; Parfrey, Patrick; Kopciuk, Karen


    Lynch Syndrome (LS) families harbor mutated mismatch repair genes,which predispose them to specific types of cancer. Because individuals within LS families can experience multiple cancers over their lifetime, we developed a progressive three-state model to estimate the disease risk from a healthy (state 0) to a first cancer (state 1) and then to a second cancer (state 2). Ascertainment correction of the likelihood was made to adjust for complex sampling designs with carrier probabilities for family members with missing genotype information estimated using their family's observed genotype and phenotype information in a one-step expectation-maximization algorithm. A sandwich variance estimator was employed to overcome possible model misspecification. The main objective of this paper is to estimate the disease risk (penetrance) for age at a second cancer after someone has experienced a first cancer that is also associated with a mutated gene. Simulation study results indicate that our approach generally provides unbiased risk estimates and low root mean squared errors across different family study designs, proportions of missing genotypes, and risk heterogeneities. An application to 12 large LS families from Newfoundland demonstrates that the risk for a second cancer was substantial and that the age at a first colorectal cancer significantly impacted the age at any LS subsequent cancer. This study provides new insights for developing more effective management of mutation carriers in LS families by providing more accurate multiple cancer risk estimates.

  8. Endogenous retroviral promoter exaptation in human cancer

    Directory of Open Access Journals (Sweden)

    Artem Babaian


    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.

  9. Cancer risk estimation caused by radiation exposure during endovascular procedure (United States)

    Kang, Y. H.; Cho, J. H.; Yun, W. S.; Park, K. H.; Kim, H. G.; Kwon, S. M.


    The objective of this study was to identify the radiation exposure dose of patients, as well as staff caused by fluoroscopy for C-arm-assisted vascular surgical operation and to estimate carcinogenic risk due to such exposure dose. The study was conducted in 71 patients (53 men and 18 women) who had undergone vascular surgical intervention at the division of vascular surgery in the University Hospital from November of 2011 to April of 2012. It had used a mobile C-arm device and calculated the radiation exposure dose of patient (dose-area product, DAP). Effective dose was measured by attaching optically stimulated luminescence on the radiation protectors of staff who participates in the surgery to measure the radiation exposure dose of staff during the vascular surgical operation. From the study results, DAP value of patients was 308.7 Gy cm2 in average, and the maximum value was 3085 Gy cm2. When converted to the effective dose, the resulted mean was 6.2 m Gy and the maximum effective dose was 61.7 milliSievert (mSv). The effective dose of staff was 3.85 mSv; while the radiation technician was 1.04 mSv, the nurse was 1.31 mSv. All cancer incidences of operator are corresponding to 2355 persons per 100,000 persons, which deemed 1 of 42 persons is likely to have all cancer incidences. In conclusion, the vascular surgeons should keep the radiation protection for patient, staff, and all participants in the intervention in mind as supervisor of fluoroscopy while trying to understand the effects by radiation by themselves to prevent invisible danger during the intervention and to minimize the harm.

  10. Modern criteria to establish human cancer etiology. (United States)

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


    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

  11. Estimation of cancer risks and benefits associated with a potential increased consumption of fruits and vegetables. (United States)

    Reiss, Richard; Johnston, Jason; Tucker, Kevin; DeSesso, John M; Keen, Carl L


    The current paper provides an analysis of the potential number of cancer cases that might be prevented if half the U.S. population increased its fruit and vegetable consumption by one serving each per day. This number is contrasted with an upper-bound estimate of concomitant cancer cases that might be theoretically attributed to the intake of pesticide residues arising from the same additional fruit and vegetable consumption. The cancer prevention estimates were derived using a published meta-analysis of nutritional epidemiology studies. The cancer risks were estimated using U.S. Environmental Protection Agency (EPA) methods, cancer potency estimates from rodent bioassays, and pesticide residue sampling data from the U.S. Department of Agriculture (USDA). The resulting estimates are that approximately 20,000 cancer cases per year could be prevented by increasing fruit and vegetable consumption, while up to 10 cancer cases per year could be caused by the added pesticide consumption. These estimates have significant uncertainties (e.g., potential residual confounding in the fruit and vegetable epidemiologic studies and reliance on rodent bioassays for cancer risk). However, the overwhelming difference between benefit and risk estimates provides confidence that consumers should not be concerned about cancer risks from consuming conventionally-grown fruits and vegetables.

  12. Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy (United States)


    AD_________________ Award Number: W81XWH-08-1-0503 TITLE: Noninvasive Subharmonic Pressure...SUBTITLE 5a. CONTRACT NUMBER Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy 5b. GRANT...SUBTITLE Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer 5. FUNDING NUMBERS W81XWH-08-1-0503 6. AUTHOR(S) Flemming

  13. Modelling mutational landscapes of human cancers in vitro (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


    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.

  14. Human-machine teaming for effective estimation and path planning (United States)

    McCourt, Michael J.; Mehta, Siddhartha S.; Doucette, Emily A.; Curtis, J. Willard


    While traditional sensors provide accurate measurements of quantifiable information, humans provide better qualitative information and holistic assessments. Sensor fusion approaches that team humans and machines can take advantage of the benefits provided by each while mitigating the shortcomings. These two sensor sources can be fused together using Bayesian fusion, which assumes that there is a method of generating a probabilistic representation of the sensor measurement. This general framework of fusing estimates can also be applied to joint human-machine decision making. In the simple case, binary decisions can be fused by using a probability of taking an action versus inaction from each decision-making source. These are fused together to arrive at a final probability of taking an action, which would be taken if above a specified threshold. In the case of path planning, rather than binary decisions being fused, complex decisions can be fused by allowing the human and machine to interact with each other. For example, the human can draw a suggested path while the machine planning algorithm can refine it to avoid obstacles and remain dynamically feasible. Similarly, the human can revise a suggested path to achieve secondary goals not encoded in the algorithm such as avoiding dangerous areas in the environment.

  15. Estimation and Projection of Lung Cancer Incidence and Mortality in China

    Directory of Open Access Journals (Sweden)

    Xiaonong ZOU


    Full Text Available Background and objective The aim of this study is to analyze lung cancer epidemiological trend and estimate lung cancer burden in China. Methods Lung cancer age specific mortality and incidence rate ratios in different areas and sexes were obtained from national cancer registration database in 2004 and 2005. Cancer crude mortalities were retrieved from the database of the third national death survey, 2004-2005. Age specific incidence rates of lung cancer were calculated using mortality and M/I ratios. Annual percent change (APC was estimated by log regression model using Joint Point software by analyzing pooled lung cancer incidence data from 10 cancer registries from 1988 to 2005. Results The total estimated new cases and deaths of lung cancer in 2005 were 536 407 and 475 768 which were higher in male than in female. There was 1.63% increase of lung cancer incidence per year from 1988 to 2005, however, the trend showed a slowdown by 0.55% annually after adjusted by age. Conclusion Lung cancer is one of major health issues in China and the burden is getting serious. Ageing population is main cause for increasing incidence and mortality of lung cancer. Effective cancer prevention and control is imperative. Especially, tobacco control should be carried out in statewide.

  16. The prognostic relevance of estimates of proliferative activity in early breast cancer

    DEFF Research Database (Denmark)

    Offersen, B V; Sørensen, Flemming Brandt; Knoop, A;


    clinicopathological parameters at diagnosis in early breast cancer patients. MATERIALS AND METHODS: Tumour specimens from 365 consecutively treated breast cancer patients were immunostained for MIB-1 and evaluated under the microscope using systematic random sampling accomplished by the CAST-grid system. RESULTS...... and number of mitoses included in the analysis, MIB-1 estimates showed no independent prognostic impact. CONCLUSIONS: High MIB-1 estimates did not add independent prognostic information at diagnosis when evaluated together with classical prognostic markers of early breast cancer....

  17. Estimating completeness of cancer registration in Saarland/Germany with capture-recapture methods. (United States)

    Brenner, H; Stegmaier, C; Ziegler, H


    Completeness of population-based cancer registration has been most commonly quantified by indirect measures, such as the death certificate only index or the mortality/incidence ratio. A major disadvantage of these measures is their strong dependence on the case fatality rate. Capture-recapture methodology offers an approach to estimate completeness directly which does not share this limitation. In this paper, a three-sources modelling approach is employed to derive estimates of completeness for the population-based cancer registry of Saarland. Overall, completeness is found to be high: estimates for all types of cancer range from 95.5 to 96.9% for calendar years 1970, 1975, 1980 and 1985. There is some variation with age (consistently high levels above age 30 years, a minimum of 87.7% in age group 15-29 years) and between cancer sites. Among the most common cancer sites, estimates of completeness are highest for gastrointestinal cancers (97.2%) and breast cancer (97.1%), while lower estimates of completeness are derived for cancers of the female genital organs (92.5%), the urinary tract (91.8%) and the prostate (91.0%). Although capture-recapture estimates are sensitive to the underlying assumptions about dependence between sources, careful application is encouraged to supplement traditional methods for evaluating completeness of cancer registration.

  18. 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


    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.

  19. The Isolation and Characterization of Human Prostate Cancer Stem Cells (United States)


    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

  20. Bacterial protein toxins in human cancers. (United States)

    Rosadi, Francesca; Fiorentini, Carla; Fabbri, Alessia


    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.

  1. Estimating the asbestos-related lung cancer burden from mesothelioma mortality (United States)

    McCormack, V; Peto, J; Byrnes, G; Straif, K; Boffetta, P


    Background: Quantifying the asbestos-related lung cancer burden is difficult in the presence of this disease's multiple causes. We explore two methods to estimate this burden using mesothelioma deaths as a proxy for asbestos exposure. Methods: From the follow-up of 55 asbestos cohorts, we estimated ratios of (i) absolute number of asbestos-related lung cancers to mesothelioma deaths; (ii) excess lung cancer relative risk (%) to mesothelioma mortality per 1000 non-asbestos-related deaths. Results: Ratios varied by asbestos type; there were a mean 0.7 (95% confidence interval 0.5, 1.0) asbestos-related lung cancers per mesothelioma death in crocidolite cohorts (n=6 estimates), 6.1 (3.6, 10.5) in chrysotile (n=16), 4.0 (2.8, 5.9) in amosite (n=4) and 1.9 (1.4, 2.6) in mixed asbestos fibre cohorts (n=31). In a population with 2 mesothelioma deaths per 1000 deaths at ages 40–84 years (e.g., US men), the estimated lung cancer population attributable fraction due to mixed asbestos was estimated to be 4.0%. Conclusion: All types of asbestos fibres kill at least twice as many people through lung cancer than through mesothelioma, except for crocidolite. For chrysotile, widely consumed today, asbestos-related lung cancers cannot be robustly estimated from few mesothelioma deaths and the latter cannot be used to infer no excess risk of lung or other cancers. PMID:22233924

  2. Human age estimation framework using different facial parts

    Directory of Open Access Journals (Sweden)

    Mohamed Y. El Dib


    Full Text Available Human age estimation from facial images has a wide range of real-world applications in human computer interaction (HCI. In this paper, we use the bio-inspired features (BIF to analyze different facial parts: (a eye wrinkles, (b whole internal face (without forehead area and (c whole face (with forehead area using different feature shape points. The analysis shows that eye wrinkles which cover 30% of the facial area contain the most important aging features compared to internal face and whole face. Furthermore, more extensive experiments are made on FG-NET database by increasing the number of missing pictures in older age groups using MORPH database to enhance the results.

  3. Stereological estimation of total brain numbers in humans

    Directory of Open Access Journals (Sweden)

    Solveig eWalloe


    Full Text Available Our knowledge of the relationship between brain structure and cognitive function is still limited. Human brains and individual cortical areas vary considerably in size and shape. Studies of brain cell numbers have historically been based on biased methods, which did not always result in correct estimates and were often very time-consuming. Within the last 20–30 years, it has become possible to rely on more advanced and unbiased methods. These methods have provided us with information about fetal brain development, differences in cell numbers between men and women, the effect of age on selected brain cell populations, and disease-related changes associated with a loss of function. In that this article concerns normal brain rather than brain disorders, it focuses on normal brain development in humans and age related changes in terms of cell numbers. For comparative purposes a few examples of neocortical neuron number in other mammals are also presented.

  4. Estimation of cancer incidence and mortality attributable to alcohol drinking in china

    Directory of Open Access Journals (Sweden)

    Xiao Huijuan


    Full Text Available Abstract Background Cancer constitutes a serious burden of disease worldwide and has become the second leading cause of death in China. Alcohol consumption is causally associated with the increased risk of certain cancers. Due to the current lack of data and the imperative need to guide policymakers on issues of cancer prevention and control, we aim to estimate the role of alcohol on the cancer burden in China in 2005. Methods We calculated the proportion of cancers attributable to alcohol use to estimate the burden of alcohol-related cancer. The population attributable fraction was calculated based on the assumption of no alcohol drinking. Data on alcohol drinking prevalence were from two large-scale national surveys of representative samples of the Chinese population. Data on relative risk were obtained from meta-analyses and large-scale studies. Results We found that a total of 78,881 cancer deaths were attributable to alcohol drinking in China in 2005, representing 4.40% of all cancers (6.69% in men, 0.42% in women. The corresponding figure for cancer incidence was 93,596 cases (3.63% of all cancer cases. Liver cancer was the main alcohol-related cancer, contributing more than 60% of alcohol-related cancers. Conclusions Particular attention needs to be paid to the harm of alcohol as well as its potential benefits when making public health recommendations on alcohol drinking.

  5. Characterizing metabolic changes in human colorectal cancer. (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


    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. Spatio-Temporal Matching for Human Pose Estimation in Video. (United States)

    Zhou, Feng; Torre, Fernando De la


    Detection and tracking humans in videos have been long-standing problems in computer vision. Most successful approaches (e.g., deformable parts models) heavily rely on discriminative models to build appearance detectors for body joints and generative models to constrain possible body configurations (e.g., trees). While these 2D models have been successfully applied to images (and with less success to videos), a major challenge is to generalize these models to cope with camera views. In order to achieve view-invariance, these 2D models typically require a large amount of training data across views that is difficult to gather and time-consuming to label. Unlike existing 2D models, this paper formulates the problem of human detection in videos as spatio-temporal matching (STM) between a 3D motion capture model and trajectories in videos. Our algorithm estimates the camera view and selects a subset of tracked trajectories that matches the motion of the 3D model. The STM is efficiently solved with linear programming, and it is robust to tracking mismatches, occlusions and outliers. To the best of our knowledge this is the first paper that solves the correspondence between video and 3D motion capture data for human pose detection. Experiments on the CMU motion capture, Human3.6M, Berkeley MHAD and CMU MAD databases illustrate the benefits of our method over state-of-the-art approaches.

  7. Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan. (United States)

    Loya, Asif; Serrano, Beatriz; Rasheed, Farah; Tous, Sara; Hassan, Mariam; Clavero, Omar; Raza, Muhammad; De Sanjosé, Silvia; Bosch, F Xavier; Alemany, Laia


    Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0-91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7-83.3), compared to Asia (71.6%; 69.9-73.4) and worldwide (70.8%; 69.9-71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9-15.7 vs. 19.8%; 18.3-21.3 and 18.5%; 17.7-19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases.

  8. Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer Response to Neoadjuvant Threapy (United States)


    TITLE AND SUBTITLE Noninvasive Subharmonic Pressure Estimation for Monitoring Breast Cancer 5. FUNDING NUMBERS W81XWH-08-1-0503 6. AUTHOR(S...u sing subharmonic aided p ressure estimation (SHAPE ) to estimate the inte rstitial fluid pressure (IFP) in LABC. To date, in vitr o experiments

  9. Reprogramming of human cancer cells to pluripotency for models of cancer progression (United States)

    Kim, Jungsun; Zaret, Kenneth S


    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


    Institute of Scientific and Technical Information of China (English)

    白银; 王琰; 周丽君; 俞莉章


    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.

  11. Qualitative analysis of cancer patients' experiences using donated human milk. (United States)

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


    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.

  12. Patients with Testicular Cancer Undergoing CT Surveillance Demonstrate a Pitfall of Radiation-induced Cancer Risk Estimates: The Timing Paradox (United States)

    Eisenberg, Jonathan D.; Lee, Richard J.; Gilmore, Michael E.; Turan, Ekin A.; Singh, Sarabjeet; Kalra, Mannudeep K.; Liu, Bob; Kong, Chung Yin; Gazelle, G. Scott


    Purpose: To demonstrate a limitation of lifetime radiation-induced cancer risk metrics in the setting of testicular cancer surveillance—in particular, their failure to capture the delayed timing of radiation-induced cancers over the course of a patient’s lifetime. Materials and Methods: Institutional review board approval was obtained for the use of computed tomographic (CT) dosimetry data in this study. Informed consent was waived. This study was HIPAA compliant. A Markov model was developed to project outcomes in patients with testicular cancer who were undergoing CT surveillance in the decade after orchiectomy. To quantify effects of early versus delayed risks, life expectancy losses and lifetime mortality risks due to testicular cancer were compared with life expectancy losses and lifetime mortality risks due to radiation-induced cancers from CT. Projections of life expectancy loss, unlike lifetime risk estimates, account for the timing of risks over the course of a lifetime, which enabled evaluation of the described limitation of lifetime risk estimates. Markov chain Monte Carlo methods were used to estimate the uncertainty of the results. Results: As an example of evidence yielded, 33-year-old men with stage I seminoma who were undergoing CT surveillance were projected to incur a slightly higher lifetime mortality risk from testicular cancer (598 per 100 000; 95% uncertainty interval [UI]: 302, 894) than from radiation-induced cancers (505 per 100 000; 95% UI: 280, 730). However, life expectancy loss attributable to testicular cancer (83 days; 95% UI: 42, 124) was more than three times greater than life expectancy loss attributable to radiation-induced cancers (24 days; 95% UI: 13, 35). Trends were consistent across modeled scenarios. Conclusion: Lifetime radiation risk estimates, when used for decision making, may overemphasize radiation-induced cancer risks relative to short-term health risks. © RSNA, 2012 Supplemental material: http

  13. Methodology for the Model-based Small Area Estimates of Cancer Risk Factors and Screening Behaviors - Small Area Estimates (United States)

    This model-based approach uses data from both the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS) to produce estimates of the prevalence rates of cancer risk factors and screening behaviors at the state, health service area, and county levels.

  14. T Cell Coinhibition and Immunotherapy in Human Breast Cancer


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


    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 ...

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

    Directory of Open Access Journals (Sweden)

    Kornel E Schuebel


    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.

  16. Differential network analysis in human cancer research. (United States)

    Gill, Ryan; Datta, Somnath; Datta, Susmita


    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.


    Institute of Scientific and Technical Information of China (English)

    张建军; 丁尔迅; 王强; 陈学云; 付志仁


    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.

  18. Estimating the indirect costs associated with the expected number of cancer cases in Mexico by 2020. (United States)

    Gutiérrez-Delgado, Cristina; Armas-Texta, Daniel; Reynoso-Noverón, Nancy; Meneses-García, Abelardo; Mohar-Betancourt, Alejandro


    To estimate the indirect costs generated by adults with cancer in Mexico from 2002-2020. Using information from national sources and the national cancer incidence from GLOBOCAN, we estimated income lost due to premature death (ILPD), short-term benefits (STBs), disability pensions (DPs), and opportunity costs for the carer (OCCs) generated by patients with cancer. Amounts were reported in Mexican pesos. We estimated 23 359 deaths and 216 679 new cases of cancer by 2020, which would be associated with a total indirect cost of 20.15 billion Mexican pesos. Men are expected to generate 54.9% of these costs. ILPD is expected to comprise the highest percentage of the cost (60%), followed by OCCs (22%), STBs (17%) and DPs (1%). From an economic perspective, the results emphasize the need to strengthen preventive interventions and early detection of cancer among adults to reduce its effect on the productivity of Mexico.

  19. Occupational radon exposure and lung cancer mortality: estimating intervention effects using the parametric G formula (United States)

    Edwards, Jessie K.; McGrath, Leah J.; Buckley, Jessie P.; Schubauer-Berigan, Mary K.; Cole, Stephen R.; Richardson, David B.


    Background Traditional regression analysis techniques used to estimate associations between occupational radon exposure and lung cancer focus on estimating the effect of cumulative radon exposure on lung cancer, while public health interventions are typically based on regulating radon concentration rather than workers’ cumulative exposure. Moreover, estimating the direct effect of cumulative occupational exposure on lung cancer may be difficult in situations vulnerable to the healthy worker survivor bias. Methods Workers in the Colorado Plateau Uranium Miners cohort (N=4,134) entered the study between 1950 and 1964 and were followed for lung cancer mortality through 2005. We use the parametric g-formula to compare the observed lung cancer mortality to the potential lung cancer mortality had each of 3 policies to limit monthly radon exposure been in place throughout follow-up. Results There were 617 lung cancer deaths over 135,275 person-years of follow-up. With no intervention on radon exposure, estimated lung cancer mortality by age 90 was 16%. Lung cancer mortality was reduced for all interventions considered, and larger reductions in lung cancer mortality were seen for interventions with lower monthly radon exposure limits. The most stringent guideline, the Mine Safety and Health Administration standard of 0.33 working level months, reduced lung cancer mortality from 16% to 10% (risk ratio 0.67; 95% confidence interval 0.61, 0.73). Conclusions This work illustrates the utility of the parametric g-formula for estimating the effects of policies regarding occupational exposures, particularly in situations vulnerable to the healthy worker survivor bias. PMID:25192403

  20. Estimation of the overall burden of cancers, precancerous lesions, and genital warts attributable to 9-valent HPV vaccine types in women and men in Europe. (United States)

    Hartwig, Susanne; St Guily, Jean Lacau; Dominiak-Felden, Géraldine; Alemany, Laia; de Sanjosé, Silvia


    In addition to cervical cancer, human papillomavirus (HPV) is responsible for a significant proportion of cancers and precancerous lesions of the vulva, vagina, anus, penis, head and neck, as well as genital warts. We estimated the annual number of new cases of these diseases attributable to 9-valent HPV vaccine types in women and men in Europe. The annual number of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and neck sites in the population of the European Medicines Agency territory was estimated based on age-specific incidence rates extracted from Cancer Incidence in 5 Continents, Volume X and Eurostat population data for 2015. The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated by applying the HPV attributable fraction from reference publications based on a large European multicenter study. For non-cervical cancers, HPV attributable fractions were based on oncogenically-active HPV infections only (i.e., detection of HPV DNA and either mRNA and/or p16 positivity). For precancerous lesions of the cervix, vulva, vagina, and anus, and for genital warts, previously published estimations were updated for the 2015 population. The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated at 47,992 (95% bound: 39,785-58,511). Cervical cancer showed the highest burden (31,130 cases), followed by head and neck cancer (6,786 cases), anal cancer (6,137 cases), vulvar cancer (1,466 cases), vaginal cancer (1,360 cases), and penile cancer (1,113 cases). About 81% were estimated to occur in women and 19% in men. The annual number of new precancerous lesions (CIN2+, VIN2/3, VaIN2/3, and AIN2/3) and genital warts attributable to 9-valent HPV vaccine types was estimated at 232,103 to 442,347 and 680,344 to 844,391, respectively. The burden of cancers associated with 9-valent HPV vaccine types in Europe is substantial in both sexes. Head and neck cancers constitute a heavy burden

  1. Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen

    NARCIS (Netherlands)

    A.J. Vickers (Andrew); D. Sjoberg (Daniel); D. Ulmert (David); E. Vertosick (Emily); M.J. Roobol-Bouts (Monique); I.M. Thompson (Ian); E.A.M. Heijnsdijk (Eveline); H.J. de Koning (Harry); C. Atoria-Swartz (Coral); P.T. Scardino (Peter); H. Lilja (Hans)


    textabstractBackground: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing b

  2. Healthcare costs associated with prostate cancer : estimates from a population-based study

    NARCIS (Netherlands)

    Krahn, Murray D.; Zagorski, Brandon; Laporte, Audrey; Alibhai, Shabbir M. H.; Bremner, Karen E.; Tomlinson, George; Warde, Padraig; Naglie, Gary

    OBJECTIVE To estimate the total healthcare costs and costs attributable to prostate cancer across all stages of disease, and to determine the predictors of those costs, as describing the cost of care for patients with prostate cancer is useful to understand the economic burden of illness, explore

  3. [Human papillomavirus detection in cervical cancer prevention]. (United States)

    Picconi, María Alejandra


    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.

  4. 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.

  5. Estimating the use of antibiotics for humans across China. (United States)

    Bu, Qingwei; Wang, Bin; Huang, Jun; Liu, Kai; Deng, Shubo; Wang, Yujue; Yu, Gang


    The present study aimed to propose a method to estimate the spatially resolved dataset for human-use antibiotics, which are highly needed in exposure models dealing with regions of various environmental characteristics. In this study, a regression model describing the relationship between the use of antibiotics and a set of socio-economic determinants was developed. It has been demonstrated that economic status (expressed using per capita gross domestic production) dominates the antibiotic use at least in China. Linear regression analysis was used to build the model, resulting in high goodness-of-fit, R(2) (>0.75). Internal and external validations along with residue plot indicated that the model was robust and predictive. The model was successfully applied to allocate the use of antibiotics in China in 2011 at national-, provincial-, prefectural-, and county-level, which are comparable to that back-calculated from the available data of wastewater analysis in some cities. Antibiotic uses were higher in East China than other regions and it was found that uses of total antibiotics vary among Chinese counties on four orders of magnitude (0.186-1645 t antibiotics per year per county). Also management practice could be worked out according to our exploration of the impact transition of social-economic factors on antibiotic uses. To our knowledge, this is the first endeavor to explore this economic dominated relationship for estimating spatially resolved use map of antibiotics in China.

  6. A framework for estimating radiation-related cancer risks in Japan from the 2011 Fukushima nuclear accident. (United States)

    Walsh, L; Zhang, W; Shore, R E; Auvinen, A; Laurier, D; Wakeford, R; Jacob, P; Gent, N; Anspaugh, L R; Schüz, J; Kesminiene, A; van Deventer, E; Tritscher, A; del Rosarion Pérez, M


    We present here a methodology for health risk assessment adopted by the World Health Organization that provides a framework for estimating risks from the Fukushima nuclear accident after the March 11, 2011 Japanese major earthquake and tsunami. Substantial attention has been given to the possible health risks associated with human exposure to radiation from damaged reactors at the Fukushima Daiichi nuclear power station. Cumulative doses were estimated and applied for each post-accident year of life, based on a reference level of exposure during the first year after the earthquake. A lifetime cumulative dose of twice the first year dose was estimated for the primary radionuclide contaminants ((134)Cs and (137)Cs) and are based on Chernobyl data, relative abundances of cesium isotopes, and cleanup efforts. Risks for particularly radiosensitive cancer sites (leukemia, thyroid and breast cancer), as well as the combined risk for all solid cancers were considered. The male and female cumulative risks of cancer incidence attributed to radiation doses from the accident, for those exposed at various ages, were estimated in terms of the lifetime attributable risk (LAR). Calculations of LAR were based on recent Japanese population statistics for cancer incidence and current radiation risk models from the Life Span Study of Japanese A-bomb survivors. Cancer risks over an initial period of 15 years after first exposure were also considered. LAR results were also given as a percentage of the lifetime baseline risk (i.e., the cancer risk in the absence of radiation exposure from the accident). The LAR results were based on either a reference first year dose (10 mGy) or a reference lifetime dose (20 mGy) so that risk assessment may be applied for relocated and non-relocated members of the public, as well as for adult male emergency workers. The results show that the major contribution to LAR from the reference lifetime dose comes from the first year dose. For a dose of 10 mGy in

  7. Up-to-date and precise estimates of cancer patient survival: model-based period analysis. (United States)

    Brenner, Hermann; Hakulinen, Timo


    Monitoring of progress in cancer patient survival by cancer registries should be as up-to-date as possible. Period analysis has been shown to provide more up-to-date survival estimates than do traditional methods of survival analysis. However, there is a trade-off between up-to-dateness and the precision of period estimates, in that increasing the up-to-dateness of survival estimates by restricting the analysis to a relatively short, recent time period, such as the most recent calendar year for which cancer registry data are available, goes along with a loss of precision. The authors propose a model-based approach to maximize the up-to-dateness of period estimates at minimal loss of precision. The approach is illustrated for monitoring of 5-year relative survival of patients diagnosed with one of 20 common forms of cancer in Finland between 1953 and 2002 by use of data from the nationwide Finnish Cancer Registry. It is shown that the model-based approach provides survival estimates that are as up-to-date as the most up-to-date conventional period estimates and at the same time much more precise than the latter. The modeling approach may further enhance the use of period analysis for deriving up-to-date cancer survival rates.

  8. Catalog of genetic progression of human cancers: breast cancer. (United States)

    Desmedt, Christine; Yates, Lucy; Kulka, Janina


    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.

  9. Role of ARPC2 in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Jun Zhang


    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.

  10. Human Papillomavirus and the Development of Different Cancers. (United States)

    Gao, Ge; Smith, David I


    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.

  11. 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: [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)


    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.

  12. TP53 mutations, expression and interaction networks in human cancers. (United States)

    Wang, Xiaosheng; Sun, Qingrong


    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.

  13. Telmisartan inhibits human urological cancer cell growth through early apoptosis (United States)



    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

  14. Screening Mammography: Patient Perceptions and Preferences Regarding Communication of Estimated Breast Cancer Risk. (United States)

    Amornsiripanitch, Nita; Mangano, Mark; Niell, Bethany L


    Many models exist to estimate a woman's risk of development of breast cancer. At screening mammography, many imaging centers collect data required for these models to identify women who may benefit from supplemental screening and referral for cancer risk assessment. The purpose of this study was to discern perceptions and preferences of screening mammography patients regarding communication of estimated breast cancer risk. An anonymous survey was distributed to screening and surveillance mammography patients between April and June 2015. Survey questions were designed to assess patient preferences regarding the receipt and complexity of risk estimate communication, including hypothetical scenarios with and without > 20% estimated risk of breast cancer. The McNemar test and the Wilcoxon signed rank test were used with p ≤ 0.05 considered statistically significant. The survey was distributed to 1061 screening and surveillance mammography patients, and 503 patients responded (response rate, 47%). Although 86% (431/503) of patients expressed interest in learning their estimated risk, only 8% (38/503) had undergone formal risk assessment. The preferred method (241 respondents [26%]) of communication of risk 20%, patients preferred oral communication and were 10-fold as likely to choose only oral communication (p 20%, patients preferred to learn their estimated risk in great detail (69% and 85%), although women were significantly more likely to choose greater detail for risk > 20% (p < 0.00001). Screening mammography patients expressed interest in learning their estimated risk of breast cancer regardless of their level of hypothetical risk.

  15. An estimate of the number of people in Italy living after a childhood cancer. (United States)

    Francisci, Silvia; Guzzinati, Stefano; Dal Maso, Luigino; Sacerdote, Carlotta; Buzzoni, Carlotta; Gigli, Anna


    Cancers diagnosed in children below the age of 15 years represent 1.2% of all cancer cases, and survival after a childhood cancer has greatly improved over the past 40 years in all high income countries. This study aims to estimate the number of people living in Italy after a childhood cancer for all cancers combined and for a selection of cancer types. We computed 15-year prevalence using data from 15 Italian population-based cancer registries (covering 19% of Italian population) and estimated complete prevalence for Italy by using the CHILDPREV method, implemented in the COMPREV software. A total of 44,135 persons were alive at January 1st, 2010 after a cancer diagnosed during childhood. This number corresponds to a proportion of 73 per 100,000 Italians and to about 2% of all prevalent cases. Among them, 54% were males and 64% had survived after being diagnosed before 1995, the start of the observation period. A quarter of all childhood prevalent cases were diagnosed with brain and central nervous system tumors, a quarter with acute lymphoid leukemia, and 7% with Hodgkin lymphoma. Nearly a quarter of prevalent patients were aged 40 years and older. Information about the number of people living after a childhood cancer in Italy by cancer type and their specific health care needs may be helpful to health-care planners and clinicians in the development of guidelines aimed to reduce the burden of late effect of treatments during childhood.

  16. Cortico-Cortical Receptive Field Estimates in Human Visual Cortex

    Directory of Open Access Journals (Sweden)

    Koen V Haak


    Full Text Available Human visual cortex comprises many visual areas that contain a map of the visual field (Wandell et al 2007, Neuron 56, 366–383. These visual field maps can be identified readily in individual subjects with functional magnetic resonance imaging (fMRI during experimental sessions that last less than an hour (Wandell and Winawer 2011, Vis Res 718–737. Hence, visual field mapping with fMRI has been, and still is, a heavily used technique to examine the organisation of both normal and abnormal human visual cortex (Haak et al 2011, ACNR, 11(3, 20–21. However, visual field mapping cannot reveal every aspect of human visual cortex organisation. For example, the information processed within a visual field map arrives from somewhere and is sent to somewhere, and visual field mapping does not derive these input/output relationships. Here, we describe a new, model-based analysis for estimating the dependence between signals in distinct cortical regions using functional magnetic resonance imaging (fMRI data. Just as a stimulus-referred receptive field predicts the neural response as a function of the stimulus contrast, the neural-referred receptive field predicts the neural response as a function of responses elsewhere in the nervous system. When applied to two cortical regions, this function can be called the cortico-cortical receptive field (CCRF. We model the CCRF as a Gaussian-weighted region on the cortical surface and apply the model to data from both stimulus-driven and resting-state experimental conditions in visual cortex.

  17. Object Detection and Tracking-Based Camera Calibration for Normalized Human Height Estimation

    Directory of Open Access Journals (Sweden)

    Jaehoon Jung


    Full Text Available This paper presents a normalized human height estimation algorithm using an uncalibrated camera. To estimate the normalized human height, the proposed algorithm detects a moving object and performs tracking-based automatic camera calibration. The proposed method consists of three steps: (i moving human detection and tracking, (ii automatic camera calibration, and (iii human height estimation and error correction. The proposed method automatically calibrates camera by detecting moving humans and estimates the human height using error correction. The proposed method can be applied to object-based video surveillance systems and digital forensic.

  18. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue. (United States)

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


    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.

  19. Human Resources for Cancer Control in Uttar Pradesh, India: A Case Study for Low and Middle Income Countries (United States)

    Daphtary, Maithili; Agrawal, Sushma; Vikram, Bhadrasain


    For addressing the growing burden of cancer in low and middle income countries, an important first step is to estimate the human resources required for cancer control in a country, province, or city. However, few guidelines are available to decision makers in that regard. Here, we propose a methodology for estimating the human and other resources needed in the state of Uttar Pradesh (UP), India as a case study. Information about the population of UP and its cities was obtained from The number of new cancer cases annually for the commonest cancers was estimated from GLOBOCAN 20081. For estimating the human resources needed, the following assumptions were made: newly diagnosed cancer patients need pathology for diagnosis and for treatment surgery, chemotherapy, and/or radiotherapy. The percentage of patients requiring each of those modalities, their average lengths of stay as in-patients, and number of in-patient oncology beds were estimated. The resources already available in UP were determined by a telephone survey and by searching the websites of radiation therapy centers and medical colleges. Twenty-four radiation oncologists at 24 cancer centers in 10 cities responded to the survey. As detailed in this manuscript, an enormous shortage of human resources for cancer control exists in UP. Human resources are the key to diagnosing cancers early and treating them appropriately. Addressing the shortage will not be easy but we hope that the methodology described here can guide decision makers and form a framework for discussion among the various stakeholders. This methodology is readily adaptable to local practices and data. PMID:25237650

  20. Human resources for cancer control in uttar pradesh, India: a case study for low and middle income countries. (United States)

    Daphtary, Maithili; Agrawal, Sushma; Vikram, Bhadrasain


    For addressing the growing burden of cancer in low and middle income countries, an important first step is to estimate the human resources required for cancer control in a country, province, or city. However, few guidelines are available to decision makers in that regard. Here, we propose a methodology for estimating the human and other resources needed in the state of Uttar Pradesh (UP), India as a case study. Information about the population of UP and its cities was obtained from The number of new cancer cases annually for the commonest cancers was estimated from GLOBOCAN 2008. For estimating the human resources needed, the following assumptions were made: newly diagnosed cancer patients need pathology for diagnosis and for treatment surgery, chemotherapy, and/or radiotherapy. The percentage of patients requiring each of those modalities, their average lengths of stay as in-patients, and number of in-patient oncology beds were estimated. The resources already available in UP were determined by a telephone survey and by searching the websites of radiation therapy centers and medical colleges. Twenty-four radiation oncologists at 24 cancer centers in 10 cities responded to the survey. As detailed in this manuscript, an enormous shortage of human resources for cancer control exists in UP. Human resources are the key to diagnosing cancers early and treating them appropriately. Addressing the shortage will not be easy but we hope that the methodology described here can guide decision makers and form a framework for discussion among the various stakeholders. This methodology is readily adaptable to local practices and data.

  1. Time of flight estimation for breast cancer margin thickness using embedded tumors (United States)

    Bowman, Tyler; El-Shenawee, Magda; Campbell, Lucas


    This work aims to enact a quick and reasonable estimation of breast cancer margin thickness using time of flight analysis of embedded breast cancer tissue. A pulsed terahertz system is used to obtain reflection imaging scans from breast cancer tumors that are formalin-fixed and embedded in paraffin blocks. Time of flight analysis is then used to compare the reflection patterns seen within the block to pathology sections and paraffin-embedded sections that are taken throughout the depth of the tumor in order to estimate the three-dimensional boundaries of the tumor.

  2. Human papillomavirus genotype prevalence in invasive penile cancers from a registry-based United States population

    Directory of Open Access Journals (Sweden)

    Brenda Y Hernandez


    Full Text Available Background. Human papillomavirus (HPV is estimated to play an etiologic role in 40%-50% of penile cancers worldwide. Estimates of HPV prevalence in U.S. penile cancer cases are limited. Methods. HPV DNA was evaluated in tumor tissue from 79 invasive penile cancer patients diagnosed in 1998-2005 within the catchment areas of 7 U.S. cancer registries. HPV was genotyped using PCR-based Linear Array and INNO-LiPA assays and compared by demographic, clinical, and pathologic characteristics and survival. Histological classification was also obtained by independent pathology review. Results. HPV DNA was present in 50 of 79 (63% of invasive penile cancer cases. Sixteen viral genotypes were detected. HPV 16, found in 46% (36/79 of all cases (72% of HPV-positive cases was the most prevalent genotype followed equally by HPV 18, 33, and 45, which each comprised 5% of all cases. Multiple genotypes were detected in 18% of viral positive cases. HPV prevalence did not significantly vary by age, race/ethnicity, population size of geographic region, cancer stage, histology, grade, penile subsite, or prior cancer history. Penile cases diagnosed in more recent years were more likely to be HPV positive. Overall survival did not significantly vary by HPV status. Conclusions. The relatively high prevalence of HPV in our study population provides limited evidence of a more prominent and, possibly, increasing role of infection in penile carcinogenesis in the U.S. compared to other parts of the world.

  3. Remarks on human body posture estimation from silhouette image based on heuristic rules and Kalman filter (United States)

    Takahashi, Kazuhiko; Naemura, Masahide


    This paper proposes a human body posture estimation method based on analysis of human silhouette and Kalman filter. The proposed method is based on both the heuristically extraction method of estimating the significant points of human body and the contour analysis of the human silhouette. The 2D coordinates of the human body's significant points, such as top of the head, and tips of feet, are located by applying the heuristically extraction method to the human silhouette, those of tips of hands are obtained by using the result of the contour analysis, and the joints of elbows and knees are estimated by introducing some heuristic rules to the contour image of the human silhouette. The estimated results are optimized and tracked by using Kalman filter. The proposed estimation method is implemented on a personal computer and runs in real-time. Experimental results show both the feasibility and the effectiveness of the proposed method for estimating human body postures.

  4. Discrepancies between estimated and perceived risk of cancer among individuals with hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Domanska, K; Nilbert, Mef; Soller, M;


    Communicating cancer risk and recommending adequate control programs is central for genetic counseling. Individuals affected by hereditary nonpolyposis colorectal cancer (HNPCC) are at about 80% life-time risk of colorectal cancer and for female carriers 40-60% risk of endometrial cancer and 10-1...

  5. Trends in all-cause five-year mortality after head and neck cancers diagnosed over a period of 33 years. Focus on estimated degree of association with human papillomavirus

    DEFF Research Database (Denmark)

    Svahn, Malene F; Munk, Christian; Nielsen, Thor S S


    associated with HPV, i.e. the base of the tongue and the tonsils, where a 28% decrease per five years (e.g. HRbase of tongue/tonsils=0.72; 95% CI 0.64-0.81) was observed. When examining sex- and age-specific time trends, the decrease in mortality was most pronounced among male patients and patients below 60......-based cohort study of all 20 925 individuals diagnosed with squamous cell carcinoma of the head and neck (HNSCC) in Denmark 1978-2010, we investigate secular trends in all-cause five-year mortality after HNSCC according to the anticipated degree of association with HPV using a Cox proportional hazards model....... Furthermore, we examine whether any trend over time differed according to sex, stage, and age at diagnosis. RESULTS: All-cause five-year mortality after HNSCC has decreased over time. The greatest decrease was seen in the last decade (2000-2010) among patients with HNSCC at sites estimated to be strongly...

  6. Human Papilloma Viruses and Breast Cancer – Assessment of Causality (United States)

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


    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

  7. 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


    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.

  8. An Estimation of Radiobiological Parameters for Head-and-Neck Cancer Cells and the Clinical Implications (United States)

    Qi, X. Sharon; Yang, Qiuhui; Lee, Steve P.; Li, X. Allen; Wang, Dian


    In vitro survival measurements using two human head-and-neck cancer (HNC) cell lines were performed. The specially designed split-dose surviving fraction was obtained and fitted to the linear-quadratic formalism. The repair halftime (Tr), the potential doubling time (Td), α/β and radiosensitivity α, were estimated. Other radiobiological models: EUD, BED, TCP, etc., were used to examine the potential treatment effectiveness of different IMRT techniques. Our data indicated the repair halftime of ~17 min based on two HNC cell lines. The combined α/β, α and Td are α/β = 8.1 ± 4.1 Gy, α = 0.22 ± 0.08 Gy−1, Td = 4.0 ± 1.8 day, respectively. The prolonged IMRT dose delivery for entire HNC treatment course could possibly result in the loss of biological effectiveness, i.e., the target EUDs decreased by 11% with fraction dose delivery time varying from 5 to 30 min. We determined the sublethal damage repair halftime and other radiobiological parameters for HNC cells, and to evaluate treatment effectiveness of the prolonged dose delivery times associated with different IMRT techniques. The estimated repair halftime for HNC is relatively short and may be comparable to the step-and-shoot IMRT fraction dose delivery time. The effectiveness of IMRT treatment may be improved by reducing the fraction delivery time for HNC treatment. PMID:24213325

  9. Estimating Survival Rates in Gastric Cancer Based on Pathologic and Demographic Factors in Fars Cancer Registry (2001-2005

    Directory of Open Access Journals (Sweden)

    Rajaeifard Abdolreza


    Full Text Available Background: Gastric cancer remains as one of the leading causes of death worldwide. In patients with gastric cancer, the survival rate after diagnosis is relatively low. The present study aimed to evaluate the impact of demographic factors in estimation of survival rate in patients with gastric cancer in order to develop updated documents in these patients. Materials and Methods: All gastric cancer patients registered in Fars cancer registry from 2001-2006 were entered in the study. Vital status of the patients was asked by telephone contact. Survival rates were estimated using Kaplan-Meier method and compared by Log-rank test. All calculations were performed using STATA (v.8 software. The p value0.05. Conclusion: Our results showed that the survival rates of gastric cancer patients in our study were relatively low. Late diagnosis and delayed therapy are important reasons for low survival in these patients. Therefore, improving public education about primary symptoms of gastric cancer by media is recommended

  10. Tea and cancer prevention: studies in animals and humans. (United States)

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


    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.

  11. Defining the cellular precursors to human breast cancer (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


    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. Primary human papillomavirus DNA screening for cervical cancer prevention: Can the screening interval be safely extended? (United States)

    Vink, Margaretha A; Bogaards, Johannes A; Meijer, Chris J L M; Berkhof, Johannes


    Cytological screening has substantially decreased the cervical cancer incidence, but even better protection may be achieved by primary high-risk human papillomavirus (hrHPV) screening. In the Netherlands, five-yearly cytological screening for women aged 30-60 years will be replaced by primary hrHPV screening in 2016. The new screening guidelines involve an extension of the screening interval from 5 to 10 years for hrHPV-negative women aged 40 or 50 years. We investigated the impact of this program change on the lifetime cancer risks in women without an hrHPV infection at age 30, 35, 40, 45 or 50 years. The time to cancer was estimated using 14-year follow-up data from a population-based screening intervention trial and the nationwide database of histopathology reports. The new screening guidelines are expected to lead to a reduced cervical cancer risk for all age groups. The average risk reduction was 34% and was smallest (25%) among women aged 35 years. The impact of hrHPV screening on the cancer risk was sensitive to the duration from cervical intraepithelial neoplasia grade 2/3 (CIN2/3) to cancer; a small increase in the cancer risk was estimated for women aged 35 or 40 years in case a substantial proportion of CIN2/3 showed fast progression to cancer. Our results indicate that primary hrHPV screening with a ten-yearly interval for hrHPV-negative women of age 40 and beyond will lead to a further reduction in lifetime cancer risk compared to five-yearly cytology, provided that precancerous lesions progress slowly to cancer.

  13. Dog bites in humans and estimating human rabies mortality in rabies endemic areas of Bhutan.

    Directory of Open Access Journals (Sweden)



    Full Text Available BACKGROUND: Dog bites in humans are a public health problem worldwide. The issues of increasing stray dog populations, rabies outbreaks, and the risk of dogs biting humans have been frequently reported by the media in Bhutan. This study aimed to estimate the bite incidence and identify the risk factors for dog bites in humans, and to estimate human deaths from rabies in rabies endemic south Bhutan. METHODS: A hospital-based questionnaire survey was conducted during 2009-2010 among dog bites victims who visited three hospitals in Bhutan for anti-rabies vaccine injection. Decision tree modeling was used to estimate human deaths from rabies following dog bite injuries in two rabies endemic areas of south Bhutan. RESULTS: Three hundred and twenty four dog bite victims were interviewed. The annual incidence of dog bites differed between the hospital catchment areas: 869.8 (95% CI: 722.8-1022.5, 293.8 (240-358.2 and 284.8 (251.2-323 per 100,000 people in Gelephu, Phuentsholing and Thimphu, respectively. Males (62% were more at risk than females (P<0.001. Children aged 5-9 years were bitten more than other age groups. The majority of victims (71% were bitten by stray dogs. No direct fatal injury was reported. In two hospital areas (Gelephu and Phuentsholing in south Bhutan the annual incidence of death from rabies was 3.14 (95% CI: 1.57-6.29 per 100,000 population. The decision tree model predicted an equivalent annual incidence of 4.67 (95% CI: 2.53-7.53 deaths/100,000 population at risk. In the absence of post exposure prophylaxis, the model predicted 19.24 (95% CI: 13.69-25.14 deaths/year in these two areas. CONCLUSIONS: Increased educational awareness of people about the risk of dog bites and rabies is necessary, particularly for children in rabies endemic areas of Bhutan.

  14. Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach (United States)

    Risso, Davide; Taglioli, Luca; De Iasio, Sergio; Gueresi, Paola; Alfani, Guido; Nelli, Sergio; Rossi, Paolo; Paoli, Giorgio; Tofanelli, Sergio


    This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447–2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8–30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics. PMID:26452043

  15. Probabilistic methodology for estimating radiation-induced cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Dunning, D.E. Jr.; Leggett, R.W.; Williams, L.R.


    The RICRAC computer code was developed at Oak Ridge National Laboratory to provide a versatile and convenient methodology for radiation risk assessment. The code allows as input essentially any dose pattern commonly encountered in risk assessments for either acute or chronic exposures, and it includes consideration of the age structure of the exposed population. Results produced by the analysis include the probability of one or more radiation-induced cancer deaths in a specified population, expected numbers of deaths, and expected years of life lost as a result of premature fatalities. These calculatons include consideration of competing risks of death from all other causes. The program also generates a probability frequency distribution of the expected number of cancers in any specified cohort resulting from a given radiation dose. The methods may be applied to any specified population and dose scenario.

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

    DEFF Research Database (Denmark)

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


    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...

  17. Estimating the cost of operating cancer registries: Experience in Colombia. (United States)

    de Vries, Esther; Pardo, Constanza; Arias, Nelson; Bravo, Luis Eduardo; Navarro, Edgar; Uribe, Claudia; Yepez, María Clara; Jurado, Daniel; Garci, Luz Stella; Piñeros, Marion; Edwards, Patrick; Beebe, Maggie Cole; Tangka, Florence; Subramanian, Sujha


    Maintaining population-based registries requires adequate and sustained resources; however, to date there has been no systematic evaluation to identify the resource needs for cancer registration in most countries, including Colombia. A systematic assessment of the costs can quantify the funding required and identify processes to improve efficiency of cancer registries. The Centers for Disease Control and Prevention's (CDC's) International Registry Costing Tool (IntRegCosting Tool) was tailored specifically for the Colombian registries and was used to collect resource use data from five regional population-based cancer registries: Barranquilla, Bucaramanga, Cali, Manizales, and Pasto. The registries provided cost data for the year 2013 and cancer cases corresponding to the year 2010. We identified an almost threefold variation in the average cost per case (77,932 to 214,082 Colombian pesos or US $41 to US $113 in 2013) across the registries, but there were also substantial differences in data collection approaches, types of data collected, and activities performed. Cost per inhabitant varied between 95 and 415 Colombian pesos (US $0.05 to US $0.22). Between 20% and 45% of the total cost was due to fixed cost activities. The detailed economic information presented in this study constitutes a valuable source of activity-based cost data that registries can use to compare operations, assess key factors that lead to differences in cost per case, and identify potential approaches to improve efficiencies. Furthermore, the knowledge gained from studying the Colombian registries can help inform the planning and operations of other registries in the region. Published by Elsevier Ltd.

  18. 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.

  19. Evaluating the risk of liver cancer in humans exposed in trichloroethylene using physiological models

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, J.W. (Armstrong Lab., Wright-Patterson AFB, OH (United States)); Allen, B.C. (Clement Assoc., Ruston, LA (United States))


    Trichloroethylene (TCE) is a widespread environmental pollutant. TCE is classified as a rodent carcinogen by the U.S. Environmental Protection Agency (EPA). Using the rodent cancer bioassay findings and estimates of metabolized dose, the SPA has estimated lifetime exposure cancer risks for humans that ingest TCE in drinking water or inhale TCE. In this study, a physiologically based pharmacokinetic (PB-PK) model for mice was used to simulate selected gavage and inhalation bioassays with TCE. Plausible dose-metrics thought to be linked with the mechanism of action for TCE carcinogenesis were selected. These dose-metrics, adjusted to reflect an average amount per day for a lifetime, were metabolism of TCE (AMET, mg/kg/day) and systemic concentration of TCA (AUCTCA, mg/L/day). These dose-metrics were then used in a linearized multistage model to estimate AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million in mice. A human PB-PK model for TCE was then used to predict TCE concentrations in drinking water and air that would provide AMET and AUCTCA values equal to the predicted mice AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million. For the dose-metrics, AMET and AUCTCA, the TCE concentrations in air wave 10.0 and 0.1 ppb TCE (continuous exposure), respectively, and in water, 7 and 4 [mu] TCE/L, respectively.

  20. Estimating the incidence of lung cancer attributable to occupational exposure in Iran

    Directory of Open Access Journals (Sweden)

    Mousavi-Jarrahi Yasaman


    Full Text Available Abstract Objective The aim of this study was to estimate the fraction of lung cancer incidence in Iran attributed to occupational exposures to the well-established lung cancer carcinogens, including silica, cadmium, nickel, arsenic, chromium, diesel fumes, beryllium, and asbestos. Methods Nationwide exposure to each of the mentioned carcinogens was estimated using workforce data from the Iranian population census of 1995, available from the International Labor Organization (ILO website. The prevalence of exposure to carcinogens in each industry was estimated using exposure data from the CAREX (CARcinogen EXposure database, an international occupational carcinogen information system kept and maintained by the European Union. The magnitude of the relative risk of lung cancer for each carcinogen was estimated from local and international literature. Using the Levin modified population attributable risk (incidence fraction, lung cancer incidence (as estimated by the Tehran Population-Based Cancer Registry attributable to workplace exposure to carcinogens was estimated. Results The total workforce in Iran according to the 1995 census identified 12,488,020 men and 677,469 women. Agriculture is the largest sector with 25% of the male and 0.27% of female workforce. After applying the CAREX exposure estimate to each sector, the proportion exposed to lung carcinogens was 0.08% for male workers and 0.02% for female workers. Estimating a relative risk of 1.9 (95% CI of 1.7–2.1 for high exposure and 1.3 (95% CI 1.2–1.4 for low exposure, and employing the Levin modified formula, the fraction of lung cancer attributed to carcinogens in the workplace was 1.5% (95% CI of 1.2–1.9 for females and 12% (95% CI of 10–15 for males. These fractions correspond to an estimated incidence of 1.3 and 0.08 cases of lung cancer per 100,000 population for males and females, respectively. Conclusion The incidence of lung cancer due to occupational exposure is low in

  1. Human Papillomavirus (HPV) and Oropharyngeal Cancer (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 ...

  2. Study of apoptosis in human liver cancers

    Institute of Scientific and Technical Information of China (English)

    Chang-Min Shan; Juan Li


    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.

  3. 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.


    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

  4. 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


    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.

  5. Human papillomavirus in cervical cancer and oropharyngeal cancer: One cause, two diseases. (United States)

    Berman, Tara A; Schiller, John T


    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.

  6. Chestnut extract induces apoptosis in AGS human gastric cancer cells. (United States)

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


    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.

  7. Dietary Acrylamide and Human Cancer: A Systematic Review of Literature (United States)

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


    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

  8. Model-based Small Area Estimates of Cancer Risk Factors and Screening Behaviors - Small Area Estimates (United States)

    These model-based estimates use two surveys, the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health Interview Survey (NHIS). The two surveys are combined using novel statistical methodology.

  9. Estimating the effect of human base excision repair protein variants on the repair of oxidative DNA base damage. (United States)

    Sokhansanj, Bahrad A; Wilson, David M


    Epidemiologic studies have revealed a complex association between human genetic variance and cancer risk. Quantitative biological modeling based on experimental data can play a critical role in interpreting the effect of genetic variation on biochemical pathways relevant to cancer development and progression. Defects in human DNA base excision repair (BER) proteins can reduce cellular tolerance to oxidative DNA base damage caused by endogenous and exogenous sources, such as exposure to toxins and ionizing radiation. If not repaired, DNA base damage leads to cell dysfunction and mutagenesis, consequently leading to cancer, disease, and aging. Population screens have identified numerous single-nucleotide polymorphism variants in many BER proteins and some have been purified and found to exhibit mild kinetic defects. Epidemiologic studies have led to conflicting conclusions on the association between single-nucleotide polymorphism variants in BER proteins and cancer risk. Using experimental data for cellular concentration and the kinetics of normal and variant BER proteins, we apply a previously developed and tested human BER pathway model to (i) estimate the effect of mild variants on BER of abasic sites and 8-oxoguanine, a prominent oxidative DNA base modification, (ii) identify ranges of variation associated with substantial BER capacity loss, and (iii) reveal nonintuitive consequences of multiple simultaneous variants. Our findings support previous work suggesting that mild BER variants have a minimal effect on pathway capacity whereas more severe defects and simultaneous variation in several BER proteins can lead to inefficient repair and potentially deleterious consequences of cellular damage.

  10. Decorin in Human Colon Cancer: Localization In Vivo and Effect on Cancer Cell Behavior In Vitro. (United States)

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


    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.

  11. Counselees' Expressed Level of Understanding of the Risk Estimate and Surveillance Recommendation are Not Associated with Breast Cancer Surveillance Adherence

    NARCIS (Netherlands)

    Albada, Akke; van Dulmen, Sandra; Dijkstra, Henrietta; Wieffer, Ivette; Witkamp, Arjen; Ausems, Margreet G E M

    We studied counselees' expressed understanding of the risk estimate and surveillance recommendation in the final consultation for breast cancer genetic counseling in relation with their risk perception, worry and cancer surveillance adherence 1 year post-counseling. Consecutive counselees were

  12. Counselees' Expressed Level of Understanding of the Risk Estimate and Surveillance Recommendation are Not Associated with Breast Cancer Surveillance Adherence

    NARCIS (Netherlands)

    Albada, A.; Dulmen, S. van; Dijkstra, H.; Wieffer, I.; Witkamp, A.; Ausems, M.G.


    We studied counselees' expressed understanding of the risk estimate and surveillance recommendation in the final consultation for breast cancer genetic counseling in relation with their risk perception, worry and cancer surveillance adherence 1 year post-counseling. Consecutive counselees were

  13. Counselees’ expressed level of understanding of the risk estimate and surveillance recommendation are not associated with breast cancer surveillance adherence.

    NARCIS (Netherlands)

    Albada, A.; Dulmen, S. van; Dijkstra, H.; Wieffer, I.; Witkamp, A.; Ausems, M.G.E.M.


    We studied counselees’ expressed understanding of the risk estimate and surveillance recommendation in the final consultation for breast cancer genetic counseling in relation with their risk perception, worry and cancer surveillance adherence 1 year post-counseling. Consecutive counselees were

  14. Multimodel estimates of premature human mortality due to intercontinental transport of air pollution (United States)

    Liang, C.; Silva, R.; West, J. J.; Sudo, K.; Lund, M. T.; Emmons, L. K.; Takemura, T.; Bian, H.


    Numerous modeling studies indicate that emissions from one continent influence air quality over others. Reducing air pollutant emissions from one continent can therefore benefit air quality and health on multiple continents. Here, we estimate the impacts of the intercontinental transport of ozone (O3) and fine particulate matter (PM2.5) on premature human mortality by using an ensemble of global chemical transport models coordinated by the Task Force on Hemispheric Transport of Air Pollution (TF HTAP). We use simulations of 20% reductions of all anthropogenic emissions from 13 regions (North America, Central America, South America, Europe, Northern Africa, Sub-Saharan Africa, Former Soviet Union, Middle East, East Asia, South Asia, South East Asia, Central Asia, and Australia) to calculate their impact on premature mortality within each region and elsewhere in the world. To better understand the impact of potential control strategies, we also analyze premature mortality for global 20% perturbations from five sectors individually: power and industry, ground transport, forest and savannah fires, residential, and others (shipping, aviation, and agriculture). Following previous studies, premature human mortality resulting from each perturbation scenario is calculated using a health impact function based on a log-linear model for O3 and an integrated exposure response model for PM2.5 to estimate relative risk. The spatial distribution of the exposed population (adults aged 25 and over) is obtained from the LandScan 2011 Global Population Dataset. Baseline mortality rates for chronic respiratory disease, ischemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, and lung cancer are estimated from the GBD 2010 country-level mortality dataset for the exposed population. Model results are regridded from each model's original grid to a common 0.5°x0.5° grid used to estimate mortality. We perform uncertainty analysis and evaluate the sensitivity

  15. Growth-stimulatory effect of resveratrol in human cancer cells. (United States)

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


    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. The oncogenic potential of human cytomegalovirus and breast cancer.

    Directory of Open Access Journals (Sweden)

    Georges eHerbein


    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.

  17. Frequency of TERT promoter mutations in human cancers. (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


    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.

  18. Pre-clinical Orthotopic Murine Model of Human Prostate Cancer. (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


    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.

  19. [Use of human recombinant erythropoietin in children with cancer]. (United States)

    Guyot, D; Margueritte, G


    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.

  20. Gene transcriptional networks integrate microenvironmental signals in human breast cancer. (United States)

    Xu, Ren; Mao, Jian-Hua


    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.

  1. Targeting human papillomavirus to reduce the burden of cervical, vulvar and vaginal cancer and pre-invasive neoplasia

    DEFF Research Database (Denmark)

    Nygård, Mari; Hansen, Bo Terning; Dillner, Joakim;


    BACKGROUND: Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination...... with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004-2006, prior to the availability of HPV vaccines, in order...... to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. METHODS: Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias...

  2. Anticancer Properties of Capsaicin Against Human Cancer. (United States)

    Clark, Ruth; Lee, Seong-Ho


    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.

  3. Estimated risk of radiation-induced cancer from paediatric chest CT: two-year cohort study

    Energy Technology Data Exchange (ETDEWEB)

    Niemann, Tilo [Cantonal Hospital Baden, Department of Radiology, Baden (Switzerland); University Lille Nord de France, Department of Thoracic Imaging, Hospital Calmette, Lille (France); Colas, Lucie; Santangelo, Teresa; Faivre, Jean Baptiste; Remy, Jacques; Remy-Jardin, Martine [University Lille Nord de France, Department of Thoracic Imaging, Hospital Calmette, Lille (France); Roser, Hans W.; Bremerich, Jens [University of Basel Hospital, Clinic of Radiology and Nuclear Medicine, Medical Physics, Basel (Switzerland)


    The increasing absolute number of paediatric CT scans raises concern about the safety and efficacy and the effects of consecutive diagnostic ionising radiation. To demonstrate a method to evaluate the lifetime attributable risk of cancer incidence/mortality due to a single low-dose helical chest CT in a two-year patient cohort. A two-year cohort of 522 paediatric helical chest CT scans acquired using a dedicated low-dose protocol were analysed retrospectively. Patient-specific estimations of radiation doses were modelled using three different mathematical phantoms. Per-organ attributable cancer risk was then estimated using epidemiological models. Additional comparison was provided for naturally occurring risks. Total lifetime attributable risk of cancer incidence remains low for all age and sex categories, being highest in female neonates (0.34%). Summation of all cancer sites analysed raised the relative lifetime attributable risk of organ cancer incidence up to 3.6% in female neonates and 2.1% in male neonates. Using dedicated scan protocols, total lifetime attributable risk of cancer incidence and mortality for chest CT is estimated low for paediatric chest CT, being highest for female neonates. (orig.)

  4. Role of ARPC2 in Human Gastric Cancer


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


    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...

  5. 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.

  6. Dose estimation for repeated phosphorus-32 ingestion in human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Chao, J.H.; Tseng, C.L.; Hsieh, W.A.; Hung, D.Z.; Chang, W.P. E-mail:


    Dose estimation was conducted for internal phosphorus-32 exposure in one young male subject from repeated oral mis-ingestion for >1 year. Since disclosure for previous continuous contamination, a series of urine samples were collected from this individual weekly for a period of >2 months. P-32 radioactivity in urine samples were measured by the acid precipitation method. Estimation for retrospective total effective dose equivalent received by this subject was conducted for cumulative internal dose estimation. A minimum of 9.4 mSv was estimated for an assumed single ingestion. As this was a rare case in radiation protection and internal radiation dosimetry, its implications were of considerable significance.

  7. Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yung-Lin Chu


    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.

  8. 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


    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.

  9. Estimation of T2 relaxation time of breast cancer: Correlation with clinical, imaging and pathological features

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Mirinae; Sohn, Yu Mee [Dept. of Radiology, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul (Korea, Republic of); Ryu, Jung Kyu; Jahng, Geon Ho; Rhee, Sun Jung; Oh, Jang Hoon; Won, Kyu Yeoun [Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul (Korea, Republic of)


    The purpose of this study was to estimate the T2* relaxation time in breast cancer, and to evaluate the association between the T2* value with clinical-imaging-pathological features of breast cancer. Between January 2011 and July 2013, 107 consecutive women with 107 breast cancers underwent multi-echo T2*-weighted imaging on a 3T clinical magnetic resonance imaging system. The Student's t test and one-way analysis of variance were used to compare the T2* values of cancer for different groups, based on the clinical-imaging-pathological features. In addition, multiple linear regression analysis was performed to find independent predictive factors associated with the T2* values. Of the 107 breast cancers, 92 were invasive and 15 were ductal carcinoma in situ (DCIS). The mean T2* value of invasive cancers was significantly longer than that of DCIS (p = 0.029). Signal intensity on T2-weighted imaging (T2WI) and histologic grade of invasive breast cancers showed significant correlation with T2* relaxation time in univariate and multivariate analysis. Breast cancer groups with higher signal intensity on T2WI showed longer T2* relaxation time (p = 0.005). Cancer groups with higher histologic grade showed longer T2* relaxation time (p = 0.017). The T2* value is significantly longer in invasive cancer than in DCIS. In invasive cancers, T2* relaxation time is significantly longer in higher histologic grades and high signal intensity on T2WI. Based on these preliminary data, quantitative T2* mapping has the potential to be useful in the characterization of breast cancer.

  10. Bionutrition and oral cancer in humans. (United States)

    Enwonwu, C O; Meeks, V I


    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

  11. Estimating Target Orientation with a Single Camera for Use in a Human-Following Robot

    CSIR Research Space (South Africa)

    Burke, Michael G


    Full Text Available This paper presents a monocular vision-based technique for extracting orientation information from a human torso for use in a robotic human-follower. Typical approaches to human-following use an estimate of only human position for navigation...

  12. Uncertainties in estimating heart doses from 2D-tangential breast cancer radiotherapy

    DEFF Research Database (Denmark)

    Laugaard Lorenzen, Ebbe; Brink, Carsten; Taylor, Carolyn W.;


    heart dose estimated from individual CT-scans varied from 8Gy, and maximum dose from 5 to 50Gy for all three regimens, so that estimates based only on regimen had substantial uncertainty. When maximum heart distance was taken into account, the uncertainty was reduced and was comparable......BACKGROUND AND PURPOSE: We evaluated the accuracy of three methods of estimating radiation dose to the heart from two-dimensional tangential radiotherapy for breast cancer, as used in Denmark during 1982-2002. MATERIAL AND METHODS: Three tangential radiotherapy regimens were reconstructed using CT...... to the uncertainty of estimates based on individual CT-scans. For right-sided breast cancer patients, mean heart dose based on individual CT-scans was always

  13. Arsenic Exposure and the Induction of Human Cancers

    Directory of Open Access Journals (Sweden)

    Victor D. Martinez


    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.

  14. Cytotoxicity of dietary flavonoids on different human cancer types

    Directory of Open Access Journals (Sweden)

    Katrin Sak


    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.

  15. Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer. (United States)

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


    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

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

    Directory of Open Access Journals (Sweden)



    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. Tissue-engineered models of human tumors for cancer research (United States)

    Villasante, Aranzazu; Vunjak-Novakovic, Gordana


    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

  18. Estimation of an optimal chemotherapy utilisation rate for cancer: setting an evidence-based benchmark for quality cancer care. (United States)

    Jacob, S A; Ng, W L; Do, V


    There is wide variation in the proportion of newly diagnosed cancer patients who receive chemotherapy, indicating the need for a benchmark rate of chemotherapy utilisation. This study describes an evidence-based model that estimates the proportion of new cancer patients in whom chemotherapy is indicated at least once (defined as the optimal chemotherapy utilisation rate). The optimal chemotherapy utilisation rate can act as a benchmark for measuring and improving the quality of care. Models of optimal chemotherapy utilisation were constructed for each cancer site based on indications for chemotherapy identified from evidence-based treatment guidelines. Data on the proportion of patient- and tumour-related attributes for which chemotherapy was indicated were obtained, using population-based data where possible. Treatment indications and epidemiological data were merged to calculate the optimal chemotherapy utilisation rate. Monte Carlo simulations and sensitivity analyses were used to assess the effect of controversial chemotherapy indications and variations in epidemiological data on our model. Chemotherapy is indicated at least once in 49.1% (95% confidence interval 48.8-49.6%) of all new cancer patients in Australia. The optimal chemotherapy utilisation rates for individual tumour sites ranged from a low of 13% in thyroid cancers to a high of 94% in myeloma. The optimal chemotherapy utilisation rate can serve as a benchmark for planning chemotherapy services on a population basis. The model can be used to evaluate service delivery by comparing the benchmark rate with patterns of care data. The overall estimate for other countries can be obtained by substituting the relevant distribution of cancer types. It can also be used to predict future chemotherapy workload and can be easily modified to take into account future changes in cancer incidence, presentation stage or chemotherapy indications.

  19. Cancer risk assessment: Optimizing human health through linear dose-response models. (United States)

    Calabrese, Edward J; Shamoun, Dima Yazji; Hanekamp, Jaap C


    This paper proposes that generic cancer risk assessments be based on the integration of the Linear Non-Threshold (LNT) and hormetic dose-responses since optimal hormetic beneficial responses are estimated to occur at the dose associated with a 10(-4) risk level based on the use of a LNT model as applied to animal cancer studies. The adoption of the 10(-4) risk estimate provides a theoretical and practical integration of two competing risk assessment models whose predictions cannot be validated in human population studies or with standard chronic animal bioassay data. This model-integration reveals both substantial protection of the population from cancer effects (i.e. functional utility of the LNT model) while offering the possibility of significant reductions in cancer incidence should the hormetic dose-response model predictions be correct. The dose yielding the 10(-4) cancer risk therefore yields the optimized toxicologically based "regulatory sweet spot". Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Estimation of the horizon in photographed outdoor scenes by human and machine.

    Directory of Open Access Journals (Sweden)

    Christian Herdtweck

    Full Text Available We present three experiments on horizon estimation. In Experiment 1 we verify the human ability to estimate the horizon in static images from only visual input. Estimates are given without time constraints with emphasis on precision. The resulting estimates are used as baseline to evaluate horizon estimates from early visual processes. Stimuli are presented for only 153 ms and then masked to purge visual short-term memory and enforcing estimates to rely on early processes, only. The high agreement between estimates and the lack of a training effect shows that enough information about viewpoint is extracted in the first few hundred milliseconds to make accurate horizon estimation possible. In Experiment 3 we investigate several strategies to estimate the horizon in the computer and compare human with machine "behavior" for different image manipulations and image scene types.

  1. Impact of microbial count distributions on human health risk estimates

    DEFF Research Database (Denmark)

    Ribeiro Duarte, Ana Sofia; Nauta, Maarten


    -lognormal distribution. We show that the impact of the choice of different probability distributions to describe concentrations at retail on risk estimates is dependent both on concentration and prevalence levels. We also show that the use of an LOQ should be done consciously, especially when zero-inflation is not used...... on risk estimates, at two different concentration scenarios and at a range of prevalence levels. By using five different parametric distributions, we investigate whether different characteristics of a good fit are crucial for an accurate risk estimate. Among the factors studied are the importance......-inflated Poisson-lognormal distributed data and an existing QMRA model from retail to consumer level, it was possible to assess the difference between expected risk and the risk estimated with using a lognormal, a zero-inflated lognormal, a Poisson-gamma, a zero-inflated Poisson-gamma and a zero-inflated Poisson...

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


    Sehrawat, Anuradha; Singh, Shivendra V.


    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 ...

  3. Inequalities in cancer distribution in Tehran; A disaggregated estimation of 2007 incidencea by 22 districts

    Directory of Open Access Journals (Sweden)

    Marzieh Rohani Rasaf


    Conclusion: This report provides an appropriate guide to estimate the cancer distribution within the districts of Tehran. Higher ASR in districts 6, 1, 2, and 3, warrant further research, to obtain robust population-based incidence data and also to investigate the background predisposing factors in the specified districts.

  4. How does early detection by screening affect disease progression?: Modeling estimated benefits in prostate cancer screening

    NARCIS (Netherlands)

    E.M. Wever (Elisabeth); G. Draisma (Gerrit); E.A.M. Heijnsdijk (Eveline); H.J. de Koning (Harry)


    textabstractBackground. Simulation models are essential tools for estimating benefits of cancer screening programs. Such models include a screening-effect model that represents how early detection by screening followed by treatment affects disease-specific survival. Two commonly used screening-effec


    Institute of Scientific and Technical Information of China (English)

    陈力真; 王树蕙; 张云; 王世真


    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.

  6. Epigenetic modifications and human pathologies: cancer and CVD. (United States)

    Duthie, Susan J


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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


    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 ...

  9. Productivity Losses Associated with Head and Neck Cancer Using the Human Capital and Friction Cost Approaches. (United States)

    Pearce, Alison M; Hanly, Paul; Timmons, Aileen; Walsh, Paul M; O'Neill, Ciaran; O'Sullivan, Eleanor; Gooberman-Hill, Rachael; Thomas, Audrey Alforque; Gallagher, Pamela; Sharp, Linda


    Previous studies suggest that productivity losses associated with head and neck cancer (HNC) are higher than in other cancers. These studies have only assessed a single aspect of productivity loss, such as temporary absenteeism or premature mortality, and have only used the Human Capital Approach (HCA). The Friction Cost Approach (FCA) is increasingly recommended, although has not previously been used to assess lost production from HNC. The aim of this study was to estimate the lost productivity associated with HNC due to different types of absenteeism and premature mortality, using both the HCA and FCA. Survey data on employment status were collected from 251 HNC survivors in Ireland and combined with population-level survival estimates and national wage data. The cost of temporary and permanent time off work, reduced working hours and premature mortality using both the HCA and FCA were calculated. Estimated total productivity losses per employed person of working age were EUR253,800 using HCA and EUR6800 using FCA. The main driver of HCA costs was premature mortality (38% of total) while for FCA it was temporary time off (73% of total). The productivity losses associated with head and neck cancer are substantial, and return to work assistance could form an important part of rehabilitation. Use of both the HCA and FCA approaches allowed different drivers of productivity losses to be identified, due to the different assumptions of the two methods. For future estimates of productivity losses, the use of both approaches may be pragmatic.

  10. 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


    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.

  11. Silencing human cancer: identification and uses of microRNAs. (United States)

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


    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.

  12. Lectins in human cancer: both a devil and an angel? (United States)

    Dan, Xiu Li; Ng, Tzi Bun


    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.

  13. Strategies of functional food for cancer prevention in human beings. (United States)

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


    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.

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


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


    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.

  15. 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.

  16. Human Papillomavirus Testing in the Prevention of Cervical Cancer (United States)

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


    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

  17. 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.

  18. The natural immunity to evolutionary atavistic endotoxin for human cancer. (United States)

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


    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.

  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.


    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


    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. Identification of cancer risk lncRNAs and cancer risk pathways regulated by cancer risk lncRNAs based on genome sequencing data in human cancers. (United States)

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


    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.

  2. Trefoil factor-3 expression in human colon cancer liver metastasis. (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


    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. Using Supervised Deep Learning for Human Age Estimation Problem (United States)

    Drobnyh, K. A.; Polovinkin, A. N.


    Automatic facial age estimation is a challenging task upcoming in recent years. In this paper, we propose using the supervised deep learning features to improve an accuracy of the existing age estimation algorithms. There are many approaches solving the problem, an active appearance model and the bio-inspired features are two of them which showed the best accuracy. For experiments we chose popular publicly available FG-NET database, which contains 1002 images with a broad variety of light, pose, and expression. LOPO (leave-one-person-out) method was used to estimate the accuracy. Experiments demonstrated that adding supervised deep learning features has improved accuracy for some basic models. For example, adding the features to an active appearance model gave the 4% gain (the error decreased from 4.59 to 4.41).

  4. Risk estimates of liver cancer due to aflatoxin exposure from peanuts and peanut products

    Energy Technology Data Exchange (ETDEWEB)

    Dichter, C.R.


    An assessment was undertaken of the risk of liver cancer in the USA associated with aflatoxin ingestion from peanuts. Both laboratory-animal data and epidemiological data collected from the scientific literature and several prominent mathematical extrapolation techniques were used. Risk estimates differed by a factor of greater than 1000 when the extrapolated results of three selected animal studies were analysed. Dose-response data for the male Fischer rat, the most sensitive mammalian species studied, produced an estimate of 158 cases of liver cancer per year in the USA at current levels of aflatoxin exposure. An estimate of 58 annual cases was predicted on the basis of epidemiological data of populations in Africa and Thailand.

  5. 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)


    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.

  6. Human development index is associated with mortality-to-incidence ratios of gastrointestinal cancers. (United States)

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


    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

  7. Estimation of the cost of treatment by chemotherapy for early breast cancer in Morocco

    Directory of Open Access Journals (Sweden)

    Boutayeb Saber


    Full Text Available Abstract Background Breast cancer is the first cancer in women both in incidence and mortality. The treatment of breast cancer benefited from the progress of chemotherapy and targeted therapies, but there was a parallel increase in treatment costs. Despite a relatively high incidence of many sites of cancer, so far, there is no national register for this disease in Morocco. The main goal of this paper is to estimate the total cost of chemotherapy in the early stages of breast cancer due to its frequency and the chances of patients being cured. This study provides health decision-makers with a first estimate of costs and the opportunity to achieve the optimal use of available data to estimate the needs of antimitotics and trastuzumab in Morocco. Method We start by evaluating the individual cost according to the therapeutic sub-groups, namely: 1. Patients needing chemotherapy with only anthracycline-based therapy. 2. Patients needing chemotherapy with both anthracycline and taxane but without trastuzumab. 3. Patients needing trastuzumab in addition to chemotherapy. For each sub-group, the protocol of treatment is described, and the individual costs per unit, and for the whole cycle, are evaluated. Then we estimate the number of women suffering from breast cancer on the basis of two data bases available in Morocco. Finally, we calculate the total annual cost of treatment of breast cancer in Morocco. Results The total cost of breast cancer in Morocco is given in Moroccan dirhams (MAD, the US dollar at the current exchange rate (MAD 10 = USD 1.30 and in international dollars or purchasing power parity (MAD 10 = PPP 1.95. The cost of a therapy with trastuzumab is 8.4 times the cost of a sequential chemotherapy combining anthracycline and taxane, and nearly 60 times the cost of chemotherapy based on anthracycline alone. Globally, between USD 13.3 million and USD 28.6 million need to be devoted every year by the Moroccan health authorities to treat

  8. Radiosensitivity of human colon cancer cell enhanced by immunoliposomal docetaxel

    Institute of Scientific and Technical Information of China (English)

    Qing-Wei Wang; Hui-Lan Lü; Chang-Cheng Song; Hong Liu; Cong-Gao Xu


    AIM: To enhance the radiosensitivity of human colon cancer cells by docetaxel.METHODS: Immunoliposomal docetaxel was prepared by coupling monodonal antibody against carcinoembryonic antigen to cyanuric chloride at the PEG terminus of liposome. LoVo adenocarcinoma cell line was treated with immunoliposomal docetaxel or/and irradiation. MTT colorimetric assay was used to estimate cytotoxicity of immunoliposomal docetaxel and radiotoxicity. Cell cycle redistribution and apoptosis were determined with flow cytometry. Survivin expression in LoVo cells was verified by immunohistochemistry. D801 morphologic analysis system was used to semi-quantify immunohistochemical staining of survivin.RESULTS: Cytotoxicity was induced by immunoliposomal docetaxel alone in a dose-dependent manner. Immunoliposomal docetaxel yielded a cytotoxicity effect at a low dose of 2 nmol/L. With a single dose irradiation, the relative surviving fraction of LoVo cells showed a dosedependent response, but there were no significant changes as radiation delivered from 4 to 8 Gy. Compared with liposomal docetaxel or single dose irradiation,strongly radiopotentiating effects of immunoliposomal docetaxel on LoVo cells were observed. A low dose of immunoliposomal docetaxel could yield sufficient radiosensitivity. Immunoliposomal docetaxel were achieved both specificity of the conjugated antibody and drug radiosensitization. Combined with radiation,immunoliposomal docetaxel significantly increased the percentage of G2/M cells and induced apoptosis, but significantly decreased the percentage of cells in G2/G1 and S phase by comparison with liposomal docetaxel.Immunohistochemical analysis showed that the brown stained survivin was mainly in cytoplasm of LoVo cells.Semi-quantitative analysis of the survivin immunostaining showed that the expression of survivin in LoVo cells under irradiation with immunoliposomal docetaxel was significantly decreased.CONCLUSION: Immunoliposomal docetaxel is strongly effective

  9. Salinomycin as a Drug for Targeting Human Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Cord Naujokat


    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.

  10. Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis (United States)

    Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun


    The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

  11. Estimates of Radiation Doses and Cancer Risk from Food Intake in Korea. (United States)

    Moon, Eun-Kyeong; Ha, Wi-Ho; Seo, Songwon; Jin, Young Woo; Jeong, Kyu Hwan; Yoon, Hae-Jung; Kim, Hyoung-Soo; Hwang, Myung-Sil; Choi, Hoon; Lee, Won Jin


    The aim of this study was to estimate internal radiation doses and lifetime cancer risk from food ingestion. Radiation doses from food intake were calculated using the Korea National Health and Nutrition Examination Survey and the measured radioactivity of (134)Cs, (137)Cs, and (131)I from the Ministry of Food and Drug Safety in Korea. Total number of measured data was 8,496 (3,643 for agricultural products, 644 for livestock products, 43 for milk products, 3,193 for marine products, and 973 for processed food). Cancer risk was calculated by multiplying the estimated committed effective dose and the detriment adjusted nominal risk coefficients recommended by the International Commission on Radiation Protection. The lifetime committed effective doses from the daily diet are ranged 2.957-3.710 mSv. Excess lifetime cancer risks are 14.4-18.1, 0.4-0.5, and 1.8-2.3 per 100,000 for all solid cancers combined, thyroid cancer, and leukemia, respectively.

  12. Multiple-reflection model of human skin and estimation of pigment concentrations (United States)

    Ohtsuki, Rie; Tominaga, Shoji; Tanno, Osamu


    We describe a new method for estimating the concentrations of pigments in the human skin using surface spectral reflectance. We derive an equation that expresses the surface spectral reflectance of the human skin. First, we propose an optical model of the human skin that accounts for the stratum corneum. We also consider the difference between the scattering coefficient of the epidermis and that of the dermis. We then derive an equation by applying the Kubelka-Munk theory to an optical model of the human skin. Unlike a model developed in a recent study, the present equation considers pigments as well as multiple reflections and the thicknesses of the skin layers as factors that affect the color of the human skin. In two experiments, we estimate the pigment concentrations using the measured surface spectral reflectances. Finally, we confirm the feasibility of the concentrations estimated by the proposed method by evaluating the estimated pigment concentrations in the skin.

  13. Multi-task GLOH feature selection for human age estimation

    CERN Document Server

    Liang, Yixiong; Xu, Ying; Xiang, Yao; Zou, Beiji


    In this paper, we propose a novel age estimation method based on GLOH feature descriptor and multi-task learning (MTL). The GLOH feature descriptor, one of the state-of-the-art feature descriptor, is used to capture the age-related local and spatial information of face image. As the exacted GLOH features are often redundant, MTL is designed to select the most informative feature bins for age estimation problem, while the corresponding weights are determined by ridge regression. This approach largely reduces the dimensions of feature, which can not only improve performance but also decrease the computational burden. Experiments on the public available FG-NET database show that the proposed method can achieve comparable performance over previous approaches while using much fewer features.

  14. 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


    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.

  15. [HPV (Human Papilloma Virus) implication in other cancers than gynaecological]. (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


    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.

  16. 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))


    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.


    Institute of Scientific and Technical Information of China (English)

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


    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.

  18. KiSS-1 expression in human breast cancer. (United States)

    Martin, Tracey A; Watkins, Gareth; Jiang, Wen G


    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.

  19. Are 20 human papillomavirus types causing cervical cancer?


    Arbyn, Marc; Tommasino, Massimo; Depuydt, Christophe; Dillner, Joakim


    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...

  20. Aurora-A Oncogene in Human Ovarian Cancer (United States)


    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

  1. Estimating the effect of childhood socioeconomic disadvantage on oral cancer in India using marginal structural models. (United States)

    Krishna Rao, Sreevidya; Mejia, Gloria C; Roberts-Thomson, Kaye; Logan, Richard M; Kamath, Veena; Kulkarni, Muralidhar; Mittinty, Murthy N


    Early life socioeconomic disadvantage could affect adult health directly or indirectly. To the best of our knowledge, there are no studies of the direct effect of early life socioeconomic conditions on oral cancer occurrence in adult life. We conducted a multicenter, hospital-based, case-control study in India between 2011 and 2012 on 180 histopathologically confirmed incident oral and/or oropharyngeal cancer cases, aged 18 years or more, and 272 controls that included hospital visitors, who were not diagnosed with any cancer in the same hospitals. Life-course data were collected on socioeconomic conditions, risk factors, and parental behavior through interview employing a life grid. The early life socioeconomic conditions measure was determined by occupation of the head of household in childhood. Adult socioeconomic measures included participant's education and current occupation of the head of household. Marginal structural models with stabilized inverse probability weights were used to estimate the controlled direct effects of early life socioeconomic conditions on oral cancer. The total effect model showed that those in the low socioeconomic conditions in the early years of childhood had 60% (risk ratio [RR] = 1.6 [95% confidence interval {CI} = 1.4, 1.9]) increased risk of oral cancer. From the marginal structural models, the estimated risk for developing oral cancer among those in low early life socioeconomic conditions was 50% (RR = 1.5 [95% CI = 1.4, 1.5]), 20% (RR = 1.2 [95% CI = 0.9, 1.7]), and 90% (RR = 1.9 [95% CI = 1.7, 2.2]) greater than those in the high socioeconomic conditions when controlled for smoking, chewing, and alcohol, respectively. When all the three mediators were controlled in a marginal structural model, the RR was 1.3 (95% CI = 1.0, 1.6). Early life low socioeconomic condition had a controlled direct effect on oral cancer when smoking, chewing tobacco, and alcohol were separately adjusted in marginal structural models.

  2. Moving Forward in Human Cancer Risk Assessment


    Paules, Richard S.; Aubrecht, Jiri; Corvi, Raffaella; Garthoff, Bernward; Kleinjans, Jos C.


    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 ...

  3. Real-time human walking estimation with radar

    NARCIS (Netherlands)

    Dorp, Ph. van; Groen, F.C.A.


    Radars can be used to observe persons. Animation of an observed human on the basis of Frequency Modulated Continuous Wave (FMCW) radar measurements in virtual reality considerably facilitates the interpretation of the radar measurements. These radar measurements give detailed information of the moti

  4. 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


    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.

  5. 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


    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

  6. Cancer risk estimation in Digital Breast Tomosynthesis using GEANT4 Monte Carlo simulations and voxel phantoms. (United States)

    Ferreira, P; Baptista, M; Di Maria, S; Vaz, P


    The aim of this work was to estimate the risk of radiation induced cancer following the Portuguese breast screening recommendations for Digital Mammography (DM) when applied to Digital Breast Tomosynthesis (DBT) and to evaluate how the risk to induce cancer could influence the energy used in breast diagnostic exams. The organ doses were calculated by Monte Carlo simulations using a female voxel phantom and considering the acquisition of 25 projection images. Single organ cancer incidence risks were calculated in order to assess the total effective radiation induced cancer risk. The screening strategy techniques considered were: DBT in Cranio-Caudal (CC) view and two-view DM (CC and Mediolateral Oblique (MLO)). The risk of cancer incidence following the Portuguese screening guidelines (screening every two years in the age range of 50-80years) was calculated by assuming a single CC DBT acquisition view as standalone screening strategy and compared with two-view DM. The difference in the total effective risk between DBT and DM is quite low. Nevertheless in DBT an increase of risk for the lung is observed with respect to DM. The lung is also the organ that is mainly affected when non-optimal beam energy (in terms of image quality and absorbed dose) is used instead of an optimal one. The use of non-optimal energies could increase the risk of lung cancer incidence by a factor of about 2.

  7. MicroRNA in human cancer and chronic inflammatory diseases. (United States)

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


    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. MicroRNA Regulation of Human Breast Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yohei Shimono


    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.

  9. Anti-cancer effects of Kochia scoparia fruit in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Hye-Yeon Han


    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.

  10. Discrepancies between estimated and perceived risk of cancer among individuals with hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Domanska, K; Nilbert, Mef; Soller, M;


    to individual characteristics. A perceived risk of colorectal cancer above 60% was reported by 22/45 individuals, and only one out of five mutation carriers reported a perceived risk > 80%. Female mutation carriers, individuals below age 50, and individuals who received their oncogenetic counseling within 1...

  11. Estimating exercise stroke volume from asymptotic oxygen pulse in humans. (United States)

    Whipp, B J; Higgenbotham, M B; Cobb, F C


    Noninvasive techniques have been devised to estimate cardiac output (Q) during exercise to obviate vascular cannulation. However, although these techniques are noninvasive, they are commonly not nonintrusive to subjects' spontaneous ventilation and gas-exchange responses. We hypothesized that the exercise stroke volume (SV) and, hence, Q might be accurately estimated simply from the response pattern of two standardly determined variables: O2 uptake (VO2) and heart rate (HR). Central to the theory is the demonstration that the product of Q and mixed venous O2 content is virtually constant (k) during steady-state exercise. Thus from the Fick equation, VO2 = Q.CaCO2-k, where CaCO2 is the arterial CO2 content, the O2 pulse (O2-P) equals SV.CaCO2-(k/HR). Because the arterial O2 content (CaO2) is usually relatively constant in normal subjects during exercise, O2-P should change hyperbolically with HR, asymptoting at SV.CaO2. In addition, because the asymptotic O2-P equals the slope (S) of the linear O2-HR relationship, exercise SV may be predicted as S/CaO2. We tested this prediction in 23 normal subjects who underwent a 3-min incremental cycle-ergometer test with direct determination of CaO2 and mixed venous O2 content from indwelling catheters. The predicted SV closely reflected the measured value (r = 0.80). We therefore conclude that, in normal subjects, exercise SV may be estimated simply as five times S of the linear VO2-HR relationship (where 5 is approximately 1/CaO2).

  12. Estimation of cerebral blood flow during cardiopulmonary resuscitation in humans

    DEFF Research Database (Denmark)

    Christensen, S F; Stadeager, Carsten Preben; Siemkowicz, E


    /kg/min). The cortical CBF was found between 14 and 211 ml 100 g-1.min-1 with mean 42 ml 100 g-1.min-1 and mean white matter CBF equal to 27 ml 100 g-1.min-1. It is suggested that the external cardiac massage in humans may be of poor efficacy in terms of brain revival. Cortical CBF after long-lasting cardiopulmonary...

  13. Estimation of human heat loss in five Mediterranean regions. (United States)

    Bilgili, M; Simsek, E; Sahin, B; Yasar, A; Ozbek, A


    This study investigates the effects of seasonal weather differences on the human body's heat losses in the Mediterranean region of Turkey. The provinces of Adana, Antakya, Osmaniye, Mersin and Antalya were chosen for the research, and monthly atmospheric temperatures, relative humidity, wind speed and atmospheric pressure data from 2007 were used. In all these provinces, radiative, convective and evaporative heat losses from the human body based on skin surface and respiration were analyzed from meteorological data by using the heat balance equation. According to the results, the rate of radiative, convective and evaporative heat losses from the human body varies considerably from season to season. In all the provinces, 90% of heat loss was caused by heat transfer from the skin, with the remaining 10% taking place through respiration. Furthermore, radiative and convective heat loss through the skin reached the highest values in the winter months at approximately between 110 and 140W/m(2), with the lowest values coming in the summer months at roughly 30-50W/m(2).

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


    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.

  15. Effect of Different Human Papillomavirus Serological and DNA Criteria on Vaccine Efficacy Estimates (United States)

    Lang Kuhs, Krystle A.; Porras, Carolina; Schiller, John T.; Rodriguez, Ana Cecilia; Schiffman, Mark; Gonzalez, Paula; Wacholder, Sholom; Ghosh, Arpita; Li, Yan; Lowy, Douglas R.; Kreimer, Aimée R.; Poncelet, Sylviane; Schussler, John; Quint, Wim; van Doorn, Leen-Jan; Sherman, Mark E.; Sidawy, Mary; Herrero, Rolando; Hildesheim, Allan; Safaeian, Mahboobeh; Lang Kuhs, Krystle A.; Schiller, John T.; Schiffman, Mark; Wacholder, Sholom; Lowy, Douglas R.; Kreimer, Aimée R.; Sherman, Mark E.; Hildesheim, Allan; Safaeian, Mahboobeh; Porras, Carolina; Rodriguez, Ana Cecilia; Gonzalez, Paula; Herrero, Rolando; Gonzalez, Paula; Herrero, Rolando; Ghosh, Arpita; Li, Yan; Poncelet, Sylviane; Schussler, John; Quint, Wim; van Doorn, Leen-Jan; Sidawy, Mary; Self, Steve; Benavides, Adriana; Calzada, Luis Diego; Karron, Ruth; Nayar, Ritu; Roach, Nancy; Cain, Joanna; Davey, Diane; DeMets, David; Fuster, Francisco; Gershon, Ann; Holly, Elizabeth; Raventós, Henriette; Rida, Wasima; Rosero-Bixby, Luis; Suthers, Kristen; Lara, Silvia; Thomas, Sarah; Alfaro, Mario; Barrantes, Manuel; Concepción Bratti, M.; Cárdenas, Fernando; Cortés, Bernal; Espinoza, Albert; Estrada, Yenory; González, Paula; Guillén, Diego; Herrero, Roland; Jiménez, Silvia E.; Morales, Jorge; Villegas, Luis; Morera, Lidia Ana; Pérez, Elmer; Porras, Carolina; Rodríguez, Ana Cecilia; Rivas, Libia; Freer, Enrique; Bonilla, José; García-Piñeres, Alfanso; Silva, Sandra; Atmella, Ivannia; Ramírez, Margarita; Hildesheim, Allan; Kreimer, Aimée R.; Lowy, Douglas R.; Macklin, Nora; Schiffman, Mark; Schiller, John T.; Sherman, Mark; Solomon, Diane; Wacholder, Sholom; Pinto, Ligia; Kemp, Troy; Eklund, Claire; Hutchinson, Martha; Sidawy, Mary; Quint, Wim; van Doorn, Leen-Jan


    Two trials of clinically approved human papillomavirus (HPV) vaccines, Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE I/II) and the Papilloma Trial Against Cancer in Young Adults (PATRICIA), reported a 22% difference in vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 2 or worse in HPV-naïve subcohorts; however, serological testing methods and the HPV DNA criteria used to define HPV-unexposed women differed between the studies. We applied previously described methods to simulate these HPV-naïve subcohorts within the Costa Rica HPV16/18 Vaccine Trial and assessed how these criteria affect the estimation of VE. We applied 2 enzyme-linked immunosorbent assay (ELISA) thresholds for HPV16 and HPV18 seropositivity (8 and 7 ELISA units/mL, respectively, for PATRICIA; 54 and 65 ELISA units/mL, respectively, for FUTURE I/II (to approximate the competitive Luminex immunoassay)) and 2 criteria for HPV DNA positivity (12 oncogenic HPV types, plus HPV66 and 68/73 for PATRICIA; or plus HPV6 and 11 for FUTURE I/II). VE was computed in the 2 naïve subcohorts. Using the FUTURE I/II and PATRICIA criteria, VE estimates against cervical intraepithelial neoplasia grade 2 or worse, regardless of HPV type, were 69.0% (95% confidence interval: 40.3%, 84.9%) and 80.8% (95% confidence interval: 52.6%, 93.5%), respectively (P = 0.1). Although the application of FUTURE I/II criteria to our cohort resulted in the inclusion of more sexually experienced women, methodological differences did not fully explain the VE differences. PMID:25139208

  16. Lnc2Cancer: a manually curated database of experimentally supported lncRNAs associated with various human cancers. (United States)

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


    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.

  17. [Estimation of the excess of lung cancer mortality risk associated to environmental tobacco smoke exposure of hospitality workers]. (United States)

    López, M José; Nebot, Manel; Juárez, Olga; Ariza, Carles; Salles, Joan; Serrahima, Eulàlia


    To estimate the excess lung cancer mortality risk associated with environmental tobacco (ETS) smoke exposure among hospitality workers. The estimation was done using objective measures in several hospitality settings in Barcelona. Vapour phase nicotine was measured in several hospitality settings. These measurements were used to estimate the excess lung cancer mortality risk associated with ETS exposure for a 40 year working life, using the formula developed by Repace and Lowrey. Excess lung cancer mortality risk associated with ETS exposure was higher than 145 deaths per 100,000 workers in all places studied, except for cafeterias in hospitals, where excess lung cancer mortality risk was 22 per 100,000. In discoteques, for comparison, excess lung cancer mortality risk is 1,733 deaths per 100,000 workers. Hospitality workers are exposed to ETS levels related to a very high excess lung cancer mortality risk. These data confirm that ETS control measures are needed to protect hospital workers.

  18. Comparison of methods of estimating body fat in normal subjects and cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Cohn, S.H. (Brookhaven National Lab., Upton, NY); Ellis, K.J.; Vartsky, D.; Sawitsky, A.; Gartenhaus, W.; Yasumura, S.; Vaswani, A.N.


    Total body fat can be indirectly estimated by the following noninvasive techniques: determination of lean body mass by measurement of body potassium or body water, and determination of density by underwater weighing or by skinfold measurements. The measurement of total body nitrogen by neutron activation provides another technique for estimating lean body mass and hence body fat. The nitrogen measurement can also be combined with the measurement of total body potassium in a two compartment model of the lean body mass from which another estimate of body fat can be derived. All of the above techniques are subject to various errors and are based on a number of assumptions, some of which are incompletely validated. These techniques were applied to a population of normal subjects and to a group of cancer patients. The advantages and disadvantages of each method are discussed in terms of their ability to estimate total body fat.

  19. Comparison of methods of estimating body fat in normal subjects and cancer patients. (United States)

    Cohn, S H; Ellis, K J; Vartsky, D; Sawitsky, A; Gartenhaus, W; Yasumura, S; Vaswani, A N


    Total body fat can be indirectly estimated by the following noninvasive techniques: determination of lean body mass by measurement of body potassium or body water, and determination of density by underwater weighing or by skinfold measurements. The measurement of total body nitrogen by neutron activation provides another technique for estimating lean body mass and hence body fat. The nitrogen measurement can also be combined with the measurement of total body potassium in a two compartment model of the lean body mass from which another estimate of body fat can be derived. All of the above techniques are subject to various errors and are based on a number of assumptions, some of which are incompletely validated. These techniques were applied to a population of normal subjects and to a group of cancer patients. The advantages and disadvantages of each method are discussed in terms of their ability to estimate total body fat.

  20. Mammographic density and estimation of breast cancer risk in intermediate risk population. (United States)

    Tesic, Vanja; Kolaric, Branko; Znaor, Ariana; Kuna, Sanja Kusacic; Brkljacic, Boris


    It is not clear to what extent mammographic density represents a risk factor for breast cancer among women with moderate risk for disease. We conducted a population-based study to estimate the independent effect of breast density on breast cancer risk and to evaluate the potential of breast density as a marker of risk in an intermediate risk population. From November 2006 to April 2009, data that included American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density categories and risk information were collected on 52,752 women aged 50-69 years without previously diagnosed breast cancer who underwent screening mammography examination. A total of 257 screen-detected breast cancers were identified. Logistic regression was used to assess the effect of breast density on breast carcinoma risk and to control for other risk factors. The risk increased with density and the odds ratio for breast cancer among women with dense breast (heterogeneously and extremely dense breast), was 1.9 (95% confidence interval, 1.3-2.8) compared with women with almost entirely fat breasts, after adjustment for age, body mass index, age at menarche, age at menopause, age at first childbirth, number of live births, use of oral contraceptive, family history of breast cancer, prior breast procedures, and hormone replacement therapy use that were all significantly related to breast density (p density and decreased with number of live births. Our finding that mammographic density is an independent risk factor for breast cancer indicates the importance of breast density measurements for breast cancer risk assessment also in moderate risk populations. © 2012 Wiley Periodicals, Inc.

  1. 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.

  2. Alterations of p63 and p73 in human cancers. (United States)

    Inoue, Kazushi; Fry, Elizabeth A


    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.

  3. Sampling strategy for estimating human exposure pathways to consumer chemicals

    Directory of Open Access Journals (Sweden)

    Eleni Papadopoulou


    Full Text Available Human exposure to consumer chemicals has become a worldwide concern. In this work, a comprehensive sampling strategy is presented, to our knowledge being the first to study all relevant exposure pathways in a single cohort using multiple methods for assessment of exposure from each exposure pathway. The selected groups of chemicals to be studied are consumer chemicals whose production and use are currently in a state of transition and are; per- and polyfluorinated alkyl substances (PFASs, traditional and “emerging” brominated flame retardants (BFRs and EBFRs, organophosphate esters (OPEs and phthalate esters (PEs. Information about human exposure to these contaminants is needed due to existing data gaps on human exposure intakes from multiple exposure pathways and relationships between internal and external exposure. Indoor environment, food and biological samples were collected from 61 participants and their households in the Oslo area (Norway on two consecutive days, during winter 2013-14. Air, dust, hand wipes, and duplicate diet (food and drink samples were collected as indicators of external exposure, and blood, urine, blood spots, hair, nails and saliva as indicators of internal exposure. A food diary, food frequency questionnaire (FFQ and indoor environment questionnaire were also implemented. Approximately 2000 samples were collected in total and participant views on their experiences of this campaign were collected via questionnaire. While 91% of our participants were positive about future participation in a similar project, some tasks were viewed as problematic. Completing the food diary and collection of duplicate food/drink portions were the tasks most frequent reported as “hard”/”very hard”. Nevertheless, a strong positive correlation between the reported total mass of food/drinks in the food record and the total weight of the food/drinks in the collection bottles was observed, being an indication of accurate performance

  4. Cadmium-induced cancers in animals and in humans. (United States)

    Huff, James; Lunn, Ruth M; Waalkes, Michael P; Tomatis, Lorenzo; Infante, Peter F


    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.

  5. The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

    Directory of Open Access Journals (Sweden)

    F. Xavier Bosch


    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.

  6. 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.

  7. Fundamentals of Semantic Web Technologies in Medical Environments: a case in breast cancer risk estimation

    CERN Document Server

    Huerga, Iker; Gerrikagoitia, Jon Kepa


    Risk estimation of developing breast cancer poses as the first prevention method for early diagnosis. Furthermore, data integration from different departments involved in the process plays a key role. In order to guarantee patient safety, the whole process should be orchestrated and monitored automatically. Support for the solution will be a linked data cloud, composed by all the departments that take part in the process, combined with rule engines.

  8. Cigarette use and the estimation of lung cancer attributable to radon in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Lubin, J.H. [National Cancer Institute, Bethesda, MD (United States); Steindorf, K. [National Cancer Institute, Bethesda, MD (United States)]|[German Cancer Research Center, Heidelberg (Germany)


    Residential exposure to radioactive radon and its decay products has been estimated to account for 10-12% of all lung cancer deaths in the US. It has been difficult to evaluate fully the impact of cigarette smoking, the most important cause of lung cancer, on this estimate, because factors for patterns of tobacco use have not been included in the risk models, since risk models are derived from studies of underground miners exposed to radon and detailed data on smoking are limited. Lung cancer risk estimates for exposure to radon progeny in smoker and non-smoker populations are obtained by applying the same risk model to each population group, thereby assuming the joint effects of smoking and exposure to radon progeny are multiplicative. However, in miners, joint relative risks (RR) for the two exposures are most consistent with an intermediate relationship between multiplicative and additive, so that the present approach likely results in an overestimate of risk in smokers and an underestimate of risk in nonsmokers. One approach for adjusting risk models to incorporate smoking status is based on the relative magnitude of the effects of radon progeny in smokers and nonsmokers and therefore may not be applicable to non-miner populations if the proportion of smokers and the RR for smoking differ. We show that the modification can be derived explicitly by assuming an arithmetic mixture model for the joint RR for smoking and exposure to radon progeny. In this way, smoking parameters in the population of interest (the proportion of smokers and the RR of smoking) can be used directly to adjust radon progeny risk models and obtain risk estimates that are specific for smokers and nonsmokers. With an intermediate RR relationship for smoking and radon progeny, the attributable percentage of lung cancer deaths from residential radon may be twofold greater in nonsmokers than in smokers. 20 refs., 1 fig., 3 tabs.

  9. Oncogenic potential of Human Papillomavirus (HPV) and its relation with cervical cancer


    Idrees Muhammad; Khan Khalida; Zahra Amreen; Faridi Rabia


    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...

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


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


    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 ...

  11. Human Age Estimation Method Robust to Camera Sensor and/or Face Movement


    Dat Tien Nguyen; So Ra Cho; Tuyen Danh Pham; Kang Ryoung Park


    Human age can be employed in many useful real-life applications, such as customer service systems, automatic vending machines, entertainment, etc. In order to obtain age information, image-based age estimation systems have been developed using information from the human face. However, limitations exist for current age estimation systems because of the various factors of camera motion and optical blurring, facial expressions, gender, etc. Motion blurring can usually be presented on face images...

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


    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. EMT is the dominant program in human colon cancer

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    Tollenaar Rob AEM


    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.

  14. Analyzing the regulation of metabolic pathways in human breast cancer

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    Schramm Gunnar


    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.

  15. Identification of differentially expressed circular RNAs in human colorectal cancer. (United States)

    Zhang, Peili; Zuo, Zhigui; Shang, Wenjing; Wu, Aihua; Bi, Ruichun; Wu, Jianbo; Li, Shaotang; Sun, Xuecheng; Jiang, Lei


    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.

  16. 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.

  17. Estimating the loss in expectation of life due to cancer using flexible parametric survival models. (United States)

    Andersson, Therese M-L; Dickman, Paul W; Eloranta, Sandra; Lambe, Mats; Lambert, Paul C


    A useful summary measure for survival data is the expectation of life, which is calculated by obtaining the area under a survival curve. The loss in expectation of life due to a certain type of cancer is the difference between the expectation of life in the general population and the expectation of life among the cancer patients. This measure is used little in practice as its estimation generally requires extrapolation of both the expected and observed survival. A parametric distribution can be used for extrapolation of the observed survival, but it is difficult to find a distribution that captures the underlying shape of the survival function after the end of follow-up. In this paper, we base our extrapolation on relative survival, because it is more stable and reliable. Relative survival is defined as the observed survival divided by the expected survival, and the mortality analogue is excess mortality. Approaches have been suggested for extrapolation of relative survival within life-table data, by assuming that the excess mortality has reached zero (statistical cure) or has stabilized to a constant. We propose the use of flexible parametric survival models for relative survival, which enables estimating the loss in expectation of life on individual level data by making these assumptions or by extrapolating the estimated linear trend at the end of follow-up. We have evaluated the extrapolation from this model using data on four types of cancer, and the results agree well with observed data.

  18. Imaging Proteolysis by Living Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mansoureh Sameni


    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.

  19. Behavioral estimates of human frequency selectivity at low frequencies

    DEFF Research Database (Denmark)

    Orellana, Carlos Andrés Jurado

    A fundamental property of our hearing organ is its ability to break down sound into different spectral components, allowing us to make use of the richness in natural sound phenomena. Auditory filters, which conceptualize this property of the ear, however, have not been appropriately described...... at low sound frequencies. As a consequence of our lack of knowledge, we cannot accurately model our perception of complex low-frequency sound (such as that emitted by wind turbines or industrial processes, which can easily produce annoyance) nor make meaningful predictions of our perception based...... on physical sound measurements. In this PhD thesis a detailed description of frequency selectivity at low frequencies is given. Different experiments have been performed to determine the properties of human auditory filters. Besides, loudness perception of low-frequency sinusoidal signals has been evaluated...

  20. A 2015 survey of established or potential epigenetic biomarkers for the accurate detection of human cancers. (United States)

    Amacher, David E


    Context The silencing or activation of cancer-associated genes by epigenetic mechanisms can ultimately lead to the clonal expansion of cancer cells. Objective The aim of this review is to summarize all relevant epigenetic biomarkers that have been proposed to date for the diagnosis of some prevalent human cancers. Methods A Medline search for the terms epigenetic biomarkers, human cancers, DNA methylation, histone modifications and microRNAs was performed. Results One hundred fifty-seven relevant publications were found and reviewed. Conclusion To date, a significant number of potential epigenetic cancer biomarkers of human cancer have been investigated, and some have advanced to clinical implementation.

  1. Human age estimation combining third molar and skeletal development. (United States)

    Thevissen, P W; Kaur, J; Willems, G


    The wide prediction intervals obtained with age estimation methods based on third molar development could be reduced by combining these dental observations with age-related skeletal information. Therefore, on cephalometric radiographs, the most accurate age-estimating skeletal variable and related registration method were searched and added to a regression model, with age as response and third molar stages as explanatory variable. In a pilot set up on a dataset of 496 (283 M; 213 F) cephalometric radiographs, the techniques of Baccetti et al. (2005) (BA), Seedat et al. (2005) (SE), Caldas et al. (2007) and Rai et al. (2008) (RA) were verified. In the main study, data from 460 (208 F, 224 M) individuals in an age range between 3 and 26 years, for which at the same day an orthopantogram and a cephalogram were taken, were collected. On the orthopantomograms, the left third molar development was registered using the scoring system described by Gleiser and Hunt (1955) and modified by Köhler (1994) (GH). On the cephalograms, cervical vertebrae development was registered according to the BA and SE techniques. A regression model, with age as response and the GH scores as explanatory variable, was fitted to the data. Next, information of BA, SE and BA + SE was, respectively, added to this model. From all obtained models, the determination coefficients and the root mean squared errors were calculated. Inclusion of information from cephalograms based on the BA, as well as the SE, technique improved the amount of explained variance in age acquired from panoramic radiographs using the GH technique with 48%. Inclusion of cephalometric BA + SE information marginally improved the previous result (+1%). The RMSE decreased with 1.93, 1.85 and 2.03 years by adding, respectively, BA, SE and BA + SE information to the GH model. The SE technique allows clinically the fastest and easiest registration of the degree of development of the cervical vertebrae. Therefore, the choice of

  2. Breast Cancer Risk Estimation Using Parenchymal Texture Analysis in Digital Breast Tomosynthesis (United States)

    Ikejimba, Lynda C.; Kontos, Despina; Maidment, Andrew D. A.


    Mammographic parenchymal texture has been shown to correlate with genetic markers of developing breast cancer. Digital breast tomosynthesis (DBT) is a novel x-ray imaging technique in which tomographic images of the breast are reconstructed from multiple source projections acquired at different angles of the x-ray tube. Compared to digital mammography (DM), DBT eliminates breast tissue overlap, offering superior parenchymal tissue visualization. We hypothesize that texture analysis in DBT could potentially provide a better assessment of parenchymal texture and ultimately result in more accurate assessment of breast cancer risk. As a first step towards validating this hypothesis, we investigated the association between DBT parenchymal texture and breast percent density (PD), a known breast cancer risk factor, and compared it to DM. Bilateral DBT and DM images from 71 women participating in a breast cancer screening trial were analyzed. Filtered-backprojection was used to reconstruct DBT tomographic planes in 1 mm increments with 0.22 mm in-plane resolution. Corresponding DM images were acquired at 0.1 mm pixel resolution. Retroareolar regions of interest (ROIs) equivalent to 2.5 cm3 were segmented from the DBT images and corresponding 2.5 cm2 ROIs were segmented from the DM images. Breast PD was mammographically estimated using the Cumulus scale. Overall, DBT texture features demonstrated a stronger correlation than DM to PD. The Pearson correlation coefficients for DBT were r = 0.40 (pbreast cancer risk assessment in the future.

  3. Candidate serological biomarkers for cancer identified from the secretomes of 23 cancer cell lines and the human protein atlas. (United States)

    Wu, Chih-Ching; Hsu, Chia-Wei; Chen, Chi-De; Yu, Chia-Jung; Chang, Kai-Ping; Tai, Dar-In; Liu, Hao-Ping; Su, Wen-Hui; Chang, Yu-Sun; Yu, Jau-Song


    Although cancer cell secretome profiling is a promising strategy used to identify potential body fluid-accessible cancer biomarkers, questions remain regarding the depth to which the cancer cell secretome can be mined and the efficiency with which researchers can select useful candidates from the growing list of identified proteins. Therefore, we analyzed the secretomes of 23 human cancer cell lines derived from 11 cancer types using one-dimensional SDS-PAGE and nano-LC-MS/MS performed on an LTQ-Orbitrap mass spectrometer to generate a more comprehensive cancer cell secretome. A total of 31,180 proteins was detected, accounting for 4,584 non-redundant proteins, with an average of 1,300 proteins identified per cell line. Using protein secretion-predictive algorithms, 55.8% of the proteins appeared to be released or shed from cells. The identified proteins were selected as potential marker candidates according to three strategies: (i) proteins apparently secreted by one cancer type but not by others (cancer type-specific marker candidates), (ii) proteins released by most cancer cell lines (pan-cancer marker candidates), and (iii) proteins putatively linked to cancer-relevant pathways. We then examined protein expression profiles in the Human Protein Atlas to identify biomarker candidates that were simultaneously detected in the secretomes and highly expressed in cancer tissues. This analysis yielded 6-137 marker candidates selective for each tumor type and 94 potential pan-cancer markers. Among these, we selectively validated monocyte differentiation antigen CD14 (for liver cancer), stromal cell-derived factor 1 (for lung cancer), and cathepsin L1 and interferon-induced 17-kDa protein (for nasopharyngeal carcinoma) as potential serological cancer markers. In summary, the proteins identified from the secretomes of 23 cancer cell lines and the Human Protein Atlas represent a focused reservoir of potential cancer biomarkers.

  4. Human Age Estimation Based on Locality and Ordinal Information. (United States)

    Li, Changsheng; Liu, Qingshan; Dong, Weishan; Zhu, Xiaobin; Liu, Jing; Lu, Hanqing


    In this paper, we propose a novel feature selection-based method for facial age estimation. The face aging is a typical temporal process, and facial images should have certain ordinal patterns in the aging feature space. From the geometrical perspective, a facial image can be usually seen as sampled from a low-dimensional manifold embedded in the original high-dimensional feature space. Thus, we first measure the energy of each feature in preserving the underlying local structure information and the ordinal information of the facial images, respectively, and then we intend to learn a low-dimensional aging representation that can maximally preserve both kinds of information. To further improve the performance, we try to eliminate the redundant local information and ordinal information as much as possible by minimizing nonlinear correlation and rank correlation among features. Finally, we formulate all these issues into a unified optimization problem, which is similar to linear discriminant analysis in format. Since it is expensive to collect the labeled facial aging images in practice, we extend the proposed supervised method to a semi-supervised learning mode including the semi-supervised feature selection method and the semi-supervised age prediction algorithm. Extensive experiments are conducted on the FACES dataset, the Images of Groups dataset, and the FG-NET aging dataset to show the power of the proposed algorithms, compared to the state-of-the-arts.

  5. Estimation of the Functional Reserve of Human Liver (United States)

    Moody, Frank G.; Rikkers, Layton F.; Aldrete, Joaquin S.


    Functional hepatic reserve was determined in 32 patients with known liver or biliary tract disease employing kinetic analysis of hepatic removal of indocyanine green (ICG). The initial removal rates of incremental doses of ICG (0.5, 1.0 and 5.0 mg/kg body weight) were plotted as a reciprocal against the inverse of dose (Lineweaver-Burk plot) to provide a means of determining maximal removal rate from submaximal doses (Rmax). This function equalled 3.40 mg/kg/min in ten patients with normal livers, but was only .24 mg/kg/min in eight patients with alcoholic cirrhosis. Portasystemic shunting did not further influence Rmax. Infiltrative liver disease had only a mild depressive effect on this function. The results show that hepatic function can be precisely quantitated by classical enzyme kinetics (Michaelis-Menten). If Rmax is an estimate of protein receptor mass for organic anions, then the technique may allow an indirect means for quantitating hepatocytes even in the presence of changes in blood flow or hepatic function. The profound depression in Rmax observed in patients with alcoholic cirrhosis is consistent with the progressive loss in hepatic mass associated with this disease. PMID:4413286

  6. Cancer risk estimates from radiation therapy for heterotopic ossification prophylaxis after total hip arthroplasty

    Energy Technology Data Exchange (ETDEWEB)

    Mazonakis, Michalis; Berris, Theoharris; Damilakis, John [Department of Medical Physics, Faculty of Medicine, University of Crete, P.O. Box 2208, 71003 Iraklion, Crete (Greece); Lyraraki, Efrossyni [Department of Radiotherapy and Oncology, University Hospital of Iraklion, 71110 Iraklion, Crete (Greece)


    Purpose: Heterotopic ossification (HO) is a frequent complication following total hip arthroplasty. This study was conducted to calculate the radiation dose to organs-at-risk and estimate the probability of cancer induction from radiotherapy for HO prophylaxis.Methods: Hip irradiation for HO with a 6 MV photon beam was simulated with the aid of a Monte Carlo model. A realistic humanoid phantom representing an average adult patient was implemented in Monte Carlo environment for dosimetric calculations. The average out-of-field radiation dose to stomach, liver, lung, prostate, bladder, thyroid, breast, uterus, and ovary was calculated. The organ-equivalent-dose to colon, that was partly included within the treatment field, was also determined. Organ dose calculations were carried out using three different field sizes. The dependence of organ doses upon the block insertion into primary beam for shielding colon and prosthesis was investigated. The lifetime attributable risk for cancer development was estimated using organ, age, and gender-specific risk coefficients.Results: For a typical target dose of 7 Gy, organ doses varied from 1.0 to 741.1 mGy by the field dimensions and organ location relative to the field edge. Blocked field irradiations resulted in a dose range of 1.4–146.3 mGy. The most probable detriment from open field treatment of male patients was colon cancer with a high risk of 564.3 × 10{sup −5} to 837.4 × 10{sup −5} depending upon the organ dose magnitude and the patient's age. The corresponding colon cancer risk for female patients was (372.2–541.0) × 10{sup −5}. The probability of bladder cancer development was more than 113.7 × 10{sup −5} and 110.3 × 10{sup −5} for males and females, respectively. The cancer risk range to other individual organs was reduced to (0.003–68.5) × 10{sup −5}.Conclusions: The risk for cancer induction from radiation therapy for HO prophylaxis after total hip arthroplasty varies considerably by

  7. MTA1 promotes proliferation and invasion in human gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Yao Y


    Full Text Available Yuan Yao,1 Shuting Feng,1 Mingming Xiao,2 Yan Li,1 Li Yang,1 Jiao Gong1 1Digestive System Department, 2Department of Pathology, The People’s Hospital of Liaoning Province, Shenyang, Liaoning, People’s Republic of China Abstract: Although metastasis-associated protein 1 (MTA1 has been widely li­nked to tumor metastasis, the relevant mechanisms remain to be elucidated, especially in gastric cancer. The aim of this study was to examine whether the MTA1 gene is associated with the process of proliferation and invasion by regulating several molecular targets in gastric cancer. MTA1 expression in 61 gastric cancer tissue and adjacent noncancerous tissues was analyzed by immunohistochemistry. The prognostic value of MTA1 for overall survival and disease-free survival was determined by Kaplan–Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. Furthermore, overexpression of MTA1 in SGC7901 and BGC823 cells promoted cell cycle progression, cell adhesion, and cell invasion. Our study found that MTA1 is overexpressed in gastric cancers, which contributes to malignant cell growth by facilitating cell cycle progression through upregulation of cyclin D1 and accelerates the migration and invasion of human gastric cancer cells by regulating expression of fibronectin and MMP2/MMP9. Taken together, MTA1 was involved in the pathogenesis of gastric cancer and might be a candidate therapeutic target in gastric cancer. Keywords: cell cycle, cell adhesion, migration

  8. Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States (United States)

    Chaturvedi, Anil K.; Engels, Eric A.; Pfeiffer, Ruth M.; Hernandez, Brenda Y.; Xiao, Weihong; Kim, Esther; Jiang, Bo; Goodman, Marc T.; Sibug-Saber, Maria; Cozen, Wendy; Liu, Lihua; Lynch, Charles F.; Wentzensen, Nicolas; Jordan, Richard C.; Altekruse, Sean; Anderson, William F.; Rosenberg, Philip S.; Gillison, Maura L.


    Purpose Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking. Patients and Methods HPV status was determined for all 271 oropharyngeal cancers (1984-2004) collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses. Results HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay (P trend < .05). For example, HPV prevalence by Inno-LiPA increased from 16.3% during 1984 to 1989 to 71.7% during 2000 to 2004. Median survival was significantly longer for HPV-positive than for HPV-negative patients (131 v 20 months; log-rank P < .001; adjusted hazard ratio, 0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar periods for HPV-positive (P = .003) but not for HPV-negative patients (P = .18). Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per 100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to 53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020. Conclusion Increases in the

  9. Interpreting the epidemiological evidence linking obesity and cancer: A framework for population-attributable risk estimations in Europe. (United States)

    Renehan, Andrew G; Soerjomataram, Isabelle; Leitzmann, Michael F


    Standard approaches to estimating population-attributable risk (PAR) include modelling estimates of exposure prevalence and relative risk. Here, we examine the associations between body mass index (BMI) and cancer risk and how effect modifications of these associations impact on PAR estimates. In 2008, sex- and population-specific risk estimates were determined for associations with BMI in a standardised meta-analysis for 20 cancer types. Since then, refinements of these estimates have emerged: (i) absence of menopausal hormonal therapy (MHT) is associated with elevated BMI associations in post-menopausal breast, endometrial and ovarian cancers; (ii) current smoking attenuates the BMI associations in oesophageal squamous cell carcinoma, lung and pancreatic cancers; (iii) prostate screening attenuates BMI associations when all prostate cancers are considered together; and (iv) BMI is differentially associated with different histological subtypes within the same cancer group. Using secondary analyses of the aforementioned meta-analysis, we show 2-3-fold shifts in PAR estimations for breast and endometrial cancers depending on the MHT usage in European countries. We also critically examine how to best handle exposures (in this example, BMI distributions) and relative risk estimates in PAR models, and argue in favour of a counterfactual approach based around BMI means. From these observations, we develop a research framework in which to optimally evaluate future trends in numbers of new cancers attributable to excess BMI. Overall, this framework gives conservative estimates for PAR - nonetheless, the numbers of avoidable cancers across Europe through avoidance of excess weight are substantial. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey (United States)

    Koç, Zeliha


    Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  11. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey (United States)

    Koç, Zeliha


    Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

  12. Breast and prostate cancer productivity costs: a comparison of the human capital approach and the friction cost approach. (United States)

    Hanly, Paul; Timmons, Aileen; Walsh, Paul M; Sharp, Linda


    Productivity costs constitute a substantial proportion of the total societal costs associated with cancer. We compared the results of applying two different analytical methods--the traditional human capital approach (HCA) and the emerging friction cost approach (FCA)--to estimate breast and prostate cancer productivity costs in Ireland in 2008. Data from a survey of breast and prostate cancer patients were combined with population-level survival estimates and a national wage data set to calculate costs of temporary disability (cancer-related work absence), permanent disability (workforce departure, reduced working hours), and premature mortality. For breast cancer, productivity costs per person using the HCA were € 193,425 and those per person using the FCA were € 8,103; for prostate cancer, the comparable estimates were € 109,154 and € 8,205, respectively. The HCA generated higher costs for younger patients (breast cancer) because of greater lifetime earning potential. In contrast, the FCA resulted in higher productivity costs for older male patients (prostate cancer) commensurate with higher earning capacity over a shorter time period. Reduced working hours postcancer was a key driver of total HCA productivity costs. HCA costs were sensitive to assumptions about discount and growth rates. FCA costs were sensitive to assumptions about the friction period. The magnitude of the estimates obtained in this study illustrates the importance of including productivity costs when considering the economic impact of illness. Vastly different results emerge from the application of the HCA and the FCA, and this finding emphasizes the importance of choosing the study perspective carefully and being explicit about assumptions that underpin the methods. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  13. A Chain Modeling Approach To Estimate the Impact of Soil Cadmium Pollution on Human Dietary Exposure

    NARCIS (Netherlands)

    Franz, E.; Romkens, P.F.A.M.; Raamsdonk, van L.W.D.; Fels-Klerx, van der H.J.


    Cadmium in soil poses a risk for human health, due to its accumulation in food and feed crops. The extent of accumulation depends strongly on soil type and the degree of pollution. The objective of the present study was to develop a predictive model to estimate human dietary cadmium exposure from so

  14. Characterizing cancer cells with cancer stem cell-like features in 293T human embryonic kidney cells


    Buchholz Thomas A; Lacerda Lara; Xu Wei; Robertson Fredika; Ueno Naoto T; Lucci Anthony; Landis Melissa D; Rodriguez Angel A; Li Li; Cohen Evan; Gao Hui; Krishnamurthy Savitri; Zhang Xiaomei; Debeb Bisrat G; Cristofanilli Massimo


    Abstract Background Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced b...

  15. Comparing adaptive and fixed bandwidth-based kernel density estimates in spatial cancer epidemiology. (United States)

    Lemke, Dorothea; Mattauch, Volkmar; Heidinger, Oliver; Pebesma, Edzer; Hense, Hans-Werner


    Monitoring spatial disease risk (e.g. identifying risk areas) is of great relevance in public health research, especially in cancer epidemiology. A common strategy uses case-control studies and estimates a spatial relative risk function (sRRF) via kernel density estimation (KDE). This study was set up to evaluate the sRRF estimation methods, comparing fixed with adaptive bandwidth-based KDE, and how they were able to detect 'risk areas' with case data from a population-based cancer registry. The sRRF were estimated within a defined area, using locational information on incident cancer cases and on a spatial sample of controls, drawn from a high-resolution population grid recognized as underestimating the resident population in urban centers. The spatial extensions of these areas with underestimated resident population were quantified with population reference data and used in this study as 'true risk areas'. Sensitivity and specificity analyses were conducted by spatial overlay of the 'true risk areas' and the significant (α=.05) p-contour lines obtained from the sRRF. We observed that the fixed bandwidth-based sRRF was distinguished by a conservative behavior in identifying these urban 'risk areas', that is, a reduced sensitivity but increased specificity due to oversmoothing as compared to the adaptive risk estimator. In contrast, the latter appeared more competitive through variance stabilization, resulting in a higher sensitivity, while the specificity was equal as compared to the fixed risk estimator. Halving the originally determined bandwidths led to a simultaneous improvement of sensitivity and specificity of the adaptive sRRF, while the specificity was reduced for the fixed estimator. The fixed risk estimator contrasts with an oversmoothing tendency in urban areas, while overestimating the risk in rural areas. The use of an adaptive bandwidth regime attenuated this pattern, but led in general to a higher false positive rate, because, in our study design

  16. Are 20 human papillomavirus types causing cervical cancer? (United States)

    Arbyn, Marc; Tommasino, Massimo; Depuydt, Christophe; Dillner, Joakim


    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 α-Papillomaviridae, in particular to the species α5 (HPV51), α6 (HPV56), α7 (HPV18, HPV39, HPV45, HPV59) and α9 (HPV16, HPV31, HPV33, HPV35, HPV52, HPV58). Less evidence is available for a thirteenth type (HPV68, α7), which is classified as a 2A carcinogen (probably carcinogenic). Moreover, seven other phylogenetically related types (HPV26, HPV53, HPV66, HPV67, HPV68, HPV70 and HPV73) were identified as single HPV infections in certain rare cases of cervical cancer and were considered possibly carcinogenic (2B carcinogens). Recently, Halec et al [7] demonstrated that the molecular signature of HPV-induced carcinogenesis (presence of type-specific spliced E6*| mRNA; increased expression of p16; and decreased expression of cyclin D1, p53 and Rb) was similar in cervical cancers containing single infections with one of the eight afore-mentioned 2A or 2B carcinogens to those in cancers with single infections with group 1 carcinogens. Ninety six percent of cervical cancers are attributable to one of the 13 most common HPV types (groups 1 and 2A). Including the additional seven HPV types (group 2B) added 2.6%, to reach a total of 98.7% of all HPV-positive cervical cancers. From recently updated meta-analyses, it was shown that HPV68, HPV26, HPV66, HPV67, HPV73 and HPV82 were significantly more common in cancer cases than in women with normal cervical cytology, suggesting that for these HPV types, an upgrading of the carcinogen classification could be considered. However, there is no need to include them in HPV screening tests or vaccines, given their rarity in

  17. Accumulation and biological effects of cobalt ferrite nanoparticles in human pancreatic and ovarian cancer cells. (United States)

    Pašukonienė, Vita; Mlynska, Agata; Steponkienė, Simona; Poderys, Vilius; Matulionytė, Marija; Karabanovas, Vitalijus; Statkutė, Urtė; Purvinienė, Rasa; Kraśko, Jan Aleksander; Jagminas, Arūnas; Kurtinaitienė, Marija; Strioga, Marius; Rotomskis, Ričardas


    Superparamagnetic iron oxide nanoparticles (SPIONs) emerge as a promising tool for early cancer diagnostics and targeted therapy. However, both toxicity and biological activity of SPIONs should be evaluated in detail. The aim of this study was to synthesize superparamagnetic cobalt ferrite nanoparticles (Co-SPIONs), and to investigate their uptake, toxicity and effects on cancer stem-like properties in human pancreatic cancer cell line MiaPaCa2 and human ovarian cancer cell line A2780. Co-SPIONs were produced by Massart's co-precipitation method. The cells were treated with Co-SPIONs at three different concentrations (0.095, 0.48, and 0.95μg/mL) for 24 and 48h. Cell viability and proliferation were analyzed after treatment. The stem-like properties of cells were assessed by investigating the cell clonogenicity and expression of cancer stem cell-associated markers, including CD24/ESA in A2780 cell line and CD44/ALDH1 in MiaPaCa2 cell line. Magnetically activated cell sorting was used for the separation of magnetically labeled and unlabeled cells. Both cancer cell lines accumulated Co-SPIONs, however differences in response to nanoparticles were observed between MiaPaCa2 and A2780 cell. In particular, A2780 cells were more sensitive to exposition to Co-SPIONs than MiaPaCa2 cells, indicating that a safe concentration of nanoparticles must be estimated individually for a particular cell type. Higher doses of Co-SPIONs decreased both the clonogenicity and ESA marker expression in A2780 cells. Co-SPIONs are not cytotoxic to cancer cells, at least when used at a concentration of up to 0.95μg/mL. Co-SPIONs have a dose-dependent effect on the clonogenic potential and ESA marker expression in A2780 cells. Magnetic detection of low concentrations of Co-SPIONS in cancer cells is a promising tool for further applications of these nanoparticles in cancer diagnosis and treatment; however, extensive research in this field is needed. Copyright © 2014 Lithuanian University of

  18. A new view of radiation-induced cancer: integrating short- and long-term processes. Part II: second cancer risk estimation


    Shuryak, Igor; Hahnfeldt, Philip; Hlatky, Lynn; Sachs, Rainer K.; David J Brenner


    As the number of cancer survivors grows, prediction of radiotherapy-induced second cancer risks becomes increasingly important. Because the latency period for solid tumors is long, the risks of recently introduced radiotherapy protocols are not yet directly measurable. In the accompanying article, we presented a new biologically based mathematical model, which, in principle, can estimate second cancer risks for any protocol. The novelty of the model is that it integrates, into a single formal...

  19. Human brain cancer studied by resonance Raman spectroscopy (United States)

    Zhou, Yan; Liu, Cheng-Hui; Sun, Yi; Pu, Yang; Boydston-White, Susie; Liu, Yulong; Alfano, Robert R.


    The resonance Raman (RR) spectra of six types of human brain tissues are examined using a confocal micro-Raman system with 532-nm excitation in vitro. Forty-three RR spectra from seven subjects are investigated. The spectral peaks from malignant meningioma, stage III (cancer), benign meningioma (benign), normal meningeal tissues (normal), glioblastoma multiforme grade IV (cancer), acoustic neuroma (benign), and pituitary adenoma (benign) are analyzed. Using a 532-nm excitation, the resonance-enhanced peak at 1548 cm-1 (amide II) is observed in all of the tissue specimens, but is not observed in the spectra collected using the nonresonance Raman system. An increase in the intensity ratio of 1587 to 1605 cm-1 is observed in the RR spectra collected from meningeal cancer tissue as compared with the spectra collected from the benign and normal meningeal tissue. The peak around 1732 cm-1 attributed to fatty acids (lipids) are diminished in the spectra collected from the meningeal cancer tumors as compared with the spectra from normal and benign tissues. The characteristic band of spectral peaks observed between 2800 and 3100 cm-1 are attributed to the vibrations of methyl (-CH3) and methylene (-CH2-) groups. The ratio of the intensities of the spectral peaks of 2935 to 2880 cm-1 from the meningeal cancer tissues is found to be lower in comparison with that of the spectral peaks from normal, and benign tissues, which may be used as a distinct marker for distinguishing cancerous tissues from normal meningeal tissues. The statistical methods of principal component analysis and the support vector machine are used to analyze the RR spectral data collected from meningeal tissues, yielding a diagnostic sensitivity of 90.9% and specificity of 100% when two principal components are used.

  20. Time trends of human papillomavirus types in invasive cervical cancer, from 1940 to 2007. (United States)

    Alemany, Laia; de Sanjosé, Silvia; Tous, Sara; Quint, Wim; Vallejos, Carlos; Shin, Hai-Rim; Bravo, Luis E; Alonso, Patricia; Lima, Marcus A; Guimerà, Núria; Klaustermeier, Joellen; Llombart-Bosch, Antonio; Kasamatsu, Elena; Tatti, Silvio A; Felix, Ana; Molina, Carla; Velasco, Julio; Lloveras, Belen; Clavero, Omar; Lerma, Enrique; Laco, Jan; Bravo, Ignacio G; Guarch, Rosa; Pelayo, Adela; Ordi, Jaume; Andújar, Miguel; Sanchez, Gloria I; Castellsagué, Xavier; Muñoz, Nubia; Bosch, F Xavier


    Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940-59 to 2000-07 (HPV16-from 61.5 to 62.1%, and HPV18-from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.

  1. An Efficient Acoustic Density Estimation Method with Human Detectors Applied to Gibbons in Cambodia.

    Directory of Open Access Journals (Sweden)

    Darren Kidney

    Full Text Available Some animal species are hard to see but easy to hear. Standard visual methods for estimating population density for such species are often ineffective or inefficient, but methods based on passive acoustics show more promise. We develop spatially explicit capture-recapture (SECR methods for territorial vocalising species, in which humans act as an acoustic detector array. We use SECR and estimated bearing data from a single-occasion acoustic survey of a gibbon population in northeastern Cambodia to estimate the density of calling groups. The properties of the estimator are assessed using a simulation study, in which a variety of survey designs are also investigated. We then present a new form of the SECR likelihood for multi-occasion data which accounts for the stochastic availability of animals. In the context of gibbon surveys this allows model-based estimation of the proportion of groups that produce territorial vocalisations on a given day, thereby enabling the density of groups, instead of the density of calling groups, to be estimated. We illustrate the performance of this new estimator by simulation. We show that it is possible to estimate density reliably from human acoustic detections of visually cryptic species using SECR methods. For gibbon surveys we also show that incorporating observers' estimates of bearings to detected groups substantially improves estimator performance. Using the new form of the SECR likelihood we demonstrate that estimates of availability, in addition to population density and detection function parameters, can be obtained from multi-occasion data, and that the detection function parameters are not confounded with the availability parameter. This acoustic SECR method provides a means of obtaining reliable density estimates for territorial vocalising species. It is also efficient in terms of data requirements since since it only requires routine survey data. We anticipate that the low-tech field requirements will

  2. Estimation model of life insurance claims risk for cancer patients by using Bayesian method (United States)

    Sukono; Suyudi, M.; Islamiyati, F.; Supian, S.


    This paper discussed the estimation model of the risk of life insurance claims for cancer patients using Bayesian method. To estimate the risk of the claim, the insurance participant data is grouped into two: the number of policies issued and the number of claims incurred. Model estimation is done using a Bayesian approach method. Further, the estimator model was used to estimate the risk value of life insurance claims each age group for each sex. The estimation results indicate that a large risk premium for insured males aged less than 30 years is 0.85; for ages 30 to 40 years is 3:58; for ages 41 to 50 years is 1.71; for ages 51 to 60 years is 2.96; and for those aged over 60 years is 7.82. Meanwhile, for insured women aged less than 30 years was 0:56; for ages 30 to 40 years is 3:21; for ages 41 to 50 years is 0.65; for ages 51 to 60 years is 3:12; and for those aged over 60 years is 9.99. This study is useful in determining the risk premium in homogeneous groups based on gender and age.

  3. Pose Estimation and Adaptive Robot Behaviour for Human-Robot Interaction

    DEFF Research Database (Denmark)

    Svenstrup, Mikael; Hansen, Søren Tranberg; Andersen, Hans Jørgen


    ’s pose. The resulting pose estimates are used to identify humans who wish to be approached and interacted with. The interaction motion of the robot is based on adaptive potential functions centered around the person that respect the persons social spaces. The method is tested in experiments......Abstract—This paper introduces a new method to determine a person’s pose based on laser range measurements. Such estimates are typically a prerequisite for any human-aware robot navigation, which is the basis for effective and timeextended interaction between a mobile robot and a human. The robot...... uses observed information from a laser range finder to detect persons and their position relative to the robot. This information together with the motion of the robot itself is fed through a Kalman filter, which utilizes a model of the human kinematic movement to produce an estimate of the person...

  4. Impact of work-related cancers in Taiwan-Estimation with QALY (quality-adjusted life year) and healthcare costs. (United States)

    Lee, Lukas Jyuhn-Hsiarn; Lin, Cheng-Kuan; Hung, Mei-Chuan; Wang, Jung-Der


    This study estimates the annual numbers of eight work-related cancers, total losses of quality-adjusted life years (QALYs), and lifetime healthcare expenditures that possibly could be saved by improving occupational health in Taiwan. Three databases were interlinked: the Taiwan Cancer Registry, the National Mortality Registry, and the National Health Insurance Research Database. Annual numbers of work-related cancers were estimated based on attributable fractions (AFs) abstracted from a literature review. The survival functions for eight cancers were estimated and extrapolated to lifetime using a semi-parametric method. A convenience sample of 8846 measurements of patients' quality of life with EQ-5D was collected for utility values and multiplied by survival functions to estimate quality-adjusted life expectancies (QALEs). The loss-of-QALE was obtained by subtracting the QALE of cancer from age- and sex-matched referents simulated from national vital statistics. The lifetime healthcare expenditures were estimated by multiplying the survival probability with mean monthly costs paid by the National Health Insurance for cancer diagnosis and treatment and summing this for the expected lifetime. A total of 3010 males and 726 females with eight work-related cancers were estimated in 2010. Among them, lung cancer ranked first in terms of QALY loss, with an annual total loss-of-QALE of 28,463 QALYs and total lifetime healthcare expenditures of US$36.6 million. Successful prevention of eight work-related cancers would not only avoid the occurrence of 3736 cases of cancer, but would also save more than US$70 million in healthcare costs and 46,750 QALYs for the Taiwan society in 2010.

  5. An Estimation of Human Error Probability of Filtered Containment Venting System Using Dynamic HRA Method

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Seunghyun; Jae, Moosung [Hanyang University, Seoul (Korea, Republic of)


    The human failure events (HFEs) are considered in the development of system fault trees as well as accident sequence event trees in part of Probabilistic Safety Assessment (PSA). As a method for analyzing the human error, several methods, such as Technique for Human Error Rate Prediction (THERP), Human Cognitive Reliability (HCR), and Standardized Plant Analysis Risk-Human Reliability Analysis (SPAR-H) are used and new methods for human reliability analysis (HRA) are under developing at this time. This paper presents a dynamic HRA method for assessing the human failure events and estimation of human error probability for filtered containment venting system (FCVS) is performed. The action associated with implementation of the containment venting during a station blackout sequence is used as an example. In this report, dynamic HRA method was used to analyze FCVS-related operator action. The distributions of the required time and the available time were developed by MAAP code and LHS sampling. Though the numerical calculations given here are only for illustrative purpose, the dynamic HRA method can be useful tools to estimate the human error estimation and it can be applied to any kind of the operator actions, including the severe accident management strategy.

  6. Parallel Wire Driven System for Joint Torque Estimation of Human Leg in Passive Motion (United States)

    Kino, Hitoshi; Saisho, Kenichi; Miyazoe, Tsutomu; Kawamura, Sadao

    This paper presents a leg torque estimation system for a passive motion that uses an incompletely restrained parallel wire driven mechanism. After comparing completely and incompletely restrained parallel wire driven systems, we organize the characteristics of both systems for human torque estimation. Defining the work spaces of four kinds for the incompletely restrained mechanism, we analyze the realization of passive tracking for a leg. Then we demonstrate that the walking motion can be achieved using low-power actuators. A case example of design is introduced to manufacture a prototype for the leg torque estimation. Finally, the result of the leg torque estimation is presented through experiments conducted using a prototype system.

  7. AFM-based analysis of human metastatic cancer cells (United States)

    Cross, Sarah E.; Jin, Yu-Sheng; Tondre, Julianne; Wong, Roger; Rao, Jian Yu; Gimzewski, James K.


    Recently biomechanics of cancer cells, in particular stiffness or elasticity, has been identified as an important factor relating to cancer cell function, adherence, motility, transformation and invasion. We report on the nanomechanical responses of metastatic cancer cells and benign mesothelial cells taken from human body cavity fluids using atomic force microscopy. Following our initial study (Cross et al 2007 Nat. Nanotechnol. 2 780-3), we report on the biophysical properties of patient-derived effusion cells and address the influence of cell morphology on measured cell stiffness. Using a cytocentrifugation method, which yields morphologically indistinguishable cells that can be prepared in 1 min and avoids any possible artifacts due to 12 h ex vivo culture, we find that metastatic tumor cells are more than 80% softer than benign cells with a distribution over six times narrower than that of normal cells. Consistent with our previous study, which yielded distinguishable cell populations based on ex vivo growth and morphological characteristics, our results show it is unlikely that morphology alone is sufficient to explain the difference in elastic moduli for these two cell types. Moreover, analysis of non-specific cell adhesion inherent to tumor and normal cells collected from patients show surface adhesion of tumor cells is ~33% less adhesive compared to that of normal cells. Our findings indicate that biomechanical-based functional analysis may provide an additional platform for cytological evaluation and diagnosis of cancer in the future.

  8. AFM-based analysis of human metastatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Cross, Sarah E; Gimzewski, James K [Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (United States); Jin Yusheng; Tondre, Julianne; Wong, Roger [Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095 (United States); Rao Jianyu [California NanoSystems Institute, University of California, Los Angeles, CA 90095 (United States)], E-mail:, E-mail:


    Recently biomechanics of cancer cells, in particular stiffness or elasticity, has been identified as an important factor relating to cancer cell function, adherence, motility, transformation and invasion. We report on the nanomechanical responses of metastatic cancer cells and benign mesothelial cells taken from human body cavity fluids using atomic force microscopy. Following our initial study (Cross et al 2007 Nat. Nanotechnol. 2 780-3), we report on the biophysical properties of patient-derived effusion cells and address the influence of cell morphology on measured cell stiffness. Using a cytocentrifugation method, which yields morphologically indistinguishable cells that can be prepared in 1 min and avoids any possible artifacts due to 12 h ex vivo culture, we find that metastatic tumor cells are more than 80% softer than benign cells with a distribution over six times narrower than that of normal cells. Consistent with our previous study, which yielded distinguishable cell populations based on ex vivo growth and morphological characteristics, our results show it is unlikely that morphology alone is sufficient to explain the difference in elastic moduli for these two cell types. Moreover, analysis of non-specific cell adhesion inherent to tumor and normal cells collected from patients show surface adhesion of tumor cells is {approx}33% less adhesive compared to that of normal cells. Our findings indicate that biomechanical-based functional analysis may provide an additional platform for cytological evaluation and diagnosis of cancer in the future.

  9. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues. (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


    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.

  10. Screening effects on thyroid cancer risk estimates for populations affected by the Chernobyl accident

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, P.; Kaiser, J. C.; Vavilov, S.E.; Bogdanova, T.; Tronko, N. D.


    Simulation calculations are performed in order to explore the ecological bias in studies as they are performed with settlement specific data in the aftemath of the Chernobyl accident. Based on methods, that were developed by Lubin for exploring the ecologic bias due to smoking in indoor radon studies of lung cancer, the influence of the introduction of ultrasound devices and enhanced medical surveillance on the detection and reporting of thyroid cancer cases was investigated. Calculations were performed by simulating thyroid doses of one million children in a total of 744 settlements and assuming a linear dependence of the risk on dose and various scenarios of the screening. The dose distributions simulate the distributions similar to those used in previous ecologic studies of the thyroid cancer risk in Ukraine after the Chernobyl accident. The ecologic bias was defined as the ratio of risk coefficients derived from an ecological study to the corresponding risk factor in the underlying risl model. the ecologic bias was estimated for each of the screening scenarios. Analytical equations were derived that allow the exact numerical compuation of the bias which is determined by covariance terms between the increased detection and reporting on one side and thyroid dose values (individual and averaged for the settlements) on the other side. Nested in th epopulation data, a cohort study was simulated with 10 000 individuals and an average thyroid dose of 0.3 Gy. the present study underlines the different scopes of the ecologic and cohort study designs perfomed in the aftermed of the Chernobyl accident. Whereas the ecologic studies give an estimate of the excess thyroid cancer risks per unit dose under the conditions of a health care system as it is typical for the affected countries after the Chernobyl accident, the cohort study gives risk estimates within a well screened cohort. Due to the strong screening effects, excess absoulte risks in the ecological study cohort are

  11. Expression of 5-Lipoxygenase in human colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Labile Togba Soumaoro; Satoru Iida; Hiroyuki Uetake; Megumi Ishiguro; Yoko Takagi; Tetsuro Higuchi; Masamichi Yasuno; Masayuki Enomoto; Kenichi Sugihara


    AIM: To evaluate the 5-lipoxygenases (Loxs) expression level in human colorectal cancer specimens in order to determine its clinicopathologic significance in human tumorigenesis.METHODS: The relative quantity of 5-Lox mRNA in paired 91 colorectal tumor and adjacent normal mucosa samples was determined by real time quantitative PCR. Additionally, the expression of 5-Lox and cyclooxygenase (Cox)-2 proteins was also examined using immunohistochemical staining methods.RESULTS: There was a marked increase in 5-Lox mRNA levels in the tumor compared with paired normal mucosa samples (P < 0.0001). Sixty six (72.5%) tumors showed high 5-Lox mRNA levels. The positivity rate of 5-Lox and Cox-2 protein expression was 68.7% and 79.1%respectively. There was a significant association between tumoral 5-Lox mRNA level and tumor size (Rho = 0.392,P = 0.0002), depth or vessel invasion.CONCLUSION: These results suggest that 5-Lox is up-regulated in colorectal cancer and that inhibition of its expression might be valuable in the prevention and treatment of colorectal cancer.

  12. Mortalin sensitizes human cancer cells to MKT-077-induced senescence. (United States)

    Deocaris, Custer C; Widodo, Nashi; Shrestha, Bhupal G; Kaur, Kamaljit; Ohtaka, Manami; Yamasaki, Kazuhiko; Kaul, Sunil C; Wadhwa, Renu


    Mortalin is a chaperone protein that functions in many cellular processes such as mitochondrial biogenesis, intracellular trafficking, cell proliferation and signaling. Its upregulation in many human cancers makes it a candidate target for therapeutic intervention by small molecule drugs. In continuation to our earlier studies showing mortalin as a cellular target of MKT-077, a mitochondrion-seeking delocalized cationic dye that causes selective death of cancer cells, in this work, we report that MKT-077 binds to the nucleotide-binding domain of mortalin, causes tertiary structural changes in the protein, inactivates its chaperone function, and induces senescence in human tumor cell lines. Interestingly, in tumor cells with elevated level of mortalin expression, fairly low drug doses were sufficient to induce senescence. Guided by molecular screening for mortalin in tumor cells, our results led to the idea that working at low doses of the drug could be an alternative senescence-inducing cancer therapeutic strategy that could, in theory, avoid renal toxicities responsible for the abortion of MKT-077 clinical trials. Our work may likely translate to a re-appraisal of the therapeutic benefits of low doses of several classes of anti-tumor drugs, even of those that had been discontinued due to adverse effects.

  13. Princess takamatsu symposium on DNA repair and human cancers. (United States)

    Loeb, Lawrence A; Nishimura, Susumu


    The 40th International Symposium of the Princess Takamatsu Cancer Research Fund, entitled "DNA Repair and Human Cancers," was held on November 10-12, 2009 at Hotel Grand Palace, Tokyo, Japan. The meeting focused on the role of DNA repair in preventing mutations by endogenous and exogenous DNA damage and increasing the efficacy of chemotherapeutic agents by interfering with DNA repair. The 14 presentations by the speakers from the United States, four from the United Kingdom, one each from Italy, The Netherlands, and France, and 13 from Japan, covered most aspects of DNA repair, spanning DNA damage, molecular structures of repair enzymes, and clinical studies on inhibition of DNA repair processes. Extensive time was reserved for discussions with the active participation of the 150 invited Japanese scientists. The choice of a symposium on DNA repair in human cancers resulted in part from the excellent basic and clinical studies that have been carried out for many years in Japan, and the general lack of recognition versus the importance of DNA repair in understanding carcinogenesis. Copyright 2010 AACR.

  14. Breast cancer size estimation with MRI in BRCA mutation carriers and other high risk patients

    Energy Technology Data Exchange (ETDEWEB)

    Mann, R.M., E-mail: [Radboud University Nijmegen Medical Centre, Department of Radiology, Nijmegen (Netherlands); Bult, P., E-mail: [Radboud University Nijmegen Medical Centre, Department of Pathology, Nijmegen (Netherlands); Laarhoven, H.W.M. van, E-mail: [Academic Medical Centre, University of Amsterdam, Department of Medical Oncology, Amsterdam (Netherlands); Radboud University Nijmegen Medical Centre, Department of Medical Oncology, Nijmegen (Netherlands); Span, P.N., E-mail: [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Schlooz, M., E-mail: [Radboud University Nijmegen Medical Centre, Department of Surgery, Nijmegen (Netherlands); Veltman, J., E-mail: [Hospital group Twente (ZGT), Department of Radiology, Almelo (Netherlands); Hoogerbrugge, N., E-mail: [Radboud University Nijmegen Medical Centre, Department of Human Genetics, Nijmegen (Netherlands)


    Objective: To assess the value of breast MRI in size assessment of breast cancers in high risk patients, including those with a BRCA 1 or 2 mutation. Guidelines recommend invariably breast MRI screening for these patients and therapy is thus based on these findings. However, the accuracy of breast MRI for staging purposes is only tested in sporadic cancers. Methods: We assessed concordance of radiologic staging using MRI with histopathology in 49 tumors in 46 high risk patients (23 BRCA1, 12 BRCA2 and 11 Non-BRCA patients). The size of the total tumor area (TTA) was compared to pathology. In invasive carcinomas (n = 45) the size of the largest focus (LF) was also addressed. Results: Correlation of MRI measurements with pathology was 0.862 for TTA and 0.793 for LF. TTA was underestimated in 8(16%), overestimated in 5(10%), and correctly measured in 36(73%) cases. LF was underestimated in 4(9%), overestimated in 5(11%), and correctly measured in 36(80%) cases. Impact of BRCA 1 or 2 mutations on the quality of size estimation was not observed. Conclusions: Tumor size estimation using breast MRI in high risk patients is comparable to its performance in sporadic cancers. Therefore, breast MRI can safely be used for treatment planning.

  15. Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro. (United States)

    Tai, Joseph; Cheung, Susan; Wu, Matthew; Hasman, David


    Rosemary (Rosmarinus officinalis L.) is a popular culinary/medicinal herb. Recent studies have shown it has pharmacologic activities for cancer chemoprevention and therapy. This study evaluated the antiproliferation activity of rosemary extract (RE) against human ovarian cancer cells, and whether the extract and its three main active ingredients carnosol (CS), carnosic acid (CA) and rosmarinic acid (RA) can enhance the antiproliferation activity of cisplatin (CDDP). Our study showed that RE has significant antiproliferation activity on human ovarian cancer A2780 and its CDDP resistant daughter cell line A2780CP70, with IC(50) (50% inhibitory concentration) estimated at 1/1000 and 1/400 dilutions respectively. RE enhanced the antiproliferation effect with CDDP on both A2780 and A2780CP70 cells. A2780 cells were consistently more sensitive to CS, CA, and RA than A2780CP70 cells between 2.5 and 20μg/ml. CS and RA also showed synergistic antiproliferation effect with CDDP on A2780 cells at some concentrations. RE treated by ultrafiltration, dialysis, and removal of phenolics lost the antiproliferation activity suggested that the activity resides in phenolics with MW<1000Da. Apoptosis array study of A2780 cells treated with RE showed that the expression of a number of genes regulating apoptosis were modulated by the treatment. This study showed that RE inhibited the proliferation of ovarian cancer cell lines by affecting the cell cycle at multiple phases. It induced apoptosis by modifying the expression of multiple genes regulating apoptosis, and holds potential as an adjunct to cancer chemotherapy.

  16. Growth suppressive efficacy of human lak cells against human lung-cancer implanted into scid mice. (United States)

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


    The purpose of our study was to determine the efficacy of immunotherapy using human lymphokine activated killer (LAK) cells against a human-lung squamous-cell carcinoma cell line (RERF-LC-AI) implanted into severe combined immunodeficient (SCID) mice. A statistically significant growth suppressive effect on RERF-LC-AI implanted into SCID mice was observed when human LAK cells were administered into the caudal vein of the mice treated with a continuous supply (initiated prior to LAK cells injection) of rIL-2. The human LAK cells stained with PKH 2, a fluorescent dye, for later detection using flow cytometry were administered into the caudal vein of RERF-LC-AI bearing SCID mice; the cells persisted for 7 days in the implanted lung cancer tissue and in the mouse peripheral blood, but for 5 days in the mouse spleen. The number of infiltrated human LAK cells in each tissue increased dose-dependently with the number of injected cells. The results indicate that the antitumor effect most likely occurred during the early implantation period of the human LAK cells. These results demonstrate the applicability of this model to the in vivo study of human lung cancer therapy.

  17. Cancer in human immunodeficiency virus-infected children : A case series from the Children's Cancer Group and the National Cancer Institute

    NARCIS (Netherlands)

    Granovsky, MO; Mueller, BU; Nicholson, HS; Rosenberg, PS; Rabkin, CS


    Purpose: To describe the spectrum of malignancies in human immunodeficiency virus (HIV)-infected children and the clinical outcome of patients with these tumors. Methods: We retrospectively surveyed the Children's Cancer Group (CCG) and the National Cancer institute (NCI) for cases of cancer that oc

  18. Cancer in human immunodeficiency virus-infected children : A case series from the Children's Cancer Group and the National Cancer Institute

    NARCIS (Netherlands)

    Granovsky, MO; Mueller, BU; Nicholson, HS; Rosenberg, PS; Rabkin, CS


    Purpose: To describe the spectrum of malignancies in human immunodeficiency virus (HIV)-infected children and the clinical outcome of patients with these tumors. Methods: We retrospectively surveyed the Children's Cancer Group (CCG) and the National Cancer institute (NCI) for cases of cancer that oc

  19. Cancer in human immunodeficiency virus-infected children : A case series from the Children's Cancer Group and the National Cancer Institute

    NARCIS (Netherlands)

    Granovsky, MO; Mueller, BU; Nicholson, HS; Rosenberg, PS; Rabkin, CS

    Purpose: To describe the spectrum of malignancies in human immunodeficiency virus (HIV)-infected children and the clinical outcome of patients with these tumors. Methods: We retrospectively surveyed the Children's Cancer Group (CCG) and the National Cancer institute (NCI) for cases of cancer that

  20. Estimating high-risk castration resistant prostate cancer (CRPC) using electronic health records. (United States)

    Hernandez, Rohini K; Cetin, Karynsa; Pirolli, Melissa; Quigley, Jane; Quach, David; Smith, Paul; Stryker, Scott; Liede, Alexander


    Canadian guidelines define castration-resistant prostate cancer (CRPC) at high risk of developing metastases using PSA doubling time (PSADT) electronic health records (EHR), covering 129 urology and 64 oncology practices across the US. We estimated the proportion of prostate cancer patients with evidence of CRPC (consecutive rising PSAs) and subsets that may be at high risk (using several PSA and PSADT cut-points). Among 3121 M0 prostate cancer patients actively treated with ADT, 1188 (38%) had evidence of CRPC. Of these, 712 (60%) qualified as high risk in 2011 based on PSADT < 8 months (equivalent to = 8 months in these data). Men = 65 years were more likely to have evidence of CRPC than younger men, although younger men were more likely to have evidence of high-risk disease. CRPC was more common among men receiving ADT in the oncology setting than the urology setting (48% versus 37%). In this large EHR study with patient-level PSA data, 38% of men with M0 prostate cancer treated with ADT had CRPC. Approximately 60% of M0 CRPC patients may experience a PSADT of < 8 months. These findings require validation in a Canadian patient population.

  1. Annual national direct and indirect cost estimates of the prevention and treatment of cervical cancer in Brazil (United States)

    Novaes, Hillegonda Maria Dutilh; Itria, Alexander; Silva, Gulnar Azevedo e; Sartori, Ana Marli Christovam; Rama, Cristina Helena; de Soárez, Patrícia Coelho


    OBJECTIVE: To estimate the annual direct and indirect costs of the prevention and treatment of cervical cancer in Brazil. METHODS: This cost description study used a "gross-costing" methodology and adopted the health system and societal perspectives. The estimates were grouped into sets of procedures performed in phases of cervical cancer care: the screening, diagnosis and treatment of precancerous lesions and the treatment of cervical cancer. The costs were estimated for the public and private health systems, using data from national health information systems, population surveys, and literature reviews. The cost estimates are presented in 2006 USD. RESULTS: From the societal perspective, the estimated total costs of the prevention and treatment of cervical cancer amounted to USD $1,321,683,034, which was categorized as follows: procedures (USD $213,199,490), visits (USD $325,509,842), transportation (USD $106,521,537) and productivity losses (USD $676,452,166). Indirect costs represented 51% of the total costs, followed by direct medical costs (visits and procedures) at 41% and direct non-medical costs (transportation) at 8%. The public system represented 46% of the total costs, and the private system represented 54%. CONCLUSION: Our national cost estimates of cervical cancer prevention and treatment, indicating the economic importance of cervical cancer screening and care, will be useful in monitoring the effect of the HPV vaccine introduction and are of interest in research and health care management. PMID:26017797

  2. 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


    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.

  3. Human RECQ helicases: roles in cancer, aging, and inherited disease

    Directory of Open Access Journals (Sweden)

    Sidorova JM


    Full Text Available Julia M Sidorova,1,* Raymond J Monnat Jr,1,2,* 1Department of Pathology, 2Department of Genome Sciences, University of Washington, Seattle, WA, USA *The authors contributed equally to this review Abstract: DNA helicases use the energy of ATP hydrolysis to disrupt DNA base pairing and displace proteins from DNA in order to facilitate replication, recombination, transcription, and repair. This article focuses on the human RECQ helicases, five DNA-dependent helicases that play key roles in cellular physiology and disease. Loss of function of three RECQ helicases causes the cancer predisposition syndromes Bloom syndrome, Werner syndrome, and Rothmund–Thomson and related syndromes. We summarize recent work on these syndromes and proteins and discuss disease pathogenesis in light of RECQ helicase biochemical activities and in vivo functions. Keywords: ATP-dependent DNA helicase, Bloom syndrome, Werner syndrome, Rothmund–Thomson syndrome, DNA replication, DNA repair, genetic instability, cancer predisposition syndrome

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

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Qin, Yi-Zhuo; Wang, Rui-Qi [Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012 (China); Li, Wen-Bao, E-mail: [Sanlugen PharmaTech, Rm 506, No. 2766 Yingxiu Road, Jinan 250101 (China); Qu, Xian-Jun, E-mail: [Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012 (China)


    Highlights: •SL-01 is an oral derivative of gemcitabine. •SL-01 possessed activity against human breast cancer growth via apoptotic induction. •SL-01’s activity was more potently than that of gemcitabine. •SL-01 inhibited cancer growth without toxicity to mice. -- Abstract: SL-01 is an oral derivative of gemcitabine that was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl) pyrazine-2-carbonyl at N4-position on cytidine ring of gemcitabine. We aimed to evaluate the efficacy of SL-01 on human breast cancer growth. SL-01 significantly inhibited MCF-7 proliferation as estimated by colorimetric assay. Flow cytometry assay indicated the apoptotic induction and cell cycle arrest in G1 phase. SL-01 modulated the expressions of p-ATM, p53 and p21 and decrease of cyclin D1 in MCF-7 cells. Further experiments were performed in a MCF-7 xenografts mouse model. SL-01 by oral administration strongly inhibited MCF-7 xenografts growth. This effect of SL-01 might arise from its roles in the induction of apoptosis. Immunohistochemistry assay showed the increase of TUNEL staining cells. Western blotting indicated the modulation of apoptotic proteins in SL-01-treated xenografts. During the course of study, there was no evidence of toxicity to mice. In contrast, the decrease of neutrophil cells in peripheral and increase of AST and ALT levels in serum were observed in the gemcitabine-treated mice. Conclusion: SL-01 possessed similar activity against human breast cancer growth with gemcitabine, whereas, with lower toxicity to gemcitabine. SL-01 is a potent oral agent that may supplant the use of gemcitabine.

  5. Estimating single nucleotide polymorphism associations using pedigree data: applications to breast cancer. (United States)

    Barnes, D R; Barrowdale, D; Beesley, J; Chen, X; James, P A; Hopper, J L; Goldgar, D; Chenevix-Trench, G; Antoniou, A C; Mitchell, G


    Pedigrees with multiple genotyped family members have been underutilised in breast cancer (BC) genetic-association studies. We developed a pedigree-based analytical framework to characterise single-nucleotide polymorphism (SNP) associations with BC risk using data from 736 BC families ascertained through multiple affected individuals. On average, eight family members had been genotyped for 24 SNPs previously associated with BC. Breast cancer incidence was modelled on the basis of SNP effects and residual polygenic effects. Relative risk (RR) estimates were obtained by maximising the retrospective likelihood (RL) of observing the family genotypes conditional on all disease phenotypes. Models were extended to assess parent-of-origin effects (POEs). Thirteen SNPs were significantly associated with BC under the pedigree RL approach. This approach yielded estimates consistent with those from large population-based studies. Logistic regression models ignoring pedigree structure generally gave larger RRs and association P-values. SNP rs3817198 in LSP1, previously shown to exhibit POE, yielded maternal and paternal RR estimates that were similar to those previously reported (paternal RR=1.12 (95% confidence interval (CI): 0.99-1.27), P=0.081, one-sided P=0.04; maternal RR=0.94 (95% CI: 0.84-1.06), P=0.33). No other SNP exhibited POE. Our pedigree-based methods provide a valuable and efficient tool for characterising genetic associations with BC risk or other diseases and can complement population-based studies.

  6. Estimating underreported N2 disease in rectal cancer patients with low lymph node counts. (United States)

    Huebner, Marianne; Therneau, Terry; Larson, David


    The variability in the number of lymph nodes examined needs to be taken into account for adequate staging. The definition of nodal staging was refined by quantifying the likelihood of N2 disease when the patient had fewer than four positive LN. In a retrospective study a total of 548 patients with node positive rectal cancer and curative surgery between 1990 and 2006 were identified. The misclassification of pN staging was estimated with a Bayesian computation. The prognostic value of the calculated probability, lymph node ratio (LNR), and nodal stage was assessed with Cox proportional hazard regression. A probability of understaging of 40% or more indicated worse prognosis of cancer-specific survival (CSS) with hazard ratio 2.6 (95%CI: 1.8-3.9, P clinical decision making. Copyright © 2011 Wiley Periodicals, Inc.

  7. Semiparametric Bayesian estimation of quantile function for breast cancer survival data with cured fraction. (United States)

    Gupta, Cherry; Cobre, Juliana; Polpo, Adriano; Sinha, Debjayoti


    Existing cure-rate survival models are generally not convenient for modeling and estimating the survival quantiles of a patient with specified covariate values. This paper proposes a novel class of cure-rate model, the transform-both-sides cure-rate model (TBSCRM), that can be used to make inferences about both the cure-rate and the survival quantiles. We develop the Bayesian inference about the covariate effects on the cure-rate as well as on the survival quantiles via Markov Chain Monte Carlo (MCMC) tools. We also show that the TBSCRM-based Bayesian method outperforms existing cure-rate models based methods in our simulation studies and in application to the breast cancer survival data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.

  8. Model-integrated estimation of normal tissue contamination for cancer SNP allelic copy number data. (United States)

    Stjernqvist, Susann; Rydén, Tobias; Greenman, Chris D


    SNP allelic copy number data provides intensity measurements for the two different alleles separately. We present a method that estimates the number of copies of each allele at each SNP position, using a continuous-index hidden Markov model. The method is especially suited for cancer data, since it includes the fraction of normal tissue contamination, often present when studying data from cancer tumors, into the model. The continuous-index structure takes into account the distances between the SNPs, and is thereby appropriate also when SNPs are unequally spaced. In a simulation study we show that the method performs favorably compared to previous methods even with as much as 70% normal contamination. We also provide results from applications to clinical data produced using the Affymetrix genome-wide SNP 6.0 platform.

  9. Biological role of β-arrestin1 in human gastric cancer BGC-823 cells

    Institute of Scientific and Technical Information of China (English)



    Objective To investigate the effects of β-arrestin1 on proliferation,migration,invasion and apoptosis of human gastric cancer BGC-823 cell line. Methods The expression of β-arrestin1 in human gastric epithelial cell line GES, human gastric cancer cell line BGC-823, MKN-28 and SGC-7901 was detected

  10. AXL is an oncotarget in human colorectal cancer (United States)

    Martinelli, Erika; Troiani, Teresa; Liguori, Giuseppina; Vitagliano, Donata; Napolitano, Stefania; Morgillo, Floriana; Rinaldi, Barbara; Melillo, Rosa Marina; Liotti, Federica; Nappi, Anna; Bianco, Roberto; Berrino, Liberato; Ciuffreda, Loreta Pia; Ciardiello, Davide; Iaffaioli, Vincenzo; Botti, Gerardo; Ferraiolo, Fiorella; Ciardiello, Fortunato


    AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC. PMID:25966280

  11. Poverty eradication and decreased human papilloma virus related cancer of the penis and vulva in Jamaica. (United States)

    Fletcher, H M; Hanchard, B


    Human papilloma virus causes genital cancers. Decreases in cervical cancer have been reported to be due to comprehensive screening programmes difficult to replicate in poorer countries. HPV cancer may be related to poverty. In Jamaica, we have seen decreases in cancer of the penis and vulva and there has also been a decrease in poverty. The decrease cannot be attributed to screening. We believe elimination of poverty has decreased HPV persistence and decreased cancer rates.

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


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


    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...

  13. Prognostic value of metastin expression in human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Kawaguchi Yoshiya


    Full Text Available Abstract Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissues obtained from 53 consecutive patients who underwent resection between July 2003 and May 2007 at Kyoto University Hospital. In 23 consecutive patients, the plasma metastin level was measured before surgery by enzyme immunoassay. Results Strong immunohistochemical expression of metastin was detected in 13 tumors (24.5%, while strong expression of GPR54 was detected in 30 tumors (56.6%. Tumors that were negative for both metastin and GPR54 expression were significantly larger than tumors that were positive for either metastin or GPR54 (p = 0.047. Recurrence was less frequent in patients who had metastin-positive tumors compared with those who had metastin-negative tumors (38.5% versus 70.0%, p = 0.04. Strong expression of metastin and GPR54 was significantly correlated with longer survival (p = 0.02. Metastin expression by pancreatic cancer was an independent prognostic factor for longer survival (hazard ratio, 2.1; 95% confidence interval, 1.1–4.7; p = 0.03, and the patients with a high plasma metastin level (n = 6 did not die after surgical resection. Conclusion Strong expression of metastin and GPR54 by pancreatic cancer is associated with longer survival. Metastin expression is an independent prognostic factor for the survival of pancreatic cancer patients. The plasma metastin level could become a noninvasive prognostic factor for the assessment of pancreatic cancer.

  14. Human Papillomavirus and Tonsillar and Base of Tongue Cancer

    Directory of Open Access Journals (Sweden)

    Torbjörn Ramqvist


    Full Text Available In 2007, human papillomavirus (HPV type 16 was recognized as a risk factor by the International Agency for Research on Cancer, for oropharyngeal squamous cell carcinoma (OSCC, where tonsillar and base of tongue cancer (TSCC and BOTSCC dominate. Furthermore, patients with HPV-positive TSCC and BOTSCC, had a much better clinical outcome than those with corresponding HPV-negative cancer and other head and neck cancer. More specifically, survival was around 80% for HPV-positive TSCC and BOTSCC vs. 40% five-year disease free survival, for the corresponding HPV-negative tumors with conventional radiotherapy and surgery, while this could not be observed for HPV-positive OSCC at other sites. In addition, the past 20–40 years in many Western Countries, the incidence of HPV-positive TSCC and BOTSCC has risen, and >70% are men. This has resulted in a relative increase of patients with HPV-positive TSCC and BOTSCC that may not need the intensified chemo-radiotherapy (with many more severe debilitating side effects often given today to patients with head and neck cancer. However, before tapering therapy, one needs to enable selection of patients for such treatment, by identifying clinical and molecular markers that together with HPV-positive status will better predict patient prognosis and response to therapy. To conclude, there is a new increasing group of patients with HPV-positive TSCC and BOTSCC with good clinical outcome, where options for better-tailored therapy are needed. For prevention, it would be of benefit to vaccinate both girls and boys against HPV16 infection. For potential future screening the ways to do so need optimizing.

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

    Directory of Open Access Journals (Sweden)

    Arul eNarayanasamy


    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.

  16. Phase I study of anticolon cancer humanized antibody A33. (United States)

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


    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.

  17. Prognostic value of metastin expression in human pancreatic cancer


    Kawaguchi Yoshiya; Masui Toshihiko; Koizumi Masayuki; Kida Atsushi; Ito Tatsuo; Katagiri Fumihiko; Doi Ryuichiro; Nagai Kazuyuki; Tomita Kenji; Oishi Shinya; Fujii Nobutaka; Uemoto Shinji


    Abstract Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcino...

  18. Prognostic value of metastin expression in human pancreatic cancer


    Nagai, Kazuyuki; Doi, Ryuichiro; Katagiri, Fumihiko; Ito, Tatsuo; Kida, Atsushi; Koizumi, Masayuki; Masui, Toshihiko; Kawaguchi, Yoshiya; Tomita, Kenji; Oishi, Shinya; Fujii, Nobutaka; Uemoto, Shinji


    Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissue...

  19. Prognostic value of metastin expression in human pancreatic cancer.


    Nagai, Kazuyuki; Doi, Ryuichiro; Katagiri, Fumihiko; Ito, Tatsuo; Kida, Atsushi; Koizumi, Masayuki; Masui, Toshihiko; Kawaguchi, Yoshiya; Tomita, Kenji; Oishi, Shinya; Fujii, Nobutaka; Uemoto, Shinji


    [Background]KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. [Methods]We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tiss...

  20. 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


    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.


    Directory of Open Access Journals (Sweden)

    Rhiannon Maudsley


    Full Text Available Cavalieri sampling and point counting are frequently applied in combination with magnetic resonance (MR imaging to estimate the volume of human brain compartments. Current practice involves arbitrarily choosing the number of sections and sampling intensity within each section, and subsequently applying error prediction formulae to estimate the precision. The aim of this study is to derive a reference table for researchers who are interested in estimating the volume of brain regions, namely grey matter, white matter, and their union, to a given precision. In particular, this table, which is based on subsampling of a large brain data set obtained from coronal MR images, offers a recommendation for the minimum number of sections and mean number of points per section that are required to achieve a pre-defined coefficient of error of the volume estimator. Further analysis onMR brain data from a second human brain shows that the sampling intensity recommended is appropriate.

  2. Postoperative Survival Estimation of Gastric Cancer Patients in Cancer Institute of Tehran, Imam Khomeini Hospital and Its Relative Factors

    Directory of Open Access Journals (Sweden)

    A. Kazemnejad


    Full Text Available Introduction & Objective: Gastric Cancer (GC is one of the most common causes of death in the world. The most important cause of high death rate related to GC is late diagnosis of the disease. The main treatment of gastric cancer in its primary stage of is surgery, and radiotherapy and chemotherapy are supplementary treatments. There are some factors that affect survival after surgery. This study aimed to assess the survival of patients with GC under surgery and to determine the risk factors of this cancer. Materials & Methods: A total of 262 patients with GC under surgery were followed and included in the study from 21st of March 2003 to 21st of March 2007 in the cancer institute of Tehran, Imam Khomeini Hospital, . The staging of the disease before the surgery was based on CT-Scan and endosonography and after the surgery was based on the pathologic reports. The survival of the patients was determined by their periodical referrals and our telephone contacts with their relatives. The survival times were considered as the time from the diagnosis up to the death or the end of the study. The effect of the various risk factors including gender, age at diagnosis, tumor site, pathologic stage of the disease, type of treatment, metastases and relapse were evaluated. Kaplan-Miere approach was used to estimate survival and Log-rank test and proportional Cox model to evaluate the related factors. Data were analyzed using Spss16 statistical software. Results: 75.2% of patients were men and 34.4% cases of patients experienced death. The mean follow-up time was 19.317.4. The mean age at diagnosis was 5811.5 and survival mean and median were 49 and 27 months respectively. The one, three and five year survival of the patients were 0.85, 0.41 and 0.3 respectively. Gender, pathologic stage, age at diagnosis and weight-loss were significantly related to the survival in multivariate analysis. Conclusion: The diagnosis of the cancer in primary stages causes

  3. Parameter estimation of the Huxley cross-bridge muscle model in humans. (United States)

    Vardy, Alistair N; de Vlugt, Erwin; van der Helm, Frans C T


    The Huxley model has the potential to provide more accurate muscle dynamics while affording a physiological interpretation at cross-bridge level. By perturbing the wrist at different velocities and initial force levels, reliable Huxley model parameters were estimated in humans in vivo using a Huxley muscle-tendon complex. We conclude that these estimates may be used to investigate and monitor changes in microscopic elements of muscle functioning from experiments at joint level.

  4. Parameters Estimation for the Spherical Model of the Human Knee Joint Using Vector Method (United States)

    Ciszkiewicz, A.; Knapczyk, J.


    Position and displacement analysis of a spherical model of a human knee joint using the vector method was presented. Sensitivity analysis and parameter estimation were performed using the evolutionary algorithm method. Computer simulations for the mechanism with estimated parameters proved the effectiveness of the prepared software. The method itself can be useful when solving problems concerning the displacement and loads analysis in the knee joint

  5. Parameters Estimation For A Patellofemoral Joint Of A Human Knee Using A Vector Method (United States)

    Ciszkiewicz, A.; Knapczyk, J.


    Position and displacement analysis of a spherical model of a human knee joint using the vector method was presented. Sensitivity analysis and parameter estimation were performed using the evolutionary algorithm method. Computer simulations for the mechanism with estimated parameters proved the effectiveness of the prepared software. The method itself can be useful when solving problems concerning the displacement and loads analysis in the knee joint.

  6. The flavonol isorhamnetin exhibits cytotoxic effects on human colon cancer cells. (United States)

    Jaramillo, Sara; Lopez, Sergio; Varela, Lourdes M; Rodriguez-Arcos, Rocio; Jimenez, Ana; Abia, Rocio; Guillen, Rafael; Muriana, Francisco J G


    The aim of this study was to determine whether isorhamnetin, an immediate 3'-O-methylated metabolite of quercetin, affects proliferation, cell death, and the cell cycle of human colon carcinoma (HCT-116) cells. Isorhamnetin was found to be a potent antiproliferative agent in a dose- and time-dependent manner, with an IC50 of 72 μM after 48 h of incubation as estimated by MTT assay. Flow cytometry and fluorescence microscopy analysis showed that isorhamnetin exerted a stimulatory effect on apoptosis and necrosis. Isorhamnetin also increased the number of cells in G2/M phase. Serum deprivation appeared to potentiate the effects of isorhamnetin on cell death and facilitated cell cycle progression to G0/G1 phase. These results suggest that isorhamnetin might mediate inhibition of HCT-116 cell growth through the perturbation of cell cycle progression and are consistent with the notion that G2/M checkpoints could be a conserved target for flavonoids in human colon cancer cells, leading to apoptotic and necrotic death. These antiproliferative, apoptotic, necrotic, and cell cycle effects suggest that isorhamnetin may have clinically significant therapeutic and chemopreventive capabilities. To our knowledge, this is the first report of the effect of isorhamnetin on human colon cancer cells.

  7. Comparison of methods for estimating the intraclass correlation coefficient for binary responses in cancer prevention cluster randomized trials. (United States)

    Wu, Sheng; Crespi, Catherine M; Wong, Weng Kee


    The intraclass correlation coefficient (ICC) is a fundamental parameter of interest in cluster randomized trials as it can greatly affect statistical power. We compare common methods of estimating the ICC in cluster randomized trials with binary outcomes, with a specific focus on their application to community-based cancer prevention trials with primary outcome of self-reported cancer screening. Using three real data sets from cancer screening intervention trials with different numbers and types of clusters and cluster sizes, we obtained point estimates and 95% confidence intervals for the ICC using five methods: the analysis of variance estimator, the Fleiss-Cuzick estimator, the Pearson estimator, an estimator based on generalized estimating equations and an estimator from a random intercept logistic regression model. We compared estimates of the ICC for the overall sample and by study condition. Our results show that ICC estimates from different methods can be quite different, although confidence intervals generally overlap. The ICC varied substantially by study condition in two studies, suggesting that the common practice of assuming a common ICC across all clusters in the trial is questionable. A simulation study confirmed pitfalls of erroneously assuming a common ICC. Investigators should consider using sample size and analysis methods that allow the ICC to vary by study condition.

  8. Cancer (United States)

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

  9. Image-based human age estimation by manifold learning and locally adjusted robust regression. (United States)

    Guo, Guodong; Fu, Yun; Dyer, Charles R; Huang, Thomas S


    Estimating human age automatically via facial image analysis has lots of potential real-world applications, such as human computer interaction and multimedia communication. However, it is still a challenging problem for the existing computer vision systems to automatically and effectively estimate human ages. The aging process is determined by not only the person's gene, but also many external factors, such as health, living style, living location, and weather conditions. Males and females may also age differently. The current age estimation performance is still not good enough for practical use and more effort has to be put into this research direction. In this paper, we introduce the age manifold learning scheme for extracting face aging features and design a locally adjusted robust regressor for learning and prediction of human ages. The novel approach improves the age estimation accuracy significantly over all previous methods. The merit of the proposed approaches for image-based age estimation is shown by extensive experiments on a large internal age database and the public available FG-NET database.

  10. A human genotyping trial to estimate the post-feeding time from mosquito blood meals. (United States)

    Hiroshige, Yuuji; Hara, Masaaki; Nagai, Atsushi; Hikitsuchi, Tomoyuki; Umeda, Mitsuo; Kawajiri, Yumi; Nakayama, Koji; Suzuki, Koichi; Takada, Aya; Ishii, Akira; Yamamoto, Toshimichi


    Mosquitoes occur almost worldwide, and females of some species feed on blood from humans and other animals to support ovum maturation. In warm and hot seasons, such as the summer in Japan, fed mosquitoes are often observed at crime scenes. The current study attempted to estimate the time that elapsed since feeding from the degree of human DNA digestion in mosquito blood meals and also to identify the individual human sources of the DNA using genotyping in two species of mosquito: Culex pipiens pallens and Aedes albopictus. After stereomicroscopic observation, the extracted DNA samples were quantified using a human DNA quantification and quality control kit and were genotyped for 15 short tandem repeats using a commercial multiplexing kit. It took about 3 days for the complete digestion of a blood meal, and genotyping was possible until 2 days post-feeding. The relative peak heights of the 15 STRs and DNA concentrations were useful for estimating the post-feeding time to approximately half a day between 0 and 2 days. Furthermore, the quantitative ratios derived from STR peak heights and the quality control kit (Q129/Q41, Q305/Q41, and Q305/Q129) were reasonably effective for estimating the approximate post-feeding time after 2-3 days. We suggest that this study may be very useful for estimating the time since a mosquito fed from blood meal DNA, although further refinements are necessary to estimate the times more accurately.

  11. The application of pharmacoeconomic modelling to estimate a value-based price for new cancer drugs. (United States)

    Dranitsaris, George; Truter, Ilse; Lubbe, Martie S; Cottrell, Wayne; Spirovski, Biljana; Edwards, Jonathan


    Value-based pricing has recently been discussed by international bodies as a means to estimate a drug price that is linked to the benefits it offers patients and society. The World Health Organization (WHO) has recommended using three times a country's per capita gross domestic product (GDP) as the threshold for economic value. Using the WHO criteria, pharmacoeconomic modelling was used to illustrate the application of value-based price towards bevacizumab, a relatively new drug that provides a 1.4-month survival benefit to patients with metastatic colorectal cancer (mCRC). A decision model was developed to simulate outcomes in mCRC patients receiving chemotherapy ± bevacizumab. Clinical data were obtained from randomized trials and costs from Canadian cancer centres. Utility estimates were determined by interviewing 24 oncology nurses and pharmacists. A price per dose of bevacizumab was then estimated using a target threshold of $CAD117,000 per quality adjusted life year gained, which is three times the Canadian per capita GDP. For a 1.4-month survival benefit, a price of $CAD830 per dose would be considered cost-effective from the Canadian public health care perspective. If the drug were able to improve patient quality of life or survival from 1.4 to 3 months, the drug price could increase to $CAD1560 and $CAD2180 and still be considered cost-effective. The use of the WHO criteria for estimating a value-based price is feasible, but a balance between what patients/governments can afford to pay and the commercial viability of the product in the reference country would be required. © 2010 Blackwell Publishing Ltd.

  12. Estimating Water Supply Arsenic Levels in the New England Bladder Cancer Study (United States)

    Freeman, Laura E. Beane; Lubin, Jay H.; Airola, Matthew S.; Baris, Dalsu; Ayotte, Joseph D.; Taylor, Anne; Paulu, Chris; Karagas, Margaret R.; Colt, Joanne; Ward, Mary H.; Huang, An-Tsun; Bress, William; Cherala, Sai; Silverman, Debra T.; Cantor, Kenneth P.


    Background: Ingestion of inorganic arsenic in drinking water is recognized as a cause of bladder cancer when levels are relatively high (≥ 150 µg/L). The epidemiologic evidence is less clear at the low-to-moderate concentrations typically observed in the United States. Accurate retrospective exposure assessment over a long time period is a major challenge in conducting epidemiologic studies of environmental factors and diseases with long latency, such as cancer. Objective: We estimated arsenic concentrations in the water supplies of 2,611 participants in a population-based case–control study in northern New England. Methods: Estimates covered the lifetimes of most study participants and were based on a combination of arsenic measurements at the homes of the participants and statistical modeling of arsenic concentrations in the water supply of both past and current homes. We assigned a residential water supply arsenic concentration for 165,138 (95%) of the total 173,361 lifetime exposure years (EYs) and a workplace water supply arsenic level for 85,195 EYs (86% of reported occupational years). Results: Three methods accounted for 93% of the residential estimates of arsenic concentration: direct measurement of water samples (27%; median, 0.3 µg/L; range, 0.1–11.5), statistical models of water utility measurement data (49%; median, 0.4 µg/L; range, 0.3–3.3), and statistical models of arsenic concentrations in wells using aquifers in New England (17%; median, 1.6 µg/L; range, 0.6–22.4). Conclusions: We used a different validation procedure for each of the three methods, and found our estimated levels to be comparable with available measured concentrations. This methodology allowed us to calculate potential drinking water exposure over long periods. PMID:21421449

  13. Functional characterization of human cancer-derived TRKB mutations.

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    Thomas R Geiger

    Full Text Available Cancer originates from cells that have acquired mutations in genes critical for controlling cell proliferation, survival and differentiation. Often, tumors continue to depend on these so-called driver mutations, providing the rationale for targeted anticancer therapies. To date, large-scale sequencing analyses have revealed hundreds of mutations in human tumors. However, without their functional validation it remains unclear which mutations correspond to driver, or rather bystander, mutations and, therefore, whether the mutated gene represents a target for therapeutic intervention. In human colorectal tumors, the neurotrophic receptor TRKB has been found mutated on two different sites in its kinase domain (TRKB(T695I and TRKB(D751N. Another site, in the extracellular part of TRKB, is mutated in a human lung adenocarcinoma cell line (TRKB(L138F. Lastly, our own analysis has identified one additional TRKB point mutation proximal to the kinase domain (TRKB(P507L in a human melanoma cell line. The functional consequences of all these point mutations, however, have so far remained elusive. Previously, we have shown that TRKB is a potent suppressor of anoikis and that TRKB-expressing cells form highly invasive and metastatic tumors in nude mice. To assess the functional consequences of these four TRKB mutations, we determined their potential to suppress anoikis and to form tumors in nude mice. Unexpectedly, both colon cancer-derived mutants, TRKB(T695I and TRKB(D751N, displayed reduced activity compared to that of wild-type TRKB. Consistently, upon stimulation with the TRKB ligand BDNF, these mutants were impaired in activating TRKB and its downstream effectors AKT and ERK. The two mutants derived from human tumor cell lines (TRKB(L138F and TRKB(P507L were functionally indistinguishable from wild-type TRKB in both in-vitro and in-vivo assays. In conclusion, we fail to detect any gain-of-function of four cancer-derived TRKB point mutations.

  14. Proteasome inhibition as a novel therapeutic target in human cancer. (United States)

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


    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.

  15. Absolute quantification of somatic DNA alterations in human cancer. (United States)

    Carter, Scott L; Cibulskis, Kristian; Helman, Elena; McKenna, Aaron; Shen, Hui; Zack, Travis; Laird, Peter W; Onofrio, Robert C; Winckler, Wendy; Weir, Barbara A; Beroukhim, Rameen; Pellman, David; Levine, Douglas A; Lander, Eric S; Meyerson, Matthew; Getz, Gad


    We describe a computational method that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. The method, named ABSOLUTE, can detect subclonal heterogeneity and somatic homozygosity, and it can calculate statistical sensitivity for detection of specific aberrations. We used ABSOLUTE to analyze exome sequencing data from 214 ovarian carcinoma tumor-normal pairs. This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12. We also used ABSOLUTE to infer absolute allelic copy-number profiles from 3,155 diverse cancer specimens, revealing that genome-doubling events are common in human cancer, likely occur in cells that are already aneuploid, and influence pathways of tumor progression (for example, with recessive inactivation of NF1 being less common after genome doubling). ABSOLUTE will facilitate the design of clinical sequencing studies and studies of cancer genome evolution and intra-tumor heterogeneity.

  16. Human papillomavirus genotypes and cervical cancer in northeast Thailand. (United States)

    Natphopsuk, Sitakan; Settheetham-Ishida, Wannapa; Pientong, Chamsai; Sinawat, Supat; Yuenyao, Pissamai; Ishida, Takafumi; Settheetham, Dariwan


    Human papillomavirus (HPV) is a major cause of cervical cancer. More than 100 HPV genotypes have been identified; however the distribution varies geographically and according to ethnicity. The purpose of this study was to investigate the prevalence and distribution of HPV subtypes among Northeast Thai women. Subjects included 198 cases of SCCA and 198 age-matched, healthy controls. HPV-DNA was amplified by PCR using the consensus primers GP5+/6+ system followed by reverse line blot hybridization genotyping. The prevalence of high-risk HPV infection was 21 (10.1%) and 152 (76.8%) in the controls and in the cases, respectively. High-risk HPV significantly increased the risk for cervical cancer with an OR of 42.4 (95%CI: 22.4-81.4, p<0.001) and an adjusted OR of 40.7-fold (95%CI: 21.5-76.8, p <0.001). HPV-16 was the most prevalent HPV type in the SCCA (56.2%) followed by HPV-58 (17.8%) and HPV-18 (13.6%); whereas HPV-58 (46.4%) was a prominent genotype in the controls followed by HPV-16 (39.3%) and unidentified HPV types (25.0%). These findings indicate that HPV infection remains a critical risk factor for SCCA; particularly, HPV-16, HPV-58 and HPV-18. In order to eradicate cervical cancer, sustained health education, promoted use of prophylactics and a HPV-58 vaccine should be introduced in this region.

  17. Organ-specific radiation-induced cancer risk estimates due to radiotherapy for benign pigmented villonodular synovitis (United States)

    Mazonakis, Michalis; Tzedakis, Antonis; Lyraraki, Efrossyni; Damilakis, John


    Pigmented villonodular synovitis (PVNS) is a benign disease affecting synovial membranes of young and middle-aged adults. The aggressive treatment of this disorder often involves external-beam irradiation. This study was motivated by the lack of data relating to the radiation exposure of healthy tissues and radiotherapy-induced cancer risk. Monte Carlo methodology was employed to simulate a patient’s irradiation for PVNS in the knee and hip joints with a 6 MV photon beam. The average radiation dose received by twenty-two out-of-field critical organs of the human body was calculated. These calculations were combined with the appropriate organ-, age- and gender-specific risk coefficients of the BEIR-VII model to estimate the lifetime probability of cancer development. The risk for carcinogenesis to colon, which was partly included in the treatment fields used for hip irradiation, was determined with a non-linear mechanistic model and differential dose-volume histograms obtained by CT-based 3D radiotherapy planning. Risk assessments were compared with the nominal lifetime intrinsic risk (LIR) values. Knee irradiation to 36 Gy resulted in out-of-field organ doses of 0.2-24.6 mGy. The corresponding range from hip radiotherapy was 1.2-455.1 mGy whereas the organ equivalent dose for the colon was up to 654.9 mGy. The organ-specific cancer risks from knee irradiation for PVNS were found to be inconsequential since they were at least 161.5 times lower than the LIRs irrespective of the patient’s age and gender. The bladder and colon cancer risk from radiotherapy in the hip joint was up to 3.2 and 6.6 times smaller than the LIR, respectively. These cancer risks may slightly elevate the nominal incidence rates and they should not be ignored during the patient’s treatment planning and follow-up. The probabilities for developing any other solid tumor were more than 20 times lower than the LIRs and, therefore, they may be considered as small.

  18. Revised Estimates for the Number of Human and Bacteria Cells in the Body. (United States)

    Sender, Ron; Fuchs, Shai; Milo, Ron


    Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial cells in the body. We estimate the total number of bacteria in the 70 kg "reference man" to be 3.8·1013. For human cells, we identify the dominant role of the hematopoietic lineage to the total count (≈90%) and revise past estimates to 3.0·1013 human cells. Our analysis also updates the widely-cited 10:1 ratio, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and their total mass is about 0.2 kg.

  19. A New View of Radiation-Induced Cancer: Integrating Short- and Long-Term Processes. Part II: Second Cancer Risk Estimation (United States)

    Shuryak, Igor; Brenner, David J.; Hahnfeldt, Philip; Hlatky, Lynn; Sachs, Rainer K.


    As the number of cancer survivors grows, prediction of radiotherapy-induced second cancer risks becomes increasingly important. Because the latency period for solid tumors is long, the risks of recently introduced radiotherapy protocols are not yet directly measurable. In the accompanying article, we presented a new biologically based mathematical model, which, in principle, can estimate second cancer risks for any protocol. The novelty of the model is that it integrates, into a single formalism, mechanistic analyses of pre-malignant cell dynamics on two different time scales: short-term during radiotherapy and recovery; long-term during the entire life span. Here, we apply the model to nine solid cancer types (stomach, lung, colon, rectal, pancreatic, bladder, breast, central nervous system, and thyroid) using data on radiotherapy-induced second malignancies, on Japanese atomic bomb survivors, and on background US cancer incidence. Potentially, the model can be incorporated into radiotherapy treatment planning algorithms, adding second cancer risk as an optimization criterion.

  20. Expression and alternative splicing pattern of human telomerase reverse transcriptase in human lung cancer cells. (United States)

    Fujiwara, Masachika; Kamma, Hiroshi; Wu, Wenwen; Hamasaki, Makoto; Kaneko, Setsuko; Horiguchi, Hisashi; Matsui-Horiguchi, Miwa; Satoh, Hiroaki


    Telomerase activity is generally considered to be necessary for cancer cells to avoid senescence. The expression of human telomerase reverse transcriptase (hTERT) is believed to be a rate-limiting step in telomerase activation. Recently, it has been proposed that the alternative splicing of hTERT is also involved in regulation of telomerase activity. However, the regulatory mechanism of telomerase in cancer cells has not been thoroughly investigated. To clarify it in lung cancer cells, we measured the expression of the hTERT transcript, analyzed its alternative splicing by RT-PCR, and compared it with telomerase activity and telomere length. The expression of the hTERT transcript was positively correlated with telomerase activity in lung cancer cells. Cancer cells with high telomerase activity contained 4 splicing variants of hTERT, and the full-length variant was 31.3-54.2% of the total transcripts. Cells of the TKB-20 cell line, which has extremely low telomerase activity, showed a different splicing pattern of hTERT in addition to low expression. The functional full-length variant was scarcely detected in TKB-20 cells, suggesting that the telomerase activity was repressed by alternative splicing of hTERT. Telomere length was not necessarily correlated with telomerase activity or hTERT expression in lung cancer cells. Cells of the TKB-4 cell line that also showed relatively low telomerase activity (as TKB-20 cells) had long telomeres. In conclusion, hTERT expression is regulated at both the transcriptional and post-transcriptional levels in lung cancer cells, and the alternative splicing of hTERT is involved in the control of telomerase activity.

  1. A taxonomy of epithelial human cancer and their metastases

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    De Moor Bart


    Full Text Available Abstract Background Microarray technology has allowed to molecularly characterize many different cancer sites. This technology has the potential to individualize therapy and to discover new drug targets. However, due to technological differences and issues in standardized sample collection no study has evaluated the molecular profile of epithelial human cancer in a large number of samples and tissues. Additionally, it has not yet been extensively investigated whether metastases resemble their tissue of origin or tissue of destination. Methods We studied the expression profiles of a series of 1566 primary and 178 metastases by unsupervised hierarchical clustering. The clustering profile was subsequently investigated and correlated with clinico-pathological data. Statistical enrichment of clinico-pathological annotations of groups of samples was investigated using Fisher exact test. Gene set enrichment analysis (GSEA and DAVID functional enrichment analysis were used to investigate the molecular pathways. Kaplan-Meier survival analysis and log-rank tests were used to investigate prognostic significance of gene signatures. Results Large clusters corresponding to breast, gastrointestinal, ovarian and kidney primary tissues emerged from the data. Chromophobe renal cell carcinoma clustered together with follicular differentiated thyroid carcinoma, which supports recent morphological descriptions of thyroid follicular carcinoma-like tumors in the kidney and suggests that they represent a subtype of chromophobe carcinoma. We also found an expression signature identifying primary tumors of squamous cell histology in multiple tissues. Next, a subset of ovarian tumors enriched with endometrioid histology clustered together with endometrium tumors, confirming that they share their etiopathogenesis, which strongly differs from serous ovarian tumors. In addition, the clustering of colon and breast tumors correlated with clinico-pathological characteristics

  2. The Prevalence of Human Papillomavirus in Cervical Cancer in Iran. (United States)

    Mortazavi, SH; Zali, MR; Raoufi, M; Nadji, M; Kowsarian, P; Nowroozi, A


    Background: The human papiloma virus (HPV), which is sexually transmitted, and most commonly causes genital warts, has been linked to cervical intraepithelial neoplasia and invasive carcinoma. Of ninety plus types of HPV, HPV-16 is the most prevalent in cervical cancer, followed by HPV-18, and HPV-33. As HPV's implication has not been assessed in the Middle East the main focus of this retrospective study was to determine the prevalence of HPV -16,18, and 33 in cases of cervical cancer from Iran. Material and Methods: This retrospective study covered 100 patients with uterine cervical carcinomas who were referred to two referral centers for cancer in Tehran-Iran. Pathological blocks were collected for these cases and initial review of the blocks showed poor specimens in 18 cases, which left 82 cases for the study. These samples were histologically examined to verify the presence and the type of carcinoma. The next step was in situ hybridzation for the detection of HPV common DNA. In Situ hybridization was preformed on all samples. Finally, Polymerase Chain Reaction (PCR) was preformed for the HPV types 16, 18, and 33. PCR amplification of exon 5 of the p53 gene was used as an internal control for the integrity of DNA. Takara PCR Human papilloma Detection method was used which includes primer for HPV 16, 18, and 33. Three primers were used alone, or in combination, in order to increase the sensitivity of the detection. Results: The majority of tumors were squamous cell carcinomas (87%). The rest were adenosquamous carcinoma and adenocarcinomas. None of the 82 different cervical carcinoma tissue samples were found to be positive by in situ hybridization. In the PCR samples, amplification of DNA was observed for 69 tumor specimens. In the remainning13 cases, the DNA in fixed tissue was degraded, as verified by the absence of an internal control band (p53). Out of the total 69 tumors (85.5%) with adequate DNA contained HPV band on PCR. The majority (73.9%) of HPV

  3. Human Progesterone A-Form as a Target for New Drug Discovery in Human Breast Cancer (United States)


    Voltz et al’(ii 3 altered recycling, and impaired regulation of the PDGFR TR4 chloride transporter by hormones. Most recent studies suggest that CFTR ...growth transporters, and other proteins localized at or near the factor receptor and ion transporters such as CFTR , plasma membrane. Consistent with this...overexpression in human breast cancers cytoskeleton. This review will focus on the signaling and mutations in NHERF targets, such as CFTR and paradigms


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    Баранова, Н.М.


    Full Text Available The article analyzes the main indicators of the knowledge economy in some countries, determining the economic condition of the state. In the "Concept 2020" long-term Russian development a large role human capital as a key factor of long-term sustainable economic growth. Examining the relationship between level of education and income of the individual obtained in the course of life. Examining the main engines of development of human capital and providing estimates of its accumulation.

  5. Generating human reliability estimates using expert judgment. Volume 1. Main report

    Energy Technology Data Exchange (ETDEWEB)

    Comer, M.K.; Seaver, D.A.; Stillwell, W.G.; Gaddy, C.D.


    The US Nuclear Regulatory Commission is conducting a research program to determine the practicality, acceptability, and usefulness of several different methods for obtaining human reliability data and estimates that can be used in nuclear power plant probabilistic risk assessment (PRA). One method, investigated as part of this overall research program, uses expert judgment to generate human error probability (HEP) estimates and associated uncertainty bounds. The project described in this document evaluated two techniques for using expert judgment: paired comparisons and direct numerical estimation. Volume 1 of this report provides a brief overview of the background of the project, the procedure for using psychological scaling techniques to generate HEP estimates and conclusions from evaluation of the techniques. Results of the evaluation indicate that techniques using expert judgment should be given strong consideration for use in developing HEP estimates. In addition, HEP estimates for 35 tasks related to boiling water reactors (BMRs) were obtained as part of the evaluation. These HEP estimates are also included in the report.

  6. Generating human reliability estimates using expert judgment. Volume 2. Appendices. [PWR; BWR

    Energy Technology Data Exchange (ETDEWEB)

    Comer, M.K.; Seaver, D.A.; Stillwell, W.G.; Gaddy, C.D.


    The US Nuclear Regulatory Commission is conducting a research program to determine the practicality, acceptability, and usefulness of several different methods for obtaining human reliability data and estimates that can be used in nuclear power plant probabilistic risk assessments (PRA). One method, investigated as part of this overall research program, uses expert judgment to generate human error probability (HEP) estimates and associated uncertainty bounds. The project described in this document evaluated two techniques for using expert judgment: paired comparisons and direct numerical estimation. Volume 2 provides detailed procedures for using the techniques, detailed descriptions of the analyses performed to evaluate the techniques, and HEP estimates generated as part of this project. The results of the evaluation indicate that techniques using expert judgment should be given strong consideration for use in developing HEP estimates. Judgments were shown to be consistent and to provide HEP estimates with a good degree of convergent validity. Of the two techniques tested, direct numerical estimation appears to be preferable in terms of ease of application and quality of results.

  7. Roles of the Y chromosome genes in human cancers

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    Tatsuo Kido


    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.

  8. Glyphosate induces human breast cancer cells growth via estrogen receptors. (United States)

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


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

  9. Long-term survival outcomes in patients with surgically treated oropharyngeal cancer and defined human papilloma virus status. (United States)

    Dale, O T; Sood, S; Shah, K A; Han, C; Rapozo, D; Mehanna, H; Winter, S C


    This study investigated long-term survival outcomes in surgically treated oropharyngeal cancer patients with known human papilloma virus status. A case note review was performed of all patients undergoing primary surgery for oropharyngeal cancer in a single centre over a 10-year period. Human papilloma virus status was determined via dual modality testing. Associations between clinicopathological variables and survival were identified using a log-rank test. Of the 107 cases in the study, 40 per cent (n = 41) were human papilloma virus positive. The positive and negative predictive values of p16 immunohistochemistry for human papilloma virus status were 57 per cent and 100 per cent, respectively. At a mean follow up of 59.5 months, 5-year overall and disease-specific survival estimates were 78 per cent and 69 per cent, respectively. Human papilloma virus status (p = 0.014), smoking status (p = 0.021) and tumour stage (p = 0.03) were significant prognostic indicators. The long-term survival rates in surgically treated oropharyngeal cancer patients were comparable to other studies. Variables including human papilloma virus status and tumour stage were associated with survival in patients treated with primary surgery; however, nodal stage and presence of extracapsular spread were non-prognostic.

  10. Immune therapy for human papillomaviruses-related cancers. (United States)

    Rosales, Ricardo; Rosales, Carlos


    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.

  11. A Gene Regulatory Program in Human Breast Cancer. (United States)

    Li, Renhua; Campos, John; Iida, Joji


    Molecular heterogeneity in human breast cancer has challenged diagnosis, prognosis, and clinical treatment. It is well known that molecular subtypes of breast tumors are associated with significant differences in prognosis and survival. Assuming that the differences are attributed to subtype-specific pathways, we then suspect that there might be gene regulatory mechanisms that modulate the behavior of the pathways and their interactions. In this study, we proposed an integrated methodology, including machine learning and information theory, to explore the mechanisms. Using existing data from three large cohorts of human breast cancer populations, we have identified an ensemble of 16 master regulator genes (or MR16) that can discriminate breast tumor samples into four major subtypes. Evidence from gene expression across the three cohorts has consistently indicated that the MR16 can be divided into two groups that demonstrate subtype-specific gene expression patterns. For example, group 1 MRs, including ESR1, FOXA1, and GATA3, are overexpressed in luminal A and luminal B subtypes, but lowly expressed in HER2-enriched and basal-like subtypes. In contrast, group 2 MRs, including FOXM1, EZH2, MYBL2, and ZNF695, display an opposite pattern. Furthermore, evidence from mutual information modeling has congruently indicated that the two groups of MRs either up- or down-regulate cancer driver-related genes in opposite directions. Furthermore, integration of somatic mutations with pathway changes leads to identification of canonical genomic alternations in a subtype-specific fashion. Taken together, these studies have implicated a gene regulatory program for breast tumor progression.

  12. To a Question of Research Team’s Human Capital Estimation

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    Sergey A. Aivazyan


    Full Text Available The approach based on the concept of stochastic frontier, to assessing of research team’s human capital, performing research with the financial support of the Science Foundation. The relevance of the problem is determined by the expansion of the use of competitive basis funding for research. As an estimate of research team’s human capital accepted the potential size of the financing in terms of effective use of research team’s human capital. Presents an econometric model, allowed to obtain estimates of the efficiency of research team’s human capital, have received financial support fund for scientific research. As a measure of efficiency is considered matching the size of the financial support of his research team characteristics of human capital. Formulated statistical hypothesis, test results which can be used to improve the competitive application forms and expert profiles, used the fund. It is noted, that when checking the hypothesis of no inefficiency of research team’s human capital, should be used the machine of copula functions, expanding the scope of the stochastic frontier methodology at the expense of rejection of the assumption of independence of the random components of the econometric model and allowing a correct estimates of the efficiency in terms of their dependence.

  13. Second cancer incidence risk estimates using BEIR VII models for standard and complex external beam radiotherapy for early breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Donovan, E. M.; James, H.; Bonora, M.; Yarnold, J. R.; Evans, P. M. [Joint Department of Physics, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton SM2 5PT (United Kingdom); Physics Department, Ipswich Hospital NHS Foundation Trust, Ipswich IP4 5PD (United Kingdom); Department of Academic Radiotherapy, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, United Kingdom and School of Radiotherapy, University of Milan, Milan 20122 (Italy); Department of Academic Radiotherapy, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton SM2 5PT (United Kingdom); Centre for Vision Speech and Signal Processing, University of Surrey, Guildford GU2 7XH (United Kingdom)


    contralateral breast doses and LAR were comparable to WBRT, despite their added complexity. The smaller irradiated volume of the ABPI plan contributed to a halving of LAR for contralateral breast compared with the other plan types. Daily image guided radiotherapy (IGRT) for a left breast protocol using kilovoltage CBCT contributed <10% to LAR for the majority of organs, and did not exceed 22% of total organ dose. Conclusions: Phantom measurements and calculations of LAR from the BEIR VII models predict that complex breast radiotherapy techniques do not increase the theoretical risk of second cancer incidence for organs distant from the treated breast, or the contralateral breast where appropriate plan constraints are applied. Complex SIB treatments are predicted to increase the risk of second cancer incidence in the lungs compared to standard whole breast radiotherapy; this is outweighed by the threefold reduction in 5 yr local recurrence risk for patients of high risk of recurrence, and young age, from the use of radiotherapy. APBI may have a favorable impact on risk of second cancer in the contralateral breast and lung for older patients at low risk of recurrence. Intensive use of IGRTincreased the estimated values of LAR but these are dominated by the effect of the dose from the radiotherapy, and any increase in LAR from IGRT is much lower than the models' uncertainties.


    Directory of Open Access Journals (Sweden)

    Kelli J Johnson


    Full Text Available End-stage renal disease (ESRD has emerged as a major health issue for Australian Aborigines. This phenomenon is paralleled in other populations that have adopted a Westernised lifestyle, including African Americans. It has been suggested that abnormal glomerular hypertrophy (glomerulomegaly is an important predisposing factor for ESRD. The pathogenesis of glomerulomegaly remains unknown. It may represent a compensatory hypertrophic response to decreased nephron endowment during fetal development. Alternatively, glomerulomegaly may represent an abnormal haemodynamic/metabolic response to repeated infections, including renal infections during postnatal life. Since glomerular number and size are important issues associated with ESRD, an optimum quantitative method is required for estimating these parameters in human kidneys. The total number of glomeruli in the normal human kidney appears to vary by a factor of three or more, ranging from approximately 300,000 to more than 1 million. Recently, unbiased stereological methods for estimating total glomerular number in kidneys have been developed. The general aim of the present study was to evaluate (in terms of precision and efficiency a stereological method for estimating total glomerular number in human kidneys; the physical disector/fractionator combination. This method provided consistent estimates of total glomerular number. Estimates of total glomerular number obtained for four human kidneys ranged from 364,161 to 586,094 (coefficients of variation 9.2% to 20.0%. Mean glomerular volume for the four kidneys ranged from 6.04 to 10.32 μm3 x 106. These results indicate that this method is a precise and consistent method for estimating total glomerular number in human kidneys. The simple sampling technique developed in this study will be employed in future studies to determine if there is a difference in total glomerular, and hence nephron, number between Australian Aborigines and Caucasians, and

  15. Dietary exposure estimation of benzo[a]pyrene and cancer risk assessment. (United States)

    Lee, Byung Mu; Shim, Geun Ae


    Dietary benzo[a]pyrene (BaP) levels were analyzed by high-performance liquid chromatography with fluorescence detection (HPLC-FLD) in various foods (e.g., snack, potato chip, bread, vegetable oil, meat, cereal, etc.) to estimate dietary intake levels of BaP for the assessment of BaP related-cancer risk in Koreans. Higher levels of BaP were detected in fried chicken (5.25-5.55 BaP microg/kg) and smoked dried beef (5.47 microg/kg) compared to relatively lower levels measured in sesame oil (0.36 microg/kg) and peanut (0.44 microg/kg). The BaP levels in nonmeat items were generally low in detection, but certain potato chip products showed levels up to 4.06 BaP microg/kg. In terms of chronic daily intake of BaP, fried chicken was shown to be the highest (70.09 ng/person/d) and perilla oil was the lowest (0.05 ng/person/d). The total daily intake of BaP due to the consumption of various food items investigated was estimated to be 124.55 ng/person/d, based on daily food consumption and the contaminant level of BaP. The dietary BaP-related cancer risk using carcinogenic potency factor of BaP as 7.3E + 0 (mg/kg/d)(-1) was assessed to be 1.52 x 10(-5). These data suggest that cancer risk due to dietary exposure to BaP is of concern in Koreans and needs to be reduced either by regulatory efforts or by modifying food manufacturing procedures.

  16. [Preventability estimates for colorectal and breast cancer in Germany. A methodological evaluation of the risk factors alcohol and overweight]. (United States)

    Wienecke, A; Knorpp, L; Stegmüller, K; Kroke, A


    Population attributable fractions (PAFs) for the risk factors alcohol intake and overweight in the German population were calculated to estimate the preventability of colorectal and breast cancer attributable to these risk factors. Estimates were based on national alcohol consumption and overweight prevalence data in the German population. Comparative analyses were used to evaluate the variation of PAF estimates according to changes in the calculation parameters. PAFs quantify the preventive potential that could result from removing or reducing the risk factor exposure, respectively. Postmenopausal breast cancer was estimated to be preventable by 13-23% if the population were normal weight. Among German men, 10-25% of colon cancers were attributable to alcohol consumption and 7-13% of colorectal cancers to overweight. The comparative analyses demonstrated that preventability estimates vary considerably with the chosen data (risk estimates, reference categories) for PAF calculation and can differ by up to 50%. Thus, data selection should be evidence based, for example, based on meta-analyses, in order to increase the validity of preventability estimates.

  17. How companion animals contribute to the fight against cancer in humans

    Directory of Open Access Journals (Sweden)

    Douglas Thamm, VMD


    Full Text Available Companion animals and their human guardians suffer from many of the same types of cancer and are often treated with many of the same drugs. Moreover, the overall tumour biology is much more similar between humans and companion animals than between humans and rodent tumor models. Therefore, it is proposed that pre-clinical evaluation of novel cancer therapeutics should more often include appropriately designed trials in companion animals with cancer to more accurately predict efficacy and toxicity in humans. For example, studies in dogs with cancer have been used to assess efficacy and design human clinical trials of immunotherapy, gene therapy, sustained release drug delivery and liposomal drug delivery. In the future, such studies will ultimately benefit not only humans, but also companion animals with cancer.

  18. A novel experimental platform for investigating cancer growth and anti-cancer therapy in a human tissue microenvironment derived from human embryonic stem cells. (United States)

    Tzukerman, Maty; Skorecki, Karl L


    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.

  19. Regulation of deleted in liver cancer-1 gene domains on the proliferation of human colon cancer HT29 cell

    Institute of Scientific and Technical Information of China (English)



    Objective To study the role of deleted in liver cancer-1(DLC-1) gene main domains on the regulation of hu-man colon cancer HT29 cell proliferation. Methods Subcloning recombinant plasmid vectors with Rho GTPase activating protein(RhoGAP),sterile alpha motif(SAM)

  20. Estimated amount of 24-hour urine sodium excretion is positively correlated with stomach and breast cancer prevalence in Korea. (United States)

    Park, Jung Hwan; Kim, Yong Chul; Koo, Ho Seok; Oh, Se Won; Kim, Suhnggwon; Chin, Ho Jun


    Stomach cancer is one of the most common cancers in Korea. The aim of this study was to identify the association between the prevalence of cancer, particularly stomach cancer, and the amount of 24-hr urine sodium excretion estimated from spot urine specimens. The study included 19,083 subjects who took part in the Korean National Health and Nutritional Examination Survey between 2009 and 2011. The total amount of urine sodium excreted in a 24-hr period was estimated by using two equations based on the values for spot urine sodium and creatinine. In subjects who had an estimated 24-hr urine sodium excretion of more than two standard deviations above the mean (group 2), the prevalence of stomach cancer was higher than in subjects with lower 24-hr sodium excretion (group 1). By using the Tanaka equation to estimate it, the prevalence of stomach cancer was 0.6% (114/18,331) in group 1, whereas it was 1.6% (9/568) in group 2 (P=0.006). By using the Korean equation, the prevalence was 0.6% (115/18,392) in group 1, and 1.6% in group 2 (8/507) (P=0.010). By using the Tanaka equation, breast cancer in women is more prevalent in group 2 (1.9%, 6/324) than group 1 (0.8%, 78/9,985, P=0.039). Higher salt intake, as defined by the estimated amount of 24-hr urine sodium excretion, is positively correlated with a higher prevalence of stomach or breast cancer in the Korean population.

  1. Human Pose Estimation from Silhouettes. A Consistent Approach Using Distance Level Sets

    NARCIS (Netherlands)

    Sminchisescu, C.; Telea, A.


    We present a novel similarity measure (likelihood) for estimating three-dimensional human pose from image silhouettes in model-based vision applications. One of the challenges in such approaches is the construction of a model-to-image likelihood that truly reflects the good configurations of the pro

  2. Probabilistic estimation of residential air exchange rates for population-based human exposure modeling (United States)

    Residential air exchange rates (AERs) are a key determinant in the infiltration of ambient air pollution indoors. Population-based human exposure models using probabilistic approaches to estimate personal exposure to air pollutants have relied on input distributions from AER meas...

  3. Estimation of selenium bioavailability from human, cow's, goat and sheep milk by an in vitro method

    NARCIS (Netherlands)

    Shen, L.; Dael, van P.; Luten, J.; Deelstra, H.


    The trace element selenium (Se) has been recognized to be essential for human health. The dependence of infants on milk as their principal food source, generally low in Se content, makes them more vulnerable to inadequate Se intake. The present study compared the Se availability as estimated by a si

  4. Multi-view 3D human pose estimation in complex environment

    NARCIS (Netherlands)

    M. Hofmann; D.M. Gavrila


    We introduce a framework for unconstrained 3D human upper body pose estimation from multiple camera views in complex environment. Its main novelty lies in the integration of three components: single-frame pose recovery, temporal integration and model texture adaptation. Single-frame pose recovery co

  5. Multi-view 3D Human Pose Estimation in Complex Environment

    NARCIS (Netherlands)

    Hofmann, K.M.; Gavrila, D.M.


    We introduce a framework for unconstrained 3D human upper body pose estimation from multiple camera views in complex environment. Its main novelty lies in the integration of three components: single-frame pose recovery, temporal integration and model texture adaptation. Single-frame pose recovery co

  6. Galangin induces human colon cancer cell death via the mitochondrial dysfunction and caspase-dependent pathway. (United States)

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


    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.

  7. Population-based estimate of prostate cancer risk for carriers of the HOXB13 missense mutation G84E.

    Directory of Open Access Journals (Sweden)

    Robert J MacInnis

    Full Text Available The HOXB13 missense mutation G84E (rs138213197 is associated with increased risk of prostate cancer, but the current estimate of increased risk has a wide confidence interval (width of 95% confidence interval (CI >200-fold so the point estimate of 20-fold increased risk could be misleading. Population-based family studies can be more informative for estimating risks for rare variants, therefore, we screened for mutations in an Australian population-based series of early-onset prostate cancer cases (probands. We found that 19 of 1,384 (1.4% probands carried the missense mutation, and of these, six (32% had a family history of prostate cancer. We tested the 22 relatives of carriers diagnosed from 1998 to 2008 for whom we had a DNA sample, and found seven more carriers and one obligate carrier. The age-specific incidence for carriers was estimated to be, on average, 16.4 (95% CI 2.5-107.2 times that for the population over the time frame when the relatives were at risk prior to baseline. We then estimated the age and birth year- specific cumulative risk of prostate cancer (penetrance for carriers. For example, the penetrance for an unaffected male carrier born in 1950 was 19% (95% CI 5-46% at age 60 years, 44% (95% CI 18-74% at age 70 years and 60% (95% CI 30-85% at age 80 years. Our study has provided a population-based estimate of the average risk of prostate cancer for HOXB13 missense mutation G84E carriers that can be used to guide clinical practice and research. This study has also shown that the majority of hereditary prostate cancers due to the HOXB13 missense mutation are 'sporadic' in the sense that unselected cases with the missense mutation do not typically report having a family history of prostate cancer.

  8. WearDY: Wearable dynamics. A prototype for human whole-body force and motion estimation (United States)

    Latella, Claudia; Kuppuswamy, Naveen; Nori, Francesco


    Motion capture is a powerful tool used in a large range of applications towards human movement analysis. Although it is a well-established technique, its main limitation is the lack of dynamic information such as forces and torques during the motion capture. In this paper, we present a novel approach for human wearable dynamic (WearDY) motion capture for the simultaneous estimation of whole-body forces along with the motion. Our conceptual framework encompasses traditional passive markers based methods, inertial and contact force sensor modalities and harnesses a probabilistic computational framework for estimating dynamic quantities originally proposed in the domain of humanoid robot control. We present preliminary experimental analysis of our framework on subjects performing a two Degrees-of-Freedom bowing task and we estimate the motion and dynamic quantities. We discuss the implication of our proposal towards the design of a novel wearable force and motion capture suit and its applications.

  9. Estimating cancer risk in relation to tritium exposure from routine operation of a nuclear-generating station in Pickering, Ontario. (United States)

    Wanigaratne, S; Holowaty, E; Jiang, H; Norwood, T A; Pietrusiak, M A; Brown, P


    Evidence suggests that current levels of tritium emissions from CANDU reactors in Canada are not related to adverse health effects. However, these studies lack tritium-specific dose data and have small numbers of cases. The purpose of our study was to determine whether tritium emitted from a nuclear-generating station during routine operation is associated with risk of cancer in Pickering, Ontario. A retrospective cohort was formed through linkage of Pickering and north Oshawa residents (1985) to incident cancer cases (1985-2005). We examined all sites combined, leukemia, lung, thyroid and childhood cancers (6-19 years) for males and females as well as female breast cancer. Tritium estimates were based on an atmospheric dispersion model, incorporating characteristics of annual tritium emissions and meteorology. Tritium concentration estimates were assigned to each cohort member based on exact location of residence. Person-years analysis was used to determine whether observed cancer cases were higher than expected. Cox proportional hazards regression was used to determine whether tritium was associated with radiation-sensitive cancers in Pickering. Person-years analysis showed female childhood cancer cases to be significantly higher than expected (standardized incidence ratio [SIR] = 1.99, 95% confidence interval [CI]: 1.08-3.38). The issue of multiple comparisons is the most likely explanation for this finding. Cox models revealed that female lung cancer was significantly higher in Pickering versus north Oshawa (HR = 2.34, 95% CI: 1.23-4.46) and that tritium was not associated with increased risk. The improved methodology used in this study adds to our understanding of cancer risks associated with low-dose tritium exposure. Tritium estimates were not associated with increased risk of radiationsensitive cancers in Pickering.

  10. Estimation of incidence and social cost of colon cancer due to nitrate in drinking water in the EU: a tentative cost-benefit assessment

    Directory of Open Access Journals (Sweden)

    Rabl Ari


    Full Text Available Abstract Background Presently, health costs associated with nitrate in drinking water are uncertain and not quantified. This limits proper evaluation of current policies and measures for solving or preventing nitrate pollution of drinking water resources. The cost for society associated with nitrate is also relevant for integrated assessment of EU nitrogen policies taking a perspective of welfare optimization. The overarching question is at which nitrogen mitigation level the social cost of measures, including their consequence for availability of food and energy, matches the social benefit of these measures for human health and biodiversity. Methods Epidemiological studies suggest colon cancer to be possibly associated with nitrate in drinking water. In this study risk increase for colon cancer is based on a case-control study for Iowa, which is extrapolated to assess the social cost for 11 EU member states by using data on cancer incidence, nitrogen leaching and drinking water supply in the EU. Health costs are provisionally compared with nitrate mitigation costs and social benefits of fertilizer use. Results For above median meat consumption the risk of colon cancer doubles when exposed to drinking water exceeding 25 mg/L of nitrate (NO3 for more than ten years. We estimate the associated increase of incidence of colon cancer from nitrate contamination of groundwater based drinking water in EU11 at 3%. This corresponds to a population-averaged health loss of 2.9 euro per capita or 0.7 euro per kg of nitrate-N leaching from fertilizer. Conclusions Our cost estimates indicate that current measures to prevent exceedance of 50 mg/L NO3 are probably beneficial for society and that a stricter nitrate limit and additional measures may be justified. The present assessment of social cost is uncertain because it considers only one type of cancer, it is based on one epidemiological study in Iowa, and involves various assumptions regarding exposure. Our

  11. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  12. Siah1 proteins enhance radiosensitivity of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Engenhart-Cabillic Rita


    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.

  13. Screening and analysis of breast cancer genes regulated by the human mammary microenvironment in a humanized mouse model (United States)

    Zheng, Mingjie; Wang, Jue; Ling, Lijun; Xue, Dandan; Wang, Shui; Zhao, Yi


    Tumor microenvironments play critical regulatory roles in tumor growth. Although mouse cancer models have contributed to the understanding of human tumor biology, the effectiveness of mouse cancer models is limited by the inability of the models to accurately present humanized tumor microenvironments. Previously, a humanized breast cancer model in severe combined immunodeficiency mice was established, in which human breast cancer tissue was implanted subcutaneously, followed by injection of human breast cancer cells. It was demonstrated that breast cancer cells showed improved growth in the human mammary microenvironment compared with a conventional subcutaneous mouse model. In the present study, the novel mouse model and microarray technology was used to analyze changes in the expression of genes in breast cancer cells that are regulated by the human mammary microenvironment. Humanized breast and conventional subcutaneous mouse models were established, and orthotopic tumor cells were obtained from orthotopic tumor masses by primary culture. An expression microarray using Illumina HumanHT-12 v4 Expression BeadChip and database analyses were performed to investigate changes in gene expression between tumors from each microenvironment. A total of 94 genes were differentially expressed between the primary cells cultured from the humanized and conventional mouse models. Significant upregulation of genes that promote cell proliferation and metastasis or inhibit apoptosis, such as SH3-domain binding protein 5 (BTK-associated), sodium/chloride cotransporter 3 and periostin, osteoblast specific factor, and genes that promote angiogenesis, such as KIAA1618, was also noted. Other genes that restrain cell proliferation and accelerate cell apoptosis, including tripartite motif containing TRIM36 and NES1, were downregulated. The present results revealed differences in various aspects of tumor growth and metabolism between the two model groups and indicated the functional

  14. An Anticancer Role of Hydrogen Sulfide in Human Gastric Cancer Cells

    Directory of Open Access Journals (Sweden)

    Li Zhang


    Full Text Available Hydrogen sulfide (H2S can be synthesized in mammalian cells by cystathionine γ-lyase (CSE and/or cystathionine β-synthase (CBS. Both CSE and CBS are expressed in rat gastric tissues but their role in human gastric neoplasia has been unclear. The aims of the present study were to detect CSE and CBS proteins in human gastric cancer and determine the effect of exogenous NaHS on the proliferation of gastric cancer cells. We found that both CSE and CBS proteins were expressed in human gastric cancer cells and upregulated in human gastric carcinoma mucosa compared with those in noncancerous gastric samples. NaHS induced apoptosis of gastric cancer cells by regulating apoptosis related proteins. Also, NaHS inhibited cancer cell migration and invasion. An antigastric cancer role of H2S is thus indicated.

  15. Cancer Secretome May Influence BSP and DSP Expression in Human Salivary Gland Cells. (United States)

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


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

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

    National Research Council Canada - National Science Library

    Banat, G-Andre; Tretyn, Aleksandra; Pullamsetti, Soni Savai; Wilhelm, Jochen; Weigert, Andreas; Olesch, Catherine; Ebel, Katharina; Stiewe, Thorsten; Grimminger, Friedrich; Seeger, Werner; Fink, Ludger; Savai, Rajkumar


    .... 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...

  17. Aberrant rel/nfkb genes and activity in human cancer. (United States)

    Rayet, B; Gélinas, C


    Rel/NF-kappaB transcription factors are key regulators of immune, inflammatory and acute phase responses and are also implicated in the control of cell proliferation and apoptosis. Remarkable progress has been made in understanding the signal transduction pathways that lead to the activation of Rel/NF-kappaB factors and the consequent induction of gene expression. Evidence linking deregulated Rel/NF-kappaB activity to oncogenesis in mammalian systems has emerged in recent years, consistent with the acute oncogenicity of the viral oncoprotein v-Rel in animal models. Chromosomal amplification, overexpression and rearrangement of genes coding for Rel/NF-kappaB factors have been noted in many human hematopoietic and solid tumors. Persistent nuclear NF-kappaB activity was also described in several human cancer cell types, as a result of constitutive activation of upstream signaling kinases or mutations inactivating inhibitory IkappaB subunits. Studies point to a correlation between the activation of cellular gene expression by Rel/NF-kappaB factors and their participation in the malignant process. Experiments implicating NF-kappaB in the control of the apoptotic response also support a role in oncogenesis and in the resistance of tumor cells to chemotherapy. This review focuses on the status of the rel, nfkb and ikb genes and their activity in human tumors and their association with the onset or progression of malignancies.

  18. A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells. (United States)

    Burgos-Ojeda, Daniela; McLean, Karen; Bai, Shoumei; Pulaski, Heather; Gong, Yusong; Silva, Ines; Skorecki, Karl; Tzukerman, Maty; Buckanovich, Ronald J


    Human tumor vessels express tumor vascular markers (TVM), proteins that are not expressed in normal blood vessels. Antibodies targeting TVMs could act as potent therapeutics. Unfortunately, preclinical in vivo studies testing anti-human TVM therapies have been difficult to do due to a lack of in vivo models with confirmed expression of human TVMs. We therefore evaluated TVM expression in a human embryonic stem cell-derived teratoma (hESCT) tumor model previously shown to have human vessels. We now report that in the presence of tumor cells, hESCT tumor vessels express human TVMs. The addition of mouse embryonic fibroblasts and human tumor endothelial cells significantly increases the number of human tumor vessels. TVM induction is mostly tumor-type-specific with ovarian cancer cells inducing primarily ovarian TVMs, whereas breast cancer cells induce breast cancer specific TVMs. We show the use of this model to test an anti-human specific TVM immunotherapeutics; anti-human Thy1 TVM immunotherapy results in central tumor necrosis and a three-fold reduction in human tumor vascular density. Finally, we tested the ability of the hESCT model, with human tumor vascular niche, to enhance the engraftment rate of primary human ovarian cancer stem-like cells (CSC). ALDH(+) CSC from patients (n = 6) engrafted in hESCT within 4 to 12 weeks whereas none engrafted in the flank. ALDH(-) ovarian cancer cells showed no engraftment in the hESCT or flank (n = 3). Thus, this model represents a useful tool to test anti-human TVM therapy and evaluate in vivo human CSC tumor biology.

  19. Subamolide A Induces Mitotic Catastrophe Accompanied by Apoptosis in Human Lung Cancer Cells


    Jen-Yu Hung; Ching-Wen Wen; Ya-Ling Hsu; En-Shyh Lin; Ming-Shyan Huang; Chung-Yi Chen; Po-Lin Kuo


    This study investigated the anticancer effects of subamolide A (Sub-A), isolated from Cinnamomum subavenium, on human nonsmall cell lung cancer cell lines A549 and NCI-H460. Treatment of cancer cells with Sub-A resulted in decreased cell viability of both lung cancer cell lines. Sub-A induced lung cancer cell death by triggering mitotic catastrophe with apoptosis. It triggered oxidant stress, indicated by increased cellular reactive oxygen species (ROS) production and decreased glutathione le...

  20. Quantitative proteomics of extracellular vesicles derived from human primary and metastatic colorectal cancer cells


    Gho, Yong Song; Choi, Dong-Sic; Choi, Do-Young; Hong, Bok Sil; Jang, Su Chul; Kim, Dae-Kyum; Lee, Jaewook; Kim, Yoon-Keun; Kim, Kwang Pyo


    Cancer cells actively release extracellular vesicles (EVs), including exosomes and microvesicles, into surrounding tissues. These EVs play pleiotropic roles in cancer progression and metastasis, including invasion, angiogenesis, and immune modulation. However, the proteomic differences between primary and metastatic cancer cell-derived EVs remain unclear. Here, we conducted comparative proteomic analysis between EVs derived from human primary colorectal cancer cells (SW480) and their metastat...

  1. Kinase Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer (United States)


    AWARD NUMBER: W81XWH-16-1-0009 TITLE: PRINCIPAL INVESTIGATOR: John Cleveland CONTRACTING ORGANIZATION: H. Lee Moffitt Cancer designated by other documentation. Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer REPORT DOCUMENTATION PAGE Form...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer 5b. GRANT NUMBER W81XWH-16-1-0009 5c

  2. Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer (United States)


    AWARD NUMBER: W81XWH-16-1-0008 TITLE: Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer PRINCIPAL INVESTIGATOR...Jan 2017 4. TITLE AND SUBTITLE Kinase-Mediated Regulation of 40S Ribosome Assembly in Human Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...Investigator [PI], Scripps) and John Cleveland (Collaborating/Partnering PI, Moffitt Cancer Center) seek to validate 40S ribosome assembly as a therapeutic

  3. [Expressions and significance of NDRG2 and Bcl-2 in human gastric cancer tissues]. (United States)

    Zhu, Ruixue; Shi, Yongquan; Zhang, Lianfeng


    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.

  4. Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar


    Full Text Available We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG accumulation in androgen-sensitive (CWR-22 and androgen-independent (PC-3 human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm3 = 14.913 e0.108 × days, R2 = .96, n = 5. The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm3 = 0.3511 × days2 + 49.418 × day −753.33, R2 = .96, n = 3. The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05. The 3-week maximal standardized uptake value (SUVmax was 0.99 ± 0.43 (mean ± SD for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUVmax was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUVmax was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18% and the 5-week (by 9.6% micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer.

  5. Single and Multiple Gene Manipulations in Mouse Models of Human Cancer (United States)

    Lehman, Heather L; Stairs, Douglas B


    Mouse models of human cancer play a critical role in understanding the molecular and cellular mechanisms of tumorigenesis. Advances continue to be made in modeling human disease in a mouse, though the relevance of a mouse model often relies on how closely it is able to mimic the histologic, molecular, and physiologic characteristics of the respective human cancer. A classic use of a genetically engineered mouse in studying cancer is through the overexpression or deletion of a gene. However, the manipulation of a single gene often falls short of mimicking all the characteristics of the carcinoma in humans; thus a multiple gene approach is needed. Here we review genetic mouse models of cancers and their abilities to recapitulate human carcinoma with single versus combinatorial approaches with genes commonly involved in cancer. PMID:26380553

  6. Correlation between the expression of vascular endothelial growth factor c and C-erbB-2 in human breast cancer

    Institute of Scientific and Technical Information of China (English)

    Shuxian Qu; Zhendong Zheng; Zhaozhe Liu; Liang Liu; Miao Zhang; Yaling Han; Xiaodong Xie


    Objective: We aimed to study the transcription level of VEGF-C in human breast cancer tissue, and explore the correlations with the expression of C-erbB-2.Methods: The expression of VEGF-C mRNA in 51 cases of human breast cancer was assessed by hybridization in situ. The expressions of C-erbB-2 was assessed by immunohistochemistry.Results:The positive rate of VEGF-C mRNA was 54.9% in 51 cases of breast cancer. The transcription level had correlation with tumor size and status of lymph nodes (P < 0.05). The expression of VEGF-C mRNA had a positive correlation with the expression of C-erbB-2 (P < 0.05).Conclusion: The up-expression of VEGF-C has a significant correlation with the malignancy level and clinical stage of breast cancer. The combined detection of VEGF-C, C-erbB-2 may help to estimate the prognosis of patients with breast cancer and study on thetherapeutic implications.

  7. Current status of cancer immunodetection with radiolabeled human monoclonal antibodies. (United States)

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


    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

  8. 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


    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.

  9. Is Human Papillomavirus Associated with Prostate Cancer Survival?

    Directory of Open Access Journals (Sweden)

    Mariarosa Pascale


    Full Text Available The role of human papillomavirus (HPV in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa, whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67% patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS (median 4.59 years compared to HPV-negative (median 8.24 years, P=0.0381. In multivariate analysis age (P<0.001, Gleason score (P<0.001, nuclear grading (P=0.002, and HPV status (P=0.034 were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.

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

    DEFF Research Database (Denmark)

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


    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...

  11. Emerging roles of deubiquitinating enzymes in human cancer1

    Institute of Scientific and Technical Information of China (English)

    Jin-ming YANG


    Protein modifications by the covalent linkage of ubiquitin have significant in-volvement in many cellular processes, including stress response, oncogenesis,viral infection, transcription, protein turnover, organelle biogenesis, DNA repair,cellular differentiation, and cell cycle control. Protein ubiquitination and subse-quent degradation by the proteasome require the participation of both ubiquitinating enzymes and deubiquitinating enzymes. Although deubiquitinatingenzymes constitute a large family in the ubiquitin system, the study of this class of proteins is still in its infant stage. Recent studies have revealed a variety of molecular and biological functions of deubiquitinating enzymes and their associa-tion with human diseases. In this review we will discuss the possible roles that deubiquitinating enzymes may play in cancers.

  12. Estimating the cost of cervical cancer screening in five developing countries

    Directory of Open Access Journals (Sweden)

    Goldie Sue J


    Full Text Available Abstract Background Cost-effectiveness analyses (CEAs can provide useful information to policymakers concerned with the broad allocation of resources as well as to local decision makers choosing between different options for reducing the burden from a single disease. For the latter, it is important to use country-specific data when possible and to represent cost differences between countries that might make one strategy more or less attractive than another strategy locally. As part of a CEA of cervical cancer screening in five developing countries, we supplemented limited primary cost data by developing other estimation techniques for direct medical and non-medical costs associated with alternative screening approaches using one of three initial screening tests: simple visual screening, HPV DNA testing, and cervical cytology. Here, we report estimation methods and results for three cost areas in which data were lacking. Methods To supplement direct medical costs, including staff, supplies, and equipment depreciation using country-specific data, we used alternative techniques to quantify cervical cytology and HPV DNA laboratory sample processing costs. We used a detailed quantity and price approach whose face validity was compared to an adaptation of a US laboratory estimation methodology. This methodology was also used to project annual sample processing capacities for each laboratory type. The cost of sample transport from the clinic to the laboratory was estimated using spatial models. A plausible range of the cost of patient time spent seeking and receiving screening was estimated using only formal sector employment and wages as well as using both formal and informal sector participation and country-specific minimum wages. Data sources included primary data from country-specific studies, international databases, international prices, and expert opinion. Costs were standardized to year 2000 international dollars using inflation adjustment and

  13. Cervical cancer precursors and hormonal contraceptive use in HIV-positive women: application of a causal model and semi-parametric estimation methods.

    Directory of Open Access Journals (Sweden)

    Hannah H Leslie

    Full Text Available OBJECTIVE: To demonstrate the application of causal inference methods to observational data in the obstetrics and gynecology field, particularly causal modeling and semi-parametric estimation. BACKGROUND: Human immunodeficiency virus (HIV-positive women are at increased risk for cervical cancer and its treatable precursors. Determining whether potential risk factors such as hormonal contraception are true causes is critical for informing public health strategies as longevity increases among HIV-positive women in developing countries. METHODS: We developed a causal model of the factors related to combined oral contraceptive (COC use and cervical intraepithelial neoplasia 2 or greater (CIN2+ and modified the model to fit the observed data, drawn from women in a cervical cancer screening program at HIV clinics in Kenya. Assumptions required for substantiation of a causal relationship were assessed. We estimated the population-level association using semi-parametric methods: g-computation, inverse probability of treatment weighting, and targeted maximum likelihood estimation. RESULTS: We identified 2 plausible causal paths from COC use to CIN2+: via HPV infection and via increased disease progression. Study data enabled estimation of the latter only with strong assumptions of no unmeasured confounding. Of 2,519 women under 50 screened per protocol, 219 (8.7% were diagnosed with CIN2+. Marginal modeling suggested a 2.9% (95% confidence interval 0.1%, 6.9% increase in prevalence of CIN2+ if all women under 50 were exposed to COC; the significance of this association was sensitive to method of estimation and exposure misclassification. CONCLUSION: Use of causal modeling enabled clear representation of the causal relationship of interest and the assumptions required to estimate that relationship from the observed data. Semi-parametric estimation methods provided flexibility and reduced reliance on correct model form. Although selected results suggest an

  14. RELAP5/MOD3.3 Best Estimate Analyses for Human Reliability Analysis

    Directory of Open Access Journals (Sweden)

    Andrej Prošek


    Full Text Available To estimate the success criteria time windows of operator actions the conservative approach was used in the conventional probabilistic safety assessment (PSA. The current PSA standard recommends the use of best-estimate codes. The purpose of the study was to estimate the operator action success criteria time windows in scenarios in which the human actions are supplement to safety systems actuations, needed for updated human reliability analysis (HRA. For calculations the RELAP5/MOD3.3 best estimate thermal-hydraulic computer code and the qualified RELAP5 input model representing a two-loop pressurized water reactor, Westinghouse type, were used. The results of deterministic safety analysis were examined what is the latest time to perform the operator action and still satisfy the safety criteria. The results showed that uncertainty analysis of realistic calculation in general is not needed for human reliability analysis when additional time is available and/or the event is not significant contributor to the risk.

  15. Estimating the risk of rabies transmission to humans in the U.S.: a delphi analysis

    Directory of Open Access Journals (Sweden)

    Meltzer Martin I


    Full Text Available Abstract Background In the United States, the risk of rabies transmission to humans in most situations of possible exposure is unknown. Controlled studies on rabies are clearly not possible. Thus, the limited data on risk has led to the frequent administration of rabies post-exposure prophylaxis (PEP, often in inappropriate circumstances. Methods We used the Delphi method to obtain an expert group consensus estimate of the risk of rabies transmission to humans in seven scenarios of potential rabies exposure. We also surveyed and discussed the merits of recommending rabies PEP for each scenario. Results The median risk of rabies transmission without rabies PEP for a bite exposure by a skunk, bat, cat, and dog was estimated to be 0.05, 0.001, 0.001, and 0.00001, respectively. Rabies PEP was unanimously recommended in these scenarios. However, rabies PEP was overwhelmingly not recommended for non-bite exposures (e.g. dog licking hand but unavailable for subsequent testing, estimated to have less than 1 in 1,000,000 (0.000001 risk of transmission. Conclusions Our results suggest that there are many common situations in which the risk of rabies transmission is so low that rabies PEP should not be recommended. These risk estimates also provide a key parameter for cost-effective models of human rabies prevention and can be used to educate health professionals about situation-specific administration of rabies PEP.

  16. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States (United States)

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin


    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects’ affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain’s motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states.

  17. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States. (United States)

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin


    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects' affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain's motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states.

  18. Emerging of fractal geometry on surface of human cervical epithelial cells during progression towards cancer (United States)

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


    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

  19. Specific binding of benzodiazepines to human breast cancer cell lines. (United States)

    Beinlich, A; Strohmeier, R; Kaufmann, M; Kuhl, H


    Binding of [3H]Ro5-4864, a peripheral benzodiazepine receptor (PBR) agonist, to BT-20 human, estrogen- (ER) and progesterone- (PR) receptor negative breast cancer cells was characterized. It was found to be specific, dose-dependent and saturable with a single population of binding sites. Dissociation constant (K(D)) was 8.5 nM, maximal binding capacity (Bmax) 339 fM/10(6) cells. Ro5-4864 (IC50 17.3 nM) and PK 11195 (IC50 12.3 nM) were able to compete with [3H]Ro5-4864 for binding, indicating specificity of interaction with PBR. Diazepam was able to displace [3H]Ro5-4864 from binding only at high concentrations (>1 microM), while ODN did not compete for PBR binding. Thymidine-uptake assay showed a biphasic response of cell proliferation. While low concentrations (100 nM) of Ro5-4864, PK 11195 and diazepam increased cell growth by 10 to 20%, higher concentrations (10-100 microM) significantly inhibited cell proliferation. PK 11195, a potent PBR ligand, was able to attenuate growth of BT-20 cells stimulated by 100 nM Ro5-4864 and to reverse growth reduction caused by 1 and 10 microM Ro5-4864, but not by 50 microM and 100 microM. This indicates that the antimitotic activity of higher concentrations of Ro5-4864 is independent of PBR binding. It is suggested, that PBR are involved in growth regulation of certain human breast cancer cell lines, possibly by supplying proliferating cells with energy, as their endogenous ligand is a polypeptide transporting Acyl-CoA.

  20. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer. (United States)

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


    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.

  1. Human Age Estimation Method Robust to Camera Sensor and/or Face Movement. (United States)

    Nguyen, Dat Tien; Cho, So Ra; Pham, Tuyen Danh; Park, Kang Ryoung


    Human age can be employed in many useful real-life applications, such as customer service systems, automatic vending machines, entertainment, etc. In order to obtain age information, image-based age estimation systems have been developed using information from the human face. However, limitations exist for current age estimation systems because of the various factors of camera motion and optical blurring, facial expressions, gender, etc. Motion blurring can usually be presented on face images by the movement of the camera sensor and/or the movement of the face during image acquisition. Therefore, the facial feature in captured images can be transformed according to the amount of motion, which causes performance degradation of age estimation systems. In this paper, the problem caused by motion blurring is addressed and its solution is proposed in order to make age estimation systems robust to the effects of motion blurring. Experiment results show that our method is more efficient for enhancing age estimation performance compared with systems that do not employ our method.

  2. Human Age Estimation Method Robust to Camera Sensor and/or Face Movement

    Directory of Open Access Journals (Sweden)

    Dat Tien Nguyen


    Full Text Available Human age can be employed in many useful real-life applications, such as customer service systems, automatic vending machines, entertainment, etc. In order to obtain age information, image-based age estimation systems have been developed using information from the human face. However, limitations exist for current age estimation systems because of the various factors of camera motion and optical blurring, facial expressions, gender, etc. Motion blurring can usually be presented on face images by the movement of the camera sensor and/or the movement of the face during image acquisition. Therefore, the facial feature in captured images can be transformed according to the amount of motion, which causes performance degradation of age estimation systems. In this paper, the problem caused by motion blurring is addressed and its solution is proposed in order to make age estimation systems robust to the effects of motion blurring. Experiment results show that our method is more efficient for enhancing age estimation performance compared with systems that do not employ our method.

  3. Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells

    DEFF Research Database (Denmark)

    Liang, Yuh-Jin; Ding, Yao; Levery, Steven B;


    Previous studies demonstrated that certain glycosphingolipids (GSLs) are involved in various cell functions, such as cell growth and motility. Recent studies showed changes in GSL expression during differentiation of human embryonic stem cells; however, little is known about expression profiles...... of GSLs in cancer stem cells (CSCs). CSCs are a small subpopulation in cancer and are proposed as cancer-initiating cells, have been shown to be resistant to numerous chemotherapies, and may cause cancer recurrence. Here, we analyzed GSLs expressed in human breast CSCs by applying a CSC model induced...... significantly reduced the expression of GD2 and GD3 and caused a phenotype change from CSC to a non-CSC, which was detected by reduced mammosphere formation and cell motility. Our results provide insight into GSL profiles in human breast CSCs, indicate a functional role of GD2 and GD3 in CSCs, and suggest...

  4. Estimating the risks of cancer mortality and genetic defects resulting from exposures to low levels of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Buhl, T.E.; Hansen, W.R.


    Estimators for calculating the risk of cancer and genetic disorders induced by exposure to ionizing radiation have been recommended by the US National Academy of Sciences Committee on the Biological Effects of Ionizing Radiations, the UN Scientific Committee on the Effects of Atomic Radiation, and the International Committee on Radiological Protection. These groups have also considered the risks of somatic effects other than cancer. The US National Council on Radiation Protection and Measurements has discussed risk estimate procedures for radiation-induced health effects. The recommendations of these national and international advisory committees are summarized and compared in this report. Based on this review, two procedures for risk estimation are presented for use in radiological assessments performed by the US Department of Energy under the National Environmental Policy Act of 1969 (NEPA). In the first procedure, age- and sex-averaged risk estimators calculated with US average demographic statistics would be used with estimates of radiation dose to calculate the projected risk of cancer and genetic disorders that would result from the operation being reviewed under NEPA. If more site-specific risk estimators are needed, and the demographic information is available, a second procedure is described that would involve direct calculation of the risk estimators using recommended risk-rate factors. The computer program REPCAL has been written to perform this calculation and is described in this report. 25 references, 16 tables.

  5. Real-time estimation of 3D human arm motion from markerless images for human-machine interaction (United States)

    Verma, Siddharth; Kofman, Jonathan


    Vision-based motion tracking is commonly used in surveillance, human-machine interfaces in robotics and automation, virtual and augmented reality applications and biomechanics. Most techniques require markers, use a predefined motion sequence or user-intervention for initialization, and do not process in real-time. This paper describes the implementation of a vision-based non-invasive technique for markerless real-time tracking of human-arm motion. Human-arm motion is tracked by processing images from two calibrated cameras in real-time to estimate the position of the 3D joint centers of the wrist and elbow, and determine the orientation of the hand from the 3D positions of the index finger and thumb. Tracking of the hand and arm was carried out without any prior knowledge of subject's arm length, texture, width and distance from the camera.

  6. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer (United States)


    and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular mechanisms controlling melanoma and breast carcinoma...Bowman Show, August 17 Molecular regulation of melanoma and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular...Institute, April 20, Pathology ofNeoplasia Cumberland Unit, American Cancer Society, April 19; Breast Cancer Research Ministerio de Sanidad y

  7. Robustness of Input features from Noisy Silhouettes in Human Pose Estimation

    DEFF Research Database (Denmark)

    Gong, Wenjuan; Fihl, Preben; Gonzàlez, Jordi;


    . In this paper, we explore this problem. First, We compare performances of several image features widely used for human pose estimation and explore their performances against each other and select one with best performance. Second, iterative closest point algorithm is introduced for a new quantitative...... measurement of noisy inputs. The proposed measurement is able to automatically discard noise, like camouflage from the background or shadows. With the proposed measurement, we split inputs into different noise levels and assess their pose estimation accuracies. Furthermore, we explore performances...

  8. 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


    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)

  9. Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing, E-mail: [Department of Breast Surgery, Qilu Hospital, Shandong Univeristy, Wenhua Xi Road 107, Shandong Province (China); Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Shandong Province (China); Yang, Qifeng, E-mail: [Department of Breast Surgery, Qilu Hospital, Shandong Univeristy, Wenhua Xi Road 107, Shandong Province (China); Haffty, Bruce G., E-mail: [Department of Radiation Oncology, UMDNJ-Robert Wood Johnson School of Medicine, Cancer Institute of New Jersey, NB (United States); Li, Xiaoyan, E-mail: [Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Shandong Province (China); Moran, Meena S., E-mail: [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States)


    Highlights: ► Fulvestrant radiosensitizes MCF-7 cells. ► Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ► Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy ± fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 ± 0.013 vs. 0.622 ± 0.029 @2 Gy, 0.599 ± 0.045 vs. 0.475 ± 0.054 @4 Gy, and 0.472 ± 0.021 vs. 0.380 ± 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT

  10. Estimation and harvesting of human heat power for wearable electronic devices (United States)

    Dziurdzia, P.; Brzozowski, I.; Bratek, P.; Gelmuda, W.; Kos, A.


    The paper deals with the issue of self-powered wearable electronic devices that are capable of harvesting free available energy dissipated by the user in the form of human heat. The free energy source is intended to be used as a secondary power source supporting primary battery in a sensor bracelet. The main scope of the article is a presentation of the concept for a measuring setup used to quantitative estimation of heat power sources in different locations over the human body area. The crucial role in the measurements of the human heat plays a thermoelectric module working in the open circuit mode. The results obtained during practical tests are confronted with the requirements of the dedicated thermoelectric generator. A prototype design of a human warmth energy harvester with an ultra-low power DC-DC converter based on the LTC3108 circuit is analysed.

  11. Characteristics of human amniotic fluid mesenchymal stem cells and their tropism to human ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Liru Li

    Full Text Available The mesenchymal stem cells (MSCs derived from amniotic fluid (AF have become an attractive stem cells source for cell-based therapy because they can be harvested at low cost and avoid ethical disputes. In human research, stem cells derived from AF gradually became a hot research direction for disease treatment, specifically for their plasticity, their reduced immunogenicity and their tumor tropism regardless of the tumor size, location and source. Our work aimed to obtain and characterize human amniotic fluid mesenchymal stem cells (AFMSCs and detect their ovarian cancer tropsim in nude mice model. Ten milliliters of twenty independent amniotic fluid samples were collected from 16-20 week pregnant women who underwent amniocentesis for fetal genetic determination in routine prenatal diagnosis in the first affiliated hospital of Harbin medical university. We successfully isolated the AFMSCs from thirteen of twenty amniotic fluid samples. AFMSCs presented a fibroblastic-like morphology during the culture. Flow cytometry analyses showed that the cells were positive for specific stem cell markers CD73,CD90, CD105, CD166 and HLA-ABC (MHC class I, but negative for CD 45,CD40, CD34, CD14 and HLA-DR (MHC class II. RT-PCR results showed that the AFMSCs expressed stem cell marker OCT4. AFMSCs could differentiate into bone cells, fat cells and chondrocytes under certain conditions. AFMSCs had the high motility to migrate to ovarian cancer site but didn't have the tumorigenicity. This study enhances the possibility of AFMSCs as drug carrier in human cell-based therapy. Meanwhile, the research emphasis in the future can also put in targeting therapy of ovarian cancer.

  12. Role of CXCL12 in metastasis of human ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Yu-ping; WU Xiao-hua; XING Han-ying; DU Xing-yan


    Background In a previous study, we have verified that CXCR4 expression is correlated with tumor aggressive progression and poor prognosis in patients with epithelial ovarian cancer. The aim of this study was to explore the effect of CXCL12-CXCR4 axis on the metastasis of human ovarian cancer.Methods The expressions of CXCR4 and CXCL12 mRNA and protein in human ovarian cancer cell line CAOV-3 was detected by RT-PCR and immunocytochemistry. Methythiazolyltetrazolium (MTT) was used to analyze the effect of different concentrations of CXCL12 on the proliferation of CAOV-3 cells. Transwell invasion chamber and matrigel were used to evaluate the effect of various concentrations of CXCL12 and ascites on the migration and invasion of CAOV-3 cells. The expressions of integrin β1 and vascular endothelial growth factor-C (VEGF-C) mRNA were detected by RT-PCR. Data were analyzed using ANOVA by SAS 6.12.Results Under serum-free suboptimal culture conditions, CXCL12 (100 ng/ml) significantly enhanced the proliferation of CAOV-3 cells compared with the control and 10 ng/ml CXCL12 groups (0.428±0.051 vs. 0.325±0.045 and 0.328±0.039, P<0.05). This enhancing effect of CXCL12 was significantly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml CXCR4 antagonist AMD3100. However, 10 μg/ml neutralizing CXCR4 antibody could not inhibit cell proliferation without CXCL12. The levels of migration and invasion of the CAOV-3 cells treated with 100 ng/ml CXCL12 were significantly higher than those in the control (migration: 523.3±25.2 vs 108.0±7.2; invasion: 39.3±4.0 vs. 4.0±1.0). The enhancing effect of CXCL12 on cell migration and invasion increased with the concentration of CXCL12 (100 ng/ml vs10 ng/ml: migration, 523.3±25.2 vs 211.7±24.7; invasion, 39.3±4.0 vs 15.7±3.1, P<0.05), and was strongly inhibited by 10 μg/ml neutralizing CXCR4 antibody or 1 μg/ml AMD3100. The number of migrated and invading cells in the CAOV-3 added with ascites was significantly

  13. Expression and roles of Slit/Robo in human ovarian cancer. (United States)

    Dai, Cai Feng; Jiang, Yi Zhou; Li, Yan; Wang, Kai; Liu, Pei Shu; Patankar, Manish S; Zheng, Jing


    The Slit glycoproteins and their Roundabout (Robo) receptors regulate migration and growth of many types of cells including human cancer cells. However, little is known about the expression and roles of Slit/Robo in human ovarian cancer. Herein, we examined the expression of Slit/Robo in human normal and malignant ovarian tissues and its potential participation in regulating migration and proliferation of human ovarian cancer cells using two ovarian cancer cell lines, OVCAR-3 and SKOV-3. We demonstrated that Slit2/3 and Robo1 were immunolocalized primarily in stromal cells in human normal ovaries and in cancer cells in many histotypes of ovarian cancer tissues. Protein expression of Slit2/3 and Robo1/4 was also identified in OVCAR-3 and SKOV-3 cells. However, recombinant human Slit2 did not significantly affect SKOV-3 cell migration, and OVCAR-3 and SKOV-3 cell proliferation. Slit2 also did not induce ERK1/2 and AKT1 phosphorylation in OVCAR-3 and SKOV-3 cells. The current findings indicate that three major members (Slit2/3 and Robo1) of Slit/Robo family are widely expressed in the human normal and malignant ovarian tissues and in OVCAR-3 and SKOV-3 cells. However, Slit/Robo signaling may not play an important role in regulating human ovarian cancer cell proliferation and migration.

  14. 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.


    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...

  15. Human papillomavirus genotype-specific prevalence across the continuum of cervical neoplasia and cancer. (United States)

    Joste, Nancy E; Ronnett, Brigitte M; Hunt, William C; Pearse, Amanda; Langsfeld, Erika; Leete, Thomas; Jaramillo, MaryAnn; Stoler, Mark H; Castle, Philip E; Wheeler, Cosette M


    The New Mexico HPV Pap Registry was established to measure the impact of cervical cancer prevention strategies in the United States. Before widespread human papillomavirus (HPV) vaccine implementation, we established the baseline prevalence for a broad spectrum of HPV genotypes across the continuum of cervical intraepithelial neoplasia (CIN) and cancer. A population-based sample of 6,272 tissue specimens was tested for 37 HPV genotypes. The number of specimens tested within each diagnostic category was: 541 negative, 1,411 CIN grade 1 (CIN1), 2,226 CIN grade 2 (CIN2), and 2,094 CIN grade 3 (CIN3) or greater. Age-specific HPV prevalence was estimated within categories for HPV genotypes targeted by HPV vaccines. The combined prevalence of HPV genotypes included in the quadrivalent and nonavalent vaccines increased from 15.3% and 29.3% in CIN1 to 58.4% and 83.7% in CIN3, respectively. Prevalence of HPV types included in both vaccines tended to decrease with increasing age for CIN1, CIN2, CIN3, and squamous cell carcinoma (SCC), most notably for CIN3 and SCC. The six most common HPV types in descending order of prevalence were HPV-16, -31, -52, -58, -33, and -39 for CIN3 and HPV-16, -18, -31, -45, -52, and -33 for invasive cancers. Health economic modeling of HPV vaccine impact should consider age-specific differences in HPV prevalence. Population-based HPV prevalence in CIN is not well described, but is requisite for longitudinal assessment of vaccine impact and to understand the effectiveness and performance of various cervical screening strategies in vaccinated and unvaccinated women. ©2014 American Association for Cancer Research.

  16. Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells. (United States)

    Villa, Nancy Y; Bartee, Eric; Mohamed, Mohamed R; Rahman, Masmudur M; Barrett, John W; McFadden, Grant


    Myxoma (MYXV) and vaccinia (VACV) viruses have recently emerged as potential oncolytic agents that can infect and kill different human cancer cells. Although both are structurally similar, it is unknown whether the pathway(s) used by these poxviruses to enter and cause oncolysis in cancer cells are mechanistically similar. Here, we compared the entry of MYXV and VACV-WR into various human cancer cells and observed significant differences: 1--low-pH treatment accelerates fusion-mediated entry of VACV but not MYXV, 2--the tyrosine kinase inhibitor genistein inhibits entry of VACV, but not MYXV, 3--knockdown of PAK1 revealed that it is required for a late stage event downstream of MYXV entry into cancer cells, whereas PAK1 is required for VACV entry into the same target cells. These results suggest that VACV and MYXV exploit different mechanisms to enter into human cancer cells, thus providing some rationale for their divergent cancer cell tropisms.

  17. Geostatistical analysis of disease data: estimation of cancer mortality risk from empirical frequencies using Poisson kriging

    Directory of Open Access Journals (Sweden)

    Goovaerts Pierre


    Full Text Available Abstract Background Cancer mortality maps are used by public health officials to identify areas of excess and to guide surveillance and control activities. Quality of decision-making thus relies on an accurate quantification of risks from observed rates which can be very unreliable when computed from sparsely populated geographical units or recorded for minority populations. This paper presents a geostatistical methodology that accounts for spatially varying population sizes and spatial patterns in the processing of cancer mortality data. Simulation studies are conducted to compare the performances of Poisson kriging to a few simple smoothers (i.e. population-weighted estimators and empirical Bayes smoothers under different scenarios for the disease frequency, the population size, and the spatial pattern of risk. A public-domain executable with example datasets is provided. Results The analysis of age-adjusted mortality rates for breast and cervix cancers illustrated some key features of commonly used smoothing techniques. Because of the small weight assigned to the rate observed over the entity being smoothed (kernel weight, the population-weighted average leads to risk maps that show little variability. Other techniques assign larger and similar kernel weights but they use a different piece of auxiliary information in the prediction: global or local means for global or local empirical Bayes smoothers, and spatial combination of surrounding rates for the geostatistical estimator. Simulation studies indicated that Poisson kriging outperforms other approaches for most scenarios, with a clear benefit when the risk values are spatially correlated. Global empirical Bayes smoothers provide more accurate predictions under the least frequent scenario of spatially random risk. Conclusion The approach presented in this paper enables researchers to incorporate the pattern of spatial dependence of mortality rates into the mapping of risk values and the

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

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


    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. Moving human full body and body parts detection, tracking, and applications on human activity estimation, walking pattern and face recognition (United States)

    Chen, Hai-Wen; McGurr, Mike


    We have developed a new way for detection and tracking of human full-body and body-parts with color (intensity) patch morphological segmentation and adaptive thresholding for security surveillance cameras. An adaptive threshold scheme has been developed for dealing with body size changes, illumination condition changes, and cross camera parameter changes. Tests with the PETS 2009 and 2014 datasets show that we can obtain high probability of detection and low probability of false alarm for full-body. Test results indicate that our human full-body detection method can considerably outperform the current state-of-the-art methods in both detection performance and computational complexity. Furthermore, in this paper, we have developed several methods using color features for detection and tracking of human body-parts (arms, legs, torso, and head, etc.). For example, we have developed a human skin color sub-patch segmentation algorithm by first conducting a RGB to YIQ transformation and then applying a Subtractive I/Q image Fusion with morphological operations. With this method, we can reliably detect and track human skin color related body-parts such as face, neck, arms, and legs. Reliable body-parts (e.g. head) detection allows us to continuously track the individual person even in the case that multiple closely spaced persons are merged. Accordingly, we have developed a new algorithm to split a merged detection blob back to individual detections based on the detected head positions. Detected body-parts also allow us to extract important local constellation features of the body-parts positions and angles related to the full-body. These features are useful for human walking gait pattern recognition and human pose (e.g. standing or falling down) estimation for potential abnormal behavior and accidental event detection, as evidenced with our experimental tests. Furthermore, based on the reliable head (face) tacking, we ha