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Sample records for human cancers due

  1. Cytotoxic activities of amentoflavone against human breast and cervical cancers are mediated by increasing of PTEN expression levels due to peroxisomes proliferate-activated receptor {gamma} activation

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    Lee, Eunjung; Shin, Soyoung; Lee, Jeeyoung; Lee, So Jung; Kim, Jinkyoung; Yoon, Doyoung; Kim, Yangmee [Konkuk Univ., Seoul (Korea, Republic of); Woo, Eunrhan [Chosun Univ., Gwangju (Korea, Republic of)

    2012-07-15

    Human peroxisomes proliferate-activated receptor gamma (hPPAR{gamma}) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. Previously, we verified that amentoflavone is an activator of hPPAR{gamma} and probed the molecular basis of its action. In this study, we investigated the mechanism of action of amentoflavone in cancer cells and demonstrated that amentoflavone showed strong cytotoxicity against MCF-7 and HeLa cancer cell lines. We showed that hPPAR{gamma} expression in MCF-7 and HeLa cells is specifically stimulated by amentoflavone, and suggested that amentoflavone-induced cytotoxic activities are mediated by activation of hPPAR{gamma} in these two cancer cell lines. Moreover, amentoflavone increased PTEN levels in these two cancer cell lines, indicating that the cytotoxic activities of amentoflavone are mediated by increasing of PTEN expression levels due to hPPAR{gamma} activation.

  2. Mortality due to lung cancer in Mexico.

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    Ruíz-Godoy, L; Rizo Rios, P; Sánchez Cervantes, F; Osornio-Vargas, A; García-Cuellar, C; Meneses García, A

    2007-11-01

    The highest mortality due to cancer worldwide for both genders corresponds to lung cancer (1,179,000 deaths). In Mexico, the crude mortality rate due to lung cancer was of 5.01 per 10(5) inhabitants in 1979. The most important risk factor is smoking. The present study was aimed at analyzing the mortality due to lung cancer in Mexico, assessing data from each of the states constituting the Mexican Republic during the 1998-2004 period. Data were obtained from the National Institute of Statistics, Geography and Informatics (INEGI, for its initials in Spanish) corresponding to deaths due to lung cancer (1998-2004). We estimated the mean annual mortality rate (MAMR) for each of the 32 states of Mexico. We used the "World Population Standard". The MAMR was standardized according to age (ARS) direct method, and the standard error was determined by Poisson's approximation at a 95% confidence interval. To know the excess risk due to mortality, we calculated the standardized mortality ratios (SMRs) of ARS for each federal state, using the national rate as reference. In this period, 397,400 deaths due to malignant neoplasms were recorded, corresponding 45,578 (11.5%) to lung cancer; for men, 31,025 (68.1%) with MAMR of 8.9 and the respective ARS of 13.2 both x10(5) inhabitants. For women, results were 4553 (31.9%) deaths with MAMR of 4.1 and ARS of 5.4 both x10(5) inhabitants. The highest mortality rates due to lung cancer in both genders were observed in the north of Mexico, whereas for women this was observed in the central states. Although smoking is the main risk for lung cancer, there are other factors such as environmental pollution or exposure to toxicants that could be associated to this cancer. The years potentially lost due to lung cancer were 258,550 for men and 133,315 for women, with a total of 391,865 according to histopathology registry neoplasm malignant RHNM (1985-1995). Studies focused on the characterization and measurement of polluting agents would be a

  3. Cancer Therapy Due to Apoptosis: Galectin-9

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    Koji Fujita

    2017-01-01

    Full Text Available Dysregulation of apoptosis is a major hallmark in cancer biology that might equip tumors with a higher malignant potential and chemoresistance. The anti-cancer activities of lectin, defined as a carbohydrate-binding protein that is not an enzyme or antibody, have been investigated for over a century. Recently, galectin-9, which has two distinct carbohydrate recognition domains connected by a linker peptide, was noted to induce apoptosis in thymocytes and immune cells. The apoptosis of these cells contributes to the development and regulation of acquired immunity. Furthermore, human recombinant galectin-9, hG9NC (null, which lacks an entire region of the linker peptide, was designed to resist proteolysis. The hG9NC (null has demonstrated anti-cancer activities, including inducing apoptosis in hematological, dermatological and gastrointestinal malignancies. In this review, the molecular characteristics, history and apoptosis-inducing potential of galectin-9 are described.

  4. Production lost due to cervical cancer in Poland in 2012.

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    Dubas-Jakóbczyk, Katarzyna; Kocot, Ewa; Seweryn, Michał; Koperny, Magdalena

    Poland has one of the highest cervical cancer mortality rates in Europe. It is related to the problem of late diagnosis and low attendance rate in screening programs. The objective of the study has been to assess the annual production loss due to the cervical cancer morbidity and mortality in Poland in 2012. The outcomes have been to provide comprehensive information on cervical cancer's influence on population's ability to work and its overall economic burden for the society. The study has also provided the methodological framework for disease-related production losses in Polish settings. The human capital method was used. The production losses were calculated in both monetary and quantitative terms (working days lost) due to 4 following reasons: 1) temporary disability to work, 2) permanent disability, 3) informal care, and 4) mortality. Cervical cancer resulted in approx. 702 964 working days lost in 2012 due to absence at work for both patients and care givers and a total number of 957 678 working days lost due to patients' mortality. The total value of production lost was assessed at 111.4 million euros. More than 66% of this value was attributed to women's mortality. The calculation of production lost due to cervical cancer burden provides strong evidence to support adequate health promotion and disease prevention actions. Actions promoting cervical cancer screening should be intensified including workplace health promotion activities. Med Pr 2016;67(3):289-299. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  5. The changes of the frequency specific impedance of the human body due to the resonance in the kHz range in cancer diagnostics

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    Michalak, K. P.; Nawrocka-Bogusz, H.

    2011-12-01

    The frequency-specific absorption of kHz signals has been postulated for different tissues, trace elements, vitamins, toxins, pathogens, allergens etc. for low-power (μV) signals. An increase in the impedance of the human body is observed only up to the given power of the applied signal. The highest amplification of the given signal being damped by the body makes it possible to determine the intensity of the given process in the body (e.g. amount of the toxin, trace element, intensity of the allergy) being connected with a given frequency spectrum of the signal. The mechanism of frequency-specific absorption can be explained by means of the Quantum Field Theory being applied to the structure of the water. Substantially high coincidence between the frequencies of the rotation of free quasi-excited electrons in coherent domains of water and the frequencies being used in the MORA diagnostics (Med-Tronic GmbH, EN ISO 13485, EN ISO 9001) can be observed. These frequencies are located in the proximity of f = 7kHz · i (i = 1,3,5,7,...). This fact suggests that the coherent domains with the admixtures of the given substances create structure-specific coherent domains that possess frequency-specific absorption spectra. The diagnostic tool called "MORA System diagnosis" was used to investigate 102 patients with different types and stages of cancer. Many signals were observed to be absorbed by many cancer patients, e.g.: 'Cellular defense system', 'Degeneration tendencies', Manganese, Magnesium, Zinc, Selenium, Vitamin E, Glutamine, Glutathione, Cysteine, Candida albicans, Mycosis. The results confirm the role of oxidative stress, immunological system deficiency and mitochondria malfunction in the development of cancer.

  6. Human Viruses and Cancer

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    Abigail Morales-Sánchez

    2014-10-01

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

  7. Human papillomaviruses and cancer.

    Science.gov (United States)

    Haedicke, Juliane; Iftner, Thomas

    2013-09-01

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

  8. Serglycin in human cancers

    Institute of Scientific and Technical Information of China (English)

    Xin-Jian Li; Chao-Nan Qian

    2011-01-01

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

  9. Burden of disease due to cancer in Spain

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    Pérez-Gómez Beatriz

    2009-01-01

    Full Text Available Abstract Background Burden of disease is a joint measure of mortality and morbidity which makes it easier to compare health problems in which these two components enjoy different degrees of relative importance. The objective of this study is ascertaining the burden of disease due to cancer in Spain via the calculation of disability-adjusted life years (DALYs. Methods DALYs are the sum of years of life lost due to premature mortality and years lost due to disability. World Health Organization methodology and the following sources of data were used: the Mortality Register and Princeton Model Life Table for Years of life lost due to premature mortality and population, incidence estimates (Spanish tumour registries and fitting of generalized linear mixed models, duration (from data of survival in Spain from the EUROCARE-3 study and fitting of Weibull distribution function and disability (weights published in the literature for Years lost due to disability. Results There were 828,997 DALYs due to cancer (20.5 DALYs/1,000 population, 61% in men. Of the total, 51% corresponded to lung, colorectal, breast, stomach and prostate cancers. Mortality (84% of DALYs predominated over disability. Subjects aged under 20 years accounted for 1.6% and those aged over 70 years accounted for 30.1% of DALYs. Conclusion Lung, colorectal and breast cancers are responsible for the highest number of DALYs in Spain. Even if the burden of disease due to cancer is predominantly caused by mortality, some cancers have a significant weight of disability. Information on 2000 burden of disease due to cancer can be useful to assess how it has evolved over time and the impact of medical advances on it in terms of mortality and disability.

  10. Colon cancer associated transcripts in human cancers.

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

    2017-08-02

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

  11. Report: Human cancer genetics

    Institute of Scientific and Technical Information of China (English)

    LI Marilyn; ALBERTSON Donna

    2006-01-01

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

  12. Human cancer genetics*

    OpenAIRE

    2006-01-01

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

  13. Telomerase activity in human cancer

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    Griffith, J.

    2000-10-01

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

  14. HUMAN PROSTATE CANCER RISK FACTORS

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

  15. Ovarian failure due to cancer treatment and fertility preservation options

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    Soheila Aminimoghaddam

    2016-04-01

    Full Text Available Primary ovarian insufficiency (POI, commonly referred to premature ovarian failure, is defined as ovarian failure before the age of 40 years. It is the loss of ovarian function caused by a process directly affecting ovaries. Cancer therapy which includes surgery, radiotherapy, and chemotherapy influence ovarian function, leading to premature menopause and loss of fertility. POI is idiopathic in most cases (74-90%. The known causes, in addition to anticancer treatment, are other processes like chromosomal abnormalities, autoimmunity, and natural aging can result in secondary ovarian failure, which is detected by an increase in serum gonadotropin levels (FSH and LH. There are evident risks of POI in women treated for cancer. Those who receive anticancer treatments have an increased risk of developing POI. There by, anticancer drugs and radiation therapy are considered as the most common toxins of ovaries. Although cancer incidence rates in women less than 50 years old continue to increase during recent years, mortality rates are dramatically decreasing due to modern advances in treatment. Increasing numbers of survivors are now confronted with the long-term consequences of exposure to these treatments. The pool of primordial follicles in the ovary is fixed and any injury to the ovary can potentially reduce this ovarian reserve, effectively advancing the patient’s reproductive age, thus narrowing the window of reproductive opportunity. Ovarian failure occurs in a significant percentage of childhood cancer survivors and many of them will seek care for reproductive dysfunction. Nevertheless, Embryo cryopreservation, oocyte cryopreservation, ovary tissue cryopreservation, ovarian suppression and oophoro-pexy are some options to preserve fertility in these groups. As a result, having foreknowledge of potential treatment related ovarian failure will allow the physician to give a better counsel to patients and their family regarding the importance and

  16. Oncogenes and human cancer

    NARCIS (Netherlands)

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

    1984-01-01

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

  17. Viruses and human cancer

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-01-01

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

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

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

    2017-06-15

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

  19. Micropapillary Lung Cancer with Breast Metastasis Simulating Primary Breast Cancer due to Architectural Distortion on Images

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    Ko, Kyung Ran; Hong, Eun Kyung; Lee, See Yeon [Center for Breast Cancer, National Cancer Center, Goyang (Korea, Republic of); Ro, Jae Yoon [The Methodist Hospital, Weill Medical College of Cornell University, Houston (United States)

    2012-03-15

    A 47-year-old Korean woman with right middle lobe lung adenocarcinoma, malignant pleural effusion, and multiple lymph node and bone metastases, after three months of lung cancer diagnosis, presented with a palpable right breast mass. Images of the right breast demonstrated architectural distortion that strongly suggested primary breast cancer. Breast biopsy revealed metastatic lung cancer with a negative result for estrogen receptor (ER), progesterone receptor (PR) and mammaglobin, and a positive result for thyroid transcription factor-1 (TTF-1). We present a case of breast metastasis from a case of lung cancer with an extensive micropapillary component, which was initially misinterpreted as a primary breast cancer due to unusual image findings with architectural distortion.

  20. Human papillomavirus and cervical cancer.

    Science.gov (United States)

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

    2013-09-07

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

  1. Septin mutations in human cancers

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    Elias T Spiliotis

    2016-11-01

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

  2. DBGC: A Database of Human Gastric Cancer.

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

    2015-01-01

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

  3. Biological stoichiometry in human cancer.

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    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

  4. Assessment of damage from reduction of expected lifespan due to cancer

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    Boris Alengordovich Korobitsyn

    2013-09-01

    Full Text Available This paper presents the theoretical and methodological approaches to the assessment of damage from premature mortality and reduction of life expectancy due to various reasons. The concepts measuring the price of a human life are analyzed: the evaluation from the standpoint of the theory of human capital; indirect estimation taking into account non-monetary social costs; evaluation of individuals’ willingness to pay for the elimination of the risk of death; estimation based on the determination of insurance premiums and compensations under court decision; evaluation of the social investments, aimed to reduce the risk of premature mortality of the individual. The following indexes were calculated for all subordinate entities of the Russian Federation: reduction of life expectancy, lost years of potential life in the working age, and gross regional product lost due to the reduction of years of potential life in the working-age population as a result of cancer

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

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    Ding, Lin; El Zaatari, Mohamad

    2017-01-01

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

  6. Epigenetic changes in virus-associated human cancers

    Institute of Scientific and Technical Information of China (English)

    Hsin Pai LI; Yu Wei LEU; Yu Sun CHANG

    2005-01-01

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

  7. Global hotspots of water scarcity impacts due to human interventions

    Science.gov (United States)

    Veldkamp, T.; Wada, Y.; Aerts, J.; Ward, P.; Satoh, Y.; Pokhrel, Y. N.; Masaki, Y.; Doll, P. M.; Ostberg, S.; Oki, T.; Gosling, S.; Liu, J.

    2016-12-01

    Water scarcity is rapidly increasing in many global river basins, due to both local increases in water demand and human interventions affecting stream flow. In a novel multi-model multi-forcing assessment over the period 1971-2010, we examine how several human interventions have affected water scarcity, namely land use change, reservoir operations, and upstream water withdrawals. We show that these human interventions have caused increased water scarcity for 16% of the global population, and decreased water scarcity for 13%, and have contributed to distinct patterns of water scarcity hotspots. We also show that a combination of human interventions and changes in local water demands have led to an increase in the duration of extreme water scarcity events in 30% of the global land area, inhabited by 49% of the global population. Upstream human interventions are the main dominant driver (in 86% of the cases) of negative impacts on downstream fresh water resources and water scarcity. Therefore, adaptation measures should be embedded in integrated river basin management plans, addressing upstream effects on downstream water scarcity.This study is the first in its kind to evaluate how human interventions affected water scarcity conditions as well as the exposure to and persistence of water scarcity events, using an ensemble of five global water impact models (H08, LPJmL, MATSIRO, PCR-GLOBWB, WaterGAP) driven by three global state-of-the art observations-based historical climate data-sets (PGFv2, GSWP3, WFD/WFDEI) and a set of socio-economic proxies (GDP, population density, livestock density, land use and land cover) to model historical demands. A novelty of this research is the use of the HYDE 3.1 - MIRCA dataset for simulating the time-varying effects of changes in irrigation and/or cropland patterns. With the incorporation of a spatially and temporally explicit indicator to describe minimum environmental flow requirements, i.e. the amount of water that ecosystems need

  8. Precocious puberty due to human chorionic gonadotropin secreting germinoma

    Directory of Open Access Journals (Sweden)

    Daiane J Nascimento

    2012-01-01

    Full Text Available This study aims to report a rare case of precocious puberty (PP due to a human chorionic gonadotropin (hCG-producing germinoma located in the suprasellar region. A 10-year-old male patient presented with sexual precocity, headache, drowsiness, loss of appetite, and papilledema. Significant acceleration of bone age in relation to chronological age, high serum total testosterone levels, and hypopituitarism (unresponsiveness to stimulation test were observed. Magnetic resonance imaging (MRI of the brain showed a large suprasellar tumor and triventricular dilatation. High hCG levels were found in both blood and cerebrospinal fluid. Hormone replacement therapy and transcranial surgery associated with radiotherapy were performed, with complete regression of sexual characteristics and normal laboratory tests post-operatively. Clinical and laboratory findings, in addition to MRI scans, led to the diagnosis of an hCG-producing tumor and PP, which represents a rare report in the literature.

  9. HCSD: the human cancer secretome database

    Science.gov (United States)

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

    2015-01-01

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

  10. Human Cancer Models Initiative | Office of Cancer Genomics

    Science.gov (United States)

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

  11. Predictors of re-operation due to post-surgical bleeding in breast cancer patients

    DEFF Research Database (Denmark)

    Lietzen, Lone Winther; Cronin-Fenton, D; Garne, J P

    2012-01-01

    To assess the risk of re-operation due to post-surgical bleeding after initial breast cancer surgery and to identify predictors of re-operation.......To assess the risk of re-operation due to post-surgical bleeding after initial breast cancer surgery and to identify predictors of re-operation....

  12. Cancer stem cells in human gastrointestinal cancer.

    Science.gov (United States)

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

    2016-11-01

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

  13. Human papillomaviruses and skin cancer.

    Science.gov (United States)

    Smola, Sigrun

    2014-01-01

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

  14. Calorimetric signatures of human cancer cells and their nuclei

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-10

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

  15. Municipal mortality due to thyroid cancer in Spain

    Directory of Open Access Journals (Sweden)

    Gómez-Barroso Diana

    2006-12-01

    Full Text Available Abstract Background Thyroid cancer is a tumor with a low but growing incidence in Spain. This study sought to depict its spatial municipal mortality pattern, using the classic model proposed by Besag, York and Mollié. Methods It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardized mortality ratios, smoothed relative risk (RR estimates, and the posterior probability that RR > 1. Results From 1989 to 1998 a total of 2,538 thyroid cancer deaths were registered in 1,041 municipalities. The highest relative risks were mostly situated in the Canary Islands, the province of Lugo, the east of La Coruña (Corunna and western areas of Asturias and Orense. Conclusion The observed mortality pattern coincides with areas in Spain where goiter has been declared endemic. The higher frequency in these same areas of undifferentiated, more aggressive carcinomas could be reflected in the mortality figures. Other unknown genetic or environmental factors could also play a role in the etiology of this tumor.

  16. Optimization of human cancer radiotherapy

    CERN Document Server

    Swan, George W

    1981-01-01

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

  17. Prevalence of Human Papillomavirus in endometrial cancer

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  18. HCSD: the human cancer secretome database

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  19. Severe Hypocalcemia due to Denosumab in Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Mohammed Muqeet Adnan

    2014-01-01

    Full Text Available Denosumab is a monoclonal antibody used for prevention of skeletal-related events (SREs in patients with bone metastases from solid tumors. Hypocalcemia is a rare and dangerous side effect of the drug Denosumab. We present a case of a patient with metastatic prostate cancer who developed severe hypocalcemia after the administration of the drug. The patient’s vitamin D levels were low when checked after administration of the drug, which likely predisposed him to the development of hypocalcemia. He was placed on high doses of oral and intravenous (IV calcium and vitamin D without any appreciable response in the serum calcium level. His ionized calcium remained below 0.71 mmol/L despite very high doses of oral and IV calcium supplements. During the hospital course, he developed hydronephrosis from the spread of a tumor and did not want to undergo percutaneous nephrostomy tube placement; therefore, it was decided to dialyse him for acute renal failure and to correct his hypocalcemia. Checking calcium and vitamin D levels prior to the administration of Denosumab is vital in preventing hypocalcemia. If hypocalcemia is severe and not responsive to high doses of vitamin D, oral and IV calcium, then hemodialysis with a high calcium bath can correct this electrolyte abnormality.

  20. Severe Hypocalcemia due to Denosumab in Metastatic Prostate Cancer.

    Science.gov (United States)

    Muqeet Adnan, Mohammed; Bhutta, Usman; Iqbal, Tanzeel; AbdulMujeeb, Sufyan; Haragsim, Lukas; Amer, Syed

    2014-01-01

    Denosumab is a monoclonal antibody used for prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. Hypocalcemia is a rare and dangerous side effect of the drug Denosumab. We present a case of a patient with metastatic prostate cancer who developed severe hypocalcemia after the administration of the drug. The patient's vitamin D levels were low when checked after administration of the drug, which likely predisposed him to the development of hypocalcemia. He was placed on high doses of oral and intravenous (IV) calcium and vitamin D without any appreciable response in the serum calcium level. His ionized calcium remained below 0.71 mmol/L despite very high doses of oral and IV calcium supplements. During the hospital course, he developed hydronephrosis from the spread of a tumor and did not want to undergo percutaneous nephrostomy tube placement; therefore, it was decided to dialyse him for acute renal failure and to correct his hypocalcemia. Checking calcium and vitamin D levels prior to the administration of Denosumab is vital in preventing hypocalcemia. If hypocalcemia is severe and not responsive to high doses of vitamin D, oral and IV calcium, then hemodialysis with a high calcium bath can correct this electrolyte abnormality.

  1. Experiences of the family caregiver of a person with intestinal ostomy due to colorectal cancer

    Directory of Open Access Journals (Sweden)

    Gláucia Sousa Oliveira

    2014-04-01

    Full Text Available This is a study with the objective to know the experiences of the family caregiver of a person with intestinal ostomy due to colorectal cancer. A qualitative research, grounded on the humanization referential, made in 2013, through serialized semi-structured interviews and inductive analysis. It was approved by the Ethics and Research Committee under legal opinion no. 237,771. Seven family caregivers participated in this study in a county of southern Minas Gerais state, Brazil. Three categories emerged from the data: Relation with the disease and its treatments; Impact facing treatment and rehabilitation and Nets of support. The representation of the disease associated to finitude is reaffirmed. In order to lessen anguish and suffering, the family caregivers search support, mainly in spirituality. The impact resulting from the illness and the rehabilitation process imposes a new order to the caregivers, with personal and social renouncing, which provides a closer and more dedicated relation with the patient.

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

    Science.gov (United States)

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

    2015-02-01

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

  3. Poverty eradication and decreased human papilloma virus related cancer of the penis and vulva in Jamaica.

    Science.gov (United States)

    Fletcher, H M; Hanchard, B

    2008-04-01

    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.

  4. Expression of polarity genes in human cancer.

    Science.gov (United States)

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

    2015-01-01

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

  5. Antiangiogenic Steroids in Human Cancer Therapy

    OpenAIRE

    2005-01-01

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

  6. Rapidly Progressive Dementia due to Carcinoma- tous Meningitis Associated with Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Chalobol Chalermsri

    2016-01-01

    Full Text Available Gastric cancer rarely presents with carcinomatous meningitis (CM and rapidly progressive dementia. The authors report two cases of carcinomatous meningitis due to gastric cancer presenting with rapidly progres- sive dementia. The MRI of the brain was different between the two cases. The diagnosis of CM was confirmed by positive cerebrospinal fluid cytology.

  7. Adrenal Failure due to Adrenal Metastasis of Lung Cancer: A Case Report

    Science.gov (United States)

    Faulhaber, Gustavo Adolpho Moreira; Borges, Flavia Kessler; Ascoli, Aline Maria; Seligman, Renato; Furlanetto, Tania Weber

    2011-01-01

    We report a case of a patient with adrenal failure due to bilateral adrenal metastasis of lung cancer. This is a rare presentation of lung cancer. We review the differential diagnosis of weight loss and how to make diagnosis of adrenal insufficiency. PMID:22606443

  8. Adrenal Failure due to Adrenal Metastasis of Lung Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Gustavo Adolpho Moreira Faulhaber

    2011-01-01

    Full Text Available We report a case of a patient with adrenal failure due to bilateral adrenal metastasis of lung cancer. This is a rare presentation of lung cancer. We review the differential diagnosis of weight loss and how to make diagnosis of adrenal insufficiency.

  9. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

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

    2011-01-01

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

  10. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

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

    2011-01-01

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

  11. Human papillomavirus infections in laryngeal cancer

    NARCIS (Netherlands)

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

    2011-01-01

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

  12. Human papillomavirus infections in laryngeal cancer

    NARCIS (Netherlands)

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

    2011-01-01

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

  13. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

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

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

  14. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue due to cancer recurrence

    DEFF Research Database (Denmark)

    Ernst, EH; Offersen, Birgitte Vrou; Andersen, Claus Yding

    2013-01-01

    To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer.......To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer....

  15. Potential Prognostic Markers for Human Prostate Cancer

    Science.gov (United States)

    2001-03-01

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

  16. Abnormalities in human pluripotent cells due to reprogramming mechanisms.

    Science.gov (United States)

    Ma, Hong; Morey, Robert; O'Neil, Ryan C; He, Yupeng; Daughtry, Brittany; Schultz, Matthew D; Hariharan, Manoj; Nery, Joseph R; Castanon, Rosa; Sabatini, Karen; Thiagarajan, Rathi D; Tachibana, Masahito; Kang, Eunju; Tippner-Hedges, Rebecca; Ahmed, Riffat; Gutierrez, Nuria Marti; Van Dyken, Crystal; Polat, Alim; Sugawara, Atsushi; Sparman, Michelle; Gokhale, Sumita; Amato, Paula; Wolf, Don P; Ecker, Joseph R; Laurent, Louise C; Mitalipov, Shoukhrat

    2014-07-10

    Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the 'gold standard', they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies.

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

    Science.gov (United States)

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

    2010-06-01

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

  18. Novel innate cancer killing activity in humans

    Directory of Open Access Journals (Sweden)

    Lovato James

    2011-08-01

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

  19. [Nosocomial infections due to human coronaviruses in the newborn].

    Science.gov (United States)

    Gagneur, A; Legrand, M C; Picard, B; Baron, R; Talbot, P J; de Parscau, L; Sizun, J

    2002-01-01

    Human coronaviruses, with two known serogroups named 229-E and OC-43, are enveloped positive-stranded RNA viruses. The large RNA is surrounded by a nucleoprotein (protein N). The envelop contains 2 or 3 glycoproteins: spike protein (or protein S), matrix protein (or protein M) and a hemagglutinin (or protein HE). Their pathogen role remains unclear because their isolation is difficult. Reliable and rapid methods as immunofluorescence with monoclonal antibodies and reverse transcription-polymerase chain reaction allow new researches on epidemiology. Human coronaviruses can survive for as long as 6 days in suspension and 3 hours after drying on surfaces, suggesting that they could be a source of hospital-acquired infections. Two prospective studies conducted in a neonatal and paediatric intensive care unit demonstrated a significant association of coronavirus-positive nasopharyngal samples with respiratory illness in hospitalised preterm neonates. Positive samples from staff suggested either a patient-to-staff or a staff-to-patient transmission. No cross-infection were observed from community-acquired respiratory-syncitial virus or influenza-infected children to neonates. Universal precautions with hand washing and surface desinfection could be proposed to prevent coronavirus transmission.

  20. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

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

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

    Science.gov (United States)

    Desmedt, Christine; Yates, Lucy; Kulka, Janina

    2016-03-01

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

  2. Cytotoxicity of dietary flavonoids on different human cancer types

    Directory of Open Access Journals (Sweden)

    Katrin Sak

    2014-01-01

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

  3. Prevalence of Telomerase Activity in Human Cancer

    Directory of Open Access Journals (Sweden)

    Chi-Hau Chen

    2011-05-01

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

  4. Cancer Metabolomics and the Human Metabolome Database

    Directory of Open Access Journals (Sweden)

    David S. Wishart

    2016-03-01

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

  5. HPV genotype distribution in older Danish women undergoing surgery due to cervical cancer

    DEFF Research Database (Denmark)

    Hammer, Anne; Mejlgaard, Else; Gravitt, Patti;

    2015-01-01

    INTRODUCTION: The prevalence of human papillomavirus (HPV)16/18 in cervical cancer may decrease with age. This study aimed to describe the HPV genotype distribution in Danish women aged 55 years or older with cervical cancer. MATERIAL AND METHODS: In this cross-sectional study we identified 153...... cases of cervical cancer diagnosed at Aarhus University Hospital, Denmark (1990-2012) and Copenhagen University Hospital Herlev, Denmark (2007-2012). All women had surgery to treat the disease. HPV genotyping was performed on cervical cancer tissue using the INNO LiPA HPV genotyping extra (Fujirebio......, Belgium) at the Department of Pathology, Aarhus University Hospital, Denmark. The main outcome was to estimate the age-specific prevalence of high-risk HPV genotypes included in the bivalent, the quadrivalent, and the nonavalent vaccine. RESULTS: Of 121 cases of cervical cancer included in this study, 113...

  6. Modeling of lung cancer risk due to radon exhalation of granite stone in dwelling houses

    Directory of Open Access Journals (Sweden)

    Akbar Abbasi

    2017-01-01

    Conclusions: The estimated numbers of lung cancer deaths attributable to indoor radon due to granite stones in 2013 were 145 (3.33% and 103 (2.37% for poor and normal ventilation systems, respectively. According to our estimations, the values of 3.33% and 2.37% of lung cancer deaths in 2013 are attributed to radon exhalation of granite stones with poor and normal ventilation systems, respectively.

  7. Computation of particle detachment from floors due to human walking

    Science.gov (United States)

    Elhadidi, Basman; Khalifa, Ezzat

    2005-11-01

    A computational model for detachment of fine particles due to the unsteady flow under a foot is developed. As the foot approaches the floor, fluid volume is displaced laterally as a wall jet from the perimeter of the contact area at high velocity and acceleration. Unsteady aerodynamic forces on particles attached to the floor are considered. Results show that the jet velocity is ˜40 m/s for a foot idealized as a 15 cm circular disk approaching the floor at 1 m/s with a final gap of 0.8 mm. This velocity is sufficient to detach small particles (1˜μm). The flow accelerates at ˜400 m/s^2 which affects the detachment of larger sized particles (˜100 μm). As the disk is brought to rest, the unsteady jet expands outwards, advecting a vortex ring closely attached to it. At the disk edge, a counter rotating vortex is generated by the sudden deceleration of the disk. Both vortices can play a role in entrainment of the suspended particles in the flowfield. Numerical studies also show that the maximum jet velocity is ˜20 m/s for a simplified foot immediately after heel contact in the stance phase of the gait.

  8. Human Papillomavirus in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Anna Rosa Garbuglia

    2014-08-01

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

  9. Oral contraceptives, human papillomavirus and cervical cancer.

    Science.gov (United States)

    La Vecchia, Carlo; Boccia, Stefania

    2014-03-01

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

  10. TGF-Beta Induction of PMEPA1: Role in Bone Metastasis Due to Prostate Cancer

    Science.gov (United States)

    2009-01-01

    receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line . Cancer Sci 2007;98:127–33. 21. Stebbins ...Zylux corporation). TGF-β significantly increased PMEPA1 promoter activity in the 3 cell lines tested which was reversed by the Tgfbr1 inhibitor...or type 2 receptor(28;29). Using sqRT-PCR in multiple prostate cancer cells lines , we measured a 150-fold decrease of Tgfbr2 expression in C4-2B

  11. Radiobiology of human cancer radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, J.R.

    1978-01-01

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

  12. Water pipe smoking and human oral cancers.

    Science.gov (United States)

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

    2010-03-01

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

  13. Pineal melatonin level disruption in humans due to electromagnetic fields and ICNIRP limits.

    Science.gov (United States)

    Halgamuge, Malka N

    2013-05-01

    The International Agency for Research on Cancer (IARC) classifies electromagnetic fields (EMFs) as 'possibly carcinogenic' to humans that might transform normal cells into cancer cells. Owing to high utilisation of electricity in day-to-day life, exposure to power-frequency (50 or 60 Hz) EMFs is unavoidable. Melatonin is a natural hormone produced by pineal gland activity in the brain that regulates the body's sleep-wake cycle. How man-made EMFs may influence the pineal gland is still unsolved. The pineal gland is likely to sense EMFs as light but, as a consequence, may decrease the melatonin production. In this study, more than one hundred experimental data of human and animal studies of changes in melatonin levels due to power-frequency electric and magnetic fields exposure were analysed. Then, the results of this study were compared with the International Committee of Non-Ionizing Radiation Protection (ICNIRP) limit and also with the existing experimental results in the literature for the biological effect of magnetic fields, in order to quantify the effects. The results show that this comparison does not seem to be consistent despite the fact that it offers an advantage of drawing attention to the importance of the exposure limits to weak EMFs. In addition to those inconsistent results, the following were also observedfrom this work: (i) the ICNIRP recommendations are meant for the well-known acute effects, because effects of the exposure duration cannot be considered and (ii) the significance of not replicating the existing experimental studies is another limitation in the power-frequency EMFs. Regardless of these issues, the above observation agrees with our earlier study in which it was confirmed that it is not a reliable method to characterise biological effects by observing only the ratio of AC magnetic field strength to frequency. This is because exposure duration does not include the ICNIRP limit. Furthermore, the results show the significance of

  14. Critical time delay of the pineal melatonin rhythm in humans due to weak electromagnetic exposure.

    Science.gov (United States)

    Halgamuge, Malka N

    2013-08-01

    Electromagnetic fields (EMFs) can increase free radicals, activate the stress response and alter enzyme reactions. Intracellular signalling is mediated by free radicals and enzyme kinetics is affected by radical pair recombination rates. The magnetic field component of an external EMF can delay the "recombination rate" of free radical pairs. Magnetic fields thus increase radical life-times in biological systems. Although measured in nanoseconds, this extra time increases the potential to do more damage. Melatonin regulates the body's sleep-wake cycle or circadian rhythm. The World Health Organization (WHO) has confirmed that prolonged alterations in sleep patterns suppress the body's ability to make melatonin. Considerable cancer rates have been attributed to the reduction of melatonin production as a result of jet lag and night shift work. In this study, changes in circadian rhythm and melatonin concentration are observed due to the external perturbation of chemical reaction rates. We further analyze the pineal melatonin rhythm and investigate the critical time delay or maturation time of radical pair recombination rates, exploring the impact of the mRNA degradation rate on the critical time delay. The results show that significant melatonin interruption and changes to the circadian rhythm occur due to the perturbation of chemical reaction rates, as also reported in previous studies. The results also show the influence of the mRNA degradation rate on the circadian rhythm's critical time delay or maturation time. The results support the hypothesis that exposure to weak EMFs via melatonin disruption can adversely affect human health.

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Characteristics of breast cancer patients who experience menopausal transition due to treatment

    NARCIS (Netherlands)

    S.F.A. Duijts; A.C. Stolk-Vos; H.S.A. Oldenburg; M. van Beurden; N.K. Aaronson

    2011-01-01

    Objective To identify patient-related and treatment-related factors associated significantly with climacteric symptoms in young patients who experience menopausal transition due to adjuvant treatment for breast cancer. Methods This cross-sectional study used questionnaire data collected to screen br

  17. Characteristics of breast cancer patients who experience menopausal transition due to treatment

    NARCIS (Netherlands)

    Duijts, S.F.A.; Stolk-Vos, A.C.; Oldenburg, H.S.A.; van Beurden, M.; Aaronson, N.K.

    2011-01-01

    Objective To identify patient-related and treatment-related factors associated significantly with climacteric symptoms in young patients who experience menopausal transition due to adjuvant treatment for breast cancer. Methods This cross-sectional study used questionnaire data collected to screen

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

    Science.gov (United States)

    Babyatsky, Mark; Lin, Jing; Yio, Xianyang; Chen, Anli; Zhang, Jie-yu; Zheng, Yan; Twyman, Christina; Bao, Xiuliang; Schwartz, Myron; Thung, Swan; Lawrence Werther, J; Itzkowitz, Steven

    2009-01-01

    Deaths from colorectal cancer are often due to liver metastasis. Trefoil factor-3 (TFF3) is expressed by normal intestinal epithelial cells and its expression is maintained throughout the colon adenoma-carcinoma sequence. Our previous work demonstrated a correlation between TFF3 expression and metastatic potential in an animal model of colon cancer. The aim of this study was to determine whether TFF3 is expressed in human colon cancer liver metastasis (CCLM) and whether inhibiting TFF3 expression in colon cancer cells would alter their invasive potential in vitro. Human CCLMs were analyzed at the mRNA and protein level for TFF3 expression. Two highly metastatic rat colon cancer cell lines that either natively express TFF3 (LN cells) or were transfected with TFF3 (LPCRI-2 cells), were treated with two rat TFF3 siRNA constructs (si78 and si365), and analyzed in an in vitro invasion assay. At the mRNA and protein level, TFF3 was expressed in 17/17 (100%) CCLMs and 10/11 (91%) primary colon cancers, but not in normal liver tissue. By real time PCR, TFF3 expression was markedly inhibited by both siRNA constructs in LN and LPCRI-2 cells. The si365 and si78 constructs inhibited invasion by 44% and 53%, respectively, in LN cells, and by 74% and 50%, respectively, in LPCRI-2 cells. These results provide further evidence that TFF3 contributes to the malignant behavior of colon cancer cells. These observations may have relevance for designing new diagnostic and treatment approaches to colorectal cancer.

  19. Clinical experience of Pseudo-Meigs' Syndrome due to colon cancer

    Institute of Scientific and Technical Information of China (English)

    HiromichiMaeda; TakehrioOkabayashi; KazuhiroHanazaki; MichiyaKobayashi

    2011-01-01

    We report a rare case of Pseudo-Meigs' Syndrome caused by ovarian metastasis from sigmoid colon cancer, which was accompanied by peritoneal dissemination. A 58-year-old female patient presented with massive right pleural effusion, ascites and a huge pelvic mass. Under the diagnosis of an advanced ovarian tumor, bilateral oophorectomy was performed and sigmoidectomy was also carried out after intraoperative diagnosis of peritoneal dissemination involving the sigmoid colon. How- ever, immunohistochemical staining revealed that the ovarian lesions were metastasis from the primary advanced colon cancer. Postoperatively, ascites and pleural effusion subsided, and the diagnosis of Pseudo-Meigs' Syndrome due to a metastatic ovarian tumor from colon cancer was determined. The patient is now undergoing a regimen of chemotherapy for colon cancer without recurrence of ascites or hydrothorax 10 mo after the surgery. Pseudo-Meigs' Syndrome due to a metastaticovarian tumor from colon cancer is rare but clinically important because long-term alleviation of symptoms can be achieved by surgical resection. This case report suggests that selected patients, even with peritoneal dissemination, may obtain palliation from surgical resection of metastatic ovarian tumors.

  20. Subcutaneous human dirofilariasis due to Dirofilaria Repens: Report of two cases

    Directory of Open Access Journals (Sweden)

    Harish S Permi

    2011-01-01

    Full Text Available Zoonotic filariasis due to Dirofilaria repens (D. repens is prevalent in several regions of the world. In view of recent rise of human D. repens infections in Europe, Africa and Asia, it is considered an emerging zoonosis in these continents. Most of the documented cases of human dirofilariasis recorded in India had ocular infections, but very few subcutaneous dirofilariasis have been reported. We hereby report two cases of subcutaneous human dirofilariasis due to D.repens with varied clinical presentations.

  1. A Research Agenda for Appearance Changes Due to Breast Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Mia K. Markey

    2008-01-01

    Full Text Available Breast cancer is one of the most prevalent forms of cancer in the US. It is estimated that more than 180,000 American women will be diagnosed with invasive breast cancer in 2008. Fortunately, the survival rate is relatively high and continually increasing due to improved detection techniques and treatment methods. However, maintaining quality of life is a factor often under emphasized for breast cancer survivors. Breast cancer treatments are invasive and can lead to deformation of the breast. Breast reconstruction is important for restoring the survivor’s appearance. However, more work is needed to develop technologies for quantifying surgical outcomes and understanding women’s perceptions of changes in their appearance. A method for objectively measuring breast anatomy is needed in order to help both the breast cancer survivors and their surgeons take expected changes to the survivor’s appearance into account when considering various treatment options. In the future, augmented reality tools could help surgeons reconstruct a survivor’s breasts to match her preferences as much as possible.

  2. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng

    2012-01-01

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

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

    Science.gov (United States)

    Badoual, C; Tartour, E; Roussel, H; Bats, A S; Pavie, J; Pernot, S; Weiss, L; Mohamed, A Si; Thariat, J; Hoffmann, C; Péré, H

    2015-08-01

    Worldwide, approximately 5 to 10% of the population is infected by a Human Papilloma Virus (HPV). Some of these viruses, with a high oncogenic risk (HPV HR), are responsible for about 5% of cancer. It is now accepted that almost all carcinomas of the cervix and the vulva are due to an HPV HR (HPV16 and 18) infection. However, these viruses are known to be involved in the carcinogenesis of many other cancers (head and neck [SCCHN], penis, anus). For head and neck cancer, HPV infection is considered as a good prognostic factor. The role of HPV HR in anal cancer is also extensively studied in high-risk patient's population. The role of HPV infection in the carcinogenesis of esophageal, bladder, lung, breast or skin cancers is still debated. Given the multiple possible locations of HPV HR infection, the question of optimizing the management of patients with a HPV+ cancer arises in the implementation of a comprehensive clinical and biological monitoring. It is the same in therapeutics with the existence of a preventive vaccination, for example.

  4. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Science.gov (United States)

    Tatlı, Ali Murat; Göksu, Sema Sezgin; Arslan, Deniz; Başsorgun, Cumhur İbrahim; Coşkun, Hasan Şenol

    2013-01-01

    Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient's history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage. PMID:23956898

  5. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ali Murat Tatlı

    2013-01-01

    Full Text Available Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient’s history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage.

  6. Human papillomavirus and gastrointestinal cancer: A review

    Science.gov (United States)

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

    2016-01-01

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

  7. MicroRNA in human cancer and chronic inflammatory diseases.

    Science.gov (United States)

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

    2010-06-01

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

  8. Diabetes Insipidus and Anterior Pituitary Insufficiency Due to Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Ayşe Arduç

    2016-03-01

    Full Text Available Metastases from breast cancer to the pituitary gland are uncommon. We present a 35-year-old woman with diabetes insipidus and anterior pituitary insufficiency resulting from breast cancer metastases to the pituitary gland. The patient presented with reduced consciousness, fatigue, polyuria, and polydipsia. Hypernatremia (sodium: 154 mmol/L, hypostenuria (urine density: 1001, and hypopituitarism were present on laboratory evaluation. Magnetic resonance imaging (MRI revealed heterogeneous pituitary gland, thickened pituitary stalk (8mm, and loss of normal hyperintense signal of the posterior pituitary. Based on the clinical, laboratory, and MRI findings, the patient was diagnosed with diabetes insipidus and anterior pituitary insufficiency due to pituitary metastases from breast cancer. She received desmopressin, L-thyroxine, and prednisolone, which resulted in improvement of her symptoms and laboratory results. The patient, who also received Gamma Knife radiosurgery and chemotherapy, died six months later due to disseminated metastases. Although pituitary metastasis is rare, it should be kept in mind in patients with breast cancer since early detection and treatment can improve symptoms of patients.

  9. Recurrence after surgery due to cervical cancer - An evaluation of the follow-up program

    DEFF Research Database (Denmark)

    Fuglsang, Katrine; Petersen, Lone Kjeld; Blaakær, Jan

    Objective During the last 20 years the follow-up program after surgical treatment for cervical cancer has remained unchanged. Surprisingly, little is communicated in relation to the follow-up program even though it has a huge impact on the life of the women and their relatives for five years....... The focus for this study is to evaluate the follow-up program in fulfilling the purpose for early diagnosis of recurrence while reminding and concerning women, who we consider healthy after surgery, 10 times during five years. Already politicians are focusing on the subject due to the socioeconomic...... consequences, but there is a need for a foundation prior to an adjustment of the follow-up program. Methods Design: retrospective study of a cohort of women attending follow-up program after surgery due to cervical cancer. Material: From the patient register at the Department of Gynaecology and Obstetrics...

  10. Urethral Fistula and Scrotal Abscess Associated with Colovesical Fistula Due to the Sigmoid Colon Cancer

    OpenAIRE

    2015-01-01

    We report here a rare case of urethral fistula and scrotal abscess associated with colovesical fistula due to sigmoid colon cancer. An 84-year-old male was referred to our hospital complaining of macrohematuria, fecaluria, pneumaturia and micturitional pain. Computed tomography (CT) showed colovesical fistula. Other examinations, including colonoscopy and cystoscopy, did not reveal a clear cause for the colovesical fistula. Only an elevated serum level of the tumor marker CA19-9 suggested the...

  11. Beau´s lines due to cytostatic drugs in a patient with breast cancer

    Directory of Open Access Journals (Sweden)

    Patricia Chang

    2014-04-01

    Full Text Available Female patient, 47 years old who was hospitalized due to urinary tract infection, during her hospitalization bullous lesions appeared on her left limb and interconsultation to the Dermatology Department was made. The patient has been treated by breast cancer with docetaxel, doxorubicin and cyclophosphamide; she had received 5 cycles of chemotherapy Clinical examination showed vesicles on an erythematous base of the left arm following a linear pattern and the diagnosis of herpes zoster was done.

  12. Comparative proteomics analysis of human gastric cancer

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  13. Human Colon Cancer Cells Cultivated in Space

    Science.gov (United States)

    1995-01-01

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

  14. Aspartame bioassay findings portend human cancer hazards.

    Science.gov (United States)

    Huff, James; LaDou, Joseph

    2007-01-01

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

  15. 1. HUMAN POPULATION MONITORING FOR CANCER PREVENTION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

  16. Assessment of human health hazard due to metal uptake via fish ...

    African Journals Online (AJOL)

    Assessment of human health hazard due to metal uptake via fish consumption from ... Ethiopian Journal of Environmental Studies and Management ... It is well known that fishes can accumulate variety of toxic chemicals including persistent ...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sergey N. Rumyantsev

    2013-03-01

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

  19. Quantitative changes in skin composition parameters due to chemotherapy in breast cancer patients: a cohort study.

    Science.gov (United States)

    Kang, Danbee; Kim, Im-Ryung; Im, Young Hyuck; Park, Yeon Hee; Ahn, Jin Seok; Lee, Jeong Eon; Nam, Seok Jin; Park, Hyeokgon; Kim, Eunjoo; Lee, Hae Kwang; Lee, Dong-Youn; Cho, Juhee

    2015-08-01

    The objective of this study is to evaluate objective changes in water content, sebum content, transepidermal water loss (TEWL), and melanin due to breast cancer chemotherapy, and their association with subjective symptoms. Prospective cohort study of 61 patients 18 years of age or older with a postoperative diagnosis of stage I-III breast cancer, who received adjuvant chemotherapy between February and September 2012 at an outpatient breast cancer clinic in Korea. Objective skin parameters, measured using a noninvasive bioengineering device, and patient-reported dryness and dullness were assessed before chemotherapy, after two cycles of chemotherapy, and 1, 3, and 6 months after completion of chemotherapy. Water content (-6.5 %), sebum (-75.5 %), and TEWL (-22.4 %) significantly decreased during chemotherapy compared to pre-chemotherapy levels (all p values skin changes were similar in patients with or without hormone therapy. Most of patients reported dryness (57.9 %) and dullness (49.1 %) after chemotherapy, and patient-reported dryness was significantly associated with decreased sebum content. Chemotherapy-induced substantial changes in objective skin composition parameters. These changes persisted after 6 months from completion of chemotherapy and were associated with patient-reported symptoms. Additional research is needed to translate these findings into interventions for improving the dermatologic quality of life of breast cancer patients undergoing chemotherapy.

  20. Antiangiogenic Steroids in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Richard J. Pietras

    2005-01-01

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

  1. Antiangiogenic Steroids in Human Cancer Therapy.

    Science.gov (United States)

    Pietras, Richard J; Weinberg, Olga K

    2005-03-01

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

  2. Epidemiologic studies of the human microbiome and cancer

    National Research Council Canada - National Science Library

    Vogtmann, Emily; Goedert, James J

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    陈力真; 王树蕙; 张云; 王世真

    1996-01-01

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

  4. Prevention of the Angiogenic Switch in Human Breast Cancer

    Science.gov (United States)

    2009-03-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

  6. Technical Evaluation of the NASA Model for Cancer Risk to Astronauts Due to Space Radiation

    Science.gov (United States)

    2012-01-01

    At the request of NASA, the National Research Council's (NRC's) Committee for Evaluation of Space Radiation Cancer Risk Model reviewed a number of changes that NASA proposes to make to its model for estimating the risk of radiation-induced cancer in astronauts. The NASA model in current use was last updated in 2005, and the proposed model would incorporate recent research directed at improving the quantification and understanding of the health risks posed by the space radiation environment. NASA's proposed model is defined by the 2011 NASA report Space Radiation Cancer Risk Projections and Uncertainties 2010 (Cucinotta et al., 2011). The committee's evaluation is based primarily on this source, which is referred to hereafter as the 2011 NASA report, with mention of specific sections or tables cited more formally as Cucinotta et al. (2011). The overall process for estimating cancer risks due to low linear energy transfer (LET) radiation exposure has been fully described in reports by a number of organizations. They include, more recently: (1) The "BEIR VII Phase 2" report from the NRC's Committee on Biological Effects of Ionizing Radiation (BEIR) (NRC, 2006); (2) Studies of Radiation and Cancer from the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR, 2006), (3) The 2007 Recommendations of the International Commission on Radiological Protection (ICRP), ICRP Publication 103 (ICRP, 2007); and (4) The Environmental Protection Agency s (EPA s) report EPA Radiogenic Cancer Risk Models and Projections for the U.S. Population (EPA, 2011). The approaches described in the reports from all of these expert groups are quite similar. NASA's proposed space radiation cancer risk assessment model calculates, as its main output, age- and gender-specific risk of exposure-induced death (REID) for use in the estimation of mission and astronaut-specific cancer risk. The model also calculates the associated uncertainties in REID. The general approach for

  7. Technical Evaluation of the NASA Model for Cancer Risk to Astronauts Due to Space Radiation

    Science.gov (United States)

    2012-01-01

    At the request of NASA, the National Research Council's (NRC's) Committee for Evaluation of Space Radiation Cancer Risk Model reviewed a number of changes that NASA proposes to make to its model for estimating the risk of radiation-induced cancer in astronauts. The NASA model in current use was last updated in 2005, and the proposed model would incorporate recent research directed at improving the quantification and understanding of the health risks posed by the space radiation environment. NASA's proposed model is defined by the 2011 NASA report Space Radiation Cancer Risk Projections and Uncertainties 2010 (Cucinotta et al., 2011). The committee's evaluation is based primarily on this source, which is referred to hereafter as the 2011 NASA report, with mention of specific sections or tables cited more formally as Cucinotta et al. (2011). The overall process for estimating cancer risks due to low linear energy transfer (LET) radiation exposure has been fully described in reports by a number of organizations. They include, more recently: (1) The "BEIR VII Phase 2" report from the NRC's Committee on Biological Effects of Ionizing Radiation (BEIR) (NRC, 2006); (2) Studies of Radiation and Cancer from the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR, 2006), (3) The 2007 Recommendations of the International Commission on Radiological Protection (ICRP), ICRP Publication 103 (ICRP, 2007); and (4) The Environmental Protection Agency s (EPA s) report EPA Radiogenic Cancer Risk Models and Projections for the U.S. Population (EPA, 2011). The approaches described in the reports from all of these expert groups are quite similar. NASA's proposed space radiation cancer risk assessment model calculates, as its main output, age- and gender-specific risk of exposure-induced death (REID) for use in the estimation of mission and astronaut-specific cancer risk. The model also calculates the associated uncertainties in REID. The general approach for

  8. A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells.

    Science.gov (United States)

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

    2013-06-15

    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.

  9. Alterations of 5-Hydroxymethylcytosine in Human Cancers

    Directory of Open Access Journals (Sweden)

    Ali Yesilkanal

    2013-06-01

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

  10. Human papillomavirus-associated diseases and cancers

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  11. [A case of meningeal carcinomatosis due to gastric cancer treated with intrathecal chemotherapy].

    Science.gov (United States)

    Kobayashi, Yuka; Sugitani, Soichi; Oseki, Koshi; Iiri, Takao

    2011-10-01

    A 71-year-old man was admitted to our hospital in September 2009 because of severe headache due to meningeal carcinomatosis. In July 2007, subtotal gastrectomy was carried out for gastric cancer. Because intraabdominal cytodiagnosis was positive, he received systemic chemotherapy for 2 years. Recurrent signs were not found on chest or abdominal CT just before hospitalization. He was given NSAIDs and corticosteroid, but his symptom did not improve. Subsequent intrathecal chemotherapy with MTX and Ara-C improved clinical symptoms dramatically. He received care at home for 3 months before he passed away due to pleural and peritoneal recurrence. Recently, since the frequency of meningeal carcinomatosis is increasing, combination treatment of intrathecal chemotherapy and systemic chemotherapy should be considered not only for improvement of clinical manifestations, but also for prognostic improvement.

  12. AFM-based analysis of human metastatic cancer cells

    Science.gov (United States)

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

    2008-09-01

    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.

  13. 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: jrao@mednet.ucla.edu, E-mail: gim@chem.ucla.edu

    2008-09-24

    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.

  14. Mortalin sensitizes human cancer cells to MKT-077-induced senescence.

    Science.gov (United States)

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

    2007-07-18

    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.

  15. [Urethral Fistula and Scrotal Abscess Associated with Colovesical Fistula Due to the Sigmoid Colon Cancer].

    Science.gov (United States)

    Nakazawa, Shigeaki; Uemura, Motohide; Miyagawa, Yasushi; Tsujimura, Akira; Nonomura, Norio

    2015-09-01

    We report here a rare case of urethral fistula and scrotal abscess associated with colovesical fistula due to sigmoid colon cancer. An 84-year-old male was referred to our hospital complaining of macrohematuria, fecaluria, pneumaturia and micturitional pain. Computed tomography (CT) showed colovesical fistula. Other examinations, including colonoscopy and cystoscopy, did not reveal a clear cause for the colovesical fistula. Only an elevated serum level of the tumor marker CA19-9 suggested the possibility of sigmoid colon cancer. Eleven days after hospitalization, bilateral scrotal contents had swollen rapidly to the size of a goose egg. CT suggested urethral fistula with scrotal abscess formation. Drainage of scrotal abscess and colostomy were performed. Intraoperatively, the fistula of the bulbar urethra was revealed. Because increased serum CA19-9 suggested a diagnosis of sigmoid colon cancer, cystectomy and sigmoid colectomy with right nephrectomy were performed. Pathological examination revealed adenocarcinoma of sigmoid colon with bladder invasion. His condition was improved with rehabilitation 6 months after operation.

  16. Indications of airway stenting for severe central airway obstruction due to advanced cancer.

    Science.gov (United States)

    Nagano, Hiroaki; Kishaba, Tomoo; Nei, Yuichirou; Yamashiro, Shin; Takara, Hiroaki

    2017-01-01

    Management of severe central airway obstruction due to advanced cancer is a medical and technical challenge. The impact of airway stenting on the clinical outcome of such patients is unclear. This single-center, retrospective study evaluated 21 patients who underwent airway stenting for advanced cancer. We examined predictors of the post-stenting mortality, including age, serum albumin, tracheal diameter, smoking, opioid use, respiratory failure, and performance status (PS). We also compared survival according to the PS. The mean survival period after stenting was 85.2 days. On univariate analysis, age, albumin, PS before airway stenting, respiratory failure, admission route, and PS grade were the candidates as possible predictors of prognosis after the procedure. On multivariate analysis, PS before airway stenting was identified as possible predictor of prognosis after stenting (HR 1.6180, 95% CI 0.969 to 2.7015, p = 0.066). The mean survival period after stenting was significantly longer in the good PS group, compared to the poor PS group (147.8 days vs. 38.2 days,p = 0.0346). Airway stenting for advanced cancer may be more effective for patients in good general condition than in those with poor performance status.

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

    Science.gov (United States)

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

    2013-12-30

    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. [Present aspects and problems regarding occupational bladder cancer due to exposure to aromatic amines].

    Science.gov (United States)

    Yamamura, J

    1989-12-01

    About a century has passed since the first case of bladder cancer due to occupational exposure to carcinogenic aromatic amines was reported. In the major developed countries of the world, it is forbidden to manufacture and/or to use such aromatic amines. In Japan in the 1950's, many workers were exposed to carcinogenic aromatic amines, but in 1972, the Labor Safety and Health Act came into force and manufacturing and/or using of four kinds of aromatic amines were forbidden. Recently it has been reported that the risk of bladder cancer in workers exposed to aromatic amines before the ban of these chemicals is approximately from several times to a hundred times compared with the general population, and some reports say that dose-response relationship was observed. The important issues now are the carcinogenicity of other kinds of aromatic amines besides benzidine and 2-naphthylamine, carcinogenicity of metabolites of several substances like synthetic dyes, and carcinogenic aromatic amines as impurities in substances imported from developing countries. The type of exposure to these carcinogens changes low level and long period exposures. In addition to the chemical or dye industries, an increased risk of bladder cancer was observed among workers handling leather and rubber and those engaged in printing, textile industries, hairdressing, truck driving and so on. In the future, it will be necessary to cooperate with the departments of epidemiology, toxicology and clinical medicine for the purpose of estimating the risk of these occupations and the health care administration of the exposed workers.

  19. Human infections due to Salmonella Blockley, a rare serotype in South Africa: a case report

    Directory of Open Access Journals (Sweden)

    Gonose Thandubuhle

    2012-10-01

    Full Text Available Abstract Background Infections due to nontyphoidal Salmonella have increased worldwide over the last couple of decades. Salmonella enterica serotype Blockley (Salmonella Blockley infections is associated with chickens and is a rarely isolated serotype in human infections in most countries. Case presentation We report a case of human infections due to Salmonella Blockley in KwaZulu-Natal, South Africa in 2011. Three African males (aged 4, 14 and 16 presented to a clinic with diarrhoea, stomach cramps and headache. They started experiencing signs of illness a day after they consumed a common meal, consisting of meat, rice and potatoes. Stool specimens from the patients cultured Salmonella Blockley. The strains showed an indistinguishable pulsed-field gel electrophoresis pattern. Conclusion This is the first recorded case of human infections due to Salmonella Blockley in South Africa.

  20. [Extended salvage pelvic and retroperitoneal lymph node dissection due to prostate cancer relapse].

    Science.gov (United States)

    Osmonov, D K; Aksenov, A V; Jünemann, K-P

    2013-01-01

    Treatment of a biochemical prostate cancer relapse represents a difficult clinical dilemma, which has remained without a definitive solution so far. Based on clinical studies, we combine radical prostatectomy with extended pelvic lymph node dissection in intermediate and high risk patients as a routine procedure at our clinic. In this paper, we report on a case of extended salvage lymphadenectomy performed due to biochemical prostate cancer recurrence. The 56-year-old patient came to our clinic in April 2012 with a finding of lymph node metastasis according to PET-CT imaging. Laparoscopic radical retropubic prostatectomy with lymphadenectomy had been performed in 2008 [pT3a, N0 (0/4), M0, R0, GS 5+4=9, iPSA 26.67 ng/mL], and followed by radiotherapy as of September 2009. The extended salvage lymphadenectomy was performed in April 2012 due to a PSA-level rise up to 24 ng/mL and the aforementioned PET-CT findings. A total of 22 lymph nodes were removed, among them 3 lymph nodes with metastases. In the fossa obturatoria on the right we identified a walnut-size lymph node relapse with tumour necrosis, which fully corresponded to the PET-CT scan. The PSA level subsequently dropped to 0.4 ng/mL postoperatively, and further to the current value of 0.02 ng/mL (August 2012).

  1. Endogenous retroviral promoter exaptation in human cancer

    Directory of Open Access Journals (Sweden)

    Artem Babaian

    2016-12-01

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

  2. Modern criteria to establish human cancer etiology.

    Science.gov (United States)

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

    2004-08-01

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

  3. Modelling mutational landscapes of human cancers in vitro

    Science.gov (United States)

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

    2014-03-01

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

  4. Utility of multidetector row computed tomography and virtual bronchoscopy in evaluation of hemoptysis due to lung cancer

    Directory of Open Access Journals (Sweden)

    Sherif A.A. Mohamed

    2016-01-01

    Conclusion: MDCT angiography is a useful and non invasive method that allows a rapid and detailed identification of abnormal vasculature responsible for hemoptysis in patients with lung cancer. MDCT-generated virtual bronchoscopy is an accurate, and non invasive method for evaluating obstructions, endoluminal masses, and external compressions in patients with hemoptysis due to lung cancer.

  5. Study of epidemiological risk of lung cancer in Mexico due indoor radon exposure

    Science.gov (United States)

    Ángeles, A.; Espinosa, G.

    2014-07-01

    In this work the lifetime relative risks (LRR) of lung cancer due to exposure to indoor 222Rn on the Mexican population is calculated. Cigarette smoking is the number one risk factor for lung cancer (LC), because that, to calculate the number of cases of LC due to exposure to 222Rn is necessary considers the number of cases of LC for smoking cigarette. The lung cancer mortality rates published by the "Secretaría de Salud" (SSA), the mexican population data published by the "Consejo Nacional de Población" (CONAPO), smoking data in the mexican population, published by the "Comisión Nacional Contra las Adicciones" (CONADIC), the "Organización Panamericana de la Salud" (OPS) and indoor 222Rn concentrations in Mexico published in several recent studies are used. To calculate the lifetime relative risks (LRR) for different segments of the Mexican population, firstly the Excess Relative Risk (ERR) is calculated using the method developed by the BEIR VI committee and subsequently modified by the USEPA and published in the report "EPA Assessment of Risks from Radon in Homes". The excess relative risks were then used to calculate the corresponding lifetime relative risks, again using the method developed by the BEIR VI committee. The lifetime relative risks for Mexican male and female eversmokers and Mexican male and female never-smokers were calculated for radon concentrations spanning the range found in recent studies of indoor radon concentrations in Mexico. The lifetime relative risks of lung cancer induced by lifetime exposure to the mexican average indoor radon concentration were estimated to be 1.44 and 1.40 for never-smokers mexican females and males respectively, and 1.19 and 1.17 for ever-smokers Mexican females and males respectively. The Mexican population LRR values obtained in relation to the USA and Canada LRR published values in ever-smokers for both gender are similar with differences less than 4%, in case of never-smokers in relation with Canada

  6. Cardiac tamponade due to bleeding as a potential lethal complication after surgery for esophageal cancer.

    Science.gov (United States)

    Ito, Shuhei; Morita, Masaru; Nanbara, Sho; Nakaji, Yu; Ando, Koji; Hiyoshi, Yukiharu; Okamoto, Tatsuro; Saeki, Hiroshi; Oki, Eiji; Kawanaka, Hirofumi; Tanoue, Yoshihisa; Maehara, Yoshihiko

    2015-01-01

    Cardiac tamponade, due to bleeding in the pericardial space after esophagectomy for esophageal cancer, is an extremely rare complication and may be associated with sudden hemodynamic instability that can lead to death unless there is prompt diagnosis and appropriate treatment. A 76-year-old man underwent sub-total esophagectomy via a cervico-right thoracoabdominal approach and reconstruction with a gastric tube through the retrosternal route. On postoperative day 4, the patient developed hypotension due to cardiac tamponade caused by bleeding into the pericardial space and he had a decreased level of consciousness. Pericardial resection and open drainage via a minimal left anterior thoracotomy was performed that resulted in hemodynamic improvement followed by an uneventful recovery. Cardiac tamponade due to postoperative bleeding, which is a rare but life-threatening complication, should be considered as a cause of hemodynamic instability in the early postoperative period after esophagectomy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Apoptosis of human pancreatic cancer cells induced by Triptolide

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Science.gov (United States)

    2015-05-01

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

  9. Acute respiratory distress syndrome due to Strongyloides stercoralis infection in a patient with cervical cancer.

    Science.gov (United States)

    Kinjo, Takeshi; Nabeya, Daijiro; Nakamura, Hideta; Haranaga, Shusaku; Hirata, Tetsuo; Nakamoto, Tomoko; Atsumi, Eriko; Fuchigami, Tatsuya; Aoki, Yoichi; Fujita, Jiro

    2015-01-01

    A 62-year-old woman complained of diarrhea and vomiting after receiving chemotherapy for cervical cancer in association with high doses of corticosteroids. Two months later, the patient developed acute respiratory distress syndrome, and numerous Strongyloides stercoralis parasites were found in the intrabronchial discharge. Ivermectin was administered daily until nematodes were no longer detected in the sputum, and the patient's condition was successfully rescued. Antibodies for human T-cell lymphotropic virus-1 (HTLV-1) were positive. HTLV-1 infection and the administration of corticosteroids are known risk factors for strongyloides hyperinfection syndrome. Therefore, physicians should consider this disease in the differential diagnosis of patients from endemic areas who present with gastrointestinal symptoms under these risk factors.

  10. ANALYSIS OF COMPLICATIONS DUE TO INTRATISSUE RADIOTHERAPY USING CONSTANT SOURCES IN PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Petrovsky

    2014-07-01

    Full Text Available Brachytherapy is a standard treatment for localized advanced prostate cancer (PC. Complications due to interstitial radiotherapy using permanent sources were analyzed in 149 patients. The incidence of early grade 3 radiation urethritis was 7.4 % and that of rectitis was 3.4%. Late radiation urethritis and rectitis were recorded in 3.4 and 0.7 %, respectively. Sexual function 12 months later was preserved in 86.6 % of the patients. Studies established no statistically significant factors that influenced the frequency of complications. The patients with a prostate volume of > 50 cm3, a preoperative international prostate symptom score of > 15, a urine flow rate of < 15 ml/min, and urethral andrectal radiation doses of > 210 and > 180 Gy, respectively, tended to have more common radiation reactions. Thus, brachytherapy is a reasonably safe treatment for PC.

  11. Induction of apoptotic cell death specifically in rat and human cancer cells by pancratistatin.

    Science.gov (United States)

    Pandey, Siyaram; Kekre, Natasha; Naderi, Jafar; McNulty, James

    2005-01-01

    The major challenge in the battle against cancer is the specific targeting of cancer cells. Most chemotherapeutics and radiotherapies induce cancer cell death by inducing DNA damage. These treatments also cause severe side effects by affecting normal cells causing toxicity and mutations that may predispose them to become cancerous. Some non-genotoxic drugs such as tamoxifen are useful but are of limited applicability. Natural compounds such as paclitaxel have been useful in cancer treatment, but due to its effect as a general microtubule stabilizer and genotoxic agent, it also induces death of normal cells. Pancratistatin is a natural compound isolated from Pancratium littorale that has been shown to have anti-viral and anti-neoplastic activity. The objective in the present study was to elucidate the mechanism of the anti-neoplastic action of pancratistatin and evaluate the specificity of this compound for cancer cells. We used cancer cell lines and normal human endothelial and fibroblast cells to investigate the effect of pancratistatin treatment. Further, we compared the toxic effects of paclitaxel and VP-16 to that of pancratistatin on non-cancerous cells. Pancratistatin induced apoptosis in all the cancer cell lines used in this study at sub-micromolar concentrations. Interestingly, normal human fibroblasts and endothelial cells remained unaffected by pancratistatin treatment under identical conditions whereas paclitaxel and VP-16 were both toxic to these two normal cell lines. The capability of pancratistatin to selectively induce apoptosis in cancer cells is an exciting finding and makes it a suitable anti-cancer agent. Since pancratistatin shows little structural similarity to any DNA intercalating drug or to paclitaxel derivatives, it appears to be non-genotoxic. Additionally, due to the unprecedented differential cytotoxicity observed in cancerous cells, we believe pancratistatin may act upon a novel target, allowing selective induction of apoptosis in

  12. Bacterial protein toxins in human cancers.

    Science.gov (United States)

    Rosadi, Francesca; Fiorentini, Carla; Fabbri, Alessia

    2016-02-01

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

  13. Necrotizing fasciitis due to Streptococcus mitis caused by accidental human bite.

    Science.gov (United States)

    Bastug, Aliye; Kislak, Sumeyye; Mutlu, Nevzat Mehmet; Akcaboy, Zeynep Nur; Koksal, Asude; Sertcelik, Ahmet; Ünlü, Ramazan Erkin; Akinci, Esragul; Bodur, Hurrem

    2016-01-31

    Human bite wounds are more prone to infection than animal bites, which may cause necrotizing soft tissue infections such as myositis, fasciitis. Both aerobic and anaerobic microorganisms may be responsible, including Streptococcus spp., Staphylococcus aureus, Peptostreptococcus spp. Necrotizing fasciitis is characterized by serious tissue destruction and systemic toxicity with high morbidity and mortality. We report a patient with Streptococcus mitis associated necrotizing fasciitis on the upper extremity resulting from an accidental human bite, which caused nearly fatal infection. Prophylactic antibiotic treatment should be given after a human bite to prevent infection. If the infection signs and symptoms develop, rapid diagnosis, appropriate antibiotic and surgical therapy should be administered immediately. Streptococcus mitis is a viridans streptococcus, usually known as a relatively benign oral streptococcus. To our knowledge, this is the first necrotizing fasciitis case due to Streptococcus mitis after human bite.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-05-01

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

  15. The cancer burden in the United Kingdom in 2007 due to radiotherapy.

    Science.gov (United States)

    Maddams, Jacob; Parkin, D Maxwell; Darby, Sarah C

    2011-12-15

    The number of long-term cancer survivors in the general population of the UK is substantial and increasing rapidly. Many cancer survivors have been treated with radiotherapy but the likely number of radiotherapy-related second cancers has not previously been estimated. We used estimates of the numbers of cancer survivors in the UK at the beginning of 2007, in conjunction with estimates of the relative risk of a second primary cancer associated with previous radiotherapy from the United States Surveillance Epidemiology and End Results (SEER) programme, to estimate the numbers of incident cancers in the UK in 2007 that were associated with radiotherapy for a previous cancer and that may have been caused by it. We estimated that 1,346 cases of cancer, or about 0.45% of the 298,000 new cancers registered in the UK in 2007, were associated with radiotherapy for a previous cancer. The largest numbers of radiotherapy-related second cancers were lung cancer (23.7% of the total), oesophageal cancer (13.3%), and female breast cancer (10.6%); 54% of radiotherapy-related second cancers were in individuals aged 75 or over. The highest percentages of second cancers related to radiotherapy were among survivors of Hodgkin's disease and cancers of the oral cavity and pharynx and cervix uteri; over 15% of second cancers among these survivors were associated with radiotherapy for the first cancer. These calculations, which involve a number of assumptions and approximations, provide a reasonable, if conservative, estimate of the fraction of incident cancers in the UK that are attributable to past radiation therapy.

  16. Characterizing metabolic changes in human colorectal cancer.

    Science.gov (United States)

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

    2015-06-01

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

  17. Trend of cancer risk of Chinese inhabitants to dioxins due to changes in dietary patterns: 1980-2009

    Science.gov (United States)

    Huang, Tao; Jiang, Wanyanhan; Ling, Zaili; Zhao, Yuan; Gao, Hong; Ma, Jianmin

    2016-02-01

    Food ingestion is a major route for human exposure and body burden to dioxins. We estimated the potential influence of changes in dietary patterns in Chinese population on human health risk to 2,3,7,8-TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) over the last three decades. We performed multiple modeling scenario investigations to discriminate the contribution of 2,3,7,8-TCDD emissions and changes in dietary patterns to the cancer risks (CR) to dioxins. Results showed that changes in dietary patterns, featured by decreasing consumption of total grain (including all unprocessed grains) and vegetables and increasing intake of animal-derived foodstuffs, caused increasing CR from 7.3 × 10-8 in 1980 to 1.1 × 10-7 in 2009. Varying dietary patterns contributed 17% to the CR of Chinese population in 2009 under the fixed emission in 1980. The CR to 2,3,7,8-TCDD in urban and eastern China residents was higher considerably than those who lived in rural area and western China, attributable to higher emissions, household income, and greater intake of animal-derived foodstuffs in urban and eastern China inhabitants. On the other hand, more rapid increasing trend of the CR was found in rural residents due to their more rapid increase in the consumption of fat-dominated foods as compared with urban residents.

  18. Cerebellar Hemorrhage due to a Direct Carotid–Cavernous Fistula after Surgery for Maxillary Cancer

    Science.gov (United States)

    Kamio, Yoshinobu; Hiramatsu, Hisaya; Kamiya, Mika; Yamashita, Shuhei; Namba, Hiroki

    2017-01-01

    Infratentorial cerebral hemorrhage due to a direct carotid–cavernous fistula (CCF) is very rare. To our knowledge, only four such cases have been reported. Cerebellar hemorrhage due to a direct CCF has not been reported. We describe a 63-year-old female who presented with reduced consciousness 3 days after undergoing a maxillectomy for maxillary cancer. Computed tomography showed a cerebellar hemorrhage. Magnetic resonance angiography showed a left-sided direct CCF draining into the left petrosal and cerebellar veins through the left superior petrosal sinus (SPS). Her previous surgery had sacrificed the pterygoid plexus and facial vein. Increased blood flow and reduced drainage could have led to increased venous pressure in infratentorial veins, including the petrosal and cerebellar veins. The cavernous sinus has several drainage routes, but the SPS is one of the most important routes for infratentorial venous drainage. Stenosis or absence of the posterior segment of the SPS can also result in increased pressure in the cerebellar and pontine veins. We emphasize that a direct CCF with cortical venous reflux should be precisely evaluated to determine the hemodynamic status and venous drainage from the cavernous sinus. PMID:28061497

  19. Roles of the Y chromosome genes in human cancers

    Directory of Open Access Journals (Sweden)

    Tatsuo Kido

    2015-06-01

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

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

    Science.gov (United States)

    Kim, Jungsun; Zaret, Kenneth S

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    白银; 王琰; 周丽君; 俞莉章

    2001-01-01

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

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

    Science.gov (United States)

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

    2009-05-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

  4. Thermal Injury in Human Subjects Due to 94-GHz Radio Frequency Radiation Exposures

    Science.gov (United States)

    2016-02-24

    AFRL-RH-FS-TR-2016-0001 Thermal Injury in Human Subjects Due to 94-GHz Radio Frequency Radiation Exposures James E. Parker General...them. This report was cleared for public release by the 88th ABW Public Affairs Office and is available to the general public, including foreign ...This report is published in the interest of scientific and technical information exchange , and its

  5. Effect of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality: A PRISMA-compliant cumulative meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhang, Sui-Liang; Chen, Ting-Song; Ma, Chen-Yun; Meng, Yong-Bin; Zhang, Yu-Fei; Chen, Yi-Wei; Zhou, Yu-Hao

    2016-08-01

    Observational studies have suggested that vitamin B supplementation is associated with cancer risk, but this association remains controversial. A pooled data-based meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCTs) investigating the effects of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality. PubMed, EmBase, and the Cochrane Library databases were searched to identify trials to fit our analysis through August 2015. Relative risk (RR) was used to measure the effect of vitamin B supplementation on the risk of cancer incidence, death due to cancer, and total mortality using a random-effect model. Cumulative meta-analysis, sensitivity analysis, subgroup analysis, heterogeneity tests, and tests for publication bias were also conducted. Eighteen RCTs reporting the data on 74,498 individuals were included in the meta-analysis. Sixteen of these trials included 4103 cases of cancer; in 6 trials, 731 cancer-related deaths occurred; and in 15 trials, 7046 deaths occurred. Vitamin B supplementation had little or no effect on the incidence of cancer (RR: 1.04; 95% confidence interval [CI]: 0.98-1.10; P = 0.216), death due to cancer (RR, 1.05; 95% CI: 0.90-1.22; P = 0.521), and total mortality (RR, 1.00; 95% CI: 0.94-1.06; P = 0.952). Upon performing a cumulative meta-analysis for cancer incidence, death due to cancer, and total mortality, the nonsignificance of the effect of vitamin B persisted. With respect to specific types of cancer, vitamin B supplementation significantly reduced the risk of skin melanoma (RR, 0.47; 95% CI: 0.23-0.94; P = 0.032). Vitamin B supplementation does not have an effect on cancer incidence, death due to cancer, or total mortality. It is associated with a lower risk of skin melanoma, but has no effect on other cancers.

  6. T Cell Coinhibition and Immunotherapy in Human Breast Cancer

    OpenAIRE

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

    2012-01-01

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

  7. Thermoacoustic contrast of prostate cancer due to heating by very high frequency irradiation

    Science.gov (United States)

    Patch, S. K.; Hull, D.; Thomas, M.; Griep, SK; Jacobsohn, K.; See, WA

    2015-01-01

    Applying the thermoacoustic (TA) effect to diagnostic imaging was first proposed in the 1980s. The object under test is irradiated by high-power pulses of electromagnetic energy, which heat tissue and cause thermal expansion. Outgoing TA pressure pulses are detected by ultrasound transducers and reconstructed to provide images of the object. The TA contrast mechanism is strongly dependent upon the frequency of the irradiating electromagnetic pulse. When very high frequency (VHF) electromagnetic irradiation is utilized, TA signal production is driven by ionic content. Prostatic fluids contain high levels of ionic metabolites, including citrate, zinc, calcium, and magnesium. Healthy prostate glands produce more ionic metabolites than diseased glands. VHF pulses are therefore expected to generate stronger TA signal in healthy prostate glands than in diseased glands. A benchtop system for performing ex vivo TA computed tomography with VHF energy is described and images are presented. The system utilizes irradiation pulses of 700 ns duration exceeding 20 kW power. Reconstructions frequently visualize anatomic landmarks such as the urethra and verumontanum. TA reconstructions from three freshly excised human prostate glands with little, moderate, and severe cancerous involvement are compared with histology. TA signal strength is negatively correlated with percent cancerous involvement in this small sample size. For the 45 regions of interest analyzed, a reconstruction value of 0.4 mV provides 100% sensitivity but only 29% specificity. This sample size is far too small to draw sweeping conclusions, but the results warrant a larger volume study including comparison of TA images to the gold standard, histology.

  8. Differential network analysis in human cancer research.

    Science.gov (United States)

    Gill, Ryan; Datta, Somnath; Datta, Susmita

    2014-01-01

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

  9. Immune therapy for human papillomaviruses-related cancers.

    Science.gov (United States)

    Rosales, Ricardo; Rosales, Carlos

    2014-12-10

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

  10. Temporal changes in loss of life expectancy due to cancer in Australia: a flexible parametric approach.

    Science.gov (United States)

    Baade, Peter D; Youlden, Danny R; Andersson, Therese M; Youl, Philippa H; Walpole, Euan T; Kimlin, Michael G; Aitken, Joanne F; Biggar, Robert J

    2016-08-01

    To evaluate changes in cancer mortality burden over time by assessing temporal trends in life expectation for Australian residents diagnosed with cancer. The study cohort consisted of all people diagnosed with cancer in the period 1990-2000 and aged 15-89 years (n = 1,275,978), with mortality follow-up to 31 December 2010. Flexible parametric survival models incorporating background age-sex-year-specific population mortality rates were applied to generate the observed survival curves for all cancers combined and selected major cancer types. Predicted values of loss of life expectancy (LOLE) in years were generated and then averaged across calendar year and age group (15-49, 50-69 and 70-89 years) or spread of disease (localized, regional, distant, unknown). The greatest LOLE burden was for lung cancer (14.3 years per diagnosis) and lowest for melanoma (2.5 years). There was a significant decrease in LOLE over time (-0.13 LOLE per year) for all cancers combined. Decreases were also observed for female breast cancer (-0.21), prostate cancer (-0.17), colorectal cancer (-0.08), melanoma (-0.07) and stomach cancer (-0.02), with slight increases for lung cancer (+0.04). When restricted to the sub-cohort from New South Wales with spread of disease information, these decreases in LOLE were primarily among cancers categorized as localized or regional spread at diagnosis. In Australia, persons diagnosed with cancer have a steadily improving outlook that exceeds that expected by general improvement in population life expectancy. The overall improvement is observed in persons with localized or regional cancers but not in those with advanced cancers, findings which encourage earlier diagnosis.

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

    Science.gov (United States)

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

    2007-10-01

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

  12. Decreased rates of advanced breast cancer due to mammography screening in The Netherlands.

    NARCIS (Netherlands)

    Fracheboud, J.; Otto, S.J.; Dijck, J.A.A.M. van; Broeders, M.J.M.; Verbeek, A.L.M.; Koning, H.J. de

    2004-01-01

    The effect of the implementation of the Dutch breast cancer screening programme during 1990-1997 on the incidence rates of breast cancer, particularly advanced breast cancer, was analysed according to stage at diagnosis in seven regions, where no screening took place before 1990. The Netherlands Can

  13. Decreased rates of advanced breast cancer due to mammography screening in The Netherlands

    NARCIS (Netherlands)

    J. Fracheboud (Jacques); S.J. Otto (Suzie); J.A.A.M. van Dijck; M.J.M. Broeders (Mireille); A.L.M. Verbeek (Andre); H.J. de Koning (Harry)

    2004-01-01

    textabstractThe effect of the implementation of the Dutch breast cancer screening programme during 1990-1997 on the incidence rates of breast cancer, particularly advanced breast cancer, was analysed according to stage at diagnosis in seven regions, where no screening took place before 1990. The Net

  14. Decreased rates of advanced breast cancer due to mammography screening in The Netherlands

    NARCIS (Netherlands)

    J. Fracheboud (Jacques); S.J. Otto (Suzie); J.A.A.M. van Dijck; M.J.M. Broeders (Mireille); A.L.M. Verbeek (Andre); H.J. de Koning (Harry)

    2004-01-01

    textabstractThe effect of the implementation of the Dutch breast cancer screening programme during 1990-1997 on the incidence rates of breast cancer, particularly advanced breast cancer, was analysed according to stage at diagnosis in seven regions, where no screening took place before 1990. The

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

    Institute of Scientific and Technical Information of China (English)

    张建军; 丁尔迅; 王强; 陈学云; 付志仁

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nyariaro Kelvin Momanyi

    2016-11-01

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

  17. A taxonomy of epithelial human cancer and their metastases

    Directory of Open Access Journals (Sweden)

    De Moor Bart

    2009-12-01

    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

  18. Immunoscintigraphy With 99mTc-Nimotuzumab for Planning Immunotherapy in Patients With Bone Metastases Due to Prostate Cancer.

    Science.gov (United States)

    Quián, Yamilé P; Crombet, Tania; Batista, Juan F; Prats, Anaís; Perera, Alejandro

    2016-03-01

    Detection of bone metastases indicates poor prognosis for patients with prostate cancer. The immunotherapy with monoclonal antibody has been an important advance in the treatment of the cancer in the last years. Nimotuzumab is a humanized IgG1 monoclonal antibody directed against epidermal growth factor receptor that has been evaluated in solid tumors. The authors show images of 2 patients with bone metastases secondary to prostate cancer, "pre-cold therapy" with nimotuzumab. Immunoscintigraphic images were acquired 4 and 24 hours after the intravenous administration of 1110 MBq (30 mCi) of Tc-labeled nimotuzumab. Bone metastases expressing the receptor are visualized.

  19. Tolvaptan Treatment in Syndrome of Inappropriate ADH Secretion due to Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Mucahit Gur

    2014-06-01

    Full Text Available Experience of ADH receptor antagonist (-vaptanes treatment in hyponatremia in malign patient is very limited. 68 years old male patient admitted to our department with a complain of nause, vomitting and epigastric pain. He has advanced stage of small cell lung cancer. He had treated with cisplatin and etoposide regimen 10 days ago as a first cure. We diagnosed inapropriate secretion of antidiuretic hormone syndrome (SIADH with low sodium level (118 meq/dl. Although the treatment with water restriction and 3% NaCl infusion, sodium level was not in normal. So we ordered 30 mg tolvaptan tablet. And then sodium levels were reached normal. After one month of discharge from hospital, he has hospitilized with same symptom and diagnosis. And again we ordered same treatment procedure and tolvaptane treatment. He had normal sodium (136 mEq/dl level during his follow up. This case demostrate that tolvaptane treatment is suitable aproaches in hyponatremia due to SIADH in oncologic patient.

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

    Science.gov (United States)

    Picconi, María Alejandra

    2013-01-01

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

  1. 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.

  2. Role of Human Polyomavirus Bkv in Prostate Cancer

    Science.gov (United States)

    2007-12-01

    been surgically removed due to prostate cancer diagnosis . A normal prostate is defined as prostate that has been removed either during autopsy or by...immunosuppressed transplant patients, in whom it is associated with haemorrhagic cystitis and polyomavirus nephropathy (5, 35, 58, 70). BKV transforms rodent cells...cystoprostatectomy specimens from bladder cancer patients with the diagnosis of muscle invasive high grade urothelial carcinoma, with no prostate cancer histology

  3. Role of ARPC2 in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2017-01-01

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

  4. Human Papillomavirus and the Development of Different Cancers.

    Science.gov (United States)

    Gao, Ge; Smith, David I

    2017-03-01

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

  5. Data Mining of Historical Human Data to Assess the Risk of Injury due to Dynamic Loads

    Science.gov (United States)

    Wells, Jesica; Somers, Jeffrey T.; Newby, N.; Gernhardt, Michael

    2014-01-01

    deflection was determined from motion capture video of the impact test. HIC- 15 and BRIC were calculated from head acceleration responses. Given the number of human subjects for each test condition a confidence interval of injury probability will be obtained. RESULTS: Results will be discussed in terms of injury-risk probability estimates based on the human data set evaluated. Also, gaps in the data set will be identified. These gaps could be one of two types. One is areas where additional THOR testing would increase the comparable human data set, thereby improving confidence in the injury probability rate. The other is where additional human testing would assist in obtaining information on other acceleration levels or directions. DISCUSSION: The historical human data showed validity of the THOR ATD for supplemental testing. The historical human data are limited in scope, however. Further data are needed to characterize the effects of sex, age, anthropometry, and deconditioning due to spaceflight on risk of injury

  6. Thyroid exposure of Belarusian and Ukrainian children due to the Chernobyl accident and resulting thyroid cancer risk. Final report of BfS project StSch 4240

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, P.; Meckbach, R.; Ulanovski, A.; Schotola, C.; Proehl, G. [GSF-Institute of Radiation Protection, Neuherberg (Germany); Kenigsberg, J.; Buglova, E.; Kruk, J. [Institute of Radiation Medicine and Endocrinology, Minsk (Belarus); Likhtarev, I.; Kovgan, L.; Vavilov, S.; Chepurniy, M. [Ukrainian Radiation Protection Inst., Kyiv (Ukraine); Tronko, M.; Bogdanova, T. [Institute of Endocrinolgoy and Metabolism of the Academy of Medical Sciences of Ukraine, Kyiv (Ukraine); Shinkarev, S.; Gavrilin, Y. [All-Russian Public Organization of Invalids ' Chernobylets' , Scientific Center ' FENIX' , Moscow (Russian Federation); Demidchik, Y. [Thyroid Cancer Center, Minsk (Belarus)

    2005-07-01

    Main objectives of the BfS Project StSch4240 Thyroid Exposure of Belarusian and Ukrainian Children due to the Chernobyl Accident and Resulting Thyroid Cancer Risk were: to establish improved estimates of average thyroid dose for both genders and for each birth-year cohort of the period 1968 - 1985 in Ukrainian and Belarusian settlements, in which more than 10 measurements of the {sup 131}I activity in the human thyroid have been performed in May/June 1986, to explore, whether this dosimetric database can be extended to neighboring settlements, to establish improved estimates of average thyroid dose for both genders and for each birth-year cohort of the period 1968 - 1985 in Ukrainian and Belarusian oblasts (regions) and larger cities, to document the thyroid cancer incidence for the period 1986 - 2001 in Ukraine and Belarus and describe morphological characteristics of the cancer cases, to assess the contribution of the baseline incidence to the total thyroid cancer incidence in the two countries and identify regional and temporal dependencies, to perform analyses of excess risks in settlements with more than 10 measurements of the {sup 131}I activity in the human thyroid. The project has been conducted in the period 6 December 1999 to 31 March 2004. (orig.)

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

    Science.gov (United States)

    Wang, Xiaosheng; Sun, Qingrong

    2017-01-03

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

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

    Science.gov (United States)

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

    2010-01-01

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

  9. Recurrent Breast Abscesses due to Corynebacterium kroppenstedtii, a Human Pathogen Uncommon in Caucasian Women

    Directory of Open Access Journals (Sweden)

    Anne Le Flèche-Matéos

    2012-01-01

    Full Text Available Background. Corynebacterium kroppenstedtii (Ck was first described in 1998 from human sputum. Contrary to what is observed in ethnic groups such as Maori, Ck is rarely isolated from breast abscesses and granulomatous mastitis in Caucasian women. Case Presentation. We herein report a case of recurrent breast abscesses in a 46-year-old Caucasian woman. Conclusion. In the case of recurrent breast abscesses, even in Caucasian women, the possible involvement of Ck should be investigated. The current lack of such investigations, probably due to the difficulty to detect Ck, may cause the underestimation of such an aetiology.

  10. Human infections due to Staphylococcus pseudintermedius, an emerging zoonosis of canine origin: report of 24 cases.

    Science.gov (United States)

    Somayaji, R; Priyantha, M A R; Rubin, J E; Church, D

    2016-08-01

    Staphylococcus pseudintermedius has been recently identified as a novel species within the genus Staphylococcus, and is commonly associated with infections in dogs. Currently, there are few reports of human infections due to this bacterium. To use a population-based approach to describe the characteristics of human S. pseudintermedius infections in a large Canadian healthcare region. All adult cases aged ≥18 years identified at a large regional laboratory from April 1, 2013 to April 1, 2015 who had at least one positive culture for S. pseudintermedius were retrospectively reviewed. A combination of phenotypic methods, mass spectrometry (i.e., MALDI-TOF), and cpn60 sequencing were used to identify S. pseudintermedius. Chart review was conducted, and cases were analysed descriptively. Twenty-seven isolates of S. pseudintermedius from 24 human cases were included for analysis. 58.3% were male with median age of 61 years (IQR 55-70.5). Most patients [22 (92.1%)] had confirmed contact with dogs at time of infection. S. pseudintermedius was isolated in 18 cases (75.0%) of skin and soft tissue infections (SSTI), and 2 invasive cases (8.3%) including a prosthetic joint and bloodstream infection. The other 4 patients were considered to be colonized (skin - 3; lung - 1). Methicillin resistance was identified in 3 cases with 6 total isolates (22.2%); multi-drug resistance was also demonstrated commonly. S. pseudintermedius is most commonly associated with SSTIs in humans. Transmission probably occurs from a pet dog. Species-level identification of S. pseudintermedius is important due to the high prevalence of antibiotic resistance, particularly to methicillin. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Clinical cancer chemoprevention: From the hepatitis B virus (HBV) vaccine to the human papillomavirus (HPV) vaccine.

    Science.gov (United States)

    Tsai, Horng-Jyh

    2015-04-01

    Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV), a risk factor of hepatocellular cancer, and human papillomavirus (HPV), a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV) vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population), and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer.

  12. Clinical cancer chemoprevention: From the hepatitis B virus (HBV vaccine to the human papillomavirus (HPV vaccine

    Directory of Open Access Journals (Sweden)

    Horng-Jyh Tsai

    2015-04-01

    Full Text Available Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV, a risk factor of hepatocellular cancer, and human papillomavirus (HPV, a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population, and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer.

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

    Science.gov (United States)

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

    1995-05-01

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

  14. Hepatic expression of detoxification enzymes is decreased in human obstructive cholestasis due to gallstone biliary obstruction.

    Directory of Open Access Journals (Sweden)

    Jin Chai

    Full Text Available Levels of bile acid metabolic enzymes and membrane transporters have been reported to change in cholestasis. These alterations (e.g. CYP7A1 repression and MRP4 induction are thought to be adaptive responses that attenuate cholestatic liver injury. However, the molecular mechanisms of these adaptive responses in human obstructive cholestasis due to gallstone biliary obstruction remain unclear.We collected liver samples from cholestatic patients with biliary obstruction due to gallstones and from control patients without liver disease (n = 22 per group. The expression levels of bile acid synthetic and detoxification enzymes, membrane transporters, and the related nuclear receptors and transcriptional factors were measured.The levels of bile acid synthetic enzymes, CYP7B1 and CYP8B1, and the detoxification enzyme CYP2B6 were increased in cholestatic livers by 2.4-fold, 2.8-fold, and 1.9-fold, respectively (p<0.05. Conversely, the expression levels of liver detoxification enzymes, UGT2B4/7, SULT2A1, GSTA1-4, and GSTM1-4, were reduced by approximately 50% (p<0.05 in human obstructive cholestasis. The levels of membrane transporters, OSTβ and OCT1, were increased 10.4-fold and 1.8-fold, respectively, (p<0.05, whereas those of OSTα, ABCG2 and ABCG8 were all decreased by approximately 40%, (p<0.05 in human cholestatic livers. Hepatic nuclear receptors, VDR, HNF4α, RXRα and RARα, were induced (approximately 2.0-fold, (p<0.05 whereas FXR levels were markedly reduced to 44% of control, (p<0.05 in human obstructive cholestasis. There was a significantly positive correlation between the reduction in FXR mRNA and UGT2B4/7, SULT2A1, GSTA1, ABCG2/8 mRNA levels in livers of obstructive cholestatic patients (p<0.05.The levels of hepatic detoxification enzymes were significantly decreased in human obstructive cholestasis, and these decreases were positively associated with a marked reduction of FXR levels. These findings are consistent with impaired

  15. Interleukin-6 expression under gravitational stress due to vibration and hypergravity in follicular thyroid cancer cells.

    Directory of Open Access Journals (Sweden)

    Xiao Ma

    Full Text Available It is known that exposing cell lines in vitro to parabolic flights changes their gene expression and protein production patterns. Parabolic flights and spaceflight in general are accompanied by transient hypergravity and vibration, which may impact the cells and therefore, have to be considered too. To estimate the possible impact of transient hypergravity and vibration, we investigated the effects of these forces separately using dedicated ground-based facilities. We placed follicular thyroid ML-1 and CGTH W-1 cancer cells in a specific centrifuge (MuSIC Multi Sample Incubator Centrifuge; SAHC Short Arm Human Centrifuge simulating the hypergravity phases that occur during one (P1 and 31 parabolas (P31 of parabolic flights, respectively. On the Vibraplex device, the same cell lines were treated with vibration waves corresponding to those that occur during a whole parabolic flight lasting for two hours. After the various treatments, cells were harvested and analyzed by quantitative real-time PCR, focusing on the genes involved in forming (ACTB, MYO9, TUBB, VIM, TLN1, and ITGB1 and modulating (EZR, RDX, and MSN the cytoskeleton, as well as those encoding growth factors (EGF, CTGF, IL6, and IL8 or protein kinases (PRKAA1 and PRKCA. The analysis revealed alterations in several genes in both cell lines; however, fewer genes were affected in ML-1 than CGTH W-1 cells. Interestingly, IL6 was the only gene whose expression was changed in both cell lines by each treatment, while PKCA transcription remained unaffected in all experiments. We conclude that a PKCa-independent mechanism of IL6 gene activation is very sensitive to physical forces in thyroid cells cultured in vitro as monolayers.

  16. Hypofractionated proton therapy for prostate cancer: Dose delivery uncertainty due to interfractional motion

    Science.gov (United States)

    Wang, Yi; Efstathiou, Jason A.; Lu, Hsiao-Ming; Sharp, Gregory C.; Trofimov, Alexei

    2013-01-01

    Purpose: The α-to-β (α/β) ratio for prostate tumor is likely lower than that for the surrounding normal organs, such as rectum and bladder (∼3 Gy). As a result, hypofractionation is expected to improve the therapeutic ratio in prostate radiation therapy. However, with the use of fewer, larger fractions, the accuracy of treatment dose delivery becomes more influenced by the physical uncertainties resulting from motion and radiobiological uncertainties in the α/β ratio of the prostate tumor. The purpose of this study is to evaluate the impact of interfractional motion on treatment dose delivery within the likely range of the tumor α/β ratio. Methods: Serial CT images acquired at simulation and daily treatment for three prostate patients were studied retrospectively. A conventional 3D-conformal proton plan was created for each patient, delivering 25 fractions of 2 Gy to ITV1 (internal target volume, expanded from the prostate and clinically involved seminal vesicles) followed by 14 fractions to ITV2 (expanded from the prostate). The plans were renormalized for a series of hypofractionated protocols of between five and 28 fractions. The fractional doses were computed on daily CT and were mapped onto simulation CT using deformable registration. In each course, the doses from the fractions with the lowest D97% of the ITV2 were summed to approximate the lower limit (worst case) of target coverage. The uncertainty in dose and coverage was estimated as the deviation of the worst case from the nominal plan. Results: For treatments in 28 to five fractions, the uncertainty arising from interfractional motion ranged from ∼1% to 4% for V100% and ∼2% to 6% for D100% of the ITV2. The uncertainties in V95% and D95% were both minimal ( 2.5 Gy, assuming the worst case for interfractional motion. Conclusions: In hypofractionated proton therapy for prostate cancer, the dosimetric uncertainties due to interfractional motion were minimal for the ITV2 coverage at 95% isodose

  17. Increase of regional total cancer incidence in north Sweden due to the Chernobyl accident?

    Science.gov (United States)

    Tondel, Martin; Hjalmarsson, Peter; Hardell, Lennart; Carlsson, Göran; Axelson, Olav

    2004-12-01

    Is there any epidemiologically visible influence on the cancer incidence after the Chernobyl fallout in Sweden? A cohort study was focused on the fallout of caesium-137 in relation to cancer incidence 1988-1996. In northern Sweden, affected by the Chernobyl accident in 1986, 450 parishes were categorised by caesium-137 deposition: accident.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Huang Wen-bin

    2009-09-01

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

  20. Elevated bladder cancer risk due to colorants--a statewide case-control study in North Rhine-Westphalia, Germany.

    Science.gov (United States)

    Golka, Klaus; Heitmann, Peter; Gieseler, Frank; Hodzic, Jasmin; Masche, Nicolas; Bolt, Hermann M; Geller, Frank

    2008-01-01

    Occupational exposure to aromatic amines is a known bladder cancer risk factor, whereas the impact of exposure to azo dyes, which may release aromatic amines in humans, is at present controversial. Therefore, the impact of occupational exposures to colorants was investigated in 156 bladder cancer cases and 336 controls in the state of North Rhine-Westphalia. All bladder cancer cases and controls (diagnosed with prostate cancer) requested after-care treatment. The subjects were investigated using a questionnaire for all occupations ever performed for more than 6 mo and for exposures to several possible occupational and nonoccupational bladder carcinogens. The relative bladder cancer risk was adjusted for age and smoking. The adjusted odds ratio (OR) for bladder cancer was elevated in 7 painters (OR 1.98, 95% CI 0.64-6.11), 4 hairdressers (OR 4.9, 95% CI 0.85-28.39), and 16 cases who reported a wood processing occupation (OR 1.19, 95% CI 0.58-2.41). Ten of these 16 cases reported chronic exposure to colorants (OR 1.84, 95% CI 0.68-4.95). The results of this epidemiological study confirm the hypothesis that individuals exposed to colorants show an elevated bladder cancer risk.

  1. Human health risk assessment due to global warming--a case study of the Gulf countries.

    Science.gov (United States)

    Husain, Tahir; Chaudhary, Junaid Rafi

    2008-12-01

    Accelerated global warming is predicted by the Intergovernmental Panel on Climatic Change (IPCC) due to increasing anthropogenic greenhouse gas emissions. The climate changes are anticipated to have a long-term impact on human health, marine and terrestrial ecosystems, water resources and vegetation. Due to rising sea levels, low lying coastal regions will be flooded, farmlands will be threatened and scarcity of fresh water resources will be aggravated. This will in turn cause increased human suffering in different parts of the world. Spread of disease vectors will contribute towards high mortality, along with the heat related deaths. Arid and hot climatic regions will face devastating effects risking survival of the fragile plant species, wild animals, and other desert ecosystems. The paper presents future changes in temperature, precipitation and humidity and their direct and indirect potential impacts on human health in the coastal regions of the Gulf countries including Yemen, Oman, United Arab Emirates, Qatar, and Bahrain. The analysis is based on the long-term changes in the values of temperature, precipitation and humidity as predicted by the global climatic simulation models under different scenarios of GHG emission levels. Monthly data on temperature, precipitation, and humidity were retrieved from IPCC databases for longitude 41.25 degrees E to 61.875 degrees E and latitude 9.278 degrees N to 27.833 degrees N. Using an average of 1970 to 2000 values as baseline, the changes in the humidity, temperature and precipitation were predicted for the period 2020 to 2050 and 2070 to 2099. Based on epidemiological studies on various diseases associated with the change in temperature, humidity and precipitation in arid and hot regions, empirical models were developed to assess human health risk in the Gulf region to predict elevated levels of diseases and mortality rates under different emission scenarios as developed by the IPCC.The preliminary assessment indicates

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

    Science.gov (United States)

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

    2003-10-01

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

  3. Defining the cellular precursors to human breast cancer

    Science.gov (United States)

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

    2012-01-01

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

  4. Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2.

    Science.gov (United States)

    Gabai-Kapara, Efrat; Lahad, Amnon; Kaufman, Bella; Friedman, Eitan; Segev, Shlomo; Renbaum, Paul; Beeri, Rachel; Gal, Moran; Grinshpun-Cohen, Julia; Djemal, Karen; Mandell, Jessica B; Lee, Ming K; Beller, Uziel; Catane, Raphael; King, Mary-Claire; Levy-Lahad, Ephrat

    2014-09-30

    In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.

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

    DEFF Research Database (Denmark)

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

    1987-01-01

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

  6. 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.

  7. Poorer survival of male breast cancer compared with female breast cancer patients may be due to biological differences.

    Science.gov (United States)

    Chen, Xingyu; Liu, Xiaodong; Zhang, Li; Li, Shufen; Shi, Yehui; Tong, Zhongsheng

    2013-10-01

    The objective of the study was to compare disease-free survival and overall survival in a group of matched males and females with breast cancer, and to analyze possible treatment- and gender-related differences. We retrospectively analyzed the data of 150 operable male breast cancer patients treated in our hospital from December 1980 to June 2012. Each male breast cancer patient recorded in the database was matched with two female breast cancer patients of equal stage. Prognosis in terms of disease-free survival and overall survival was evaluated. The mean age at diagnosis was 58.6 ± 9.7 years for males and 57.2 ± 10.3 years for females. The median follow-up was 69 months for males and 81 months for females. Significant differences were identified for tumor location, hormone receptor status, molecular subtypes and hormone therapy between the two groups. Monofactorial analysis demonstrated that tumor size, lymph node state, American Joint Committee on Cancer stage, molecular subtypes and adjuvant chemotherapy treatment were prognostic factors in male breast cancer patients. The 5- and 10-year disease-free survival rates were 65.6 and 40.1% for males, and 74.9 and 51.5% for females, respectively. The 5- and 10-year overall survival rates were 72.9 and 53.9% for males, and 83.2 and 68.5% for females, respectively. There was significantly difference in disease-free survival and overall survival between the two matched groups (P = 0.002). Male breast cancer patients had inferior outcome despite of equal stage in comparison with matched female breast cancer patients, which demonstrates that biological differences may contribute to the worse prognosis.

  8. Investigation of dental pulp stem cells isolated from discarded human teeth extracted due to aggressive periodontitis.

    Science.gov (United States)

    Sun, Hai-Hua; Chen, Bo; Zhu, Qing-Lin; Kong, Hui; Li, Qi-Hong; Gao, Li-Na; Xiao, Min; Chen, Fa-Ming; Yu, Qing

    2014-11-01

    Recently, human dental pulp stem cells (DPSCs) isolated from inflamed dental pulp tissue have been demonstrated to retain some of their pluripotency and regenerative potential. However, the effects of periodontal inflammation due to periodontitis and its progression on the properties of DPSCs within periodontally compromised teeth remain unknown. In this study, DPSCs were isolated from discarded human teeth that were extracted due to aggressive periodontitis (AgP) and divided into three experimental groups (Groups A, B and C) based on the degree of inflammation-induced bone resorption approaching the apex of the tooth root before tooth extraction. DPSCs derived from impacted or non-functional third molars of matched patients were used as a control. Mesenchymal stem cell (MSC)-like characteristics, including colony-forming ability, proliferation, cell cycle, cell surface antigens, multi-lineage differentiation capability and in vivo tissue regeneration potential, were all evaluated in a patient-matched comparison. It was found that STRO-1- and CD146-positive DPSCs can be isolated from human teeth, even in very severe cases of AgP. Periodontal inflammation and its progression had an obvious impact on the characteristics of DPSCs isolated from periodontally affected teeth. Although all the isolated DPSCs in Groups A, B and C showed decreased colony-forming ability and proliferation rate (P biomaterials were transplanted directly into an ectopic transplantation model. However, when cell-seeded scaffolds were placed in the root fragments of human teeth, all the cells formed significant dentin- and pulp-like tissues. The ability of DPSCs to generate dental tissues decreased when the cells were isolated from periodontally compromised teeth (P < 0.05). Again, increased periodontal destruction was not necessarily followed by a decrease in the amount of dentin- and pulp-like tissue formed. These findings provide preliminary evidence that periodontally compromised teeth might

  9. Human Papillomavirus (HPV) and Oropharyngeal Cancer

    Science.gov (United States)

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

  10. Study of apoptosis in human liver cancers

    Institute of Scientific and Technical Information of China (English)

    Chang-Min Shan; Juan Li

    2002-01-01

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

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

    NARCIS (Netherlands)

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

    1990-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Mehmet Yaman; Gokce Kaya; Hayrettin Yekeler

    2007-01-01

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

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

    Science.gov (United States)

    Berman, Tara A; Schiller, John T

    2017-06-15

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

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

    Science.gov (United States)

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

    2011-06-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Multimodel estimates of premature human mortality due to intercontinental transport of air pollution

    Science.gov (United States)

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

    2015-12-01

    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

  17. Inherited human sex reversal due to impaired nucleocytoplasmic trafficking of SRY defines a male transcriptional threshold.

    Science.gov (United States)

    Chen, Yen-Shan; Racca, Joseph D; Phillips, Nelson B; Weiss, Michael A

    2013-09-17

    Human testis determination is initiated by SRY (sex determining region on Y chromosome). Mutations in SRY cause gonadal dysgenesis with female somatic phenotype. Two subtle variants (V60L and I90M in the high-mobility group box) define inherited alleles shared by an XY sterile daughter and fertile father. Whereas specific DNA binding and bending are unaffected in a rat embryonic pre-Sertoli cell line, the variants exhibited selective defects in nucleocytoplasmic shuttling due to impaired nuclear import (V60L; mediated by Exportin-4) or export (I90M; mediated by chromosome region maintenance 1). Decreased shuttling limits nuclear accumulation of phosphorylated (activated) SRY, in turn reducing occupancy of DNA sites regulating Sertoli-cell differentiation [the testis-specific SRY-box 9 (Sox9) enhancer]. Despite distinct patterns of biochemical and cell-biological perturbations, V60L and I90M each attenuated Sox9 expression in transient transfection assays by twofold. Such attenuation was also observed in studies of V60A, a clinical variant associated with ovotestes and hence ambiguity between divergent cell fates. This shared twofold threshold is reminiscent of autosomal syndromes of transcription-factor haploinsufficiency, including XY sex reversal associated with mutations in SOX9. Our results demonstrate that nucleocytoplasmic shuttling of SRY is necessary for robust initiation of testicular development. Although also characteristic of ungulate orthologs, such shuttling is not conserved among rodents wherein impaired nuclear export of the high-mobility group box and import-dependent phosphorylation are compensated by a microsatellite-associated transcriptional activation domain. Human sex reversal due to subtle defects in the nucleocytoplasmic shuttling of SRY suggests that its transcriptional activity lies near the edge of developmental ambiguity.

  18. An experimental investigation of composite floor vibration due to human activities. A case study

    Directory of Open Access Journals (Sweden)

    Yasser G. Mohamed Fahmy

    2012-12-01

    Full Text Available Composite steel floor decks are used in a large variety of constructions with long spans, such as administration and commercial buildings, hotels and bridges. Due to decreased floor mass and longer span lengths, floor vibrations have become an area of concern. Floor decks with low frequencies may be in resonance with the vibrations due to human activities and the resulting acceleration may exceed human comfort levels. The design of slender floor structures, with steel or composite cross sections, is often limited by the serviceability criteria such as deflection limits and vibration behavior, rather than the strength criteria. Control of deflections under AISC specifications requirement is not enough to satisfy the serviceability requirements of the floor systems for vibration. In addition, vibration analysis procedures introduced by AISC design Guide No. 11 are based on regularly-shaped structures and simple boundary conditions. In this paper, a case study for full scale testing of a composite floor system proposed for a tower at Kuwait state that was tested prior to construction. The heel-drop and walking tests are performed on floor systems with and without raised floor respectively. Since heel-drop and walking test results would vary in light of person performance, both tests are carried out three or four times to reduce uncertainty. The fundamental frequencies and damping ratio of the floor system are measured. Comparison of the experimental results with results based on the AISC hand calculations shows that there is no significant difference; therefore the results based on AISC are generally acceptable.

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

    Science.gov (United States)

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

    2015-09-01

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

  20. Is the inverse association between selenium and bladder cancer due to confounding by smoking?

    Science.gov (United States)

    Beane Freeman, Laura E; Karagas, Margaret R; Baris, Dalsu; Schwenn, Molly; Johnson, Alison T; Colt, Joanne S; Jackson, Brian; Hosain, G M Monawar; Cantor, Kenneth P; Silverman, Debra T

    2015-04-01

    Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001-2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels. We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association.

  1. Computational dosimetry for grounded and ungrounded human models due to contact current

    Science.gov (United States)

    Chan, Kwok Hung; Hattori, Junya; Laakso, Ilkka; Hirata, Akimasa; Taki, Masao

    2013-08-01

    This study presents the computational dosimetry of contact currents for grounded and ungrounded human models. The uncertainty of the quasi-static (QS) approximation of the in situ electric field induced in a grounded/ungrounded human body due to the contact current is first estimated. Different scenarios of cylindrical and anatomical human body models are considered, and the results are compared with the full-wave analysis. In the QS analysis, the induced field in the grounded cylindrical model is calculated by the QS finite-difference time-domain (QS-FDTD) method, and compared with the analytical solution. Because no analytical solution is available for the grounded/ungrounded anatomical human body model, the results of the QS-FDTD method are then compared with those of the conventional FDTD method. The upper frequency limit for the QS approximation in the contact current dosimetry is found to be 3 MHz, with a relative local error of less than 10%. The error increases above this frequency, which can be attributed to the neglect of the displacement current. The QS or conventional FDTD method is used for the dosimetry of induced electric field and/or specific absorption rate (SAR) for a contact current injected into the index finger of a human body model in the frequency range from 10 Hz to 100 MHz. The in situ electric fields or SAR are compared with the basic restrictions in the international guidelines/standards. The maximum electric field or the 99th percentile value of the electric fields appear not only in the fat and muscle tissues of the finger, but also around the wrist, forearm, and the upper arm. Some discrepancies are observed between the basic restrictions for the electric field and SAR and the reference levels for the contact current, especially in the extremities. These discrepancies are shown by an equation that relates the current density, tissue conductivity, and induced electric field in the finger with a cross-sectional area of 1 cm2.

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

    Science.gov (United States)

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

    2010-08-01

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

  3. DETECTION OF OXIDATIVE STRESS, APOPTOSIS AND MOLECULAR LESIONS IN HUMAN OVARIAN CANCER CELLS

    Directory of Open Access Journals (Sweden)

    H. I. Falfushynska

    2016-05-01

    Full Text Available Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development. Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones. Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage in blood as the consequence of overexpression of oxyradicals (by 300%. Higher level of glutathione (by 366%, lower level of metallothioneins (by 65% as well as higher level of lipid peroxidation (by 174% and protein carbonyls (by 186% in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control level of DNA fragmentation (by 160%, choline esterase (up to twice, higher rate of both caspase dependent and caspase independent lysosomal mediated apoptosis. Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of human ovarian cancer.

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

    Directory of Open Access Journals (Sweden)

    Georges eHerbein

    2014-08-01

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

  5. Frequency of TERT promoter mutations in human cancers.

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-08-29

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

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

    Science.gov (United States)

    Guyot, D; Margueritte, G

    2005-09-01

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

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

    Science.gov (United States)

    Xu, Ren; Mao, Jian-Hua

    2011-04-01

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

  9. Anticancer Properties of Capsaicin Against Human Cancer.

    Science.gov (United States)

    Clark, Ruth; Lee, Seong-Ho

    2016-03-01

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

  10. Mortality due to lung, laryngeal and bladder cancer in towns lying in the vicinity of combustion installations

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Perez, Javier [Environmental and Cancer Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, C/Sinesio Delgado, 6, 28029 Madrid (Spain); CIBER en Epidemiologia y Salud Publica (CIBERESP) (Spain)], E-mail: jgarcia@isciii.es; Pollan, Marina; Boldo, Elena; Perez-Gomez, Beatriz; Aragones, Nuria; Lope, Virginia; Ramis, Rebeca; Vidal, Enrique; Lopez-Abente, Gonzalo [Environmental and Cancer Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, C/Sinesio Delgado, 6, 28029 Madrid (Spain); CIBER en Epidemiologia y Salud Publica (CIBERESP) (Spain)

    2009-04-01

    Background: Installations that burn fossil fuels to generate power may represent a health problem due to the toxic substances which they release into the environment. Objectives: To investigate whether there might be excess mortality due to tumors of lung, larynx and bladder in the population residing near Spanish combustion installations included in the European Pollutant Emission Register. Methods: Ecologic study designed to model sex-specific standardized mortality ratios for the above three tumors in Spanish towns, over the period 1994-2003. Population exposure to pollution was estimated on the basis of distance from town of residence to pollution source. Using mixed Poisson regression models, we analyzed: risk of dying from cancer in a 5-kilometer zone around installations that commenced operations before 1990; effect of type of fuel used; and risk gradient within a 50-kilometer radius of such installations. Results: Excess mortality (relative risk, 95% confidence interval) was detected in the vicinity of pre-1990 installations for lung cancer (1.066, 1.041-1.091 in the overall population; 1.084, 1.057-1.111 in men), and laryngeal cancer among men (1.067, 0.992-1.148). Lung cancer displayed excess mortality for all types of fuel used, whereas in laryngeal and bladder cancer, the excess was associated with coal-fired industries. There was a risk gradient effect in the proximity of a number of installations. Conclusions: Our results could support the hypothesis of an association between risk of lung, laryngeal and bladder cancer mortality and proximity to Spanish combustion installations.

  11. Role of ARPC2 in Human Gastric Cancer

    OpenAIRE

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

    2017-01-01

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

  12. 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.

  13. Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yung-Lin Chu

    2013-07-01

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

  14. Expression of Obesity Hormone Leptin in Human Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  15. False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening.

    NARCIS (Netherlands)

    Rossum, L.G.M. van; Rijn, A.F. van; Oijen, M.G.H. van; Fockens, P.; Laheij, R.J.F.; Verbeek, A.L.M.; Jansen, J.B.M.J.; Dekker, E.

    2009-01-01

    Delayed return of immunochemical fecal occult blood test (iFOBT) samples to a laboratory might cause false negatives because of hemoglobin degradation. Quantitative iFOBT's became increasingly more accepted in colorectal cancer screening. Therefore, we studied the effects of delay between sampling a

  16. Catheter-Related Bacteremia Due to Kocuria kristinae in a Patient with Ovarian Cancer

    Science.gov (United States)

    Basaglia, G.; Carretto, E.; Barbarini, D.; Moras, L.; Scalone, S.; Marone, P.; De Paoli, P.

    2002-01-01

    We report on the first case of a catheter-related recurrent bacteremia caused by Kocuria kristinae, a gram-positive microorganism belonging to the family Micrococcaceae, in a 51-year-old woman with ovarian cancer. This unusual pathogen may cause opportunistic infections in patients with severe underlying diseases. PMID:11773142

  17. Cancer mortality risk of nuclear power workers due to the exposure of ionising radiation in Germany

    Energy Technology Data Exchange (ETDEWEB)

    Fehringer, F.; Seitz, G. [Berufsgenossenschaft der Feinmechanik und Elektrotechnik, Koln (Germany); Hammer, G.P.; Blettner, M. [Johannes Gutenberg-Universitat Mainz, Institut fur Medizinische Biometrie, Epidemiologie und Informatik des Klinikums (Germany)

    2006-07-01

    A cohort study of German nuclear power workers was set up to investigate overall and cancer mortality risk related to a chronic exposure to ionising radiation of low-level dose. The German study was performed as a part of an international study carried out by the International Agency for Research on Cancer (IARC), Lyon. First results of the international study have been published recently [1]. German data are not yet included in this analysis. The German cohort consists of 4844 employees from 10 nuclear power plants. All persons who worked in these nuclear power plants in 1991 or started employment between 1991 und 1997 are included (except for employees of one plant, whose observation period started in 1992). These persons accumulated about 31,000 person years. Overall, 68 deaths were observed in the observation period between 1.1.1991-31.12.1997. Standardized mortality ratios (SMR) were computed for all causes of death, all cancers, cardiovascular diseases, external causes, and all other causes. Overall, a strong healthy worker effect was observed (SMR=0.52 [95% CI: 0.41;0.67]). No increase in total cancer mortality was seen (SMR=0.85 [95% CI: 0.53;1.30]). However, numbers are too small for stable risk estimates and further effort is under way to complete the cohort in terms of power plants and to extend the follow-up until 2005. (authors)

  18. Caspase 8 and maspin are downregulated in breast cancer cells due to CpG site promoter methylation

    Directory of Open Access Journals (Sweden)

    Koeffler Phillip

    2010-02-01

    Full Text Available Abstract Background Epigenetic changes associated with promoter DNA methylation results in silencing of several tumor suppressor genes that lead to increased risk for tumor formation and for progression of the cancer. Methods Methylation specific PCR (MSP and bisulfite sequencing were used for determination of proapoptotic gene Caspase 8 (CASP8 and the tumor suppressor gene maspin promoter methylation in four breast cancer and two non-tumorigenic breast cell lines. Involvement of histone H3 methylation in those cell lines were examined by CHIP assay. Results The CpG sites in the promoter region of CASP8 and maspin were methylated in all four breast cancer cell lines but not in two non-tumorigenic breast cell lines. Demethylation agent 5-aza-2'-deoxycytidine (5-aza-dc selectively inhibits DNA methyltransferases, DNMT3a and DNMT3b, and restored CASP8 and maspin gene expression in breast cancer cells. 5-aza-dc also reduced histone H3k9me2 occupancy on CASP8 promoter in SKBR3cells, but not in MCF-7 cells. Combination of histone deacetylase inhibitor Trichostatin A (TSA and 5-aza-dc significant decrease in nuclear expression of Di-methyl histone H3-Lys27 and slight increase in acetyl histone H3-Lys9 in MCF-7 cells. CASP8 mRNA and protein level in MCF-7 cells were increased by the 5-aza-dc in combination with TSA. Data from our study also demonstrated that treatment with 5-FU caused a significant increase in unmethylated CASP8 and in CASP8 mRNA in all 3 cancer lines. Conclusions CASP8 and maspin expression were reduced in breast cancer cells due to promoter methylation. Selective application of demethylating agents could offer novel therapeutic opportunities in breast cancer.

  19. Bionutrition and oral cancer in humans.

    Science.gov (United States)

    Enwonwu, C O; Meeks, V I

    1995-01-01

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

  20. An autopsy case of subacute cor pulmonale due to pulmonary tumor cell emboli in a patient with gastric cancer.

    Science.gov (United States)

    Iwakami, Shin-ichiro; Sato, Teruhiko; Takagi, Haruhi; Fujii, Mitsuhiro; Iwakami, Naoko; Yoshimi, Kaku; Koyama, Ryo; Ichikawa, Masako; Yoshioka, Masakata; Takahashi, Kazuhisa

    2009-01-01

    A 53-year-old woman was admitted to our hospital due to a severe respiratory condition and malnutrition. Radiological and electrophysiological findings suggested the existence of inexplicable cor pulmonale. Although we commenced to determine the causes of her severe condition, she suddenly died 3 days after admission. Postmortem autopsy revealed tumor cell microemboli in the small pulmonary arteries due to gastric cancer. Such a case of cor pulmonale as the first clinical manifestation is exceptionally rare. Occult malignancy should be considered as a differential diagnosis when one encounters a patient with subacutely aggravated respiratory condition and inexplicable cor pulmonale.

  1. When grief turns into love: understanding the experience of parents who have revived after losing a child due to cancer.

    Science.gov (United States)

    Vega, Paula; Rivera, Maria Soledad; González, Rina

    2014-01-01

    A child's death caused by cancer generates a deep impact on his/her parents, who can be affected by serious health problems due to an impairment of their lifestyle. Notwithstanding their suffering, some parents manage to overcome it and discover a new meaning for their lives. The goal of this phenomenological study is to understand the lived experiences that help parents to revive after the death of their child due to cancer. The participants were fathers and mothers who believe that they have elaborated their mourning. Their lived experiences were collected in interviews they had previously agreed to give. The question that steered the interview was: "What is the experience you went through that helped you to revive after your child died due to cancer?" Data were analyzed using Streubert's method. Analyzing the interviews of the participants, 3 interweaved essences were detected: transition from surviving to reviving themselves; ascribing a sense and meaning to the life, agony, and death of a child; and helping other parents through one's own experience.

  2. Arsenic Exposure and the Induction of Human Cancers

    Directory of Open Access Journals (Sweden)

    Victor D. Martinez

    2011-01-01

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

  3. Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

    Directory of Open Access Journals (Sweden)

    Assunta Catalano

    2011-05-01

    Full Text Available Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk.

  4. Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

    Energy Technology Data Exchange (ETDEWEB)

    Palozza, Paola, E-mail: p.palozza@rm.unicatt.it; Simone, Rossella E.; Catalano, Assunta [Institute of General Pathology, School of Medicine, Catholic University, L. Go F. Vito, Rome 1 00168 (Italy); Mele, Maria Cristina [Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, L. Go F. Vito, Rome 1 00168 (Italy)

    2011-05-11

    Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk.

  5. The Impact of Individual Anthropogenic Emissions Sectors on the Global Burden of Human Mortality due to Ambient Air Pollution.

    Science.gov (United States)

    Silva, Raquel A; Adelman, Zachariah; Fry, Meridith M; West, J Jason

    2016-11-01

    Exposure to ozone and fine particulate matter (PM2.5) can cause adverse health effects, including premature mortality due to cardiopulmonary diseases and lung cancer. Recent studies quantify global air pollution mortality but not the contribution of different emissions sectors, or they focus on a specific sector. We estimated the global mortality burden of anthropogenic ozone and PM2.5, and the impact of five emissions sectors, using a global chemical transport model at a finer horizontal resolution (0.67° × 0.5°) than previous studies. We performed simulations for 2005 using the Model for Ozone and Related Chemical Tracers, version 4 (MOZART-4), zeroing out all anthropogenic emissions and emissions from specific sectors (All Transportation, Land Transportation, Energy, Industry, and Residential and Commercial). We estimated premature mortality using a log-linear concentration-response function for ozone and an integrated exposure-response model for PM2.5. We estimated 2.23 (95% CI: 1.04, 3.33) million deaths/year related to anthropogenic PM2.5, with the highest mortality in East Asia (48%). The Residential and Commercial sector had the greatest impact globally-675 (95% CI: 428, 899) thousand deaths/year-and in most regions. Land Transportation dominated in North America (32% of total anthropogenic PM2.5 mortality), and it had nearly the same impact (24%) as Residential and Commercial (27%) in Europe. Anthropogenic ozone was associated with 493 (95% CI: 122, 989) thousand deaths/year, with the Land Transportation sector having the greatest impact globally (16%). The contributions of emissions sectors to ambient air pollution-related mortality differ among regions, suggesting region-specific air pollution control strategies. Global sector-specific actions targeting Land Transportation (ozone) and Residential and Commercial (PM2.5) sectors would particularly benefit human health. Citation: Silva RA, Adelman Z, Fry MM, West JJ. 2016. The impact of individual

  6. The Impact of Individual Anthropogenic Emissions Sectors on the Global Burden of Human Mortality due to Ambient Air Pollution

    Science.gov (United States)

    Silva, Raquel A.; Adelman, Zachariah; Fry, Meridith M.; West, J. Jason

    2016-01-01

    Background: Exposure to ozone and fine particulate matter (PM2.5) can cause adverse health effects, including premature mortality due to cardiopulmonary diseases and lung cancer. Recent studies quantify global air pollution mortality but not the contribution of different emissions sectors, or they focus on a specific sector. Objectives: We estimated the global mortality burden of anthropogenic ozone and PM2.5, and the impact of five emissions sectors, using a global chemical transport model at a finer horizontal resolution (0.67° × 0.5°) than previous studies. Methods: We performed simulations for 2005 using the Model for Ozone and Related Chemical Tracers, version 4 (MOZART-4), zeroing out all anthropogenic emissions and emissions from specific sectors (All Transportation, Land Transportation, Energy, Industry, and Residential and Commercial). We estimated premature mortality using a log-linear concentration–response function for ozone and an integrated exposure–response model for PM2.5. Results: We estimated 2.23 (95% CI: 1.04, 3.33) million deaths/year related to anthropogenic PM2.5, with the highest mortality in East Asia (48%). The Residential and Commercial sector had the greatest impact globally—675 (95% CI: 428, 899) thousand deaths/year—and in most regions. Land Transportation dominated in North America (32% of total anthropogenic PM2.5 mortality), and it had nearly the same impact (24%) as Residential and Commercial (27%) in Europe. Anthropogenic ozone was associated with 493 (95% CI: 122, 989) thousand deaths/year, with the Land Transportation sector having the greatest impact globally (16%). Conclusions: The contributions of emissions sectors to ambient air pollution–related mortality differ among regions, suggesting region-specific air pollution control strategies. Global sector-specific actions targeting Land Transportation (ozone) and Residential and Commercial (PM2.5) sectors would particularly benefit human health. Citation: Silva RA

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

    Science.gov (United States)

    Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2015-01-01

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

  8. Sudden hearing loss due to oxaliplatin use in a patient with colon cancer.

    Science.gov (United States)

    Güvenç, M Güven; Dizdar, Denizhan; Dizdar, Senem Kurt; Okutur, Sadi Kerem; Demir, Gökhan

    2016-08-01

    Oxaliplatin is used to treat advanced colorectal cancer. Platinum-containing chemotherapeutic agents are known to be ototoxic. However, ototoxicity is rare with newer generation platinum-derived agents, such as oxaliplatin. This case report presents a rare case of sudden unilateral sensorineural hearing loss following intravenous (IV) infusion of oxaliplatin in a 64-year-old woman with advanced colon cancer. The hearing loss was severe and did not respond to treatment. To the best of our knowledge, this is the fifth reported case of oxaliplatin ototoxicity. Although oxaliplatin ototoxicity is rare, physicians must be aware of this important adverse effect, and an audiometric evaluation must be performed when necessary. Patients treated with oxaliplatin should be followed closely for early signs and symptoms of hearing loss, and if hearing loss is detected, treatment should be stopped immediately.

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

    Energy Technology Data Exchange (ETDEWEB)

    Dichter, C.R.

    1984-06-01

    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.

  10. Dies1/VISTA expression loss is a recurrent event in gastric cancer due to epigenetic regulation.

    Science.gov (United States)

    Oliveira, Patrícia; Carvalho, Joana; Rocha, Sara; Azevedo, Mafalda; Reis, Inês; Camilo, Vânia; Sousa, Bárbara; Valente, Sofia; Paredes, Joana; Almeida, Raquel; Huntsman, David; Oliveira, Carla

    2016-10-10

    Dies1/VISTA induces embryonic stem-cell differentiation, via BMP-pathway, but also acts as inflammation regulator and immune-response modulator. Dies1 inhibition in a melanoma-mouse model led to increased tumour-infiltrating T-cells and decreased tumour growth, emphasizing Dies1 relevance in tumour-microenvironment. Dies1 is involved in cell de/differentiation, inflammation and cancer processes, which mimic those associated with Epithelial-to-Mesenchymal-Transition (EMT). Despite this axis linking Dies1 with EMT and cancer, its expression, modulation and relevance in these contexts is unknown. To address this, we analysed Dies1 expression, its regulation by promoter-methylation and miR-125a-5p overexpression, and its association with BMP-pathway downstream-effectors, in a TGFβ1-induced EMT-model, cancer cell-lines and primary samples. We detected promoter-methylation as a mechanism controlling Dies1 expression in our EMT-model and in several cancer cell-lines. We showed that the relationship between Dies1 expression and BMP-pathway effectors observed in the EMT-model, was not present in all cell-lines, suggesting that Dies1 has other cell-specific effectors, beyond the BMP-pathway. We further demonstrated that: Dies1 expression loss is a recurrent event in GC, caused by promoter methylation and/or miR-125a-5p overexpression and; GC-microenvironment myofibroblasts overexpress Dies1. Our findings highlight Dies1 as a novel player in GC, with distinct roles within tumour cells and in the tumour-microenvironment.

  11. An automatic framework for assessing breast cancer risk due to various hormone replacement therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal; Brandt, Sami; Nielsen, Mads

    It is well known that menopausal hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998), J.M. Boone(...... features describing the local elongatedness or stripiness, especially trained to see the effect of HRT (Hormone Replacement Therapy ) thereby providing a non-subjective and reproducible measure and compare it to the BIRADS and percentage density measure....

  12. Characteristics of the vibratory reflex in humans with reduced suprasegmental influence due to spinal cord injury.

    Science.gov (United States)

    Sherwood, A M; Dimitrijevic, M R; Bacia, T; McKay, W B

    1993-01-01

    The tonic stretch reflex elicited by vibration of a muscle or tendon provides a means of studying segmental reflex activity in humans with impaired volitional motor activity due to spinal cord injury (SCI). Vibration applied to the achilles or patellar tendon in a group of 51 SCI subjects elicited motor unit activity different from that found in 12 healthy subjects. Four distinct features of motor unit responses to vibration of a single tendon (achilles or patellar) could be seen in the SCI subjects: (i) a rapid onset, tonic response, frequently beginning with a single burst analogous to a tendon jerk, in 72% of vibrated sites; (ii) repetitive, phasic bursts of activity or vibratory-induced clonus in 23% of the tonic responses; (iii) spread of activity to muscles distant from the vibration in 44% of the tonic responses; and vibratory-induced withdrawal reflexes (VWR) which occurred after vibration of 37% of the sites. Overall, 81% of stimulated sites responded to vibration in SCI subjects. In contrast, only 54% of vibrated sites responded in control subjects, always with a gradual onset tonic response, never accompanied by a VWR. The VWR in SCI subjects was typically of much larger amplitude than the tonic responses and involved a mean of 5 muscles (41% bilaterally). Features of these responses provide an insight into underlying neurocontrol mechanisms which may provide guidance in the selection of appropriate intervention or management strategies.

  13. Acute liver failure due to Human Herpesvirus 6 in an infant

    Directory of Open Access Journals (Sweden)

    G.M. Tronconi

    2012-10-01

    Full Text Available We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus, drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6 genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases’ review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus’s genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

  14. [Acute liver failure due to human herpesvirus 6 in an infant].

    Science.gov (United States)

    Tronconi, G M; Mariani, B; Pajno, R; Fomasi, M; Cococcioni, L; Biffi, V; Bove, M; Corsin, P; Garbetta, G; Barera, G

    2012-01-01

    We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6) genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases' review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus's genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

  15. Malignancies and infection due to the human immunodeficiency virus. Are these emerging diseases?

    Science.gov (United States)

    Valencia Ortega, M E

    2017-09-02

    Since the start of the human immunodeficiency virus (HIV) epidemic, tumour disease among patients has been significant. The collection of malignancies can be divided primarily into 2 groups: those associated with HIV (all of which are related to viral diseases) and those not associated with HIV (only some of which are associated with viral diseases). The origin of these malignancies is multifactorial, and the main causes that have led to an increase in tumour disease are immunosuppression, coinfection with oncogenic viruses and life prolongation secondary to the use of antiretroviral therapy. Establishing the general characteristics of the undiagnosed AIDS tumours is difficult, mainly because they are a highly heterogeneous group formed by malignancies of a diverse nature. The treatments do not differ from those used in the general population, although the management can be more difficult due to the late diagnosis, drug interactions and associated comorbidities. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  16. Quantifying Biodiversity Losses Due to Human Consumption: A Global-Scale Footprint Analysis.

    Science.gov (United States)

    Wilting, Harry C; Schipper, Aafke M; Bakkenes, Michel; Meijer, Johan R; Huijbregts, Mark A J

    2017-03-21

    It is increasingly recognized that human consumption leads to considerable losses of biodiversity. This study is the first to systematically quantify these losses in relation to land use and greenhouse gas (GHG) emissions associated with the production and consumption of (inter)nationally traded goods and services by presenting consumption-based biodiversity losses, in short biodiversity footprint, for 45 countries and world regions globally. Our results showed that (i) the biodiversity loss per citizen shows large variations among countries, with higher values when per-capita income increases; (ii) the share of biodiversity losses due to GHG emissions in the biodiversity footprint increases with income; (iii) food consumption is the most important driver of biodiversity loss in most of the countries and regions, with a global average of 40%; (iv) more than 50% of the biodiversity loss associated with consumption in developed economies occurs outside their territorial boundaries; and (v) the biodiversity footprint per dollar consumed is lower for wealthier countries. The insights provided by our analysis might support policymakers in developing adequate responses to avert further losses of biodiversity when population and incomes increase. Both the mitigation of GHG emissions and land use related reduction options in production and consumption should be considered in strategies to protect global biodiversity.

  17. Assessing absolute changes in breast cancer risk due to modifiable risk factors.

    Science.gov (United States)

    Quante, Anne S; Herz, Julia; Whittemore, Alice S; Fischer, Christine; Strauch, Konstantin; Terry, Mary Beth

    2015-07-01

    Clinical risk assessment involves absolute risk measures, but information on modifying risk and preventing cancer is often communicated in relative terms. To illustrate the potential impact of risk factor modification in model-based risk assessment, we evaluated the performance of the IBIS Breast Cancer Risk Evaluation Tool, with and without current body mass index (BMI), for predicting future breast cancer occurrence in a prospective cohort of 665 postmenopausal women. Overall, IBIS's accuracy (overall agreement between observed and assigned risks) and discrimination (AUC concordance between assigned risks and outcomes) were similar with and without the BMI information. However, in women with BMI > 25 kg/m(2), adding BMI information improved discrimination (AUC = 63.9 % and 61.4 % with and without BMI, P risk difference for a woman with high (27 kg/m(2)) versus low (21 kg/m(2)) BMI was only 0.3 % for a woman with neither affected first-degree relatives nor BRCA1 mutation, compared to 4.5 % for a mutation carrier with three such relatives. This contrast illustrates the value of using information on modifiable risk factors in risk assessment and in sharing information with patients of their absolute risks with and without modifiable risk factors.

  18. Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress.

    Science.gov (United States)

    Lu, Jun; Chen, Jian; Xu, Nianjun; Wu, Jun; Kang, Yani; Shen, Tingting; Kong, Hualei; Ma, Chao; Cheng, Ming; Shao, Zhifeng; Xu, Ling; Zhao, Xiaodong

    2016-09-01

    Application of cisplatin (DDP) for treating lung cancer is restricted due to its toxicity and lung cancer's drug resistance. In this study, we examined the effect of Jinfukang (JFK), an effective herbal medicine against lung cancer, on DDP-induced cytotoxicity in lung cancer cells. Morphologically, we observed that JFK increases DDP-induced pro-apoptosis in A549 cells in a synergistic manner. Transcriptome profiling analysis indicated that the combination of JFK and DDP regulates genes involved in apoptosis-related signaling pathways. Moreover, we found that the combination of JFK and DDP produces synergistic pro-apoptosis effect in other lung cancer cell lines, such as NCI-H1975, NCI-H1650, and NCI-H2228. Particularly, we demonstrated that AIFM2 is activated by the combined treatment of JFK and DDP and partially mediates the synergistic pro-apoptosis effect. Collectively, this study not only offered the first evidence that JFK promotes DDP-induced cytotoxicity, and activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress, but also provided a novel insight for improving cytotoxicity by combining JFK with DDP to treat lung cancer cells.

  19. Does cancer start in the womb? altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors.

    Science.gov (United States)

    Soto, Ana M; Brisken, Cathrin; Schaeberle, Cheryl; Sonnenschein, Carlos

    2013-06-01

    We are now witnessing a resurgence of theories of development and carcinogenesis in which the environment is again being accepted as a major player in phenotype determination. Perturbations in the fetal environment predispose an individual to disease that only becomes apparent in adulthood. For example, gestational exposure to diethylstilbestrol resulted in clear cell carcinoma of the vagina and breast cancer. In this review the effects of the endocrine disruptor bisphenol-A (BPA) on mammary development and tumorigenesis in rodents is used as a paradigmatic example of how altered prenatal mammary development may lead to breast cancer in humans who are also widely exposed to it through plastic goods, food and drink packaging, and thermal paper receipts. Changes in the stroma and its extracellular matrix led to altered ductal morphogenesis. Additionally, gestational and lactational exposure to BPA increased the sensitivity of rats and mice to mammotropic hormones during puberty and beyond, thus suggesting a plausible explanation for the increased incidence of breast cancer.

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

    OpenAIRE

    Sehrawat, Anuradha; Singh, Shivendra V.

    2011-01-01

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

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

    Science.gov (United States)

    Duthie, Susan J

    2011-02-01

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

  2. CERVICAL CANCER AND THE HUMAN IMMUNODEFICIENCY ...

    African Journals Online (AJOL)

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

    Dan, Xiu Li; Ng, Tzi Bun

    2013-09-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  7. Increasing incidence of base of tongue cancers from 2000 to 2010 due to HPV

    DEFF Research Database (Denmark)

    Garnaes, E; Kiss, K; Andersen, L

    2015-01-01

    for all (n=210) BSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and the Danish Pathology Data Bank, and genotyped all HPV-positive specimens with amplicon-based next-generation sequencing. RESULTS: The overall crude incidence of BSCCs increased significantly significant increase......BACKGROUND: We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence. METHODS: We performed HPV DNA PCR and p16 immunohistochemistry analysis...

  8. Facial skin metastasis due to small-cell lung cancer: a case report

    OpenAIRE

    Barbetakis Nikolaos; Samanidis Georgios; Paliouras Dimitrios; Samanidou Elpida; Tzimorota Zoi; Asteriou Christos; Xirou Persefoni; Tsilikas Christodoulos

    2009-01-01

    Abstract Introduction Cutaneous metastases in the facial region occur in less than 0.5% of patients with metastatic cancer. They are an important finding and are not often the first sign leading to diagnosis. Case presentation We describe the case of a 64-year-old male patient who presented with dyspnea, pleuritic pain, loss of weight and a nodule on his left cheek. A chest X-ray revealed a left upper lobe mass with mediastinal lymphadenopathy. Excision biopsy of the facial nodule revealed sm...

  9. Intraarticular hemorrhage due to bevacizumab in a patient with metastatic colorectal cancer: a case report

    Directory of Open Access Journals (Sweden)

    Uysal Mukremin

    2012-07-01

    Full Text Available Abstract Introduction Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. It is widely used in the treatment of metastatic colorectal cancer. It has some specific side effects including severe bleeding, wound healing problems, gastrointestinal perforation, proteinuria and hypertension. Case presentation We present the case of a 65-year old Asian man with synovial metastasis of the knee who experienced intraarticular hemorrhage after bevacizumab treatment. He presented with monoarthritis of the left knee. Conclusion Bevacizumab-related hemorrhage can cause serious morbidity and unusual sites of hemorrhage may be seen.

  10. Human Papilloma Virus Vaccine: Future of Cervical Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Jannatul Fardows

    2016-09-01

    Full Text Available Cervical cancer is a deadly cancer that clutches lives of the women in most of the cases due to lack of consciousness about the disease in the developing countries. It remains a threat which is second only to breast cancer in overall disease burden for women throughout the world. Cervical cancer is almost a preventable disease by prophylactic vaccine and routine screening. Both Cervarix and Gardasil vaccines have been effective in preventing persistent infection with targeted HPV types and in preventing cervical intraepithelial lesions. It is safe and nearly 100% effective if given before onset of sexual activity. This review article is aimed to explore different aspects of this vaccine as well as to develop awareness among health professionals of different disciplines.

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

    OpenAIRE

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

    2010-01-01

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

  12. 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.

  13. Human Papillomavirus Testing in the Prevention of Cervical Cancer

    Science.gov (United States)

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

    2011-01-01

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

  14. 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.

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

    Science.gov (United States)

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

    2015-11-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Young, J; Nielsen, J E

    2014-01-01

    limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. METHODS: Human testis and testis cancer specimens from orchidectomies were...

  18. Successful Self-Expandable Metallic Stent Placement for a Case of Distal Rectal Stenosis due to Gastric Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Takuya Okugawa

    2013-05-01

    Full Text Available A 47-year-old woman was diagnosed as having advanced gastric cancer with malignant ascites. Despite chemotherapy, recurrent peritoneal dissemination was seen 1.5 years after operation. A computed tomography scan revealed rectal stenosis due to Schnitzler's metastasis. When the distance from the distal end of the obstruction to the anal verge is less than 5 cm, stent replacement has been said to be contraindicated due to the development of anal pain and foreign body sensation. Although the distance from the distal end of the obstruction to the anal verge was 4 cm in this case, a WallFlex™ colonic stent could be placed. She stayed home, and luminal patency remained until she died 270 days after stent insertion. This report demonstrates that rectal obstruction located less than 5 cm from the anal verge due to Schnitzler's metastasis could be treated by stenting without any symptomatic or technical complications.

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

    Science.gov (United States)

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

    2016-12-19

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

  20. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    NARCIS (Netherlands)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Herve; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Oehlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H. M.; Molenaar, IQ; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G. J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  1. Organoid models of human and mouse ductal pancreatic cancer

    NARCIS (Netherlands)

    Boj, Sylvia F; Hwang, Chang-Il; Baker, Lindsey A; Chio, Iok In Christine; Engle, Dannielle D; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D; Wilson, John P; Feigin, Michael E; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H M; Molenaar, I Quintus; Borel Rinkes, Inne H; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J; Iacobuzio-Donahue, Christine; Leach, Steven D; Pappin, Darryl J; Hammell, Molly; Klimstra, David S; Basturk, Olca; Hruban, Ralph H; Offerhaus, George Johan; Vries, Robert G J; Clevers, Hans; Tuveson, David A

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  2. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    NARCIS (Netherlands)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Herve; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Oehlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H. M.; Molenaar, IQ; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G. J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  3. Organoid models of human and mouse ductal pancreatic cancer

    NARCIS (Netherlands)

    Boj, Sylvia F; Hwang, Chang-Il; Baker, Lindsey A; Chio, Iok In Christine; Engle, Dannielle D; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D; Wilson, John P; Feigin, Michael E; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H M; Molenaar, I Quintus; Borel Rinkes, Inne H; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J; Iacobuzio-Donahue, Christine; Leach, Steven D; Pappin, Darryl J; Hammell, Molly; Klimstra, David S; Basturk, Olca; Hruban, Ralph H; Offerhaus, George Johan; Vries, Robert G J; Clevers, Hans; Tuveson, David A

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  4. Referral patterns of patients with liver metastases due to colorectal cancer for resection.

    LENUS (Irish Health Repository)

    Al-Sahaf, O

    2012-02-01

    INTRODUCTION: Colorectal carcinoma accounts for 10% of cancer deaths in the Western World, with the liver being the most common site of distant metastases. Resection of liver metastases is the treatment of choice, with a 5-year survival rate of 35%. However, only 5-10% of patients are suitable for resection at presentation. AIMS: To examine the referral pattern of patients with liver metastases to a specialist hepatic unit for resection. METHODOLOGY: Retrospective review of patient\\'s charts diagnosed with colorectal liver metastases over a 10-year period. RESULTS: One hundred nine (38 women, 71 men) patients with liver metastases were included, mean age 61 years; 79 and 30 patients had synchronous and metachronus metastases, respectively. Ten criteria for referral were identified; the referral rate was 8.25%, with a resection rate of 0.9%. Forty two percent of the patients had palliative chemotherapy; 42% had symptomatic treatment. CONCLUSION: This study highlights the advanced stage of colorectal cancer at presentation; in light of modern evidence-based, centre-oriented therapy of liver metastasis, we conclude that criteria of referral for resection should be based on the availability of treatment modalities.

  5. Occult Breast Cancer due to Multiple Calcified Hamartomas in a Patient with Cowden Syndrome

    Directory of Open Access Journals (Sweden)

    E. B. Gómez García

    2012-01-01

    Full Text Available Cowden syndrome (CS is an autosomal dominant disorder characterized by presence of multiple hamartomas, and other benign and malignant abnormalities of the breasts, skin, thyroid, endometrium, gastrointestinal tract, and central nervous system. Hamartomas are benign, developmentally disorganized tumors that can develop in any of the above mentioned organs. The presence of massive calcifications in the breasts in very young women is an indication to perform a breast MRI to exclude a neoplasm since, like in the current case report, presence of breast calcifications may obscure a neoplasm. Although fibrocystic disease and cooccurrence of fibrocystic disease and breast cancer are much more common than CS, the presence of massive calcifications in the breasts of very young women should elicit the possibility of an underlying genetic disease. Furthermore, breast cancer and macrocephaly are considered major criteria for the diagnosis of CS and the combination of both is enough to establish the clinical diagnosis of this entity. Fibrocystic disease of the breasts and multinodular goiter are minor criteria. Family history is also important for the diagnosis of (any hereditary disease.

  6. Hydro-ecological degradation due to human impacts in the Twin Streams Watershed, Auckland, New Zealand

    Science.gov (United States)

    Torrecillas Nunez, C.; Miguel-rodriguez, A.

    2012-12-01

    wide range of impacts due to human actions which will exacerbated by future development as the population in the watershed is forecast to increase by at least 65% and the likely impacts of global warming. The rural watershed generates sediment which smothers the streams and harbor, while the urban watershed is the source of point and diffuse contamination with heavy metals which damage ecosystems. Evidence of impacts is given by the extent of flooding, reduced ecological flows and sampling results showing that more than 50% of the sites do not comply with environmental guidelines for: water clarity, turbidity, suspended solids, nitrogen, phosphorus, copper, zinc, conductivity, Dieldrin, DDT, Dissolved Oxygen, E.Coli, macroinvertebrates ,etc. , with water quality deteriorating progressively downstream where there is greater urbanization. But perhaps the most stunning evidence of the impacts was established by comparing aerial photographs of the 1940s and 2006 and seeing the build-up of sediments in the estuaries, the change in vegetation cover and discolored water. It is highly likely that the tipping point was reached before urbanization started but there is no doubt that urban development has accelerated the impacts, which has been corroborated by studies in other watersheds in Auckland.

  7. [One-lung ventilation using dexmedetomidine in an emphysema patient with pneumothorax due to metastatic lung cancer].

    Science.gov (United States)

    Ono, Naomi; Komasawa, Nobuyasu; Nakano, Shoko; Tatsumi, Shinichi; Nakao, Kenta; Minami, Toshiaki

    2014-05-01

    We report a case of double-lumen tube intubation and intraoperative one-lung ventilation under spontaneous breathing with continuous dexmedetomidine administration. A 61-year-old man developed pneumothorax due to multiple metastatic cancer, had multiple bilateral bullae, and underwent bullae resection under general anesthesia. An epidural catheter was placed at T8-9. Under dexmedetomidine sedation and regional anesthesia with lidocaine, a double-lumen tube was inserted with a Macintosh laryngoscope. The patient was under one-lung ventilation with spontaneous breathing during the operation. There were no complications from one-lung ventilation and the patient was extubated in the operating room. One-lung ventilation, which preserves spontaneous breathing, under dexmedetomidine sedation is considered effective for preventing barotrauma in patients with multiple metastatic cancer.

  8. Clinicopathological significance of PTPN12 expression in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Xunyi [Breast Disease Diagnosis and Treatment Centre, Affiliated Hospital of Medical College, Qingdao University, Qingdao Shandong Province (China); Yuan, Zhentao [Department of Anesthesiology, Shengli Oilfield Central Hospital, Dongying Shandong Province (China); Jiang, Dandan; Li, Funian [Breast Disease Diagnosis and Treatment Centre, Affiliated Hospital of Medical College, Qingdao University, Qingdao Shandong Province (China)

    2012-10-15

    Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a recently identified tumor suppressor gene (TSG) that is frequently compromised in human triple-negative breast cancer. In the present study, we investigated the expression of PTPN12 protein by patients with breast cancer in a Chinese population and the relationship between PTPN12 expression levels and patient clinicopathological features and prognosis. Additionally, we explored the underlying down-regulation mechanism from the perspective of an epigenetic alteration. We examined PTPN12 mRNA expression in five breast cancer cell lines using semi-quantitative reverse-transcription PCR, and detected PTPN12 protein expression using immunohistochemistry in 150 primary invasive breast cancer cases and paired adjacent non-tumor tissues. Methylation-specific PCR was performed to analyze the promoter CpG island methylation status of PTPN12. PTPN12 was significantly down-regulated in breast cancer cases (48/150) compared to adjacent noncancerous tissues (17/150; P < 0.05). Furthermore, low expression of PTPN12 showed a significant positive correlation with tumor size (P = 0.047), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), histological grade (P = 0.012), and survival time (P = 0.019). Additionally, promoter CpG island hypermethylation occurs more frequently in breast cancer cases and breast cancer cell lines with low PTPN12 expression. Our findings suggest that PTPN12 is potentially a methylation-silenced TSG for breast cancer that may play an important role in breast carcinogenesis and could potentially serve as an independent prognostic factor for invasive breast cancer patients.

  9. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongtao [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China); Gao, Peng [Department of Internal Medicine, University of Iowa, Iowa City, IA 52242 (United States); Zheng, Jie, E-mail: jiezheng54@126.com [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China)

    2014-09-05

    Highlights: • As{sub 2}O{sub 3} inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As{sub 2}O{sub 3} is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As{sub 2}O{sub 3}) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As{sub 2}O{sub 3} induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As{sub 2}O{sub 3} on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As{sub 2}O{sub 3} than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As{sub 2}O{sub 3} than HPV 16-positive CaSki and SiHa cells. After As{sub 2}O{sub 3} treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As{sub 2}O{sub 3} is a potential anticancer drug for cervical cancer.

  10. Active co-infection with HBV and/or HCV in South African HIV positive patients due for cancer therapy.

    Science.gov (United States)

    Musyoki, Andrew M; Msibi, Thembeni L; Motswaledi, Mojakgomo H; Selabe, Selokela G; Monokoane, Tshweu S; Mphahlele, M Jeffrey

    2015-02-01

    Human immunodeficiency virus (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) share routes of transmission. There is limited data on the incidence of active co-infection with HBV and/or HCV in cancer patients infected with HIV in Africa. This was a prospective study based on 34 patients with varied cancer diagnosis, infected with HIV and awaiting cancer therapy in South Africa. HIV viral load, CD4+ cell counts, Alanine-aminotransferase and aspartate aminotransferase levels were tested. Exposure to HBV and HCV was assessed serologically using commercial kits. Active HBV and/or HCV co-infection was detected using viral specific nested PCR assays. HCV 5'-UTR PCR products were sequenced to confirm active HCV infection. Active viral infection was detected in 64.7% of patients for HBV, 38.2% for HCV, and 29.4% for both HBV and HCV. Occult HBV infection was observed in 63.6% of the patients, while seronegative HCV infection was found in 30.8% of patients. In addition, CD4+ cell count HCV or both HBV and HCV co-infections. A total of 72.7%, 18.2% and 9.1% of the HCV sequences were assigned genotype 5, 1 and 4 respectively.The study revealed for the first time a high active HBV and/or HCV co-infection rate in cancer patients infected with HIV. The findings call for HBV and HCV testing in such patients, and where feasible, appropriate antiviral treatment be indicated, as chemotherapy or radiotherapy has been associated with reactivation of viral hepatitis and termination of cancer therapy.

  11. Development of Severe Hyponatremia due to Salt-Losing Nephropathy after Esophagectomy for Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Katsunobu Yoshioka

    2009-01-01

    Full Text Available A 72-year-old woman was admitted to our hospital for esophagectomy for esophageal cancer. On the third postoperative day, she developed polyuria (3.8 L/day, massive natriuresis, hyponatremia (112 mEq/L, hyperkalemia (5.6 mEq/L, and decreased central venous pressure, which was refractory to isotonic saline infusion. Laboratory findings indicated proximal tubular injury (high urinary β2-microglobulin, coexistence of hypouricemia together with reduced aldosterone action at the cortical collecting duct. A diagnosis of salt-losing nephropathy was made and sodium correction was done with 3% saline and fludrocortisone. She responded well to therapy. The cause of hyponatremia was considered renal tubular dysfunction together with elevated antidiuretic hormone level. Postoperatively, it is important to look for the development of salt-losing nephropathy.

  12. Facial skin metastasis due to small-cell lung cancer: a case report

    Directory of Open Access Journals (Sweden)

    Barbetakis Nikolaos

    2009-01-01

    Full Text Available Abstract Introduction Cutaneous metastases in the facial region occur in less than 0.5% of patients with metastatic cancer. They are an important finding and are not often the first sign leading to diagnosis. Case presentation We describe the case of a 64-year-old male patient who presented with dyspnea, pleuritic pain, loss of weight and a nodule on his left cheek. A chest X-ray revealed a left upper lobe mass with mediastinal lymphadenopathy. Excision biopsy of the facial nodule revealed small-cell lung carcinoma. Palliative chemo-radiotherapy was administered and the patient survived for 12 months. Conclusion A high index of suspicion is necessary for the early detection of facial cutaneous metastases. Appropriate treatment may prolong patient survival.

  13. A Case of Hyperemesis Gravidarum due to Gastric Cancer Masquerading as Preeclampsia

    Directory of Open Access Journals (Sweden)

    Daniel R. Hersh

    2011-12-01

    Full Text Available Nausea and vomiting are symptoms frequently seen in normal pregnancy. We report a patient with gastric carcinoma who presented with severe hyperemesis gravidarum that led to extreme volume depletion, hypertension, proteinuria, and acute renal failure. A 35-year-old woman (para 2-1-0-1 with a prenatal course significant for persistent nausea, vomiting, and poor weight gain presented at 36 weeks' gestation with elevated blood pressure (157/114 mm Hg, proteinuria (4+, hypochloremic metabolic alkalosis, and severe intravascular volume contraction. A presumptive diagnosis of severe preeclampsia was made, the patient was given intravenous MgSO4, and cesarean delivery was accomplished uneventfully. When significant emesis persisted in the postoperative period, esophagogastroduodenoscopy revealed an antral/prepyloric mass with a biopsy-proven poorly differentiated adenocarcinoma. To our knowledge, this is the first report of a case of hyperemesis gravidarum with gastric cancer masquerading as preeclampsia.

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

    Directory of Open Access Journals (Sweden)

    Cord Naujokat

    2012-01-01

    Full Text Available Cancer stem cells (CSCs represent a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of malignant cells that comprise a tumor. CSCs possess multiple intrinsic mechanisms of resistance to chemotherapeutic drugs, novel tumor-targeted drugs, and radiation therapy, allowing them to survive standard cancer therapies and to initiate tumor recurrence and metastasis. Various molecular complexes and pathways that confer resistance and survival of CSCs, including expression of ATP-binding cassette (ABC drug transporters, activation of the Wnt/β-catenin, Hedgehog, Notch and PI3K/Akt/mTOR signaling pathways, and acquisition of epithelial-mesenchymal transition (EMT, have been identified recently. Salinomycin, a polyether ionophore antibiotic isolated from Streptomyces albus, has been shown to kill CSCs in different types of human cancers, most likely by interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, and other CSC pathways. Promising results from preclinical trials in human xenograft mice and a few clinical pilote studies reveal that salinomycin is able to effectively eliminate CSCs and to induce partial clinical regression of heavily pretreated and therapy-resistant cancers. The ability of salinomycin to kill both CSCs and therapy-resistant cancer cells may define the compound as a novel and an effective anticancer drug.

  15. Association between micronuclei frequency in pollen mother cells of Tradescantia and mortality due to cancer and cardiovascular diseases: A preliminary study in Sao Jose dos Campos, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Mariani, Rauda Lucia [Department of Geochemistry, Fluminense Federal University (UFF), Niteroi, RJ (Brazil); Martins Jorge, Maria Paulete; Pereira, Sergio Silva; Melione, Luiz Paulo [National Institute for Space Research, Sao Jose dos Campos, SP (Brazil); Carvalho-Oliveira, Regiani [Experimental Air Pollution Laboratory, Department of Pathology, Sao Paulo University Medical School, Sao Paulo (Brazil); Ma, Te Hsiu [Department of Biological Sciences, Western Illinois University, Macomb, IL 61455 (United States); Nascimento Saldiva, Paulo Hilario, E-mail: pepino@usp.b [Experimental Air Pollution Laboratory, Department of Pathology, Sao Paulo University Medical School, Sao Paulo (Brazil)

    2009-06-15

    The present study was designed to explore the correlation between the frequency of micronuclei in Trad-MN, measured across 28 biomonitoring stations during the period comprised between 11 of May and 2 of October, 2006, and adjusted mortality rates due to cardiovascular, respiratory diseases and cancer in Sao Jose dos Campos, Brazil, an area with different sources of air pollution. For controlling purposes, mortality rate due to gastrointestinal diseases (an event less prone to be affected by air pollution) was also considered in the analysis. Spatial distribution of micronuclei frequency was determined using average interpolation. The association between health estimators and micronuclei frequency was determined by measures of Pearson's correlation. Higher frequencies of micronuclei were detected in areas with high traffic and close to a petrochemical pole. Significant associations were detected between micronuclei frequency and adjusted mortality rate due to cardiovascular diseases (r = 0.841, p = 0.036) and cancer (r = 0.890, p = 0.018). The association between mortality due to chronic obstructive pulmonary diseases was positive but did not reach statistical significance (r = 0.640, p = 0.172), probably because of the small number of events. Gastrointestinal mortality did not exhibit significant association with micronuclei frequency. Because the small number of observations and the nature of an ecological study, the present findings must be considered with caution and considered as preliminary. Further studies, performed in different conditions of contamination and climate should be done before considering Trad-MN in the evaluation of human health risk imposed by air pollutants. - Bioassay used to explore the correlation between air pollution exposition and mortality rates.

  16. Characterization of Dielectric Responses of Human Cancer Cells in the Terahertz Region

    Science.gov (United States)

    Shiraga, Keiichiro; Ogawa, Yuichi; Suzuki, Tetsuhito; Kondo, Naoshi; Irisawa, Akiyoshi; Imamura, Motoki

    2014-05-01

    Terahertz time-domain attenuated total reflection spectroscopy, in combination with a two-interface model, is used to determine the complex dielectric constants of cultured human cancer cells (DLD-1, HEK293 and HeLa). Picosecond and sub-picosecond water dynamics are dominant in the measured complex dielectric constants of these cells. We demonstrate that dielectric responses below 1.0 THz best characterize the particular water dynamics of cancer cells when compared with extracellular water. Debye-Lorentz fitting revealed that this is due to a significantly attenuated slow relaxation mode and enhanced fast relaxation mode of the water in these cancer cells. These findings could lead to a new procedure to digitally evaluate cellular activities or functions, in terms of intracellular water dynamics, and remove the veil from the mysterious intracellular milieu.

  17. Characterization of black raspberry functional food products for cancer prevention human clinical trials.

    Science.gov (United States)

    Gu, Junnan; Ahn-Jarvis, Jennifer H; Riedl, Kenneth M; Schwartz, Steven J; Clinton, Steven K; Vodovotz, Yael

    2014-05-07

    Our team is designing and fully characterizing black raspberry (BRB) food products suitable for long-term cancer prevention studies. The processing, scale-up, and storage effects on the consistency, quality, bioactive stability, and sensory acceptability of two BRB delivery systems of various matrices are presented. BRB dosage, pH, water activity, and texture were consistent in the scale-up production. Confections retained >90% of anthocyanins and ellagitannin after processing. Nectars had >69% of anthocyanins and >66% of ellagitannin retention, which varied with BRB dosage due to the processing difference. Texture remained unchanged during storage. BRB products consumed in a prostate cancer clinical trial were well accepted in sensory tests. Thus, this study demonstrates that two different BRB foods can be formulated to meet quality standards with a consistent bioactive pattern and successfully scaled up for a large human clinical trial focusing on cancer risk and other health outcomes.

  18. Energy Dissipation from Vibrating Floor Slabs due to Human-Structure Interaction

    Directory of Open Access Journals (Sweden)

    James M.W. Brownjohn

    2001-01-01

    Full Text Available Lightweight pre-cast flooring systems using post-tensioning to increase strength but not stiffness are increasingly popular, and vibration serviceability problems tend to govern design of such floors where human occupants are increasingly concerned with vibrations. At the same time as inducing response, stationary human observers can also participate in the response as mitigating influence and it is clear that a human behaves as a highly effective damper, even when seated.

  19. Osthole inhibits proliferation of human breast cancer cells by inducing cell cycle arrest and apoptosis

    Institute of Scientific and Technical Information of China (English)

    Lintao Wang; Yanyan Peng; Kaikai Shi; Haixiao Wang; Jianlei Lu; Yanli Li; Changyan Ma

    2015-01-01

    Recent studies have revealed that osthole,an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson,a traditional Chinese medicine,possesses anticancer activity.However,its effect on breast cancer cells so far has not been elucidated clearly.In the present study,we evaluated the effects of osthole on the proliferation,cell cycle and apoptosis of human breast cancer cells MDA-MB 435.We demonstrated that osthole is effective in inhibiting the proliferation of MDA-MB 435 cells,The mitochondrion-mediated apoptotic pathway was involved in apoptosis induced by osthole,as indicated by activation of caspase-9 and caspase-3 followed by PARP degradation.The mechanism underlying its effect on the induction of G1 phase arrest was due to the up-regulation of p53 and p21 and down-regulation of Cdk2 and cyclin D1 expression.Were observed taken together,these findings suggest that the anticancer efficacy of osthole is mediated via induction of cell cycle arrest and apoptosis in human breast cancer cells and osthole may be a potential chemotherapeutic agent against human breast cancer.

  20. A Review of Human Health and Ecological Risks due to CO2 Exposure

    Science.gov (United States)

    Hepple, R. P.; Benson, S. M.

    2001-05-01

    Nyos in Cameroon, Mammoth Mountain in California, Dieng Volcanic Complex in Java, Indonesia, and industrial accidents with CO2 fire suppression systems teach that slow leakage rates and effective dilution must be proven to ensure human and environmental safety. Monitoring CO2 levels in occupational settings is done with reliable IR sensors. Remote sensing of low levels of CO2 over long distances cannot be done easily yet, although LIDAR, an airborne laser technique under development, may have good potential. The environmental impacts of elevated CO2 levels on vegetation are being investigated now in free-air CO2 enrichment studies. In general, persistent elevated CO2 levels cause a change in species composition, favoring C3 plants over C4 or CAM. The ecological effects of catastrophic releases are severe but depend upon (a) release rate and amount, (b) surface topography and rate of atmospheric mixing (c) exposure concentrations and duration, (d) the respiratory mechanism of the form of life under discussion, (e) its tolerance for oxygen deprivation, and (f) its ability to maintain homeostatic pH levels. Suppression of root respiration due to elevated soil-gas CO2 concentrations and acidifiction of the root zone are known mechanisms of tree-kill. Soil-gas CO2 in the tree-kill areas at Mammoth Mountain exceeded 20-30% at 15 cm depth. Surface masses of concentrated CO2 probably smother the canopy through oxygen deprivation, but the precise mechanism is not known. Lake Nyos and Mammoth Mountain reveal that catastrophic releases can result in complete dead zones.

  1. Experimental response of Salix cuttings to different flow regimes due to human activities

    Science.gov (United States)

    Gorla, Lorenzo; Signarbieux, Constant; Turberg, Pascal; Buttler, Alexandre; Perona, Paolo

    2014-05-01

    Hydropower production and other human activities change the natural flow regime of rivers, in turn impacting the riparian environment. The main challenge in order to define eco-sustainable flows is to quantify the effects in terms of geomorphology and ecosystem adaptation. We present 2-years controlled experiments to investigate riparian vegetation (Salix Viminalis) response to forced water table changing dynamics, from one water regime to another, in a temperate region (Switzerland). Three synthetic flow regimes have been simulated and applied to three batteries of Salix cuttings growing outdoor within plastic pots, each about 1 meter tall. In 2012 one treatment simulated a minimal flow policy for small run-of-river hydropower plants, which drastically impacts the low and the medium-low components of the hydrograph, but not the extremes. In 2013 we confirmed and completed some of 2012 results, by reproducing typical hydropeaking effects due to dam management and focusing on daily water table variations and offsets. For both the seasons, after an initial period where all pots undergone the same oscillations in order to uniform the plants initial conditions, the experiment started, and the water dynamic was changed. Cuttings transitory response dynamics has been quantified by continuous sap flow and water potential measurements, and by regularly collecting growth parameters, as well as leaves photosynthesis, fluorescence, and pictures of each plant. At the end of the experiment, all cuttings were carefully removed and the both above and below ground biomass analyzed in detail. Particularly, the 3D root structure was obtained by High Resolution Computer Tomography. Our analyses revealed a clear dependence between roots distribution and water regime reflecting the need for adaptation, in agreement with field observations of Pasquale et al. (2012). In particular, an initial strong difference in terms of stress and growth performances was then followed by a later

  2. Human Papillomavirus 16E6 Oncogene Mutation in Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  3. Marker evaluation of human breast and bladder cancers

    Energy Technology Data Exchange (ETDEWEB)

    Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. (California Univ., San Francisco, CA (USA))

    1990-11-02

    We are investigating multiple markers in human breast and bladder cancers. Our aim is to identify markers that are clinically relevant and that contribute to our understanding of the disease process in individual patients. Good markers accurately assess the malignant potential of a cancer in an individual patient. Thus, they help identify those cancers that will recur, and they may be used to predict more accurately time to recurrence, response to treatment, and overall prognosis. Therapy and patient management may then be optimized to the individual patient. Relevant markers reflect the underlying pathobiology of individual tumors. As a tissue undergoes transformation from benign to malignant, the cells lose their differentiated phenotype. As a generalization, the more the cellular phenotype, cellular proliferation and cellular genotype depart from normal, the more advanced is the tumor in its biological evolution and the more likely it is that the patient has a poor prognosis. We use three studies to illustrate our investigation of potential tumor markers. Breast cancers are labeled in vivo with 5-bromodeoxyuridine (BrdUrd) to give a direct measure of the tumor labeling index. Bladder cancers are analyzed immunocytochemically using an antibody against proliferation. Finally, the techniques of molecular genetics are used to detect allelic loss in breast cancers. 6 refs., 3 figs.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  5. Thymosin β10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production.

    Directory of Open Access Journals (Sweden)

    Young-Chae Kim

    Full Text Available Thymosin β(10 (Tβ(10 regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that Tβ(10 diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biological function. In the present study, we establish a new gene therapy model using a genetically modified adenovirus, referred to as Ad.TERT.Tβ(10, that can overexpress the Tβ(10 gene in cancer cells. This was accomplished by replacing the native Tβ(10 gene promoter with the human TERT promoter in Ad.TERT.Tβ(10. We investigated the cancer suppression activity of Tβ(10 and found that Ad.TERT.Tβ(10 strikingly induced cancer-specific expression of Tβ(10 as well as apoptosis in a co-culture model of human primary ovarian cancer cells and normal fibroblasts. Additionally, Ad.TERT.Tβ(10 decreased mitochondrial membrane potential and increased reactive oxygen species (ROS production. These effects were amplified by co-treatment with anticancer drugs, such as paclitaxel and cisplatin. These findings indicate that the rise in ROS production due to actin disruption by Tβ(10 overexpression increases apoptosis of human ovarian cancer cells. Indeed, the cancer-specific overexpression of Tβ(10 by Ad.TERT.Tβ(10 could be a valuable anti-cancer therapeutic for the treatment of ovarian cancer without toxicity to normal cells.

  6. KiSS-1 expression in human breast cancer.

    Science.gov (United States)

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

    2005-01-01

    The KiSS-1 gene encodes a 145 amino acid residue peptide that is further processed to a final peptide, metastin, a ligand to a G-coupled orphan receptor (OT7T175/AXOR12). KiSS-1 has been identified as a putative human metastasis suppressor gene in melanomas and in breast cancer cell lines. This study aimed to determine the expression and distribution of KiSS-1 and its receptor in human breast cancer tissues and to identify a possible link between expression levels and patient prognosis. Frozen sections from breast cancer primary tumours (matched tumour 124 and background 33) were immuno-stained with KiSS-1 antibody. RNA was reverse transcribed and analyzed by Q-PCR (standardized using beta-actin, and normalized with cytokeratin-19 levels). Levels of expression of KiSS-1 were higher in tumour compared to background tissues (3,124+/-1,262 vs 2,397+/-1,181) and significantly increased in node positive tumours compared to node negative (3,637+/-1,719 vs 2,653+/-1,994, P = 0.02). KiSS-1 expression was also increased with increasing grade and TNM status. There were no such trends with the KiSS-1 receptor. Expression of KiSS-1 was higher in patients who had died from breast cancer than those who had remained healthy (4,631+/-3,024 vs 2,280+/-1,403) whereas expression of the receptor was reduced (480+/-162 vs 195+/-134). Immunohistochemical staining showed increased expression of KiSS-1 in tumour sections. Insertion of the KiSS-1 gene into the human breast cancer cell line MDA-MB-231, resulted in cells that were significantly more motile and invasive in behaviour, with reduced adhesion to matrix, using respective assays. In conclusion, KiSS-1 expression is increased in human breast cancer, particularly in patients with aggressive tumours and with mortality. Over-expression of KiSS-1 in breast cancer cells result in more aggressive phenotype. Together, it suggests that KiSS-1 plays a role beyond the initial metastasis repressor in this cancer type.

  7. Are 20 human papillomavirus types causing cervical cancer?

    OpenAIRE

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

    2014-01-01

    Abstract: In 2012, the International Agency for Research on Cancer concluded that there was consistent and sufficient epidemiological, experimental and mechanistic evidence of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer. Therefore, these types were considered as 1A carcinogens. They all belong to the family of the -Papillomaviridae, in particular to the species 5 (HPV51), 6 (HPV56), 7 (H...

  8. Aurora-A Oncogene in Human Ovarian Cancer

    Science.gov (United States)

    2006-11-01

    in Human Ovarian Cancer 5b. GRANT NUMBER W81XWH-05-1-0021 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Jin Q. Cheng, M.D...this project : 1) examine the clinicalpathological significance and the mechanism of Aurora-A overexpression/activation in ovarian cancer; 2) determine...kinase is required to localize D-TACC to centro- somes and to regulate astral microtubules. J Cell Biol 2002;156:437–51. 33. Castro A, Mandart E, Lorca T

  9. Moving Forward in Human Cancer Risk Assessment

    OpenAIRE

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

    2010-01-01

    Background The current safety paradigm for assessing carcinogenic properties of drugs, cosmetics, industrial chemicals, and environmental exposures relies mainly on in vitro genotoxicity testing followed by 2-year rodent bioassays. This testing battery is extremely sensitive but has low specificity. Furthermore, rodent bioassays are associated with high costs, high animal burden, and limited predictive value for human risks. Objectives We provide a response to a growing appeal for a paradigm ...

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

    Directory of Open Access Journals (Sweden)

    Cegolon Luca

    2013-01-01

    Full Text Available Abstract Background Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity, hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Discussion Human endogenous retroviruses (HERVs are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well

  11. BRG1 is a prognostic marker and potential therapeutic target in human breast cancer.

    Directory of Open Access Journals (Sweden)

    Jin Bai

    Full Text Available BRG1, a core component of the SWI/SNF chromatin-remodeling complex, has been implicated in cancer development; however, the biological significance of BRG1 in breast cancer remains unknown. We explored the role of BRG1 in human breast cancer pathogenesis. Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 437 breast cancer specimens and investigated its role in breast cancer cell proliferation, migration and invasion. Our Kaplan-Meier survival curves showed that high BRG1 expression is inversely correlated with both overall (P = 0.000 and disease-specific (P = 0.000 5-year patient survival. Furthermore, we found that knockdown of BRG1 by RNA interference markedly inhibits cell proliferation and causes cessation of cell cycle. This reduced cell proliferation is due to G1 phase arrest as cyclin D1 and cyclin E are diminished whereas p27 is upregulated. Moreover, BRG1 depletion induces the expression of TIMP-2 but reduces MMP-2, thereby inhibiting the ability of cells to migrate and to invade. These results highlight the importance of BRG1 in breast cancer pathogenesis and BRG1 may serve as a prognostic marker as well as a potentially selective therapeutic target.

  12. Sulforaphane, a cruciferous vegetable-derived isothiocyanate, inhibits protein synthesis in human prostate cancer cells.

    Science.gov (United States)

    Wiczk, Aleksandra; Hofman, Dagmara; Konopa, Grażyna; Herman-Antosiewicz, Anna

    2012-08-01

    Sulforaphane (SFN) is a compound derived from cruciferous plants. Its anticancer properties have been demonstrated both, in cancer cell lines as well as tumors in animal models. It has been shown that SFN inhibits cell proliferation, induces apoptosis, autophagy, and sensitizes cancer cells to therapies. As induction of catabolic processes is often related to perturbation in protein synthesis we aimed to investigate the impact of SFN on this process in PC-3 human prostate cancer cells. In the present study we show that SFN inhibits protein synthesis in PC-3 cells in a dose- and time-dependent manner which is accompanied by a decreased phosphorylation of mTOR substrates. Translation inhibition is independent of mitochondria-derived ROS as it is observed in PC-3 derivatives devoid of functional mitochondrial respiratory chain (Rho0 cells). Although SFN affects mitochondria and slightly decreases glycolysis, the ATP level is maintained on the level characteristic for control cells. Inhibition of protein synthesis might be a protective response of prostate cancer cells to save energy. However, translation inhibition contributes to the death of PC-3 cells due to decreased level of a short-lived protein, survivin. Overexpression of this anti-apoptotic factor protects PC-3 cells against SFN cytotoxicity. Protein synthesis inhibition by SFN is not restricted to prostate cancer cells as we observed similar effect in SKBR-3 breast cancer cell line. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Characterization of metastasis formation and virotherapy in the human C33A cervical cancer model.

    Directory of Open Access Journals (Sweden)

    Ulrike Donat

    Full Text Available More than 90% of cancer mortalities are due to cancer that has metastasized. Therefore, it is crucial to intensify research on metastasis formation and therapy. Here, we describe for the first time the metastasizing ability of the human cervical cancer cell line C33A in athymic nude mice after subcutaneous implantation of tumor cells. In this model, we demonstrated a steady progression of lumbar and renal lymph node metastases during tumor development. Besides predominantly occurring lymphatic metastases, we visualized the formation of hematogenous metastases utilizing red fluorescent protein (RFP expressing C33A-RFP cells. RFP positive cancer cells were found migrating in blood vessels and forming micrometastases in lungs of tumor-bearing mice. Next, we set out to analyze the influence of oncolytic virotherapy in the C33A-RFP model and demonstrated an efficient virus-mediated reduction of tumor size and metastatic burden. These results suggest the C33A-RFP cervical cancer model as a new platform to analyze cancer metastases as well as to test novel treatment options to combat metastases.

  14. Differentially expressed genes during human cutaneous melanocytic tumor progression : a focus on cancer/testis-associated genes

    NARCIS (Netherlands)

    Zendman, Albert Johan Willem

    2003-01-01

    Human cutaneous melanoma, the skin cancer originating from the pigment producing melanocyte, is one of the most aggressive types of tumors due to its early dissemination. The progression of melanoma surpasses several stages from common nevi to metastatic tumors. For diagnostic and clinical purposes

  15. Apoptosis mechanisms of human gastric cancer cell line MKN-45 infected with human mutant p27

    Institute of Scientific and Technical Information of China (English)

    Jin-Shui Zhu; Long Wang; Guo-Qiang Cheng; Qin Li; Zu-Ming Zhu; Li Zhu

    2005-01-01

    AIM: To explore the inducing effect of human mutant p27 gene on the apoptosis of the human gastric cancer cell line MKN-45 and its associated mechanisms. METHODS: The recombinant adenovirus Ad-p27mt was constructed to infect the human gastric cancer cell line MKN-45. Using flow cytometry, TUNEL assay and DNA fragment analysis, we measured the apoptotic effect of Ad-p27mt on the human gastric cancer cells. RESULTS: Ad-p27mt was successfully constructed and the infection efficiency reached 100%. After 18 h of infection, we observed an apoptotic hypodiploid peak on the flow cytometer before G1-S and apoptotic characteristic bands in the DNA electrophoresis. The apoptotic rate detected by TUNEL method was significantly higher in the Ad-p27mt group (89.4±3.12%)compared to the control group (3.12±0.13%, P < 0.01).CONCLUSION: Human mutant p27 can induce apoptosis of the human gastric cancer cells in vitro.

  16. Abdominal angina due to recurrence of cancer of the papilla of Vater: a case report

    Directory of Open Access Journals (Sweden)

    Rapaccini Gian

    2009-12-01

    Full Text Available Abstract Introduction Abdominal angina is usually caused by atherosclerotic disease, and other causes are considered uncommon. This is the first report of a case of abdominal angina secondary to neoplastic vascular stenosis caused by local recurrence of an adenocarcinoma of the papilla of Vater. Case presentation An 80-year-old woman of Caucasian origin presented with abdominal pain and diarrhea. She had undergone a pancreaticoduodenectomy for adenocarcinoma of the papilla of Vater four years earlier. Computed tomography revealed a mass surrounding her celiac trunk and superior mesenteric artery. Her abdominal pain responded poorly to analgesic drugs, but disappeared when oral feedings were withheld. A duplex ultrasonography of the patient's splanchnic vessels was consistent with vascular stenosis. Parenteral nutrition was started and the patient remained pain free until her death. Conclusion Pain relief is an important therapeutic target in patients with cancer. In this case, abdominal pain was successfully managed only after the ischemic cause had been identified. The conventional analgesic therapy algorithm based on nonsteroidal anti-inflammatory drugs and opioids had been costly and pointless, whereas the simple withdrawal of oral feeding spared the patient of the discomfort of additional invasive procedures and allowed her to spend her remaining days in a completely pain-free state.

  17. Clinicopathological study of cardiac tamponade due to pericardial metastasis originating from gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Michiya Kobayashi; Takehiro Okabayashi; Ken Okamoto; Tsutomu Namikawa; Keijiro Araki

    2005-01-01

    AIM: To review the cases reported in the literature,examined their clinicopathological features, and evaluated the efficacy of different therapeutic modalities for this rare condition.METHODS: A search of the MEDLINE database revealed 16 cases of pericarditis carcinomatosa (PC)originating from GC reported in the literature between1982 and 2005. Additional detailed data were obtained from the authors of these studies for subsequent clinicopathological investigation. We have also described about a case study from our own clinic.RESULTS: The mean age of cases with pericarditis carcinomatosa originating from GC was 54 years.Females were diagnosed at a younger age (46.3 years)compared to males (58 years). The mean survival period after diagnosis was 4.5 mo. No statistical differences in the length of survival time were found between different therapeutic modalities, such as drainage, and local and/or systemic chemotherapy after drainage. However,three cases who underwent systemic chemotherapy survived for more than 10 mo. Cases that developed metachronous cardiac tamponade for more than 2years after the diagnosis of GC generally survived for a longer period of time, although this was not statistically significant. Multivariate analysis revealed that low levels of carcinoembryonic antigen (CEA), and CEA and/or cancer antigen 19-9 (CA 19-9) were associated with longer survival.CONCLUSION: Cases with low levels of CEA, and CEA and/or CA 19-9 should undergo systemic chemotherapy with or without local chemotherapy after drainage.

  18. Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2.

    Science.gov (United States)

    Biernacka, K M; Uzoh, C C; Zeng, L; Persad, R A; Bahl, A; Gillatt, D; Perks, C M; Holly, J M P

    2013-10-01

    Clinically relevant prostate cancer (PCa) is more frequent in Westernised societies and increasingly men have co-morbidities associated with a Western lifestyle, primarily diabetes, characterised by hyperinsulinaemia and hyperglycaemia. IGFs and their binding proteins (IGFBPs) are important mediators of the effects of nutrition on growth and play a key role in the development of PCa. We used DU145, PC3 and LNCaP PCa cell lines to examine how hyperglycaemia altered their response to docetaxel. Trypan Blue dye-exclusion assay was used to determine the percentage of cell death. Protein abundance was determined using western immunoblotting. Levels of IGFBP2 were measured using an ELISA. IGFBP2 gene silencing was achieved using siRNA technology. DNA methylation was assessed using combined bisulphide restriction analysis. Acetylation status of histones H3 and H4 associated with IGFBP2 gene was assessed using chromatin immunoprecipitation assay. Hyperglycaemia reduced docetaxel-induced apoptosis by 40% for DU145 cells and by 88% for LNCaP cells. This reduced cell death was mediated by a glucose-induced up-regulation of IGFBP2, as silencing IGFBP2 negated the survival effect of high glucose. Glucose increased IGFBP2 via increasing the acetylation of histones associated with the IGFBP2 gene promoter. This finding could have important implications in relation to therapeutic strategies as epigenetic modulation could be reversible.

  19. Momordica cochinchinensis Aril Extract Induced Apoptosis in Human MCF-7 Breast Cancer Cells.

    Science.gov (United States)

    Petchsak, Phuchong; Sripanidkulchai, Bungorn

    2015-01-01

    Momordica cochinchinensis Spreng (MC) has been used in traditional medicine due to its high carotenoid content. The objective of this study was to investigate mechanisms underlying apoptotic effects of MC on human MCF-7 breast cancer cells. A lycopene-enriched aril extract of MC (AE) showed cytotoxicity and antiestrogenicity to MCF-7 cells. On DAPI staining, AE induced cell shrinkage and chromatin condensation were evident. With flow cytometric analysis, AE increased the percentage of cells in an early apoptosis stage when compared with the control group. RT-PCR analysis showed AE to significantly increase the expression of the proapoptotic bax gene without effect on expression of the anti-apoptotic bcl-2 gene. Moreover, AE enhanced caspase 6, 8 and 9 activity. Taken together, we conclude that AE of MC fruit has anticancer effects on human MCF-7 breast cancer cells by induction of cell apoptosis via both intrinsic and extrinsic pathways of signaling.

  20. NASA space cancer risk model-2014: Uncertainties due to qualitative differences in biological effects of HZE particles

    Science.gov (United States)

    Cucinotta, Francis

    Uncertainties in estimating health risks from exposures to galactic cosmic rays (GCR) — comprised of protons and high-energy and charge (HZE) nuclei are an important limitation to long duration space travel. HZE nuclei produce both qualitative and quantitative differences in biological effects compared to terrestrial radiation leading to large uncertainties in predicting risks to humans. Our NASA Space Cancer Risk Model-2012 (NSCR-2012) for estimating lifetime cancer risks from space radiation included several new features compared to earlier models from the National Council on Radiation Protection and Measurements (NCRP) used at NASA. New features of NSCR-2012 included the introduction of NASA defined radiation quality factors based on track structure concepts, a Bayesian analysis of the dose and dose-rate reduction effectiveness factor (DDREF) and its uncertainty, and the use of a never-smoker population to represent astronauts. However, NSCR-2012 did not include estimates of the role of qualitative differences between HZE particles and low LET radiation. In this report we discuss evidence for non-targeted effects increasing cancer risks at space relevant HZE particle absorbed doses in tissue (Mars exploration will be described, and compared to those of our earlier NSCR-2012 model.

  1. Constitutional mosaic genome-wide uniparental disomy due to diploidisation: an unusual cancer-predisposing mechanism.

    Science.gov (United States)

    Romanelli, Valeria; Nevado, Julián; Fraga, Mario; Trujillo, Alex Martín; Mori, Maria Ángeles; Fernández, Luis; Pérez de Nanclares, Guiomar; Martínez-Glez, Víctor; Pita, Guillermo; Meneses, Heloisa; Gracia, Ricardo; García-Miñaur, Sixto; García de Miguel, Purificación; Lecumberri, Beatriz; Rodríguez, José Ignacio; González Neira, Anna; Monk, David; Lapunzina, Pablo

    2011-03-01

    Molecular studies in a patient with Beckwith-Wiedemann syndrome phenotype who developed two different tumours revealed an unexpected observation of almost complete loss of heterozygosity of all chromosomes. It is shown, by means of numerous molecular methods, that the absence of maternal contribution in somatic cells is due to high-degree (∼ 85%) genome-wide paternal uniparental disomy (UPD). The observations indicate that the genome-wide UPD results from diploidisation, and have important implications for genetic counselling and tumour surveillance for the growing number of UPD associated imprinting disorders.

  2. A rare case of repeated anastomotic recurrence due to tumor implantation after curative surgery for sigmoid colon cancer

    Directory of Open Access Journals (Sweden)

    Shiokawa Hiroyuki

    2007-08-01

    Full Text Available Abstract Background Anastomotic recurrence is often experienced at colocolic or colorectal anastomoses. Tumor cell implantation has been reported as the mechanism of anastomotic recurrence. However, anastomotic recurrence occurring repeatedly after curative surgery is rare. We herein report a rare case of repeated anastomotic recurrence after curative surgery for sigmoid colon cancer. Case presentation A 51-year-old man underwent radical surgery for sigmoid colon cancer. However, anastomotic recurrence developed three times during three years and six months after the initial operation in spite of irrigation with 5% povidone-iodine before anastomosis. The serum carcinoembryonic antigen (CEA level had been within normal limits after sigmoidectomy. Finally, the patient underwent abdominoperineal resection. The clinico-pathological findings revealed that possible tumor cell implantation caused these anastomotic recurrences. The patients survived without recurrence during the follow-up period of seven years and nine months. Conclusion We experienced a rare case of repeated anastomotic recurrence due to possible tumor implantation after curative surgery for sigmoid colon cancer; however the prognosis was ultimately very good. CEA monitoring was insensitive for detection of anastomotic recurrence in this case.

  3. Hypercalcemia in Lung Cancer due to Simultaneously Elevated PTHrP and Ectopic Calcitriol Production: First Case Report

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    Saed Nemr

    2017-01-01

    Full Text Available Calcitriol-mediated hypercalcemia has been reported in malignant lymphomas and granulomatous diseases but not in lung carcinoma. We describe a patient with squamous cell lung carcinoma with hypercalcemia and elevated calcitriol levels. A 60-year-old Caucasian male patient with stage IIIB squamous cell lung cancer developed hypercalcemia at 14.8 mg/dL two years after receiving chemotherapy and radiotherapy where labs showed a serum intact PTH: 7 pg/mL, PTHrP: 30 pmol/L, 1,25-hydroxyvitamin D (calcitriol: 76 pg/mL, and 25-hydroxyvitamin D levels: <4 ng/mL. Calcitriol levels were elevated despite undetectable 25-hydroxyvitamin D levels. There are no reported lung cancer cases with elevated calcitriol as an etiology of hypercalcemia. We believe that the elevated calcitriol levels in this case were due to a PTHrP-independent mechanism, possibly from either ectopic production of calcitriol in tumor cells or from increased activity of 1-alpha hydroxylase in the same cells. The patient died before the effects of prednisone therapy could be assessed. Studies are needed to investigate the cellular source of calcitriol and its role in hypercalcemia in patients with lung cancer.

  4. Heterogeneity between triple negative breast cancer cells due to differential activation of Wnt and PI3K/AKT pathways.

    Science.gov (United States)

    Martínez-Revollar, Gabriela; Garay, Erika; Martin-Tapia, Dolores; Nava, Porfirio; Huerta, Miriam; Lopez-Bayghen, Esther; Meraz-Cruz, Noemí; Segovia, José; González-Mariscal, Lorenza

    2015-11-15

    The lack of a successful treatment for triple-negative breast cancer demands the study of the heterogeneity of cells that constitute these tumors. With this aim, two clones from triple negative breast MDA-MB-231 cancer cells were isolated: One with fibroblast-like appearance (F) and another with semi-epithelial (SE) morphology. Cells of the F clone have a higher migration and tumorigenesis capacity than SE cells, suggesting that these cells are in a more advanced stage of epithelial to mesenchymal transformation. In agreement, F cells have a diminished expression of the tight junction proteins claudins 1 and 4, and an increased content of β-catenin. The latter is due to an augmented activity of the canonical Wnt route and of the EGFR/PI3K/mTORC2/AKT pathway favoring the cytoplasmic accumulation of β-catenin and its transcriptional activity. In addition, F cells display increased phosphorylation of β-catenin at Tyr654 by Src. These changes favor in F cells, the over-expression of Snail that promotes EMT. Finally, we observe that both F and SE cells display markers of cancer stem cells, which are more abundant in the F clone.

  5. MicroRNA Regulation of Human Breast Cancer Stem Cells

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    Yohei Shimono

    2015-12-01

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

  6. Cancer-selective death of human breast cancer cells by leelamine is mediated by bax and bak activation.

    Science.gov (United States)

    Sehrawat, Anuradha; Kim, Su-Hyeong; Hahm, Eun-Ryeong; Arlotti, Julie A; Eiseman, Julie; Shiva, Sruti S; Rigatti, Lora H; Singh, Shivendra V

    2017-02-01

    The present study is the first to report inhibition of breast cancer cell growth in vitro and in vivo and suppression of self-renewal of breast cancer stem cells (bCSC) by a pine bark component (leelamine). Except for a few recent publications in melanoma, anticancer pharmacology of this interesting phytochemical is largely elusive. Leelamine (LLM) dose-dependently inhibited viability of MDA-MB-231 (triple-negative), MCF-7 (estrogen receptor-positive), and SUM159 (triple-negative) human breast cancer cells in association with apoptotic cell death induction. To the contrary, a normal mammary epithelial cell line derived from fibrocystic breast disease and spontaneously immortalized (MCF-10A) was fully resistant to LLM-mediated cell growth inhibition and apoptosis induction. LLM also inhibited self-renewal of breast cancer stem cells. Apoptosis induction by LLM in breast cancer cells was accompanied by a modest increase in reactive oxygen species production, which was not due to inhibition of mitochondrial electron transport chain complexes. Nevertheless, ectopic expression of manganese superoxide dismutase conferred partial protection against LLM-induced cell death but only at a lower yet pharmacologically relevant concentration. Exposure of breast cancer cells to LLM resulted in (a) induction and/or activation of multidomain proapoptotic proteins Bax and Bak, (b) caspase-9 activation, and (c) cytosolic release of cytochrome c. Bax and Bak deficiency in immortalized fibroblasts conferred significant protection against cell death by LLM. Intraperitoneal administration of LLM (7.5 mg/kg; 5 times/wk) suppressed the growth of orthotopic SUM159 xenografts in mice without any toxicity. In conclusion, the present study provides critical preclinical data to warrant further investigation of LLM. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Hye-Yeon Han

    2014-01-01

    Full Text Available Background: The fruit of Kochia scoparia Scharder is widely used as a medicinal ingredient for the treatment of dysuria and skin diseases in China, Japan and Korea. Especially, K. scoparia had been used for breast masses and chest and flank pain. Objective: To investigate the anti-cancer effect of K. scoparia on breast cancer. Materials and Methods: We investigated the anti-cancer effects of K. scoparia, methanol extract (MEKS in vitro. We examined the effects of MEKS on the proliferation rate, cell cycle arrest, reactive oxygen species (ROS generation and activation of apoptosis-associated proteins in MDA-MB-231, human breast cancer cells. Results: MTT assay results demonstrated that MEKS decreased the proliferation rates of MDA-MB-231 cells in a dose-dependent manner with an IC 50 value of 36.2 μg/ml. MEKS at 25 μg/ml significantly increased the sub-G1 DNA contents of MDA-MB-231 cells to 44.7%, versus untreated cells. In addition, MEKS induced apoptosis by increasing the levels of apoptosis-associated proteins such as cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and cleaved Poly (ADP-ribose polymerase (PARP. Conclusion: These results suggest that MEKS inhibits cell proliferation and induces apoptosis in breast cancer cells and that MEKS may have potential chemotherapeutic value for the treatment of human breast cancer.

  8. Self-Sampling for Human Papillomavirus Testing among Non-Attenders Increases Attendance to the Norwegian Cervical Cancer Screening Programme

    DEFF Research Database (Denmark)

    Enerly, Espen; Bonde, Jesper; Schee, Kristina;

    2016-01-01

    Increasing attendance to screening offers the best potential for improving the effectiveness of well-established cervical cancer screening programs. Self-sampling at home for human papillomavirus (HPV) testing as an alternative to a clinical sampling can be a useful policy to increase attendance....... To determine whether self-sampling improves screening attendance for women who do not regularly attend the Norwegian Cervical Cancer Screening Programme (NCCSP), 800 women aged 25-69 years in the Oslo area who were due to receive a 2nd reminder to attend regular screening were randomly selected and invited...... alternative for increasing cervical cancer screening coverage in Norway....

  9. Resonance Raman Spectroscopy of human brain metastasis of lung cancer analyzed by blind source separation

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-Hui; Pu, Yang; Cheng, Gangge; Yu, Xinguang; Zhou, Lixin; Lin, Dongmei; Zhu, Ke; Alfano, Robert R.

    2017-02-01

    Resonance Raman (RR) spectroscopy offers a novel Optical Biopsy method in cancer discrimination by a means of enhancement in Raman scattering. It is widely acknowledged that the RR spectrum of tissue is a superposition of spectra of various key building block molecules. In this study, the Resonance Raman (RR) spectra of human metastasis of lung cancerous and normal brain tissues excited by a visible selected wavelength at 532 nm are used to explore spectral changes caused by the tumor evolution. The potential application of RR spectra human brain metastasis of lung cancer was investigated by Blind Source Separation such as Principal Component Analysis (PCA). PCA is a statistical procedure that uses an orthogonal transformation to convert a set of observations of possibly correlated variables into a set of values of linearly uncorrelated variables called principal components (PCs). The results show significant RR spectra difference between human metastasis of lung cancerous and normal brain tissues analyzed by PCA. To evaluate the efficacy of for cancer detection, a linear discriminant analysis (LDA) classifier is utilized to calculate the sensitivity, and specificity and the receiver operating characteristic (ROC) curves are used to evaluate the performance of this criterion. Excellent sensitivity of 0.97, specificity (close to 1.00) and the Area Under ROC Curve (AUC) of 0.99 values are achieved under best optimal circumstance. This research demonstrates that RR spectroscopy is effective for detecting changes of tissues due to the development of brain metastasis of lung cancer. RR spectroscopy analyzed by blind source separation may have potential to be a new armamentarium.

  10. Novel analogue of colchicine induces selective pro-death autophagy and necrosis in human cancer cells.

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    Kristen Larocque

    Full Text Available Colchicine, a natural product of Colchicum autumnae currently used for gout treatment, is a tubulin targeting compound which inhibits microtubule formation by targeting fast dividing cells. This tubulin-targeting property has lead researchers to investigate the potential of colchicine and analogs as possible cancer therapies. One major study conducted on an analogue of allocolchicine, ZD 6126, was halted in phase 2 clinical trials due to severe cardio-toxicity associated with treatment. This study involves the development and testing of novel allocolchicine analogues that hold non-toxic anti-cancer properties. Currently we have synthesized and evaluated the anti-cancer activities of two analogues; N-acetyl-O-methylcolchinol (NSC 51046 or NCME, which is structurally similar to ZD 6126, and (S-3,8,9,10-tetramethoxyallocolchicine (Green 1, which is a novel derivative of allocolchicine that is isomeric in the A ring. NSC 51046 was found to be non-selective as it induced apoptosis in both BxPC-3 and PANC-1 pancreatic cancer cells and in normal human fibroblasts. Interestingly, we found that Green 1 was able to modestly induce pro-death autophagy in these pancreatic cancer cells and E6-1 leukemia cells but not in normal human fibroblasts. Unlike colchicine and NSC 51046, Green 1 does not appear to affect tubulin polymerization indicating that it has a different molecular target. Green 1 also caused increased reactive oxygen species (ROS production in mitochondria isolated from pancreatic cancer cells. Furthermore, in vivo studies revealed that Green 1 was well tolerated in mice. Our findings suggest that a small change in the structure of colchicine has apparently changed the mechanism of action and lead to improved selectivity. This may lead to better selective treatments in cancer therapy.

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

    Science.gov (United States)

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

    2013-12-01

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

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

    Science.gov (United States)

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

    2016-01-04

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

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

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    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.

  14. An Automatic Framework for Assessing Breast Cancer Risk Due to Various Hormone Replacement Therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Brandt, Sami; Nielsen, Mads

    features describing the local elongatedness or stripiness, especially trained to see the effect of HRT thereby providing a non-subjective and reproducible measure and compare it to the BIRADS and percentage density measure. Objective: 1) To provide a framework for obtaining more accurate and sensitive....... No treatment induced significant density changes measured by BI-RADS. Both treatments made the area percentage density increase and the estradiol significantly. Both treatments induced significant changes in E2-specific heterogeneity scoring (E2-HER) and the raloxifene treatment a significantly higher change....... Conclusion: The proposed methodology shows substantial merit as it qualify considerably better in consistency and ROC statistics than both BIRADS and percentage density method. This approach can be trained to detect changes due to HRT. From the experiment, we also conclude that, Low dose transdermal...

  15. Immune reconstitution syndrome in a human immunodeficiency virus infected child due to giardiasis leading to shock

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    Sneha Nandy

    2015-01-01

    Full Text Available Human immunodeficiency virus (HIV-associated immune reconstitution inflammatory syndrome has been reported in association with tuberculosis, herpes zoster (shingles, Cryptococcus neoformans, Kaposi′s sarcoma, Pneumocystis pneumonia, hepatitis B virus, hepatitis C virus, herpes simplex virus, Histoplasma capsulatum, human papillomavirus, and Cytomegalovirus. However, it has never been documented with giardiasis. We present a 7-year-old HIV infected girl who developed diarrhea and shock following the initiation of antiretroviral therapy, and her stool showed the presence of giardiasis.

  16. Alterations of p63 and p73 in human cancers.

    Science.gov (United States)

    Inoue, Kazushi; Fry, Elizabeth A

    2014-01-01

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

  17. Cadmium-induced cancers in animals and in humans.

    Science.gov (United States)

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

    2007-01-01

    Discovered in the early 1800s, the use of cadmium and various cadmium salts started to become industrially important near the close of the 19th century, rapidly thereafter began to flourish, yet has diminished more recently. Most cadmium used in the United States is a byproduct from the smelting of zinc, lead, or copper ores, and is used to manufacture batteries. Carcinogenic activity of cadmium was discovered first in animals and only subsequently in humans. Cadmium and cadmium compounds have been classified as known human carcinogens by the International Agency for Research on Cancer and the National Toxicology Program based on epidemiologic studies showing a causal association with lung cancer, and possibly prostate cancer, and studies in experimental animals, demonstrating that cadmium causes tumors at multiple tissue sites, by various routes of exposure, and in several species and strains. Epidemiologic studies published since these evaluations suggest that cadmium is also associated with cancers of the breast, kidney, pancreas, and urinary bladder. The basic metal cationic portion of cadmium is responsible for both toxic and carcinogenic activity, and the mechanism of carcinogenicity appears to be multifactorial. Available information about the carcinogenicity of cadmium and cadmium compounds is reviewed, evaluated, and discussed.

  18. The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

    Directory of Open Access Journals (Sweden)

    F. Xavier Bosch

    2007-01-01

    Full Text Available Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI. The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs. The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC, the adenocarcinomas and the vast majority (i.e. > 95% of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL/Cervical Intraepithelial Neoplasia 3 (CIN3/Carcinoma in situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC for five or more years, smoking, high parity (five or more full term pregnancies and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT and Herpes Simplex Virus type 2 (HSV-2. Women exposed to the Human Immunodeficiency Virus (HIV are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.

  19. Cancer genes hypermethylated in human embryonic stem cells.

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    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.

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

    OpenAIRE

    Idrees Muhammad; Khan Khalida; Zahra Amreen; Faridi Rabia

    2011-01-01

    Abstract Human Papillomavirus (HPV) is the most common cause of cervical cancer. Cervical cancer being the second most common cancer after lung cancer, affecting women of different age groups; has a prevalence of about 20% in young sexually active women. Among different types of HPV, HPV16 the major strain causing this cancer and is sexually transmitted had been unnoticed for decades. Keeping in mind the multiple risk factors related with cervical cancer such as early age sexual activities, t...

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

    OpenAIRE

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

    2016-01-01

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

  2. THE CONSTRUCTION AND EXPRESSION OF THE MURINE SCFV GENE IN E.COLI AGAINST HUMAN CERVICAL CANCER

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Human cervical cancer is one of the most com-mon malignant neoplas m in women with a highdeath rate.It is characterized by a lot of factors andits pathological process is very complicated.In spiteof progress in the diagnosis and therapy of humancervical cancer,ti mely and accurate methods are ur-gently needed[1].Application of murine monoclonal antibodies(McAb)for the study of diagnosis and treat mentsfor human tumors is li mited by a number of fac-tors.Due to the progress in gene engineering andphage displ...

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

    Science.gov (United States)

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

    2016-09-01

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

  4. EMT is the dominant program in human colon cancer

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    Tollenaar Rob AEM

    2011-01-01

    Full Text Available Abstract Background Colon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging. Methods We performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1 of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence. Results Here we report that the most dominant pattern of intrinsic gene expression in colon cancer (PC1 was tightly correlated (Pearson R = 0.92, P -135 with the EMT signature-- both in gene identity and directionality. In a global micro-RNA screen, we further identified the most anti-correlated microRNA with PC1 as MiR200, known to regulate EMT. Conclusions These data demonstrate that the biology underpinning the native, molecular classification of human colon cancer--previously thought to be highly heterogeneous-- was clarified through the lens of comprehensive transcriptome analysis.

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

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    Schramm Gunnar

    2010-09-01

    Full Text Available Abstract Background Tumor therapy mainly attacks the metabolism to interfere the tumor's anabolism and signaling of proliferative second messengers. However, the metabolic demands of different cancers are very heterogeneous and depend on their origin of tissue, age, gender and other clinical parameters. We investigated tumor specific regulation in the metabolism of breast cancer. Methods For this, we mapped gene expression data from microarrays onto the corresponding enzymes and their metabolic reaction network. We used Haar Wavelet transforms on optimally arranged grid representations of metabolic pathways as a pattern recognition method to detect orchestrated regulation of neighboring enzymes in the network. Significant combined expression patterns were used to select metabolic pathways showing shifted regulation of the aggressive tumors. Results Besides up-regulation for energy production and nucleotide anabolism, we found an interesting cellular switch in the interplay of biosynthesis of steroids and bile acids. The biosynthesis of steroids was up-regulated for estrogen synthesis which is needed for proliferative signaling in breast cancer. In turn, the decomposition of steroid precursors was blocked by down-regulation of the bile acid pathway. Conclusion We applied an intelligent pattern recognition method for analyzing the regulation of metabolism and elucidated substantial regulation of human breast cancer at the interplay of cholesterol biosynthesis and bile acid metabolism pointing to specific breast cancer treatment.

  6. Identification of differentially expressed circular RNAs in human colorectal cancer.

    Science.gov (United States)

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

    2017-03-01

    Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.

  7. Integrated proteomic analysis of human cancer cells and plasma from tumor bearing mice for ovarian cancer biomarker discovery.

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    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.

  8. Human health and pollution due to solid waste incinetators (SWI: a selection of two recent well conducted studies

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    V. Gennaro

    2011-01-01

    Full Text Available Incinerators reduce the volume of visible waste, turning it into ashes and smoke which can cause local and global environmental pollution due to particulate matter (PM, dioxins, furans, hydrochloric acid, hydrocarbons, heavy metals, sulfur and nitrogen dioxides. In order to describe cancers and non-neoplastic diseases in populations exposed to incinerator pollution, the scientific literature available since 1987 has been selected on the basis of the best epidemiological evidences. In Italy, women who lived for at least 5 years in areas that were likely to be the most polluted by heavy metals, showed increased risk of death from all causes (relative risk, RR=1.17-1.54. In France, an incidence study found increases in all cancer risks both in males (RR=1.06 who resided in areas where dioxin pollution was estimated to be higher than it was in the referent areas (less dioxin polluted.

  9. Biochemical and biomolecular aspects of oxidative stress due to acute and severe hypoxia in human muscle tissue.

    Science.gov (United States)

    Corbucci, G G; Sessego, R; Velluti, C; Salvi, M

    1995-01-01

    Mitochondrial oxidative stress was investigated in severe and acute hypoxia and in reperfusion applied to human muscle tissues. The biochemical and biomolecular relationship between the response of the respiratory-chain enzymic complexes and the metabolism of specific hypoxia stress proteins (HSP) suggest an adaptive mechanism which antagonizes the oxidative damage due to acute and severe tissue hypoxia.

  10. Imaging Proteolysis by Living Human Breast Cancer Cells

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    Mansoureh Sameni

    2000-01-01

    Full Text Available Malignant progression is accompanied by degradation of extracellular matrix proteins. Here we describe a novel confocal assay in which we can observe proteolysis by living human breast cancer cells (BT20 and BT549 through the use of quenchedfluorescent protein substrates. Degradation thus was imaged, by confocal optical sectioning, as an accumulation of fluorescent products. With the BT20 cells, fluorescence was localized to pericellular focal areas that coincide with pits in the underlying matrix. In contrast, fluorescence was localized to intracellular vesicles in the BT549 cells, vesicles that also label for lysosomal markers. Neither intracellular nor pericellular fluorescence was observed in the BT549 cells in the presence of cytochalasin B, suggesting that degradation occurred intracellularly and was dependent on endocytic uptake of substrate. In the presence of a cathepsin 13-selective cysteine protease inhibitor, intracellular fluorescence was decreased ~90% and pericellular fluorescence decreased 67% to 96%, depending on the protein substrate. Matrix metallo protease inhibitors reduced pericellular fluorescence ~50%, i.e., comparably to a serine and a broad spectrum cysteine protease inhibitor. Our results suggest that: 1 a proteolytic cascade participates in pericellular digestion of matrix proteins by living human breast cancer cells, and 2 the cysteine protease cathepsin B participates in both pericellular and intracellular digestion of matrix proteins by living human breast cancer cells.

  11. A 2015 survey of established or potential epigenetic biomarkers for the accurate detection of human cancers.

    Science.gov (United States)

    Amacher, David E

    2016-07-01

    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.

  12. A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.

    Science.gov (United States)

    Goebel, Katie; Merner, Nancy D

    2017-05-01

    Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.

  13. Organ-specific radiation-induced cancer risk estimates due to radiotherapy for benign pigmented villonodular synovitis

    Science.gov (United States)

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

    2016-09-01

    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.

  14. Candidate serological biomarkers for cancer identified from the secretomes of 23 cancer cell lines and the human protein atlas.

    Science.gov (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

    2010-06-01

    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.

  15. CargoVibes: human response to vibration due to freight rail traffic

    NARCIS (Netherlands)

    Waddington, D.; Woodcock, J.; Smith, M.G.; Janssen, S.A.; Persson Waye, K.

    2015-01-01

    The aim of this paper is to present an overview of the research concerning human response to vibration conducted in the EU FP7 CargoVibes project. The European Union-funded project CargoVibes involved 10 partners from 8 nations and ran from April 2011 to April 2014. The project was concerned with ra

  16. CargoVibes: human response to vibration due to freight rail traffic

    NARCIS (Netherlands)

    Waddington, D.; Woodcock, J.; Smith, M.G.; Janssen, S.A.; Persson Waye, K.

    2015-01-01

    The aim of this paper is to present an overview of the research concerning human response to vibration conducted in the EU FP7 CargoVibes project. The European Union-funded project CargoVibes involved 10 partners from 8 nations and ran from April 2011 to April 2014. The project was concerned with

  17. Severe respiratory failure due to co-infection with human metapneumovirus and Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Masafumi Seki

    2014-01-01

    Full Text Available A 64-year-old male patient was admitted with respiratory failure, although chest X-rays revealed only mild bronchiolitis. Streptococcus pneumoniae, which usually presents as massive lobular pneumonia, was isolated from sputum, however, pan-pathogen screening using a next-generation sequencer also detected human metapneumovirus genome fragments.

  18. New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line.

    Science.gov (United States)

    Terawaki, Kiyoshi; Sawada, Yumi; Kashiwase, Yohei; Hashimoto, Hirofumi; Yoshimura, Mitsuhiro; Suzuki, Masami; Miyano, Kanako; Sudo, Yuka; Shiraishi, Seiji; Higami, Yoshikazu; Yanagihara, Kazuyoshi; Kase, Yoshio; Ueta, Yoichi; Uezono, Yasuhito

    2014-02-15

    Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss due to low fat-free mass levels, including reduced musculature, markedly worsens patient quality of life. Although stomach cancer patients have the highest incidence of cachexia, few experimental models for the study of stomach CC have been established. Herein, we developed stomach CC animal models using nude rats subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established from the human stomach cancer cell line MKN-45, and 85As2, derived from peritoneal dissemination of orthotopically implanted MKN45c185 cells in mice. Both CC models showed marked weight loss, anorexia, reduced musculature and muscle strength, increased inflammatory markers, and low plasma albumin levels; however, CC developed earlier and was more severe in rats implanted with 85As2 than in those implanted with MKN45cl85. Moreover, human leukemia inhibitory factor (LIF), a known cachectic factor, and hypothalamic orexigenic peptide mRNA levels increased in the models, whereas hypothalamic anorexigenic peptide mRNA levels decreased. Surgical removal of the tumor not only abolished cachexia symptoms but also reduced plasma LIF levels to below detectable limits. Importantly, oral administration of rikkunshito, a traditional Japanese medicine, substantially ameliorated CC-related anorexia and body composition changes. In summary, our novel peritoneal dissemination-derived 85As2 rat model developed severe cachexia, possibly caused by LIF from cancer cells, that was ameliorated by rikkunshito. This model should provide a useful tool for further study into the mechanisms and treatment of stomach CC.

  19. A Review on Level of Specific Absorption Rate Due to High Power Transmission Lines: Analysis toward Human Position Posture

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    Ghazali Z.

    2016-01-01

    Full Text Available The main contribution of this project is the development of a homogeneous model of a man to presents the specific absorption rate (SAR due to high power transmission line. As a low frequency application under high power transmission line of 50 Hz in electrical engineering, to studies the influence of human’s posture on specific absorption rate. This project designs two types of human body which one design uses most cylinder block and another design use brick block where both blocks have a different value of mesh cells. For each design has four types of posture are standing, sitting, arms up and arms out by using Computer Simulation Technology (CST Studio Software. This analysis does toward for four types of the human position postures because each posture has different value of specific absorption rate (SAR based on the size of the mesh cells of the design. Based on two designs of the human body, the lowest of the mesh cells value will reduce time to simulate SAR. For each posture has different value of SAR for each part of the human body because the whole human body has different types of tissues. Therefore, the CST studio software uses extremely to simulate the SAR value toward human position posture due to high power transmission line.

  20. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

    Science.gov (United States)

    Koç, Zeliha

    2015-01-01

    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…

  1. University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

    Science.gov (United States)

    Koç, Zeliha

    2015-01-01

    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…

  2. 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.

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

    OpenAIRE

    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

    2010-01-01

    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...

  4. Are 20 human papillomavirus types causing cervical cancer?

    Science.gov (United States)

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

    2014-12-01

    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

  5. A lincRNA connected to cell mortality and epigenetically-silenced in most common human cancers

    Science.gov (United States)

    Vrba, Lukas; Garbe, James C; Stampfer, Martha R; Futscher, Bernard W

    2015-01-01

    Immortality is an essential characteristic of human carcinoma cells. We recently developed an efficient, reproducible method that immortalizes human mammary epithelial cells (HMEC) in the absence of gross genomic changes by targeting 2 critical senescence barriers. Consistent transcriptomic changes associated with immortality were identified using microarray analysis of isogenic normal finite pre-stasis, abnormal finite post-stasis, and immortal HMECs from 4 individuals. A total of 277 genes consistently changed in cells that transitioned from post-stasis to immortal. Gene ontology analysis of affected genes revealed biological processes significantly altered in the immortalization process. These immortalization-associated changes showed striking similarity to the gene expression changes seen in The Cancer Genome Atlas (TCGA) clinical breast cancer data. The most dramatic change in gene expression seen during the immortalization step was the downregulation of an unnamed, incompletely annotated transcript that we called MORT, for mortality, since its expression was closely associated with the mortal, finite lifespan phenotype. We show here that MORT (ZNF667-AS1) is expressed in all normal finite lifespan human cells examined to date and is lost in immortalized HMEC. MORT gene silencing at the mortal/immortal boundary was due to DNA hypermethylation of its CpG island promoter. This epigenetic silencing is also seen in human breast cancer cell lines and in a majority of human breast tumor tissues. The functional importance of DNA hypermethylation in MORT gene silencing is supported by the ability of 5-aza-2′-deoxycytidine to reactivate MORT expression. Analysis of TCGA data revealed deregulation of MORT expression due to DNA hypermethylation in 15 out of the 17 most common human cancers. The epigenetic silencing of MORT in a large majority of the common human cancers suggests a potential fundamental role in cellular immortalization during human carcinogenesis. PMID

  6. Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin": a novel strategy for human cancer therapy

    Directory of Open Access Journals (Sweden)

    Maitra Amarnath

    2007-04-01

    Full Text Available Abstract Background Curcumin, a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa, has potent anti-cancer properties as demonstrated in a plethora of human cancer cell line and animal carcinogenesis models. Nevertheless, widespread clinical application of this relatively efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility, and consequently, minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic agents like curcumin dispersible in aqueous media, thus circumventing the pitfalls of poor solubility. Results We have synthesized polymeric nanoparticle encapsulated formulation of curcumin – nanocurcumin – utilizing the micellar aggregates of cross-linked and random copolymers of N-isopropylacrylamide (NIPAAM, with N-vinyl-2-pyrrolidone (VP and poly(ethyleneglycolmonoacrylate (PEG-A. Physico-chemical characterization of the polymeric nanoparticles by dynamic laser light scattering and transmission electron microscopy confirms a narrow size distribution in the 50 nm range. Nanocurcumin, unlike free curcumin, is readily dispersed in aqueous media. Nanocurcumin demonstrates comparable in vitro therapeutic efficacy to free curcumin against a panel of human pancreatic cancer cell lines, as assessed by cell viability and clonogenicity assays in soft agar. Further, nanocurcumin's mechanisms of action on pancreatic cancer cells mirror that of free curcumin, including induction of cellular apoptosis, blockade of nuclear factor kappa B (NFκB activation, and downregulation of steady state levels of multiple pro-inflammatory cytokines (IL-6, IL-8, and TNFα. Conclusion Nanocurcumin provides an opportunity to expand the clinical repertoire of this efficacious agent by enabling ready aqueous dispersion. Future studies utilizing nanocurcumin are warranted in pre-clinical in vivo models of cancer and other diseases that might benefit

  7. In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Giuseppe Perrone

    Full Text Available Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23% of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001; in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively. No relationship was evident with tumour size (T and regional lymph node (N status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004. Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.

  8. Massive Bleeding as the First Clinical Manifestation of Metastatic Prostate Cancer due to Disseminated Intravascular Coagulation with Enhanced Fibrinolysis

    Science.gov (United States)

    Lopes, João Madeira; Victorino, Rui M. M.; Meneses Santos, João

    2016-01-01

    Disseminated intravascular coagulation (DIC) is the most frequent coagulation disorder associated with metastatic prostate adenocarcinoma. However, DIC with enhanced fibrinolysis as an initial presentation of prostate cancer is extremely rare. The appropriate treatment to control bleeding in these situations is challenging, controversial, and based on isolated case reports in the literature. A 66-year-old male presented at the emergency department with acute severe spontaneous ecchymoses localized to the limbs, laterocervical hematoma, and hemothorax. Prostate specific antigen level was 385 μg/L, bone scintigraphy revealed multiple bone metastases, and prostate biopsy confirmed adenocarcinoma (Gleason 9; 4 + 5). Laboratory investigation showed a pattern of enhanced fibrinolysis rather than the more common intravascular coagulation mechanism. Epsilon aminocaproic acid in monotherapy was initiated with a clear and rapid control of bleeding manifestations. This rare case of massive bleeding due to DIC with enhanced fibrinolysis as the first manifestation of prostate cancer suggests that in selected cases where the acute bleeding dyscrasia is clearly associated with a dominant fibrinolysis mechanism it is possible to use an approach of monotherapy with antifibrinolytics. PMID:27803823

  9. A Thai family with hereditary pancreatitis and increased cancer risk due to a mutation in PRSS1 gene

    Institute of Scientific and Technical Information of China (English)

    Theeraphong Pho-Iam; Wanna Thongnoppakhun; Pa-Thai Yenchitsomanus; Chanin Limwongse

    2005-01-01

    AIM: To investigate mutation of serine protease 1-cationic trypsinogen (CT, PRSS1) gene in members of a Thai family with hereditary pancreatitis and pancreatic cancer.METHODS: Polymerase chain reaction and direct sequencing were performed to analyze the PRSS1 gene in two members of the family affected by pancreatitis.Allele specific amplification (ASA) method was then developed to detect the mutation of the PRSS1 gene in all available members of the family and normal control subjects.RESULTS: A cytosine (C) to thymine (T) mutation at position 2441 (g.2441C>T) of the PRSS1 gene, which results in a substitution of arginine by cysteine at position 116 (R116C) of CT, was identified by direct sequencing in both clinically affected members of the family but was not found in the unaffected member. This mutation, which might be arising from deamination of methylated cytosine in CpG dinucleotide of codon 116 (CGT>FGT), was also detected by the ASA method in the two affected members and a proband's brother but was not observed in unaffected members and 54 normal control subjects.CONCLUSION: Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1gene.

  10. Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and Vomiting due to Metastatic Brain Tumors of Rectal Cancer

    Directory of Open Access Journals (Sweden)

    M. Suzuki

    2014-01-01

    Full Text Available Brain lesions originating from metastasis of colorectal cancer represent 3-5% of all brain metastases and are relatively rare. Of all distant metastases of colorectal cancer, those to the liver are detected in 22-29% of cases, while those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for metastatic brain tumors include surgery, radiotherapy, chemotherapy and supportive care with steroids, etc. Untreated patients exhibit a median survival of only approximately 1 month. The choice of treatment for brain metastasis depends on the number of lesions, the patient's general condition, nerve findings and presence of other metastatic lesions. We herein report the case of a 78-year-old male who presented with brain metastases originating from rectal carcinoma. He suffered from nausea, vomiting, anorexia and vertigo during body movement. He received antiemetics, glycerol and whole brain radiation therapy; however, these treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25 mg every night. The persistent nausea disappeared the next day, and the frequency of vomiting subsequently decreased. The patient was able to consume solid food. Olanzapine is an antipsychotic that has recently been used as palliative therapy for refractory nausea and vomiting in patients receiving chemotherapy. We consider that olanzapine was helpful as a means of supportive care for the treatment of nausea and vomiting due to brain metastasis.

  11. Human brain cancer studied by resonance Raman spectroscopy

    Science.gov (United States)

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

    2012-11-01

    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.

  12. Posttraumatic Stress Disorder After Bereavement: Early Psychological Sequelae of Losing a Close Relative Due to Terminal Cancer

    DEFF Research Database (Denmark)

    Kristensen, T. E.; Elklit, A.; Karstoft, K. I.

    2012-01-01

    Very few studies have investigated posttraumatic stress disorder (PTSD) as a consequence of bereavement from terminal illness. Therefore, knowledge on the traumatizing effects of bereavement and risk factors for traumatization from bereavement is rather sparse. This study investigated prevalence...... and predictors of PTSD in a group of people who had recently lost a close relative due to incurable cancer. The participants were 132 persons who were assessed with the Harvard Trauma Questionnaire, the Trauma Symptom Checklist, and the Crisis Support Scale. One month after the loss, 29.5% of the subjects had...... clinical PTSD and an additional 26.2% reached a subclinical PTSD level. Negative affectivity, social support, and locus of control in relation to the loss predicted 57% of the variance in PTSD severity. A focus on these risk factors in early assessment after bereavement will help identify subjects at risk...

  13. Prevention of Infection Due to Pneumocystis spp. in Human Immunodeficiency Virus-Negative Immunocompromised Patients

    OpenAIRE

    Rodriguez, Martin; Fishman, Jay A.

    2004-01-01

    Pneumocystis infection in humans was originally described in 1942. The organism was initially thought to be a protozoan, but more recent data suggest that it is more closely related to the fungi. Patients with cellular immune deficiencies are at risk for the development of symptomatic Pneumocystis infection. Populations at risk also include patients with hematologic and nonhematologic malignancies, hematopoietic stem cell transplant recipients, solid-organ recipients, and patients receiving i...

  14. Response of Degarelix treatment in human prostate cancer monitored by HR-MAS (1)H NMR spectroscopy.

    Science.gov (United States)

    Madhu, Basetti; Shaw, Greg L; Warren, Anne Y; Neal, David E; Griffiths, John R

    The androgen receptor (AR) is the master regulator of prostate cancer cell metabolism. Degarelix is a novel gonadotrophin-releasing hormone blocker, used to decrease serum androgen levels in order to treat advanced human prostate cancer. Little is known of the rapid metabolic response of the human prostate cancer tissue samples to the decreased androgen levels. To investigate the metabolic responses in benign and cancerous tissue samples from patients after treatment with Degarelix by using HRMAS (1)H NMR spectroscopy. Using non-destructive HR-MAS (1)H NMR spectroscopy we analysed the metabolic changes induced by decreased AR signalling in human prostate cancer tissue samples. Absolute concentrations of the metabolites alanine, lactate, glutamine, glutamate, citrate, choline compounds [t-choline = choline + phosphocholine (PC) + glycerophosphocholine (GPC)], creatine compounds [t-creatine = creatine (Cr) + phosphocreatine (PCr)], taurine, myo-inositol and polyamines were measured in benign prostate tissue samples (n = 10), in prostate cancer specimens from untreated patients (n = 7) and prostate cancer specimens from patients treated with Degarelix (n = 6). Lactate, alanine and t-choline concentrations were significantly elevated in high-grade prostate cancer samples when compared to benign samples in untreated patients. Decreased androgen levels resulted in significant decreases of lactate and t-choline concentrations in human prostate cancer biopsies. The reduced concentrations of lactate and t-choline metabolites due to Degarelix could in principle be monitored by in vivo (1)H MRS, which suggests that it would be possible to monitor the effects of physical or chemical castration in patients by that non-invasive method.

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

    Science.gov (United States)

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

    2015-01-01

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

  16. 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

    2006-01-01

    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.

  17. Princess takamatsu symposium on DNA repair and human cancers.

    Science.gov (United States)

    Loeb, Lawrence A; Nishimura, Susumu

    2010-06-01

    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.

  18. Human papillomavirus genotypes distribution in 175 invasive cervical cancer cases from Brazil

    Science.gov (United States)

    2013-01-01

    Background Invasive cervical cancer is the second most common malignant tumor affecting Brazilian women. Knowledge on Human Papillomavirus (HPV) genotypes in invasive cervical cancer cases is crucial to guide the introduction and further evaluate the impact of new preventive strategies based on HPV. We aimed to provide updated comprehensive data about the HPV types’ distribution in patients with invasive cervical cancer. Methods Fresh tumor tissue samples of histologically confirmed invasive cervical cancer were collected from 175 women attending two cancer reference hospitals from São Paulo State: ICESP and Hospital de Câncer de Barretos. HPV detection and genotyping were performed by the Linear Array HPV Genotyping Test (Roche Molecular Diagnostics, Pleasanton,USA). Results 170 out of 172 valid samples (99%) were HPV DNA positive. The most frequent types were HPV16 (77.6%), HPV18 (12.3%), HPV31 (8.8%), HPV33 (7.1%) and HPV35 (5.9%). Most infections (75%) were caused by individual HPV types. Women with adenocarcinoma were not younger than those with squamous cell carcinoma, as well, as women infected with HPV33 were older than those infected by other HPV types. Some differences between results obtained in the two hospitals were observed: higher overall prevalence of HPV16, absence of single infection by HPV31 and HPV45 was verified in HC-Barretos in comparison to ICESP patients. Conclusions To our knowledge, this is one of the largest studies made with fresh tumor tissues of invasive cervical cancer cases in Brazil. This study depicted a distinct HPV genotype distribution between two centers that may reflect the local epidemiology of HPV transmission among these populations. Due to the impact of these findings on cervical cancer preventive strategies, extension of this investigation to routine screening populations is warranted. PMID:23883423

  19. New methods for dete rmining the relative load due to physical effort of the human body

    Directory of Open Access Journals (Sweden)

    Józef Szubert

    2014-04-01

    Full Text Available Background: The relative physical load (% VO2max is the quotient of oxygen uptake (Vo2 during physical effort and maximum oxygen uptake (VO2max by the human body. For this purpose the stress test must be performed. The relative load shows a high correlation with minute ventilation, cardiac output, heart rate, stroke volume, increased concentrations of catecholamines in the blood, inner temperature, weight, height and human body surface area. The relative load is a criterion for the maximum workloads admissible for healthy and sick workers. Besides, the classification of effort can be more precise when based on the relative load than on the energy output. Material and Methods: Based on our own and international empirical evidence and the laws of heat transfer and fluid mechanics, a model of temperature control system has been developed, involving the elements of human cardiovascular and respiratory systems. Using this model, we have been able to develop our own methods of determining the relative load, applying only the body core temperature (TW or heart rate within one minute (HR, body mass (m, height (H, and body surface area (AD instead of VO2max. Results: The values of the relative physical load (% VO2max obtained by using our own methods do not differ significantly from those obtained by other methods and by other researchers. Conclusions: The developed methods for determining the relative physical load (% VO2max do not require the exercise test to be performed, therefore, they may be considered (after verification in an experimental study a feasible alternative to current methods. Med Pr 2014;65(2:189–195

  20. No evidence for clonal selection due to lentiviral integration sites in human induced pluripotent stem cells.

    Science.gov (United States)

    Winkler, Thomas; Cantilena, Amy; Métais, Jean-Yves; Xu, Xiuli; Nguyen, Anh-Dao; Borate, Bhavesh; Antosiewicz-Bourget, Jessica E; Wolfsberg, Tyra G; Thomson, James A; Dunbar, Cynthia E

    2010-04-01

    Derivation of induced pluripotent stem (iPS) cells requires the expression of defined transcription factors (among Oct3/4, Sox2, Klf4, c-Myc, Nanog, and Lin28) in the targeted cells. Lentiviral or standard retroviral gene transfer remains the most robust and commonly used approach. Low reprogramming frequency overall, and the higher efficiency of derivation utilizing integrating vectors compared to more recent nonviral approaches, suggests that gene activation or disruption via proviral integration sites (IS) may play a role in obtaining the pluripotent phenotype. We provide for the first time an extensive analysis of the lentiviral integration profile in human iPS cells. We identified a total of 78 independent IS in eight recently established iPS cell lines derived from either human fetal fibroblasts or newborn foreskin fibroblasts after lentiviral gene transfer of Oct4, Sox2, Nanog, and Lin28. The number of IS ranged from 5 to 15 IS per individual iPS clone, and 75 IS could be assigned to a unique chromosomal location. The different iPS clones had no IS in common. Expression analysis as well as extensive bioinformatic analysis did not reveal functional concordance of the lentiviral targeted genes between the different clones. Interestingly, in six of the eight iPS clones, some of the IS were found in pairs, integrated into the same chromosomal location within six base pairs of each other or in very close proximity. Our study supports recent reports that efficient reprogramming of human somatic cells is not dependent on insertional activation or deactivation of specific genes or gene classes.

  1. [Pseudo-tumoral human African trypanosomiasis due to Trypanosoma gambiense. Clinical and tomodensitometry study (author's transl)].

    Science.gov (United States)

    Poisson, M; Bleibel, J M; Regnier, A; Mashaly, R; Le Bigot, P; Danis, M; Buge, A

    The authors report an observation of african trypanosomiasis due to Trypanosoma Gambiense, clinical signs included massive and progressive hemiplegia, papillary edema and vascular shift from median line at arteriography. These pseudo tumoral clinical features are unusual in this disease. Asymetrical heterogenous hypodensities of the centrum semioval are dominant in the initial CT scanner aspect. The confrontation of CT scanner images to the clinical and evolutive data suggests the presence of associated cerebral edema and demyelination. With treatment, hypodensities were regressing while images of subcortical atrophy appeared. Lastly, in spite of severe general signs and the importance of neurological deficit, arsenical treatment associated with high doses of corticotherapy lead to a rapid improvement.

  2. Growth suppressive efficacy of human lak cells against human lung-cancer implanted into scid mice.

    Science.gov (United States)

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

    1995-06-01

    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.

  3. Contact-independent cell death of human microglial cells due to pathogenic Naegleria fowleri trophozoites.

    Science.gov (United States)

    Kim, Jong-Hyun; Kim, Daesik; Shin, Ho-Joon

    2008-12-01

    Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increase of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.

  4. Human brain microvascular endothelial cells resist elongation due to shear stress.

    Science.gov (United States)

    Reinitz, Adam; DeStefano, Jackson; Ye, Mao; Wong, Andrew D; Searson, Peter C

    2015-05-01

    Endothelial cells in straight sections of vessels are known to elongate and align in the direction of flow. This phenotype has been replicated in confluent monolayers of bovine aortic endothelial cells and human umbilical vein endothelial cells (HUVECs) in cell culture under physiological shear stress. Here we report on the morphological response of human brain microvascular endothelial cells (HBMECs) in confluent monolayers in response to shear stress. Using a microfluidic platform we image confluent monolayers of HBMECs and HUVECs under shear stresses up to 16 dyne cm(-2). From live-cell imaging we quantitatively analyze the cell morphology and cell speed as a function of time. We show that HBMECs do not undergo a classical transition from cobblestone to spindle-like morphology in response to shear stress. We further show that under shear stress, actin fibers are randomly oriented in the cells indicating that there is no cytoskeletal remodeling. These results suggest that HBMECs are programmed to resist elongation and alignment under shear stress, a phenotype that may be associated with the unique properties of the blood-brain barrier.

  5. 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

    1998-01-01

    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

  6. 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

    1998-01-01

    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

  7. 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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  9. 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

    2014-01-01

    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....

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

    Directory of Open Access Journals (Sweden)

    Sidorova JM

    2014-12-01

    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

  11. Biological effects on human health due to radiofrequency/microwave exposure

    DEFF Research Database (Denmark)

    Breckenkamp, Jürgen; Berg, Gabriele; Blettner, Maria

    2003-01-01

    electromagnetic pulses similar to those after a nuclear explosion. In all studies (except one that used a qualitative job-exposure-matrix) either the duration of occupational work as an approximation to actual exposure was determined or a simple yes/no differentiation was used based on a definition of high......We evaluated the methods and results of nine cohort studies dealing with the biological effects on human health from exposure to radiofrequencies/microwaves, published between 1980 and 2002. The size of the cohorts varied between 304 (3,362 person years) and nearly 200,000 persons (2.7 million...... person years). As exposures were defined: dielectric heaters in a plastic manufacturing plant, working with radio devices (professional and amateur), production of wireless communication technologies, radar devices of the Canadian police, radar units used by the military as well as artificially produced...

  12. Electronic tracking of human resource skills and knowledge, just in time training, manageable due diligence

    Energy Technology Data Exchange (ETDEWEB)

    Kolodziej, M.A. [Quick Test International Inc., (Canada). Canadian Technology Human Resource Board; Baker, O. [KeySpan Energy Canada, Calgary, AB (Canada)

    2001-06-01

    KeySpan Energy Canada is in the process of obtaining recognition of various occupational profiles including pipeline operators, inspectors, and field and plant operators from various certifying organizations. The process of allowing individuals to obtain certification is recognized by Canadian Technology Human Resources Board as a step towards national standards for technologists and technicians. Proven competency is a must for workers in todays oil industry in response to increasingly stringent government safety regulations, environmental concerns and high public scrutiny. Quick Test international Inc. has developed a management tool in collaboration with end users at KeySpan Energy Canada. It is an electronic, Internet based competency tool for tracking personal competencies and maintaining continued competency. Response to the tool has been favourable. 2 refs., 4 figs.

  13. Emerging infections due to filamentous fungi in humans and animals: only the tip of the iceberg?

    Science.gov (United States)

    Debourgogne, Anne; Dorin, Joséphine; Machouart, Marie

    2016-06-01

    Over the last few decades, the number of patients susceptible to invasive filamentous fungal infections has steadily increased, especially in populations suffering from hematological diseases. The pathogens responsible for such mycoses are now quite well characterized, such as Aspergillus spp. - the most commonly isolated mold -, Mucorales, Fusarium spp., Scedosporium spp. or melanized fungi. An increase in the incidence of this category of 'emerging' fungi has been recently highlighted, evoking a shift in fungal ecology. Starting from these medical findings, taking a step back and adopt a wider perspective offers possible explanations of this phenomenon on an even larger scale than previously reported. In this review, we illustrate the link between emerging fungi in medicine and changes in ecology or human behaviours, and we encourage integrative approaches to apprehend the adverse effects of progress and develop preventive measures in vast domains, such as agriculture or medicine. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  14. Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients.

    Science.gov (United States)

    Rodriguez, Martin; Fishman, Jay A

    2004-10-01

    Pneumocystis infection in humans was originally described in 1942. The organism was initially thought to be a protozoan, but more recent data suggest that it is more closely related to the fungi. Patients with cellular immune deficiencies are at risk for the development of symptomatic Pneumocystis infection. Populations at risk also include patients with hematologic and nonhematologic malignancies, hematopoietic stem cell transplant recipients, solid-organ recipients, and patients receiving immunosuppressive therapies for connective tissue disorders and vasculitides. Trimethoprim-sulfamethoxazole is the agent of choice for prophylaxis against Pneumocystis unless a clear contraindication is identified. Other options include pentamidine, dapsone, dapsone-pyrimethamine, and atovaquone. The risk for PCP varies based on individual immune defects, regional differences, and immunosuppressive regimens. Prophylactic strategies must be linked to an ongoing assessment of the patient's risk for disease.

  15. Kalilo river pollution due to limited land settlement and human behavior along the Kalilo riverbanks

    Directory of Open Access Journals (Sweden)

    H. Suprihatin

    2014-04-01

    Full Text Available Kalilo River is one of the sights that is always visible to the people who come cross to Banyuwangi. However, there are many trash and animal (human defecation in the Kalilo river that may impair the beautiful scenery of the river. This study was aimed to measure whether or not the physical, chemical and bacteriological parameters of the river water meets the criteria of Class II Water Quality Standard. River water samples were collected from upstream, midstream and downstream of the Kalilo river for suspended solid, sulfate, total phosphate, BOD, COD, DO, anionic detergent, total coliforms. Results of water analysis showed that the suspended solid, sulfate, total phosphate, BOD, COD, DO, anionic detergent, total coliform contents exceeded standard limit of the of Class II Water Quality Standard. Such conditions affect physical, environmental and economic development of the district. A Communal Waste Treatment Plant, Anaerobic Baffle Reactor (ABR, is recommended to overcome the problems.

  16. Physical geography and the study of human vulnerability due to natural and other hazards

    Directory of Open Access Journals (Sweden)

    Karel Natek

    2003-12-01

    Full Text Available Physical geography in Slovenia has achieved a significant level of knowledge on natural and other hazards, after studying these phenomena since 1950s. These extremely complex features are clearly showing the interconnections between the nature and man and the increasing vulnerability of modern societies. The article is based on geographical approach to hazards, which does not consider them as casual events, but as constituent parts of the environment, including very different ways of human adaptation. The rapid development of science and technology have even increased our vulnerability and direct exposure to hazards, what is considered as new challenge to physical geographers in looking for new approaches to increase the possibilities of sustainable 'co-existence' with natural and other hazards.

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

    Institute of Scientific and Technical Information of China (English)

    王旭

    2012-01-01

    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

  18. Human dirofilariasis due to Dirofilaria repens in Ukraine, an emergent zoonosis: epidemiological report of 1465 cases.

    Science.gov (United States)

    Sałamatin, Rusłan V; Pavlikovska, Tamara M; Sagach, Olga S; Nikolayenko, Svitlana M; Kornyushin, Vadim V; Kharchenko, Vitaliy O; Masny, Aleksander; Cielecka, Danuta; Konieczna-Sałamatin, Joanna; Conn, David Bruce; Golab, Elzbieta

    2013-12-01

    The filarial nematode Dirofilaria repens is currently considered to be one of the most extensively spreading human and animal parasites in Europe. In Ukraine, reporting cases of dirofilariasis has been mandatory since 1975, and the disease was included in the national surveillance system for notifiable diseases. Up until December 31st 2012, a total of 1533 cases have been registered, with 1465 cases occurring within the previous 16 years. Most of the cases of dirofilariasis were registered in 6 regions: Kyiv, and the Donetsk, Zaporizhzhya, Dnipropetrovsk, Kherson and Chernihiv oblasts. In the years 1997-2002 the highest incidence rate was noted in the Kherson oblast in the south of the country (9.79 per 100 000 people), and the lowest in western Ukraine (0.07-1.68 per 100 000 people). D. repens infections were registered in all oblasts. Parasitic lesions were most often located in the head, the subconjunctival tissue and around the eyes. D. repens lesions were also found in the limbs, torso, male sexual organs, and female mammary glands. Dirofilariasis was diagnosed in persons aged from 11 months to 90 years old, most often among people between 21-40 years of age. Most patients had only one parasitic skin lesion; the majority of isolated nematodes were female. The results of our analysis point to a constant increase in D. repens dirofilariasis incidence in humans in Ukraine. Despite educational efforts, infections have become more frequent and the territory in which the disease occurs has enlarged to encompass the whole of Ukraine. Nevertheless, the Ukrainian sanitary-epidemiological services managed to achieve some measure of success, e.g. by creating a registration system for D. repens infections and establishing proper diagnostics for the disease.

  19. AXL is an oncotarget in human colorectal cancer

    Science.gov (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

    2015-01-01

    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

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

    OpenAIRE

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

    2016-01-01

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

  1. Prognostic value of metastin expression in human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Kawaguchi Yoshiya

    2009-01-01

    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.

  2. Human Papillomavirus and Tonsillar and Base of Tongue Cancer

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    Torbjörn Ramqvist

    2015-03-01

    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.

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

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    Arul eNarayanasamy

    2013-08-01

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

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

    Science.gov (United States)

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

    2003-04-01

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

  5. Human Auditory Communication Disturbances Due To Road Traffic Noise Pollution in Calabar City, Nigeria

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    E. O. Obisung

    2016-10-01

    Full Text Available Study on auditory communication disturbances due to road transportation noise in Calabar Urban City, Nigeria was carried out. Both subjective (psycho-social and objective (acoustical measurements were made for a period of twelve months. Questionnaire/interview schedules containing pertinent questions were administered randomly to 500 respondents of age 15 year and above, who were also with a good level of literacy skills (reading writing and leaving in houses sited along or parallel to busy road, with heavy traffic volume for at least three (3 years. The questionnaires provided the psycho-social responses of respondents used in this study, their reactions to road traffic noise effect on communication activities (listening to radio, listening and watching television, verbal communication between individuals, speech communication and telephone/GSM communication. Acoustical measurements were made at the facades of respondents' houses facing the road using precision digital sound level meter, Bruel and Kjaer (B & K type 732 following ISO standards 1996. The meter read the road traffic noise levels at measurement sites (facades of respondents' houses. From the results obtained in this study residents of Calabar City suffer serious communication interferences as a result of excessive road traffic noise levels. The noise indices used for this study were LAeq and Ldn. Noise levels obtained were over 93 dB(A (daytime and 60 dB(A, (nighttime for LAeq and 80 dB(A for Ldn. These far exceeded the recommended theoretical values of 45-55 and 70 dB(A, for LAeqand Ldn respectively. A-weighted sound pressure level (SPLS range between 87.0 and 100.0 dB(A. In this study it was also observed that over 98% of the respondents reported their television watching/radio listening disturbed, 99% recorded telephone/GSM disturbed, and 98% reported face-to-face verbal conversation disturbed, and 98% reported speech communication disturbed. The background noise levels (BNLs of

  6. Prognostic value of metastin expression in human pancreatic cancer

    OpenAIRE

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

    2009-01-01

    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...

  7. Prognostic value of metastin expression in human pancreatic cancer

    OpenAIRE

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

    2009-01-01

    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...

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

    OpenAIRE

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

    2009-01-01

    [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...

  9. Involuntary human hand movements due to FM radio waves in a moving van.

    Science.gov (United States)

    Huttunen, P; Savinainen, A; Hänninen, Osmo; Myllylä, R

    2011-06-01

    Finland TRACT Involuntary movements of hands in a moving van on a public road were studied to clarify the possible role of frequency modulated radio waves on driving. The signals were measured in a direct 2 km test segment of an international road during repeated drives to both directions. Test subjects (n=4) had an ability to sense radio frequency field intensity variations of the environment. They were sitting in a minivan with arm movement detectors in their hands. A potentiometer was used to register the hand movements to a computer which simultaneously collected data on the amplitude of the RF signal of the local FM tower 30 km distance at a frequency of about 100 MHz. Involuntary hand movements of the test subjects correlated with electromagnetic field, i.e. FM radio wave intensity measured. They reacted also on the place of a geomagnetic anomaly crossing the road, which was found on the basis of these recordings and confirmed by the public geological maps of the area.In conclusion, RF irradiation seems to affect the human hand reflexes of sensitive persons in a moving van along a normal public road which may have significance in traffic safety.

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

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    Yun-Jung Choi

    2016-12-01

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

  11. Early developed ASD (adjacent segmental disease) in patients after surgical treatment of the spine due to cancer metastases.

    Science.gov (United States)

    Guzik, Grzegorz

    2017-05-12

    The causes of ASD are still relatively unknown. Correlation between clinical status of patients and radiological MRI findings is of primary importance. The radiological classifications proposed by Pfirmann and Oner are most commonly used to assess intradiscal degenerative changes. The aim of the study was to assess the influence of the extension of spine fixation on the risk of developing ASD in a short time after surgery. A total of 332 patients with spinal tumors were treated in our hospital between 2010 and 2013. Of these patients, 287 underwent surgeries. A follow-up MRI examination was performed 12 months after surgical treatment. The study population comprised of 194 patients. Among metastases, breast cancer was predominant (29%); neurological deficits were detected in 76 patients. Metastases were seen in the thoracic (45%) and lumbar (30%) spine; in 25% of cases, they were of multisegmental character. Pathological fractures concerned 88% of the patients. Statistical calculations were made using the χ2 test. Statistical analysis was done using the Statistica v. 10 software. A p value ASD were noted in only seven patients. Two patients had symptoms of nerve root irritation in the lumbar spine. Twenty-two patients (11%) were diagnosed with ASD according to the MRI classifications by Oner, Rijt, and Ramos, while the more sensitive Pfirmann classification allowed to detect the disease in 46 patients (24%). Healthy or almost healthy discs of Oner type I correlated with the criteria of Pfirmann types II and III. The percentage of the incidence of ASD diagnosed 1 year after the surgery using the Pfirmann classifications was significantly higher than diagnosed according to the clinical examination. The incidence of ASD in patients after spine surgeries due to cancer metastases does not differ between the study groups. ASD detectability based on clinical signs is significantly lower than ASD detectability based on MR images according to the system by Pfirrmann et

  12. Pattern of adverse drug reactions due to cancer chemotherapy in a tertiary care hospital in South India

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    Ajitha Sharma

    2015-01-01

    Full Text Available Purpose: Studies regarding pattern of adverse drug reactions (ADRs in cancer chemotherapy patients are scarce in India. This study was conducted to evaluate the pattern of occurrence of ADRs due to cancer chemotherapy in hospitalized patients and to assess the causality, severity, predictability, and preventability of these reactions. Materials and Methods: This was a retrospective, descriptive study and the occurrence and nature of ADR, suspected drug, duration of hospital stay and outcome were noted from case records. These ADRs were assessed for causality using both World Health Organization (WHO causality assessment scale and Naranjo′s algorithm. The severity and preventability of the reported reactions were assessed using modified Hartwig and Siegel scale and modified Schumock and Thornton scale respectively. Results: Five hundred ADRs were recorded from 195 patients. Most common ADRs were infections (22.4%, nausea/vomiting (21.6% and febrile neutropenia (13%. Platinum compounds, nitrogen mustards, taxanes, antibiotics and 5-fluorouracil were the most common drugs causing ADRs. WHO causality assessment scale showed 65% of the reactions to be "probable" and 35% to be "possible," while Naranjo′s algorithm indicated that 65.6% of ADRs were "probable" and 34.4% were "possible". Modified Hartwig and Siegel scale showed most reactions (41.4% to be of "moderate level 4(a" severity, while 30.6% of reactions were of "mild level 1" severity. About 30.8% of the ADRs were "definitely preventable" according to the modified Schumock and Thornton scale. Conclusion: ADRs are most important causes of morbidity and mortality and increase the economic burden on patient and society. By careful ADR monitoring, their incidence can be decreased.

  13. The Transferrin Receptor: A Potential Molecular Imaging Marker for Human Cancer

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    Dagmar Högemann-Savellano

    2003-11-01

    Full Text Available Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date.

  14. Average years of life lost due to breast and cervical cancer and the association with the marginalization index in Mexico in 2000 and 2010

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    Claudio Alberto Dávila Cervantes

    2014-05-01

    Full Text Available The objective of this study was to calculate average years of life lost due to breast and cervical cancer in Mexico in 2000 and 2010. Data on mortality in women aged between 20 and 84 years was obtained from the National Institute for Statistics and Geography. Age-specific mortality rates and average years of life lost, which is an estimate of the number of years that a person would have lived if he or she had not died prematurely, were estimated for both diseases. Data was disaggregated into five-year age groups and socioeconomic status based on the 2010 marginalization index obtained from the National Population Council. A decrease in average years of life lost due to cervical cancer (37.4% and an increase in average years of life lost due breast cancer (8.9% was observed during the period studied. Average years of life lost due to cervical cancer was greater among women living in areas with a high marginalization index, while average years of life lost due to breast cancer was greater in women from areas with a low marginalization index.

  15. Average years of life lost due to breast and cervical cancer and the association with the marginalization index in Mexico in 2000 and 2010.

    Science.gov (United States)

    Cervantes, Claudio Alberto Dávila; Botero, Marcela Agudelo

    2014-05-01

    The objective of this study was to calculate average years of life lost due to breast and cervical cancer in Mexico in 2000 and 2010. Data on mortality in women aged between 20 and 84 years was obtained from the National Institute for Statistics and Geography. Age-specific mortality rates and average years of life lost, which is an estimate of the number of years that a person would have lived if he or she had not died prematurely, were estimated for both diseases. Data was disaggregated into five-year age groups and socioeconomic status based on the 2010 marginalization index obtained from the National Population Council. A decrease in average years of life lost due to cervical cancer (37.4%) and an increase in average years of life lost due breast cancer (8.9%) was observed during the period studied. Average years of life lost due to cervical cancer was greater among women living in areas with a high marginalization index, while average years of life lost due to breast cancer was greater in women from areas with a low marginalization index.

  16. Parotid enlargement due to adenovirus infection in patient with human immunodeficiency virus infection

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    Maria Irma Seixas Duarte

    1996-10-01

    Full Text Available The authors report a case of adenovirus- induced enlargement of the parotid gland involving a patient infected with human immunodeficiency virus (HIV. Physical examination revealed good general condition, no fever and bilateral enlargement of the parotid region, which was of increased consistency and slightly tender to palpation. Histological examination of the parotid gland demonstrated a slight periductal lymphomononuclear inflammatory infiltrate with the presence of focal points of necrosis. Tests to determine the presence of fungi and alcohol-acid resistent bacilli were negative. Immunohistochemistry for cytomegalovirus, heipes simplex, HIV p24 antigen and adenovirus showed positivity only for adenovirus in the epithelial nuclei of numerous gland ducts. Tins is the third case of this type reported in the literature, indicating the importance of including adenovirus in the differential diagnosis of this condition.Os autores relatam um caso de aumento da glândula parótida ocasionado por adenovirus, em paciente infectado pelo vírus da imunodeficiência humana. Ao exame físico, este se apresentava em bom estado geral, afebril e com aumento bilateral de parõtidas, de consistência aumentada e discretamente dolorosas ã palpação. O exame histológico da parótida demonstrou discreto infiltrado inflamatório linfomononuclear periductal com presença de focos de necrose, as pesquisas para fungos e bacilos ãlcool ãcido resistentes foram negativas. A técnica de imuno-histoquímica para citomegalovírus, beipes simples, antígeno p24 do HIVe adenovirus, somente evidenciou posítividade para o último. Este é o terceiro caso descrito na literatura, destacando a importância de incluir o adenovíms, no diagnóstico diferencial, deste acometimento.

  17. Antitumor activity of Bulgarian herb Tribulus terrestris L. on human breast cancer cells

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    Svetla Angelova

    2013-01-01

    Full Text Available Medicinal plants have been intensively studied as a source of antitumor compounds. Due to the beneficial climate conditions Bulgarian herbs have high pharmacological potential. Currently, the antitumor effect of the Bulgarian medicinal plant Tribulus terrestris L. on human cancer cell lines is not studied. The main active compounds of the plant are the steroid saponins.The present study aims to analyze the effect on cell viability and apoptotic activity of total extract and saponin fraction of Bulgarian Tribulus terrestris L. on human breast cancer (MCF7 and normal (MCF10A cell lines. Antitumor effect was established by МТТ cell viability assay and assessment of apoptotic potential was done through analysis of genomic integrity (DNA fragmentation assay and analysis of morphological cell changes (Fluorescence microscopy. The results showed that total extract of the herb has a marked dose-dependent inhibitory effect on viability of MCF7 cells (half maximal inhibitory concentration is 15 μg/ml. Cell viability of MCF10A was moderately decreased without visible dose-dependent effect. The saponin fraction has increased inhibitory effect on breast cancer cells compared to total extract. Morphological changes and DNA fragmentation were observed as markers for early and late apoptosis predominantly in tumor cells after treatment. Apoptotic processes were intensified with the increase of treatment duration.The obtained results are the first showing selective antitumor activity of Bulgarian Tribulus terrestris L. on human cancer cells in vitro. Apoptotic processes are involved in the antitumor mechanisms induced by the herb. This results give directions for future investigations concerning detailed assessment of its pharmacological potential.

  18. Role of oxidative stress in cytotoxicity of grape seed extract in human bladder cancer cells.

    Science.gov (United States)

    Raina, Komal; Tyagi, Alpna; Kumar, Dileep; Agarwal, Rajesh; Agarwal, Chapla

    2013-11-01

    In present study, we evaluated grape seed extract (GSE) efficacy against bladder cancer and associated mechanism in two different bladder cancer cell lines T24 and HTB9. A significant inhibitory effect of GSE on cancer cell viability was observed, which was due to apoptotic cell death. Cell death events were preceded by vacuolar appearance in cytoplasm, which under electron microscopy was confirmed as swollen mitochondrial organelle and autophagosomes. Through detailed in vitro studies, we established that GSE generated oxidative stress that initiated an apoptotic response as indicated by the reversal of GSE-mediated apoptosis when the cells were pre-treated with antioxidants prior to GSE. However, parallel to a strong apoptotic cell death event, GSE also caused a pro-survival autophagic event as evidenced by tracking the dynamics of LC3-II within the cells. Since the pro-death apoptotic response was stronger than the pro-survival autophagy induction within the cells, cell eventually succumbed to cellular death after GSE exposure. Together, the findings in the present study are both novel and highly significant in establishing, for the first time, that GSE-mediated oxidative stress causes a strong programmed cell death in human bladder cancer cells, suggesting and advocating the effectiveness of this non-toxic agent against this deadly malignancy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Cancer

    Science.gov (United States)

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

  20. Productivity Losses Associated with Head and Neck Cancer Using the Human Capital and Friction Cost Approaches.

    Science.gov (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

    2015-08-01

    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.

  1. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

    Directory of Open Access Journals (Sweden)

    Hummel Michael

    2010-11-01

    Full Text Available Abstract Background Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2005-01-20

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

  5. Absolute quantification of somatic DNA alterations in human cancer.

    Science.gov (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

    2012-05-01

    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.

  6. Human papillomavirus genotypes and cervical cancer in northeast Thailand.

    Science.gov (United States)

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

    2013-01-01

    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.

  7. Progression of Mortality due to Diseases of the Circulatory System and Human Development Index in Rio de Janeiro Municipalities

    Science.gov (United States)

    Soares, Gabriel Porto; Klein, Carlos Henrique; Silva, Nelson Albuquerque de Souza e; de Oliveira, Glaucia Maria Moraes

    2016-01-01

    Background Diseases of the circulatory system (DCS) are the major cause of death in Brazil and worldwide. Objective To correlate the compensated and adjusted mortality rates due to DCS in the Rio de Janeiro State municipalities between 1979 and 2010 with the Human Development Index (HDI) from 1970 onwards. Methods Population and death data were obtained in DATASUS/MS database. Mortality rates due to ischemic heart diseases (IHD), cerebrovascular diseases (CBVD) and DCS adjusted by using the direct method and compensated for ill-defined causes. The HDI data were obtained at the Brazilian Institute of Applied Research in Economics. The mortality rates and HDI values were correlated by estimating Pearson linear coefficients. The correlation coefficients between the mortality rates of census years 1991, 2000 and 2010 and HDI data of census years 1970, 1980 and 1991 were calculated with discrepancy of two demographic censuses. The linear regression coefficients were estimated with disease as the dependent variable and HDI as the independent variable. Results In recent decades, there was a reduction in mortality due to DCS in all Rio de Janeiro State municipalities, mainly because of the decline in mortality due to CBVD, which was preceded by an elevation in HDI. There was a strong correlation between the socioeconomic indicator and mortality rates. Conclusion The HDI progression showed a strong correlation with the decline in mortality due to DCS, signaling to the relevance of improvements in life conditions. PMID:27849263

  8. Expression and alternative splicing pattern of human telomerase reverse transcriptase in human lung cancer cells.

    Science.gov (United States)

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

    2004-04-01

    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.

  9. The Prevalence of Human Papillomavirus in Cervical Cancer in Iran.

    Science.gov (United States)

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

    2002-01-01

    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

  10. Human Progesterone A-Form as a Target for New Drug Discovery in Human Breast Cancer

    Science.gov (United States)

    2001-07-01

    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

  11. Quantification of Hydrological Responses Due to Climate Change and Human Activities over Various Time Scales in South Korea

    Directory of Open Access Journals (Sweden)

    Sangho Lee

    2017-01-01

    Full Text Available Hydrological responses are being impacted by both climate change and human activities. In particular, climate change and regional human activities have accelerated significantly during the last three decades in South Korea. The variation in runoff due to the two types of factors should be quantitatively investigated to aid effective water resources’ planning and management. In water resources’ planning, analysis using various time scales is useful where rainfall is unevenly distributed. However, few studies analyzed the impacts of these two factors over different time scales. In this study, hydrologic model-based approach and hydrologic sensitivity were used to separate the relative impacts of these two factors at monthly, seasonal and annual time scales in the Soyang Dam upper basin and the Seom River basin in South Korea. After trend analysis using the Mann–Kendall nonparametric test to identify the causes of gradual change, three techniques, such as the double mass curve method, Pettitt’s test and the BCP (Bayesian change point analysis, were used to detect change points caused by abrupt changes in the collected observed runoff. Soil and Water Assessment Tool (SWAT models calibrated from the natural periods were used to calculate the impacts of human activities. Additionally, six Budyko-based methods were used to verify the results obtained from the hydrological-based approach. The results show that impacts of climate change have been stronger than those of human activities in the Soyang Dam upper basin, while the impacts of human activities have been stronger than those of climate change in the Seom River basin. Additionally, the quantitative characteristics of relative impacts due to these two factors were identified at the monthly, seasonal and annual time scales. Finally, we suggest that the procedure used in this study can be used as a reference for regional water resources’ planning and management.

  12. Human health risk due to consumption of vegetables contaminated with carcinogenic polycyclic aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Sardar [Chinese Academy of Sciences, Xiamen (China). Inst. of Urban Environment; Peshawar Univ. (Pakistan). Dept. of Environmental Science; Cao, Qing [Chinese Academy of Sciences, Beijing (China). Research Center for Eco-Environemntal Sciences

    2012-02-15

    Polycyclic aromatic hydrocarbons (PAH) are persistent, toxic, and carcinogenic contaminants present in soil ecosystem globally. These pollutants are gradually accumulating in wastewater-irrigated soils and lead to the contamination of vegetables. Food chain contamination with PAH is considered as one of the major pathways for human exposure. This study was aimed to investigate the concentrations of PAH in soils and vegetables collected from wastewater-irrigated fields from metropolitan areas of Beijing, China. Origin of PAH, daily intake, and health risks of PAH through consumption of contaminated vegetables were studied. Soil samples were collected from the upper horizon (0-20 cm) of both wastewater-irrigated and reference sites and sieved (<2 mm mesh) and then followed by freeze-drying at -50 C and 123 {+-} 2 Pa. Standing vegetables were also collected from the same sites used for soil sampling and divided into roots and shoots, thoroughly washed with deionized water, and freeze-dried. PAH were extracted using the Soxhlet method with 200 mL DCM for 24 h, and the extracts were cleaned with silica adsorption chromatography prepared with silica gel, alumina, and capped with anhydrous sodium. The final concentrated extracts (soil and vegetable) were analyzed using gas chromatography-mass spectrometry (Agilent 6890). Bioaccumulation factors, daily intake of PAH, and carcinogenicity of PAH were calculated by different statistical equations. Results indicate that the soils and grown vegetables were contaminated with all possible carcinogenic PAH (declared by USEPA 2002) except indeno[1,2,3-c,d]pyrene. The highest concentration (242.9 {mu}g kg{sup -1}) was found for benzo(k)fluoranthene (BkF), while lowest (79.12 {mu}g kg{sup -1}) for benzo[a]pyrene (BaP). The emission sources of PAH were both pyrogenic and petrogenic in nature. However, the total concentrations of PAH were lower than the permissible limits set by different countries like Canada, Denmark and Germany

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

    Science.gov (United States)

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

    2013-09-01

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

  14. Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan.

    Science.gov (United States)

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

    2016-07-30

    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.

  15. A Gene Regulatory Program in Human Breast Cancer.

    Science.gov (United States)

    Li, Renhua; Campos, John; Iida, Joji

    2015-12-01

    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.

  16. In Vitro Drug Transfer Due to Drug Retention in Human Epidermis Pretreated with Application of Marketed Estradiol Transdermal Systems.

    Science.gov (United States)

    Krishnaiah, Yellela S R; Pavurala, Naresh; Yang, Yang; Manda, Prashanth; Katragadda, Usha; Yang, Yongsheng; Shah, Rakhi; Fang, Guodong; Khan, Mansoor A

    2016-12-27

    Study objective was to assess skin-to-skin drug transfer potential that may occur due to drug retention in human epidermis (DRE) pretreated with application of estradiol transdermal drug delivery systems (TDDS) and other estradiol transdermal dosage forms (gels and sprays). TDDS (products-A, B, and C) with varying formulation design and composition, and other estradiol transdermal products (gel and spray) were applied to heat separated human epidermis (HSE) and subjected to in vitro drug permeation study. Amounts of DRE were quantified after 24 h. The DRE with product-B was significantly (P  0.05) amounts of DRE. A separate in vitro permeation study was carried out to determine amounts of drug transferred from drug-retaining epidermis to untreated HSE. The amounts of drug transferred, due to DRE after 8 h, with product-C were significantly (P drug transfer due to the DRE after labeled period of using estradiol TDDS, though the clinical relevance of these findings is yet to be determined.

  17. High-fat Western diet-induced obesity contributes to increased tumor growth in mouse models of human colon cancer.

    Science.gov (United States)

    O'Neill, Ann Marie; Burrington, Christine M; Gillaspie, Erin A; Lynch, Darin T; Horsman, Melissa J; Greene, Michael W

    2016-12-01

    Strong epidemiologic evidence links colon cancer to obesity. The increasing worldwide incidence of colon cancer has been linked to the spread of the Western lifestyle, and in particular consumption of a high-fat Western diet. In this study, our objectives were to establish mouse models to examine the effects of high-fat Western diet-induced obesity on the growth of human colon cancer tumor xenografts, and to examine potential mechanisms driving obesity-linked human colon cancer tumor growth. We hypothesize that mice rendered insulin resistant due to consumption of a high-fat Western diet will show increased and accelerated tumor growth. Homozygous Rag1(tm1Mom) mice were fed either a low-fat Western diet or a high-fat Western diet (HFWD), then human colon cancer xenografts were implanted subcutaneously or orthotopically. Tumors were analyzed to detect changes in receptor tyrosine kinase-mediated signaling and expression of inflammatory-associated genes in epididymal white adipose tissue. In both models, mice fed an HFWD weighed more and had increased intra-abdominal fat, and tumor weight was greater compared with in the low-fat Western diet-fed mice. They also displayed significantly higher levels of leptin; however, there was a negative correlation between leptin levels and tumor size. In the orthotopic model, tumors and adipose tissue from the HFWD group displayed significant increases in both c-Jun N-terminal kinase activation and monocyte chemoattractant protein 1 expression, respectively. In conclusion, this study suggests that human colon cancer growth is accelerated in animals that are obese and insulin resistant due to the consumption of an HFWD. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. A case of rectovagino-vesical fistula due to radiation therapy for uterine cancer treated with covered expandable metallic stent

    Energy Technology Data Exchange (ETDEWEB)

    Ohtsukasa, Shunroh; Okabe, Satoshi; Tanami, Hideaki [Tokyo Medical and Dental Univ. (Japan). School of Medicine] (and others)

    2002-04-01

    A 65-year-old woman had received a panhysterectomy and radiation therapy for a uterine cancer in 1974 and underwent a drainage operation for a peritonitis due to rupture of the bladder associated with radiation cystitis in 1983. A rectovesical fistula was revealed and partial resection of the bladder and rectum was performed in 1996. In 1998, rectovesical fistula recurred and symptom of fecaluria and contact-type dermatitis at perineal region subsequently worsened. In February, 2000, colonoscopy and gastrograffin-enema revealed a giant recto-vagino-vesical fistula. Although we recommended ileostomy, the patient refused our offer. She gave informed consent to our proposal about the insertion of a covered expandable metallic stent (EMS) into the rectum to treat for fecaluria. After insertion of a covered EMS, fecaluria and contact-type dermatitis at perineal region subsequently improved. Three months later, fecaluria appeared again. Finally, seven months later, severe inflammation occurred at perineal and pubic region because of migration of the covered EMS into the bladder, then we removed the covered EMS and performed ileostomy. It is difficult to use the covered EMS treatment for benign rectovesical or rectovaginal fistula for a long term. (author)

  19. Circumcision related to urinary tract infections, sexually transmitted infections, human immunodeficiency virus infections, and penile and cervical cancer.

    Science.gov (United States)

    Hayashi, Yutaro; Kohri, Kenjiro

    2013-08-01

    Male circumcision has been carried out as a prophylactic measure against future diseases, as well as a rite of passage due to religious practice and definite medical indication. The present review discusses the benefits of male circumcision on the prevention of urinary tract infections, and the importance of circumcision in congenital urinary system anomalies, such as vesicoureteral reflux. Additionally the present review examines the associations between circumcision and sexually transmitted infections, including human immunodeficiency virus, and the preventive effect of circumcision on penile cancer and cervical cancer of female partners. © 2013 The Japanese Urological Association.

  20. SPA-1 controls the invasion and metastasis of human prostate cancer.

    Science.gov (United States)

    Shimizu, Yosuke; Hamazaki, Yoko; Hattori, Masakazu; Doi, Keiko; Terada, Naoki; Kobayashi, Takashi; Toda, Yoshinobu; Yamasaki, Toshinari; Inoue, Takahiro; Kajita, Yoichiro; Maeno, Atsushi; Kamba, Tomomi; Mikami, Yoshiki; Kamoto, Toshiyuki; Yamada, Tomomi; Kanno, Toru; Yoshikawa, Kiyotsugu; Ogawa, Osamu; Minato, Nagahiro; Nakamura, Eijiro

    2011-04-01

    Recent studies suggest that SIPA1 encoding a Rap GTPase-activating protein SPA-1 is a candidate metastasis efficiency-modifying gene in human breast cancer. In this study, we investigated the expression and function of SPA-1 in human prostate cancer (CaP). Immunohistochemical studies of tumor specimens from CaP patients revealed a positive correlation of SPA-1 expression with disease progression and metastasis. The correlation was recapitulated in human CaP cell lines; LNCaP that rarely showed metastasis in SCID mice expressed an undetectable level of SPA-1, whereas highly metastatic PC3 showed abundant SPA-1 expression. Moreover, SIPA1 transduction in LNCaP caused prominent abdominal lymph node metastasis without affecting primary tumor size, whereas shRNA-mediated SIPA1 knockdown or expression of a dominant-active Rap1 mutant (Rap1V12) in PC3 suppressed metastasis. LNCaP transduced with SPA-1 (LNCaP/SPA-1) showed attenuated adhesion to the precoated extracellular matrices (ECM) including collagens and fibronectin, due to defective ECM-medicated Rap1 activation. In addition, LNCaP/SPA-1 showed a diminished level of nuclear Brd4, which is known to bind SPA-1, resulting in reduced expression of a series of ECM-related genes. These results suggest that SPA-1 plays an important role in controlling metastasis efficiency of human CaP by regulating the expression of and interaction with ECM in the primary sites. © 2011 Japanese Cancer Association.

  1. Barnase as a new therapeutic agent triggering apoptosis in human cancer cells.

    Directory of Open Access Journals (Sweden)

    Evelina Edelweiss

    Full Text Available BACKGROUND: RNases are currently studied as non-mutagenic alternatives to the harmful DNA-damaging anticancer drugs commonly used in clinical practice. Many mammalian RNases are not potent toxins due to the strong inhibition by ribonuclease inhibitor (RI presented in the cytoplasm of mammalian cells. METHODOLOGY/PRINCIPAL FINDINGS: In search of new effective anticancer RNases we studied the effects of barnase, a ribonuclease from Bacillus amyloliquefaciens, on human cancer cells. We found that barnase is resistant to RI. In MTT cell viability assay, barnase was cytotoxic to human carcinoma cell lines with half-inhibitory concentrations (IC(50 ranging from 0.2 to 13 microM and to leukemia cell lines with IC(50 values ranging from 2.4 to 82 microM. Also, we characterized the cytotoxic effects of barnase-based immunoRNase scFv 4D5-dibarnase, which consists of two barnase molecules serially fused to the single-chain variable fragment (scFv of humanized antibody 4D5 that recognizes the extracellular domain of cancer marker HER2. The scFv 4D5-dibarnase specifically bound to HER2-positive cells and was internalized via receptor-mediated endocytosis. The intracellular localization of internalized scFv 4D5-dibarnase was determined by electronic microscopy. The cytotoxic effect of scFv 4D5-dibarnase on HER2-positive human ovarian carcinoma SKOV-3 cells (IC(50 = 1.8 nM was three orders of magnitude greater than that of barnase alone. Both barnase and scFv 4D5-dibarnase induced apoptosis in SKOV-3 cells accompanied by internucleosomal chromatin fragmentation, membrane blebbing, the appearance of phosphatidylserine on the outer leaflet of the plasma membrane, and the activation of caspase-3. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that barnase is a potent toxic agent for targeting to cancer cells.

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

    Directory of Open Access Journals (Sweden)

    Douglas Thamm, VMD

    2009-03-01

    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.

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

    Science.gov (United States)

    Tzukerman, Maty; Skorecki, Karl L

    2006-01-01

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

  4. 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)

    吴平平

    2013-01-01

    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)

  5. Colloquium paper: human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency.

    Science.gov (United States)

    Hancock, Angela M; Witonsky, David B; Ehler, Edvard; Alkorta-Aranburu, Gorka; Beall, Cynthia; Gebremedhin, Amha; Sukernik, Rem; Utermann, Gerd; Pritchard, Jonathan; Coop, Graham; Di Rienzo, Anna

    2010-05-11

    Human populations use a variety of subsistence strategies to exploit an exceptionally broad range of ecoregions and dietary components. These aspects of human environments have changed dramatically during human evolution, giving rise to new selective pressures. To understand the genetic basis of human adaptations, we combine population genetics data with ecological information to detect variants that increased in frequency in response to new selective pressures. Our approach detects SNPs that show concordant differences in allele frequencies across populations with respect to specific aspects of the environment. Genic and especially nonsynonymous SNPs are overrepresented among those most strongly correlated with environmental variables. This provides genome-wide evidence for selection due to changes in ecoregion, diet, and subsistence. We find particularly strong signals associated with polar ecoregions, with foraging, and with a diet rich in roots and tubers. Interestingly, several of the strongest signals overlap with those implicated in energy metabolism phenotypes from genome-wide association studies, including SNPs influencing glucose levels and susceptibility to type 2 diabetes. Furthermore, several pathways, including those of starch and sucrose metabolism, are enriched for strong signals of adaptations to a diet rich in roots and tubers, whereas signals associated with polar ecoregions are overrepresented in genes associated with energy metabolism pathways.

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

    Science.gov (United States)

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

    2013-09-01

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

  7. First report of a human case of polycystic echinococcosis due to Echinococcus vogeli from neotropical area of Peru, South America.

    Science.gov (United States)

    Somocurcio, José R; Sánchez, Elizabeth L; Náquira, César; Schilder, José; Rojas, Francisco; Chacón, Pedro; Yabar, Alejandro

    2004-01-01

    We report a human case of polycystic hidatidosis due to Echinococcus vogeli from Contamana (Department of Loreto) village located in the central jungle of Peru. The patient is a 44 year-old lady, teacher, who carried a painless liver mass since a year ago. She was submitted to abdominal surgery and the liver mass was removed and showed multiple cysts containing colorless liquid as is showed in the polycystic hidatidosis. The morphology and measure of the hooks obtained from the liquid contained in the cysts are from Echinococcus vogeli. It is the first report of this parasitism in Perú.

  8. Acute post-infectious cerebellar ataxia due to co-infection of human herpesvirus-6 and adenovirus mimicking myositis.

    Science.gov (United States)

    Naselli, Aldo; Pala, Giovanna; Cresta, Federico; Finetti, Martina; Biancheri, Roberta; Renna, Salvatore

    2014-11-26

    Acute cerebellar ataxia (ACA) is a relatively common neurological disease in children. Most common types of ACA are acute post-infectious (APCA) and acute disseminated encephalomyelitis (ADEM). Less common but important causes include opsoclonus-myoclonus syndrome (OMS) and acute cerebellitis. Cerebellar neoplasms and acute hydrocephalus are additional causes of paediatric ataxia. APCA is the most common cause of ACA in children, comprising about 30-50% of total cases. This is a report about an immunocompetent 4-yrs-old male affected by APCA, due to co-infection by human herpesvirus-6 (HHV-6) and adenovirus, with symptoms mimicking myositis.

  9. STAT3 signaling is activated preferentially in tumor-initiating cells in claudin-low models of human breast cancer.

    Science.gov (United States)

    Wei, Wei; Tweardy, David J; Zhang, Mei; Zhang, Xiaomei; Landua, John; Petrovic, Ivana; Bu, Wen; Roarty, Kevin; Hilsenbeck, Susan G; Rosen, Jeffrey M; Lewis, Michael T

    2014-10-01

    In breast cancer, a subset of tumor-initiating cells (TIC) or "cancer stem cells" are thought to be responsible for tumor maintenance, treatment resistance, and disease recurrence. While current breast cancer stem cell markers (e.g., CD44(high) /CD24(low/neg) , ALDH positive) have allowed enrichment for such cells, they are not universally expressed and may actually identify distinct TIC subpopulations in the same tumor. Thus, additional markers of functional stem cells are needed. The STAT3 pathway is a critical regulator of the function of normal stem cells, and evidence is accumulating for its important role in breast cancer stem cells. However, due to the lack of a method for separating live cells based on their level of STAT3 activity, it remains unknown whether STAT3 functions in the cancer stem cells themselves, or in surrounding niche cells, or in both. To approach this question, we constructed a series of lentiviral fluorescent (enhanced green fluorescent protein, EGFP) reporters that enabled flow cytometric enrichment of cells differing in STAT3-mediated transcriptional activity, as well as in vivo/in situ localization of STAT3 responsive cells. Using in vivo claudin-low cell line xenograft models of human breast cancer, we found that STAT3 signaling reporter activity (EGFP(+) ) is associated with a subpopulation of cancer cells enriched for mammosphere-forming efficiency, as well as TIC function in limiting dilution transplantation assays compared to negative or unsorted populations. Our results support STAT3 signaling activity as another functional marker for human breast cancer stem cells thus making it an attractive therapeutic target for stem-cell-directed therapy in some breast cancer subtypes. © AlphaMed Press.

  10. 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

  11. Siah1 proteins enhance radiosensitivity of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Engenhart-Cabillic Rita

    2010-08-01

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

  12. Screening and analysis of breast cancer genes regulated by the human mammary microenvironment in a humanized mouse model

    Science.gov (United States)

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

    2016-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2015-01-01

    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.

  14. Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xuchen Cao; Bowen Liu; Wenfeng Cao; Weiran Zhang; Fei Zhang; Hongmeng Zhao; Ran Meng

    2013-01-01

    Apigenin (4',5,7-trihydroxyflavone) is a member of the flavone subclass of flavonoids present in fruits and vegetables.The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated.Cell proliferation and viability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays.Flow cytometry,fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy,and the role of autophagy was assessed using autophagy inhibitors.Apigenin dose-and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines.The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3,PARP cleavage and Bax/Bcl-2 ratios.The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis.In addition,the apigenin-treated cells exhibited autophagy,as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles (AVOs)by flow cytometry.Furthermore,the results of the Western blot analysis revealed that the level of LC3-Ⅱ,the processed form of LC3-Ⅰ,was increased.Treatment with the autophagy inhibitor,3-methyladenine (3-MA),significantly enhanced the apoptosis induced by apigenin,which was accompanied by an increase in the level of PARP cleavage.Similar results were also confirmed by flow cytometry and fluorescence microscopy.These results indicate that apigenin has apoptosis-and autophagy-inducing effects in breast cancer cells.Autophagy plays a cyto-protective role in apigenin-induced apoptosis,and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.

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

    Science.gov (United States)

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

    2017-03-01

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

  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

    2015-01-01

    .... 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.

    Science.gov (United States)

    Rayet, B; Gélinas, C

    1999-11-22

    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. Sensitization of multidrug-resistant human cancer cells to Hsp90 inhibitors by down-regulation of SIRT1.

    Science.gov (United States)

    Kim, Hak-Bong; Lee, Su-Hoon; Um, Jee-Hyun; Oh, Won Keun; Kim, Dong-Wan; Kang, Chi-Dug; Kim, Sun-Hee

    2015-11-03

    The effectiveness of Hsp90 inhibitors as anticancer agents was limited in multidrug-resistant (MDR) human cancer cells due to induction of heat shock proteins (Hsps) such as Hsp70/Hsp27 and P-glycoprotein (P-gp)-mediated efflux. In the present study, we showed that resistance to Hsp90 inhibitors of MDR human cancer cells could be overcome with SIRT1 inhibition. SIRT1 knock-down or SIRT1 inhibitors (amurensin G and EX527) effectively suppressed the resistance to Hsp90 inhibitors (17-AAG and AUY922) in several MDR variants of human lymphoblastic leukemia and human breast cancer cell lines. SIRT1 inhibition down-regulated the expression of heat shock factor 1 (HSF1) and subsequently Hsps and facilitated Hsp90 multichaperone complex disruption via hyperacetylation of Hsp90/Hsp70. These findings were followed by acceleration of ubiquitin ligase CHIP-mediated mutant p53 (mut p53) degradation and subsequent down-regulation of P-gp in 17-AAG-treated MDR cancer cells expressing P-gp and mut p53 after inhibition of SIRT1. Therefore, combined treatment with Hsp90 inhibitor and SIRT1 inhibitor could be a more effective therapeutic approach for Hsp90 inhibitor-resistant MDR cells via down-regulation of HSF1/Hsps, mut p53 and P-gp.

  19. Subamolide A Induces Mitotic Catastrophe Accompanied by Apoptosis in Human Lung Cancer Cells

    OpenAIRE

    Jen-Yu Hung; Ching-Wen Wen; Ya-Ling Hsu; En-Shyh Lin; Ming-Shyan Huang; Chung-Yi Chen; Po-Lin Kuo

    2013-01-01

    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

    OpenAIRE

    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

    2012-01-01

    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

    Science.gov (United States)

    2017-02-01

    AWARD NUMBER: W81XWH-16-1-0009 TITLE: PRINCIPAL INVESTIGATOR: John Cleveland CONTRACTING ORGANIZATION: H. Lee Moffitt Cancer Center...so 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

    Science.gov (United States)

    2017-02-01

    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. Phospholipase C-beta 2 promotes mitosis and migration of human breast cancer-derived cells.

    Science.gov (United States)

    Bertagnolo, Valeria; Benedusi, Mascia; Brugnoli, Federica; Lanuti, Paola; Marchisio, Marco; Querzoli, Patrizia; Capitani, Silvano

    2007-08-01

    Like most human neoplasm, breast cancer has aberrations in signal transduction elements that can lead to increased proliferative potential, apoptosis inhibition, tissue invasion and metastasis. Due to the high heterogeneity of this tumor, currently, no markers are clearly associated with the insurgence of breast cancer, as well as with its progression from in situ lesion to invasive carcinoma. We have recently demonstrated an altered expression of the beta2 isoform of the phosphoinositide-dependent phospholipase C (PLC) in invasive breast tumors with different histopathological features. In primary breast tumor cells, elevated amounts of this protein are closely correlated with a poor prognosis of patients with mammary carcinoma, suggesting that PLC-beta2 may be involved in the development and worsening of the malignant phenotype. Here we demonstrate that PLC-beta2 may improve some malignant characteristics of tumor cells, like motility and invasion capability, but it fails to induce tumorigenesis in non-transformed breast-derived cells. We also report that, compared with the G(0)/G(1) phases of the cell cycle, the cells in S/G(2)/M phases show high PLC-beta2 expressions that reach the greatest levels during the late mitotic stages. In addition, even if unable to modify the proliferation rate and the expression of cell cycle-related enzymes of malignant cells, PLC-beta2 may promote the G(2)/M progression, a critical event in cancer evolution. Since phosphoinositides, substrates of PLC, are involved in regulating cytoskeleton architecture, PLC-beta2 in breast tumor cells may mediate the modification of cell shape that characterizes cell division, motility and invasion. On the basis of these data, PLC-beta2 may constitute a molecular marker of breast tumor cells able to monitor the progression to invasive cancers and a target for novel therapeutic breast cancer strategies.

  4. Anticancer activity of silver nanoparticles from Panax ginseng fresh leaves in human cancer cells.

    Science.gov (United States)

    Castro-Aceituno, Verónica; Ahn, Sungeun; Simu, Shakina Yesmin; Singh, Priyanka; Mathiyalagan, Ramya; Lee, Hyun A; Yang, Deok Chun

    2016-12-01

    The pharmaceutical role of silver nanoparticles has been increased over the last decades, especially those synthesized through herbal medicinal plants, due to their variety of pharmacological importance. Panax ginseng Meyer (P. ginseng) has been widely used as a therapeutic herbal medicine for a long time in cancer treatment. In this study, the cytotoxic and oxidative effect of a novel silver nanoparticles synthesized from P. ginseng fresh leaves (P.g AgNPs) were evaluated in different human cancer cell lines. In addition, the effect of P.g AgNPs on cell migration, apoptosis and the determination of the mechanism involve was determinate by the use of A549 lung cancer cell line. It was found that P.g AgNPs treatment inhibited cell viability and induced oxidative stress in A549, MCF7 and HepG2 cancer cell lines. Likewise, P.g AgNPs treatment inhibited the epidermal growth factor (EGF)-enhanced migration, as well as decreased the mRNA levels and phosphorylation of EGF receptors in A549 cells. Moreover, P.g AgNPs modified the morphology of the cell nucleus and increase apoptosis percentage; this effect was linked to the stimulation of p38 MAPK/p53 pathway. Taken together, our results showed that P.g AgNPs exhibited anti-cancer activity in A549 and the regulation of EGFR/p38 MAPK/p53 pathway might be the possible mechanism of its anti-activity. Further experiments are suggested to determinate the mechanism by which P.g AgNPs induce cytotoxicity and ROS generation in MCF-7 and HepG2 cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Clinical Usefulness between High Dose Radioiodine Therapy and Helicobacter Pylori Infection after Total Thyroidectomy due to Well Differentiated Thyroid Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Kuk No; Lim, Seok Tae; Moon, Eun Ha; Kim, Jin Suk; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2009-12-15

    Helicobacter (H) pylori infection has been considered the most important cause of gastritis, dyspepsia, and gastroduodenal ulcer. Radioiodine can be accumulated in the remaining thyroid tissue, salivary gland, and stomach. We investigated if the high radiation induced by radioiodine in the stomach after high dose radioiodine therapy (HD-RIT) is effective in the eradication of H. pylori infection. One hundred ninety nine patients (M:F=33:166, age 46.7{+-}12.3 years) who had HD-RIT (dose 159.1{+-}25.9 mCi, range 120-250 mCi) after thyroidectomy due to well differentiated thyroid cancer were enrolled. To detect H. pylori infection, the urea breath tests (UBT) were performed at 1 hour before HD-RIT and at 4 weeks after HD-RIT. The results of UBT were classified as positive ({>=}50 dpm) or negative (<50 dpm), and analyzed its values. Of 199 patients, 103 (51.8%) patients had positive UBT before HD-RIT. Of these, 80 patients had follow-up UBT after HD-RIT. Among them, 76 (95.0%) patients had persistent positive UBT and only 4 (5.0%) patients were changed negative UBT. Among 76 patients with persistent positive UBT, 26 (34.2%) patients had increased the values of follow-up UBT, 49 (64.5%) had decreased them, and 1 (1.3%) had shown the same value. The different values of UBT between before and after HD-RIT were 62{+-}66.1 dpm in increased one of follow-up UBT, and 153.3{+-}157.1 dpm in decreased one of follow-up UBT. We conclude that the radiation induced by HD-RIT is ineffective in the eradication of H. pylori infection. However, it could be influential the degree or distribution of H. pylori infection.

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

    Science.gov (United States)

    Zhu, Ruixue; Shi, Yongquan; Zhang, Lianfeng

    2015-04-01

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

  7. Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2005-04-01

    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.

  8. Single and Multiple Gene Manipulations in Mouse Models of Human Cancer

    Science.gov (United States)

    Lehman, Heather L; Stairs, Douglas B

    2015-01-01

    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

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

    Science.gov (United States)

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

    1993-04-01

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

  10. Hypoxia-regulated microRNAs in human cancer

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  11. Is Human Papillomavirus Associated with Prostate Cancer Survival?

    Directory of Open Access Journals (Sweden)

    Mariarosa Pascale

    2013-01-01

    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.

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

    DEFF Research Database (Denmark)

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

    1990-01-01

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

  13. Emerging roles of deubiquitinating enzymes in human cancer1

    Institute of Scientific and Technical Information of China (English)

    Jin-ming YANG

    2007-01-01

    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.

  14. Evaluation of Melatonin Effect on Human Breast Cancer Stem Cells Using a Threedimensional Growth Method of Mammospheres.

    Science.gov (United States)

    Lopes, Juliana Ramos; da Silva Kavagutti, Mayume; de Medeiros, Felipe Arthur Faustino; de Campos Zuccari, Debora Aparecida Pires

    2017-01-01

    The high rates of women's death from breast cancer occur due to acquired resistance by patients to certain treatments, enabling the recurrence and/or tumor growth, invasion and metastasis. It has been demonstrated that the presence of cancer stem cells in human tumors, as responsible for recurrence and resistance to therapy. Studies have identified OCT4 as responsible for self-renewal and maintenance of pluripotency of stem cells. Thus, it is interesting to study potential drugs that target this specific population in breast cancer. Melatonin, appears to have oncostatic effects on cancer cells, however, little is known about its therapeutic effect on cancer stem cells. Evaluate the viability and the expression of OCT4 in breast cancer stem cells, MCF-7 and MDA-MB- 231, after melatonin treatment. The cells were grown in a 3-dimensional model of mammospheres, representing the breast cancer stem cell population and treated or not with melatonin. The cell viability of mammospheres were evaluated by MTT assay and the OCT4 expression, a cancer stem cells marker, was verified by immunocitochemistry. Our results demonstrated that the melatonin treatment decreased the cell viability of MCF-7 and MDAMB- 231 mammospheres. Furthermore, it was observed that in both cell lines, the expression of OCT4 was decreased in melatonin-treated cells compared to the control group. This fact suggests that melatonin is effective against breast cancer stem cells inhibiting the cell viability via OCT 4. Based on that, we believe that melatonin has a high potential to be used as an alternative treatment for breast cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

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

    2015-01-01

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

  16. Specific binding of benzodiazepines to human breast cancer cell lines.

    Science.gov (United States)

    Beinlich, A; Strohmeier, R; Kaufmann, M; Kuhl, H

    1999-01-01

    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.

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

    Science.gov (United States)

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

    2003-01-01

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

  18. 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;

    2013-01-01

    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...

  19. From Human Papillomavirus (HPV) Detection to Cervical Cancer Prevention in Clinical Practice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sin Hang, E-mail: shlee01@snet.net; Vigliotti, Jessica S.; Vigliotti, Veronica S.; Jones, William [Department of Pathology, Milford Hospital, 300 Seaside Ave., Milford, CT 06460 (United States)

    2014-10-02

    The newly gained knowledge of the viral etiology in cervical carcinogenesis has prompted industrial interests in developing virology-based tools for cervical cancer prevention. Due to the long incubation period from viral infection to developing an invasive cancer, a process whose outcome is influenced by numerous life-style and genetic factors, the true efficacy of the genotype-specific human papillomavirus (HPV) vaccines in cervical cancer prevention cannot be determined for another 30 years. Most HPV DNA test kits designed to replace the traditional Papanicolaou (Pap) smears for precancer detection lack the analytical sensitivity and specificity to comprehensively detect all potentially carcinogenic HPVs and to perform reliable genotyping. The authors implemented the classic nested PCR and Sanger DNA-sequencing technology for routine HPV testing. The results showed a true negative HPV PCR invariably indicates the absence of precancerous cells in the cytology samples. However, 80.5% of single positive HPV-16 tests and 97.3% of single positive HPV-18 tests were associated with a negative or a largely self-reversible Pap cytology. Routine sensitive and reliable HPV type-specific or perhaps even variant-specific methods are needed to address the issues of persistence of HPV infection if a virology-based primary cervical screen is used to replace the Pap cytology screening paradigm.

  20. Bioactive Compound Content and Cytotoxic Effect on Human Cancer Cells of Fresh and Processed Yellow Tomatoes

    Directory of Open Access Journals (Sweden)

    Assunta Raiola

    2015-12-01

    Full Text Available Tomato, as a fresh or processed product, has a high nutritional value due to its content of bioactive components such as phenolic compounds. Few studies describe the effect of processing on antioxidant content and the cancer cell growth inhibition activity. In this study we determined the phenolic and ascorbic acid content of three yellow tomato varieties, before and after thermal processing. Moreover, we determined the antioxidative power and tested the effects of tomato extracts on three human cancer cell lines. We found that the amount of phenolic acids (chlorogenic acid and caffeic acid decreased in all the samples after processing, whereas the flavonoid content increased after the heat treatment in two samples. A cytotoxic effect of tomato extracts was observed only after processing. This result well correlates with the flavonoid content after processing and clearly indicates that processed yellow tomatoes have a high content of bioactive compounds endowed with cytotoxicity towards cancer cells, thus opening the way to obtain tomato-based functional foods.

  1. Human papillomavirus related cervical cancer and anticipated vaccination challenges in Ethiopia.

    Science.gov (United States)

    Gebremariam, TeweldeTesfaye

    2016-01-01

    Cervical cancer is the leading cause of cancer deaths among women in Ethiopia. This may be due to the high prevalence of high-risk human papillomavirus (HR-HPV) genotypes in the population. So far, few studies have been done that showed the presence of HR-HPV genotypes. The HR-HPV-16, -18, -52, -56, -31 and -58 were the most common genotypes reported in Ethiopia. The introduction of HPV vaccines in Ethiopia is likely to go a long way in reducing cervical cancer deaths. However, there are few challenges to the introduction of the vaccines. The target population for HPV vaccination is at the moment not well-defined. Besides, the current HPV vaccines confer only type-specific (HPV-16 and -18) immunity, leaving a small proportion of Ethiopian women unprotected against other HR-HPV genotypes such as 52, 56, 31 and 58. Thus, future HPV vaccines such as the nanovalent vaccine may be more useful to Ethiopia as they will protect women against more genotypes.

  2. CLINICAL IMPACT AND IMPLICATION OF HUMAN PAPILLOMAVIRUS (HPV IN CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    Lilian Pustan

    2007-12-01

    Full Text Available The social and economic evolution of the world’s population in the last years has brought changes also in the prevalence of some diseases. Lately, viral infections have attracted specialists’ interest due to the unexpected complications they cause. Until not so long ago incriminated only for the development of warts, the Human papillomavirus infections have been found also to induce cellular abnormalities, such as the koilocytes, which in their turn indicate low grade squamous intraepithelial lesions (HSIL. According to the latest assessments worldwide, the HPV is responsible for 70% of the cervical cancer cases. The extensive research studies conducted by specialists came to know success when the HPV vaccines were launched on the market. In the summer of 2006, the first vaccine able to stop the expansion of HPV-induced cervical cancer came out, GARDASILTM, produced by Merck and Co., Whitehouse Station, New Jersey. It is a tetravalent vaccine (generates immunity against the oncogenic viral types 16 and 18, and the nononcogenic types 6 and 11. In our drugstores, one can find SILGARD, efficient and safe, providing 5-year protection, but not eradicating the effects of the viral infections acquired prior to vaccination. Apparition of the vaccine does not exclude cytological screening, which remains the most effective way to detect early a potential cancer of the cervix.

  3. From Human Papillomavirus (HPV Detection to Cervical Cancer Prevention in Clinical Practice

    Directory of Open Access Journals (Sweden)

    Sin Hang Lee

    2014-10-01

    Full Text Available The newly gained knowledge of the viral etiology in cervical carcinogenesis has prompted industrial interests in developing virology-based tools for cervical cancer prevention. Due to the long incubation period from viral infection to developing an invasive cancer, a process whose outcome is influenced by numerous life-style and genetic factors, the true efficacy of the genotype-specific human papillomavirus (HPV vaccines in cervical cancer prevention cannot be determined for another 30 years. Most HPV DNA test kits designed to replace the traditional Papanicolaou (Pap smears for precancer detection lack the analytical sensitivity and specificity to comprehensively detect all potentially carcinogenic HPVs and to perform reliable genotyping. The authors implemented the classic nested PCR and Sanger DNA-sequencing technology for routine HPV testing. The results showed a true negative HPV PCR invariably indicates the absence of precancerous cells in the cytology samples. However, 80.5% of single positive HPV-16 tests and 97.3% of single positive HPV-18 tests were associated with a negative or a largely self-reversible Pap cytology. Routine sensitive and reliable HPV type-specific or perhaps even variant-specific methods are needed to address the issues of persistence of HPV infection if a virology-based primary cervical screen is used to replace the Pap cytology screening paradigm.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

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

  5. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    2000-07-01

    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

  6. PXRF characterization of gold nanoparticles in human cancer cell

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

  7. Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing, E-mail: wangstella5@163.com [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: qifengy@gmail.com [Department of Breast Surgery, Qilu Hospital, Shandong Univeristy, Wenhua Xi Road 107, Shandong Province (China); Haffty, Bruce G., E-mail: hafftybg@umdnj.edu [Department of Radiation Oncology, UMDNJ-Robert Wood Johnson School of Medicine, Cancer Institute of New Jersey, NB (United States); Li, Xiaoyan, E-mail: xiaoyanli1219@gmail.com [Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Shandong Province (China); Moran, Meena S., E-mail: meena.moran@yale.edu [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States)

    2013-02-08

    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

  8. In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer.

    Science.gov (United States)

    Hamilton, Amanda M; Foster, Paula J

    2017-02-01

    Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge. Mouse models have been developed to permit in depth evaluation of breast cancer metastasis to the brain. In this study, we compare the efficiency and metastatic potential of two experimental mouse models of TNBC. Longitudinal MRI analysis and end point histology were used to quantify initial cell arrest as well as the number and volume of metastases that developed in mouse brain over time. We showed significant differences in MRI appearance, tumor progression and model efficiency between the syngeneic 4T1-BR5 model and the xenogeneic 231-BR model. Since TNBC does not respond to many standard breast cancer treatments and TNBC brain metastases lack effective targeted therapies, these preclinical TNBC models represent invaluable tools for the assessment of novel systemic therapeutic approaches. Further pursuits of therapeutics designed to bypass the blood tumor barrier and permit access to the brain parenchyma and metastatic cells within the brain will be paramount in the fight to control and treat lethal metastatic cancer.

  9. In Situ Identification of CD44+/CD24− Cancer Cells in Primary Human Breast Carcinomas

    Science.gov (United States)

    Perrone, Giuseppe; Gaeta, Laura Maria; Zagami, Mariagiovanna; Nasorri, Francesca; Coppola, Roberto; Borzomati, Domenico; Bartolozzi, Francesco; Altomare, Vittorio; Trodella, Lucio; Tonini, Giuseppe; Santini, Daniele; Cavani, Andrea; Muda, Andrea Onetti

    2012-01-01

    Breast cancer cells with the CD44+/CD24− phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24− cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24− population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24− cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%–21.23%) of the tumour. A strong correlation was found between the percentage of CD44+/CD24− cells in primary tumours and distant metastasis development (p = 0.0001); in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively). No relationship was evident with tumour size (T) and regional lymph node (N) status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24− cancer cells was an independent factor related to metastasis development (p = 0.004). Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24− tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24− cell percentage. PMID:23028444

  10. 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.

  11. Spatial Analysis of Human Health Risk Due to Arsenic Exposure through Drinking Groundwater in Taiwan’s Pingtung Plain

    Directory of Open Access Journals (Sweden)

    Ching-Ping Liang

    2017-01-01

    Full Text Available Chronic arsenic (As exposure continues to be a public health problem of major concern worldwide, affecting hundreds of millions of people. A long-term groundwater quality survey has revealed that 20% of the groundwater in southern Taiwan’s Pingtung Plain is clearly contaminated with a measured As concentration in excess of the maximum level of 10 µg/L recommended by the World Health Organization. The situation is further complicated by the fact that more than half of the inhabitants in this area continue to use groundwater for drinking. Efforts to assess the health risk associated with the ingestion of As from the contaminated drinking water are required in order to determine the priorities for health risk management. The conventional approach to conducting a human health risk assessment may be insufficient for this purpose, so this study adopts a geostatistical Kriging method to perform a spatial analysis of the health risk associated with ingesting As through drinking groundwater in the Pingtung Plain. The health risk is assessed based on the hazard quotient (HQ and target cancer risk (TR established by the U.S. Environmental Protection Agency. The results show that most areas where the HQ exceeds 1 are in the southwestern part of the study area. In addition, the high-population density townships of Daliao, Linyuan, Donggang, Linbian, Jiadong, and Fangliao presently have exceedingly high TR values that are two orders of magnitude higher than the acceptable standard. Thus, the use of groundwater for drinking in these townships should be strictly avoided. A map that delineates areas with high TR values and high population densities is provided. The findings broaden the scope of the spatial analysis of human health risk and provide a basis for improving the decision-making process.

  12. Spatial Analysis of Human Health Risk Due to Arsenic Exposure through Drinking Groundwater in Taiwan’s Pingtung Plain

    Science.gov (United States)

    Liang, Ching-Ping; Chien, Yi-Chi; Jang, Cheng-Shin; Chen, Ching-Fang; Chen, Jui-Sheng

    2017-01-01

    Chronic arsenic (As) exposure continues to be a public health problem of major concern worldwide, affecting hundreds of millions of people. A long-term groundwater quality survey has revealed that 20% of the groundwater in southern Taiwan’s Pingtung Plain is clearly contaminated with a measured As concentration in excess of the maximum level of 10 µg/L recommended by the World Health Organization. The situation is further complicated by the fact that more than half of the inhabitants in this area continue to use groundwater for drinking. Efforts to assess the health risk associated with the ingestion of As from the contaminated drinking water are required in order to determine the priorities for health risk management. The conventional approach to conducting a human health risk assessment may be insufficient for this purpose, so this study adopts a geostatistical Kriging method to perform a spatial analysis of the health risk associated with ingesting As through drinking groundwater in the Pingtung Plain. The health risk is assessed based on the hazard quotient (HQ) and target cancer risk (TR) established by the U.S. Environmental Protection Agency. The results show that most areas where the HQ exceeds 1 are in the southwestern part of the study area. In addition, the high-population density townships of Daliao, Linyuan, Donggang, Linbian, Jiadong, and Fangliao presently have exceedingly high TR values that are two orders of magnitude higher than the acceptable standard. Thus, the use of groundwater for drinking in these townships should be strictly avoided. A map that delineates areas with high TR values and high population densities is provided. The findings broaden the scope of the spatial analysis of human health risk and provide a basis for improving the decision-making process. PMID:28098817

  13. Spatial Analysis of Human Health Risk Due to Arsenic Exposure through Drinking Groundwater in Taiwan's Pingtung Plain.

    Science.gov (United States)

    Liang, Ching-Ping; Chien, Yi-Chi; Jang, Cheng-Shin; Chen, Ching-Fang; Chen, Jui-Sheng

    2017-01-14

    Chronic arsenic (As) exposure continues to be a public health problem of major concern worldwide, affecting hundreds of millions of people. A long-term groundwater quality survey has revealed that 20% of the groundwater in southern Taiwan's Pingtung Plain is clearly contaminated with a measured As concentration in excess of the maximum level of 10 µg/L recommended by the World Health Organization. The situation is further complicated by the fact that more than half of the inhabitants in this area continue to use groundwater for drinking. Efforts to assess the health risk associated with the ingestion of As from the contaminated drinking water are required in order to determine the priorities for health risk management. The conventional approach to conducting a human health risk assessment may be insufficient for this purpose, so this study adopts a geostatistical Kriging method to perform a spatial analysis of the health risk associated with ingesting As through drinking groundwater in the Pingtung Plain. The health risk is assessed based on the hazard quotient (HQ) and target cancer risk (TR) established by the U.S. Environmental Protection Agency. The results show that most areas where the HQ exceeds 1 are in the southwestern part of the study area. In addition, the high-population density townships of Daliao, Linyuan, Donggang, Linbian, Jiadong, and Fangliao presently have exceedingly high TR values that are two orders of magnitude higher than the acceptable standard. Thus, the use of groundwater for drinking in these townships should be strictly avoided. A map that delineates areas with high TR values and high population densities is provided. The findings broaden the scope of the spatial analysis of human health risk and provide a basis for improving the decision-making process.

  14. 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

    2007-01-01

    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

  15. Expression and roles of Slit/Robo in human ovarian cancer.

    Science.gov (United States)

    Dai, Cai Feng; Jiang, Yi Zhou; Li, Yan; Wang, Kai; Liu, Pei Shu; Patankar, Manish S; Zheng, Jing

    2011-05-01

    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.

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  17. Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells.

    Science.gov (United States)

    Villa, Nancy Y; Bartee, Eric; Mohamed, Mohamed R; Rahman, Masmudur M; Barrett, John W; McFadden, Grant

    2010-06-05

    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.

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

    Science.gov (United States)

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

    2016-01-19

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

  19. Vaccines against human papillomavirus and perspectives for the prevention and control of cervical cancer

    Directory of Open Access Journals (Sweden)

    García-Carrancá Alejandro

    2003-01-01

    Full Text Available Today, "persistent" infections by certain types of human papillomavirus (HPV are considered necessary for developing cervical cancer. Producing efficient vaccines against these viruses may eventually lead to a great reduction in incidence and mortality rates of this cancer. In the case of HPV, the production of traditional vaccines usually based in dead or attenuated viruses is not possible due in part to the lack of systems where large quantities of viral particles could be obtained. Fortunately, the expression of the late L1 protein alone, or in combination with L2, leads to the generation of structures resembling true virions that have been called virus-like particles (VLPs and constitute excellent candidates as prophylactic vaccines. VLPs have shown to be very immunogenic, and have prevented development of natural or challenged infections in both animal systems and humans. Recently, HPV16 VLPs were shown to be very efficient to prevent the development of "persistent" infections, as determined by PCR assays, in a large group of vaccinated women. Therapeutic vaccines, on the other hand, are expected to have an impact on advanced lesions and residual illness, by taking advantaje of the fact that early E6 and E7 genes are thought to be constitutively expressed in cervical tumors and precursor lesions. Finally, DNA-based vaccines could represent a useful alternative for preventing infections by genital HPV.

  20. Laser light induced modulations in metabolic activities in human brain cancer

    Science.gov (United States)

    Tata, Darrell B.; Waynant, Ronald W.

    2008-03-01

    The role of low visible or near infra-red laser intensity in suppressing metabolic activity of malignant human brain cancer (glioblastoma) cells was investigated through the application of either a continuous wave 633nm HeNe or a pulsed picosecond 1,552nm wavelength laser. Human glioblastomas were exposed in their growth culture medium with serum for several energy doses. For both types of laser exposures the glioblastomas exhibited a maximal decline in the metabolic activity relative to their respective sham control counterparts at 10 J/cm2. The cellular metabolic activities for various treatment doses were measured through the colorimetric MTS metabolic assay after the laser exposure. Interestingly, addition of (the enzyme) catalase in the growth medium prior to the laser exposure was found to diminish the laser induced metabolic suppression for all fluence treatment conditions, thus suggesting a functional role of H IIO II in the metabolic suppression. Taken together, our findings reveal that visible or near infra-red low level light exposures could potentially be a viable tool in reducing the metabolic activity of cancers; evidence at hand implicates a role of light induced H IIO II in bringing about in part, suppression in the metabolic activity. Due to the cellular "biphasic" response to the laser exposure, further research needs to be undertaken to determine exposure parameters which would optimize metabolic and cellular growth suppression in-vivo.