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Sample records for human cancers including

  1. Risk factors for breast cancer, including occupational exposures.

    Science.gov (United States)

    Weiderpass, Elisabete; Meo, Margrethe; Vainio, Harri

    2011-03-01

    The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr). For breast cancer the following substances have been classified as "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification "probably carcinogenic to humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women.

  2. Risk Factors for Breast Cancer, Including Occupational Exposures

    Directory of Open Access Journals (Sweden)

    Elisabete Weiderpass

    2011-03-01

    Full Text Available The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr. For breast cancer the following substances have been classified as “carcinogenic to humans” (Group 1: alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure. Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification “probably carcinogenic to humans” (Group 2A includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women.

  3. Human Viruses and Cancer

    Directory of Open Access Journals (Sweden)

    Abigail Morales-Sánchez

    2014-10-01

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

  4. Colon cancer associated transcripts in human cancers.

    Science.gov (United States)

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

    2017-08-02

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

  5. Endometrial cancer risk prediction including serum-based biomarkers

    DEFF Research Database (Denmark)

    Fortner, Renée T; Hüsing, Anika; Kühn, Tilman;

    2017-01-01

    Endometrial cancer risk prediction models including lifestyle, anthropometric, and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case......-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum...... concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines, and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at pdiscrimination was assessed using...

  6. 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.

  7. 4-IBP, a σ1 Receptor Agonist, Decreases the Migration of Human Cancer Cells, Including Glioblastoma Cells, In Vitro and Sensitizes Them In Vitro and In Vivo to Cytotoxic Insults of Proapoptotic and Proautophagic Drugs

    Directory of Open Access Journals (Sweden)

    Veronique Mégalizzi

    2007-05-01

    Full Text Available Although the molecular function of cr receptors has not been fully defined and the natural ligand(s is still not known, there is increasing evidence that these receptors and their ligands might play a significant role in cancer biology. 4-(N-tibenzylpiperidin-4-yl-4iodobenzamide (4-IBP, a selective σ1, agonist, has been used to investigate whether this compound is able to modify: 1 in vitro the migration and proliferation of human cancer cells; 2 in vitro the sensitivity of human glioblastoma cells to cytotoxic drugs; and 3 in vivo in orthotopic glioblastoma and non-small cell lung carcinoma (NSCLC models the survival of mice coadministered cytotoxic agents. 4-IBP has revealed weak anti proliferative effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked concentration-dependent decreases in the growth of human A549 NSCLC and PC3 prostate cancer cells. The compound was also significantly antimigratory in all four cancer cell lines. This may result, at least in U373-MG cells, from modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373-MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and markedly decreased the expression of two proteins involved in drug resistance: glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.

  8. Targeted therapy of ovarian cancer including immune check point inhibitor.

    Science.gov (United States)

    Kim, Jin Young; Cho, Chi Heum; Song, Hong Suk

    2017-08-22

    Epithelial ovarian cancer is the eighth most common cause of cancer-related deaths in women because most patients present with advanced stage disease at the time of diagnosis. Although cytoreductive surgery and platinum-based chemotherapy remain the gold standards of treatment, the recurrence rate of ovarian cancer remains high. Attempts to improve this standard two-drug chemotherapy by adding a third cytotoxic drug have failed to affect either progression-free survival or overall survival and have resulted in an increase in toxic side effects. Some anti-angiogenic agents, poly(ADP-ribose) polymerase, and immune checkpoint inhibitors have shown efficacy in early stages of development for the treatment of epithelial ovarian cancer. As demonstrated in recent clinical trials, the use of bevacizumab, cediranib, pazopanib, olaparib, and rucaparib, either alone or in combination with conventional cytotoxic agents, improves progression-free survival. Trials on immune checkpoint inhibitors such as nivolumab have revealed prolonged responses in a small set of ovarian cancer cases but require further exploration. In this review, we discuss the role of targeted therapies against ovarian cancer, including the use of immune checkpoint inhibitors.

  9. 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.

  10. Oncolytic virotherapy for treatment of breast cancer, including triple-negative breast cancer.

    Science.gov (United States)

    Bramante, Simona; Koski, Anniina; Liikanen, Ilkka; Vassilev, Lotta; Oksanen, Minna; Siurala, Mikko; Heiskanen, Raita; Hakonen, Tiina; Joensuu, Timo; Kanerva, Anna; Pesonen, Sari; Hemminki, Akseli

    2016-02-01

    Breast cancer is a heterogeneous disease, characterized by several distinct biological subtypes, among which triple-negative breast cancer (TNBC) is one associated with a poor prognosis. Oncolytic virus replication is an immunogenic phenomenon, and viruses can be armed with immunostimulatory molecules to boost virus triggered antitumoral immune responses. Cyclophosphamide (CP) is a chemotherapy drug that is associated with cytotoxicity and immunosuppression at higher doses, whereas immunostimulatory and anti-angiogenic properties are observed at low continuous dosage. Therefore, the combination of oncolytic immuno-virotherapy with low-dose CP is an appealing approach. We investigated the potency of oncolytic adenovirus Ad5/3-D24-GMCSF on a TNBC cell line and in vivo in an orthotopic xenograft mouse model, in combination with low-dose CP or its main active metabolite 4-hydroperoxycyclophosphamide (4-HP-CP). Furthermore, we summarized the breast cancer-specific human data on this virus from the Advanced Therapy Access Program (ATAP). Low-dose CP increased the efficacy of Ad5/3-D24-GMCSF in vitro and in a TNBC mouse model. In ATAP, treatments appeared safe and well-tolerated. Thirteen out of 16 breast cancer patients treated were evaluable for possible benefits with modified RECIST 1.1 criteria: 1 patient had a minor response, 2 had stable disease (SD), and 10 had progressive disease (PD). One patient is alive at 1,771 d after treatment. Ad5/3-D24-GMCSF in combination with low-dose CP showed promising efficacy in preclinical studies and possible antitumor activity in breast cancer patients refractory to other forms of therapy. This preliminary data supports continuing the clinical development of oncolytic adenoviruses for treatment of breast cancer, including TNBC.

  11. 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

  12. 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...

  13. 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.

  14. 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.

  15. Prevention of carcinogen and inflammation-induced dermal cancer by oral rapamycin includes reducing genetic damage.

    Science.gov (United States)

    Dao, Vinh; Pandeswara, Srilakshmi; Liu, Yang; Hurez, Vincent; Dodds, Sherry; Callaway, Danielle; Liu, Aijie; Hasty, Paul; Sharp, Zelton D; Curiel, Tyler J

    2015-05-01

    Cancer prevention is a cost-effective alternative to treatment. In mice, the mTOR inhibitor rapamycin prevents distinct spontaneous, noninflammatory cancers, making it a candidate broad-spectrum cancer prevention agent. We now show that oral microencapsulated rapamycin (eRapa) prevents skin cancer in dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) carcinogen-induced, inflammation-driven carcinogenesis. eRapa given before DMBA/TPA exposure significantly increased tumor latency, reduced papilloma prevalence and numbers, and completely inhibited malignant degeneration into squamous cell carcinoma. Rapamycin is primarily an mTORC1-specific inhibitor, but eRapa did not reduce mTORC1 signaling in skin or papillomas, and did not reduce important proinflammatory factors in this model, including p-Stat3, IL17A, IL23, IL12, IL1β, IL6, or TNFα. In support of lack of mTORC1 inhibition, eRapa did not reduce numbers or proliferation of CD45(-)CD34(+)CD49f(mid) skin cancer initiating stem cells in vivo and marginally reduced epidermal hyperplasia. Interestingly, eRapa reduced DMBA/TPA-induced skin DNA damage and the hras codon 61 mutation that specifically drives carcinogenesis in this model, suggesting reduction of DNA damage as a cancer prevention mechanism. In support, cancer prevention and DNA damage reduction effects were lost when eRapa was given after DMBA-induced DNA damage in vivo. eRapa afforded picomolar concentrations of rapamycin in skin of DMBA/TPA-exposed mice, concentrations that also reduced DMBA-induced DNA damage in mouse and human fibroblasts in vitro. Thus, we have identified DNA damage reduction as a novel mechanism by which rapamycin can prevent cancer, which could lay the foundation for its use as a cancer prevention agent in selected human populations.

  16. Molecular phylogeny of coronaviruses including human SARS-CoV

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Phylogenetic tree of coronaviruses (CoVs) including the human SARS-associated virus is reconstructed from complete genomes by using our newly developed K- string composition approach. The relation of the human SARS-CoV to other coronaviruses, i.e. the rooting of the tree is suggested by choosing an appropriate outgroup. SARS-CoV makes a separate group closer but still distant from G2 (CoVs in mammalian host). The relation between different isolates of the human SARS virus is inferred by first constructing an ultrametric distance matrix from counting sequence variations in the genomes. The resulting tree is consistent with clinic relations between the SARS-CoV isolates. In addition to a larger variety of coronavirus genomes these results provide phylogenetic knowledge based on independent novel methodology as compared to recent phylogenetic studies on SARS-CoV.

  17. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

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

  18. Telomerase activity in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, J.

    2000-10-01

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

  19. Does and should breast cancer genetic counselling include lifestyle advice?

    NARCIS (Netherlands)

    Albada, A.; Vernooij, M.; Osch, L. van; Pijpe, A.; Dulmen, S. van; Ausems, M.G.E.M.

    2014-01-01

    To optimally inform counselees about their and their relatives' risks, information about lifestyle risk factors, e.g. physical activity and alcohol consumption, might be discussed in breast cancer genetic counselling. This study explored whether lifestyle was discussed, on whose initiative, whether

  20. [Guideline thyroid cancer including diagnostics of the nodule

    NARCIS (Netherlands)

    Links, T.P.; Heide, L.J. de; Janssen, M; Nederveen, F.H. Van; Lugt, A. van der; Vriens, M.R.; Smit, J.W.A.

    2015-01-01

    - Thyroid cancer is comparatively rare. Thyroid nodules, on the other hand, are frequently diagnosed as a result of increasing use of diagnostic imaging.- Cytological investigation of small nodules that have been found by chance often reveals micropapillary carcinoma that is probably not clinically

  1. Olfactory and tissue markers of fear in mammals including humans.

    Science.gov (United States)

    Hauser, Roman; Wiergowski, Marek; Kaliszan, Michał; Gos, Tomasz; Kernbach-Wighton, Gerhard; Studniarek, Michał; Jankowski, Zbigniew; Namieśnik, Jacek

    2011-12-01

    Pheromones are a mysterious world of chemical signals involved in conspecific communication. They play a number of key functions important for preservation of life of individual organisms, for their defence, survival of offspring and preservation of species. The best-known groups of pheromones include: trail pheromones, territorial pheromones, sex pheromones, aggregation pheromones, dispersion pheromones, repellent pheromones, social pheromones and alarm pheromones. Alarm pheromones are pheromones that are emitted by animals in threatening situations and inform members of the same species of danger. The identified alarm pheromones are synthesised by insects and aquatic organisms. Also humans are able to emit and perceive pheromones. Although alarm pheromones have not been isolated and identified in man so far, there is presumably evidence for their presence in humans. Pinpointing human alarm pheromones, determinants of experienced stress and inductors of provoked fear could have widespread consequences. Their identification could also be of significant importance for the practical utilisation of results by institutions responsible for safety and defence as well as law enforcement/crime detection and antiterrorist activities.

  2. Multidisciplinary treatment including chemoradiotherapy for advanced esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Kenji; Fukuda, Kazuhiro; Kikkawa, Nobuteru; Kobayashi, Tetsurou; Yagyu, Toshio; Hasuike, Yasunori; Mishima, Hideyuki; Shin, Eisei [Osaka National Hospital (Japan)

    1997-03-01

    Over 3 years, concurrent chemoradiotherapy was performed in 16 patients with advanced esophageal cancer (clinical Stage IV) and suspected noncurative resection. The subjects were {>=}A3 or N3, or were stage IV with distant metastasis on preoperative diagnosis. Two courses of 5FU and CDDP were given with concurrent radiotherapy. The predominant side effects were nausea, vomiting and anorexia. Mild or moderate leukopenia also occurred. The response was complete remission (CR) in two patients, partial remission (PR) in eight, minor response (MR) in two, no change (NC) in two and progressive disease (PD) in two. The overall response rate was 62.5%. Esophagectomy was performed in four patients (histological stage II in one, stage III in one, and stage IV in two). Two of 4 resected patients are alive (33.8 months), while the other died of unrelated causes. One of the 6 non-resected PR patients has survived for 18 months, but all other patients died of cancer within nine months of starting treatment. The survival rate of 16 patients undergoing chemoradiotherapy was 16.7% at one and two years. Thus, chemoradiotherapy may improve the prognosis of advanced esophageal cancer with suspected noncurative resection by increasing the response rate and the curative resection rate. (author)

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Endometrial cancer risk prediction including serum-based biomarkers : results from the EPIC cohort

    NARCIS (Netherlands)

    Fortner, Renée T.; Hüsing, Anika; Kühn, Tilman; Konar, Meric; Overvad, Kim; Tjønneland, Anne; Hansen, Louise; Boutron-Ruault, Marie Christine; Severi, Gianluca; Fournier, Agnès; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Orfanos, Philippos; Masala, Giovanna; Agnoli, Claudia; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H. Bas; Peeters, Petra H M; Weiderpass, Elisabete; Gram, Inger T.; Gavrilyuk, Oxana; Quirós, J. Ramón; Maria Huerta, José; Ardanaz, Eva; Larrañaga, Nerea; Lujan-Barroso, Leila; Sánchez-Cantalejo, Emilio; Butt, Salma Tunå; Borgquist, Signe; Idahl, Annika; Lundin, Eva; Khaw, Kay Tee; Allen, Naomi E.; Rinaldi, Sabina; Dossus, Laure; Gunter, Marc; Merritt, Melissa A.; Tzoulaki, Ioanna; Riboli, Elio; Kaaks, Rudolf

    2017-01-01

    Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested

  9. Septin mutations in human cancers

    Directory of Open Access Journals (Sweden)

    Elias T Spiliotis

    2016-11-01

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

  10. DBGC: A Database of Human Gastric Cancer.

    Science.gov (United States)

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

    2015-01-01

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

  11. BIOLOGY OF HUMAN MALARIA PLASMODIA INCLUDING PLASMODIUM KNOWLESI

    Directory of Open Access Journals (Sweden)

    Spinello Antinori

    2012-03-01

    Full Text Available Malaria is a vector-borne infection caused by unicellular parasite of the genus Plasmodium. Plasmodia are obligate intracellular parasites that in humans after a clinically silent replication phase in the liver are able to infect and replicate within the erythrocytes. Four species (P.falciparum, P.malariae, P.ovale and P.vivax are traditionally recognized as responsible of natural infection in human beings but the recent upsurge of P.knowlesi malaria in South-East Asia has led clinicians to consider it as the fifth human malaria parasite. Recent studies in wild-living apes in Africa have revealed that P.falciparum, the most deadly form of human malaria, is not only human-host restricted as previously believed and its phylogenetic lineage is much more complex with new species identified in gorilla, bonobo and chimpanzee. Although less impressive, new data on biology of P.malariae, P.ovale and P.vivax are also emerging and will be briefly discussed in this review.

  12. 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

  13. Oogenesis in adult mammals, including humans: a review.

    Science.gov (United States)

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Wimalasena, Jay; Ayala, Maria E; Dominguez, Roberto

    2005-04-01

    The origin of oocytes and primary follicles in ovaries of adult mammalian females has been a matter of dispute for over 100 yr. The prevailing belief that all oocytes in adult mammalian females must persist from the fetal period of life seems to be a uniquely retrogressive reproductive mechanism requiring humans to preserve their gametes from the fetal period for several decades. The utilization of modern techniques during last 10 yr clearly demonstrates that mammalian primordial germ cells originate from somatic cell precursors. This indicates that if somatic cells are precursors of germ cells, then somatic mutations can be passed on to progeny. Mitotically active germline stem cells have been described earlier in ovaries of adult prosimian primates and recently have been reported to also be present in the ovaries of adult mice. We have earlier shown that in adult human females, mesenchymal cells in the ovarian tunica albuginea undergo a mesenchymal-epithelial transition into ovarian surface epithelium cells, which differentiate sequentially into primitive granulosa and germ cells. Recently, we have reported that these structures assemble in the deeper ovarian cortex and form new follicles to replace earlier primary follicles undergoing atresia (follicular renewal). Our current observations also indicate that follicular renewal exists in rat ovaries, and human oocytes can differentiate from ovarian surface epithelium in fetal ovaries in vivo and from adult ovaries in vitro. These reports challenge the established dogma regarding the fetal origin of eggs and primary follicles in adult mammalian ovaries. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. Yet, the follicular renewal may cease at a certain age, and this may predetermine the onset of the natural menopause or premature ovarian failure. A lack of follicular renewal in aging ovaries

  14. Pedestrian-bridge dynamic interaction, including human participation

    Science.gov (United States)

    Qin, J. W.; Law, S. S.; Yang, Q. S.; Yang, N.

    2013-02-01

    The pedestrian-bridge dynamic interaction problem based on bipedal walking model and damped compliant legs is presented in this work. A time-variant damper is modeled at a given walking speed. A control force is applied by the pedestrian to compensate for energy dissipated with the system damping in walking and to regulate the walking performance of the pedestrian. The effects of stiffness, damping of the leg and the landing angle of attack are investigated in the numerical studies. Simulation results show that the dynamic interaction will increase with a larger vibration level of structure. More external energy must be input to maintain steady walking and uniform dynamic behavior of the pedestrian in the process. The simple bipedal walking model could well describe the human-structure dynamic interaction.

  15. Human sperm chromatin stabilization: a proposed model including zinc bridges.

    Science.gov (United States)

    Björndahl, Lars; Kvist, Ulrik

    2010-01-01

    The primary focus of this review is to challenge the current concepts on sperm chromatin stability. The observations (i) that zinc depletion at ejaculation allows a rapid and total sperm chromatin decondensation without the addition of exogenous disulfide cleaving agents and (ii) that the human sperm chromatin contains one zinc for every protamine for every turn of the DNA helix suggest an alternative model for sperm chromatin structure may be plausible. An alternative model is therefore proposed, that the human spermatozoon could at ejaculation have a rapidly reversible zinc dependent chromatin stability: Zn(2+) stabilizes the structure and prevents the formation of excess disulfide bridges by a single mechanism, the formation of zinc bridges with protamine thiols of cysteine and potentially imidazole groups of histidine. Extraction of zinc enables two biologically totally different outcomes: immediate decondensation if chromatin fibers are concomitantly induced to repel (e.g. by phosphorylation in the ooplasm); otherwise freed thiols become committed into disulfide bridges creating a superstabilized chromatin. Spermatozoa in the zinc rich prostatic fluid (normally the first expelled ejaculate fraction) represent the physiological situation. Extraction of chromatin zinc can be accomplished by the seminal vesicular fluid. Collection of the ejaculate in one single container causes abnormal contact between spermatozoa and seminal vesicular fluid affecting the sperm chromatin stability. There are men in infertile couples with low content of sperm chromatin zinc due to loss of zinc during ejaculation and liquefaction. Tests for sperm DNA integrity may give false negative results due to decreased access for the assay to the DNA in superstabilized chromatin.

  16. 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

  17. 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 ...

  18. 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.

  19. Non-Human Primates Harbor Diverse Mammalian and Avian Astroviruses Including Those Associated with Human Infections.

    Directory of Open Access Journals (Sweden)

    Erik A Karlsson

    Full Text Available Astroviruses (AstVs are positive sense, single-stranded RNA viruses transmitted to a wide range of hosts via the fecal-oral route. The number of AstV-infected animal hosts has rapidly expanded in recent years with many more likely to be discovered because of the advances in viral surveillance and next generation sequencing. Yet no study to date has identified human AstV genotypes in animals, although diverse AstV genotypes similar to animal-origin viruses have been found in children with diarrhea and in one instance of encephalitis. Here we provide important new evidence that non-human primates (NHP can harbor a wide variety of mammalian and avian AstV genotypes, including those only associated with human infection. Serological analyses confirmed that >25% of the NHP tested had antibodies to human AstVs. Further, we identified a recombinant AstV with parental relationships to known human AstVs. Phylogenetic analysis suggests AstVs in NHP are on average evolutionarily much closer to AstVs from other animals than are AstVs from bats, a frequently proposed reservoir. Our studies not only demonstrate that human astroviruses can be detected in NHP but also suggest that NHP are unique in their ability to support diverse AstV genotypes, further challenging the paradigm that astrovirus infection is species-specific.

  20. An overview of drug delivery vehicles for cancer treatment: Nanocarriers and nanoparticles including photovoltaic nanoparticles.

    Science.gov (United States)

    Chowdhury, Silvia; Yusof, Faridah; Salim, Wan Wardatul Amani Wan; Sulaiman, Nadzril; Faruck, Mohammad Omer

    2016-11-01

    Cancer is a complicated disease for which finding a cure presents challenges. In recent decades, new ways to treat cancer are being sought; one being nanomedicine, which manipulates nanoparticles to target a cancer and release drugs directly to the cancer cells. A number of cancer treatments based on nanomedicine are under way and mostly are in preclinical trials owing to challenges in administration, safety, and effectiveness. One alternative method for drug delivery is the use of photovoltaic nanoparticles, which has the potential to deliver drugs via light activation. The concepts are based on standard photovoltaic cell that holds opposite charges on its surfaces and releases drugs when charge intensity or polarity changes upon photo-stimulation such as from a laser source or sunlight. This review will cover some recent progress in cancer treatment using nanoparticles, including photovoltaic nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. ETS-Associated Genomic Alterations including ETS2 Loss Markedly Affect Prostate Cancer Progression

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-13-1-0385 TITLE: ETS -Associated Genomic Alterations including ETS2 Loss Markedly Affect Prostate Cancer Progression...29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0385 ETS -Associated Genomic Alterations including ETS2 Loss Markedly Affect...upregulation of ERG, a transcription factor with oncogenic roles in other cancers such as leukemias and sarcomas (Tomlins, Rhodes et al. 2005; Turner

  2. European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer.

    Science.gov (United States)

    Friis, Søren; Kesminiene, Ausrele; Espina, Carolina; Auvinen, Anssi; Straif, Kurt; Schüz, Joachim

    2015-12-01

    The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events.

  3. 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

  4. 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

  5. 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.

  6. Alcohol intake and colorectal cancer: a comparison of approaches for including repeated measures of alcohol consumption

    DEFF Research Database (Denmark)

    Thygesen, Lau Caspar; Wu, Kana; Grønbaek, Morten

    2008-01-01

    BACKGROUND: In numerous studies, alcohol intake has been found to be positively associated with colorectal cancer risk. However, the majority of studies included only one exposure measurement, which may bias the results if long-term intake is relevant.METHODS: We compared different approaches...... for including repeated measures of alcohol intake among 47,432 US men enrolled in the Health Professionals Follow-up Study. Questionnaires including questions on alcohol intake had been completed in 1986, 1990, 1994, and 1998. The outcome was incident colorectal cancer during follow-up from 1986 to 2002.RESULTS......: During follow-up, 868 members of the cohort experienced colorectal cancer. Baseline, updated, and cumulative average alcohol intakes were positively associated with colorectal cancer, with only minor differences among the approaches. These results support moderately increased risk for intake >30 g...

  7. 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.

  8. 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.

  9. 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.

  10. 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...

  11. 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....

  12. 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.

  13. 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.

  14. 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.

  15. 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 ...

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. Biological stoichiometry in human cancer.

    Directory of Open Access Journals (Sweden)

    James J Elser

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

  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. Should abdominal sequences be included in prostate cancer MR staging studies?

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    McEvoy, S.H., E-mail: sineadhmcevoy@gmail.com [Department of Radiology, St. Vincent' s University Hospital, Dublin 4 (Ireland); Lavelle, L.P.; Purcell, Y.M. [Department of Radiology, St. Vincent' s University Hospital, Dublin 4 (Ireland); Quinlan, D.M. [Department of Urology, St. Vincent' s University Hospital, Dublin 4 (Ireland); Skehan, S.J.; Collins, C.D.; McMahon, C.J. [Department of Radiology, St. Vincent' s University Hospital, Dublin 4 (Ireland)

    2015-06-15

    Highlights: • ESUR guideline that abdominal MR sequences are reserved for high-risk prostate cancer is tested. • Routine abdominal sequences are of low yield in prostate cancer MR staging. • Routine abdominal staging sequences frequently result in incidental findings. • Abdominal staging sequences should be reserved for high-risk prostate cancer cases. - Abstract: Objectives: Prostate cancer staging MR examinations commonly include abdominal sequences to assess for non-regional (common iliac or para-aortic) nodal metastasis. In our experience the diagnostic yield of this is limited, but incidental findings are frequent, often necessitating further investigations. The aim of this study is to assess the diagnostic utility of abdominal sequences in routine prostate cancer MR staging studies. Methods: Findings on abdominal sequences of consecutive MRI prostate studies performed for staging newly diagnosed prostate cancer between September 2011 and September 2013 were reviewed with respect to adenopathy and additional incidental findings. Results were correlated with Gleason grade and serum prostate-specific antigen (PSA) level in each case. Results: 355 MRI prostate examinations were reviewed. 4 (1.1%) showed enlarged non-regional lymph nodes. Incidental findings were found in 82(23.1%) cases, neccessitating further investigation in 45 (12.7%) cases. Enlarged non-regional nodes were associated with higher PSA level and Gleason grade (p = 0.007, p = 0.005 respectively). With a combined threshold of PSA > 20 ng/mL and/or Gleason grade ≥8 the sensitivity, specificity, PPV and NPV were 100, 60, 3 and 100% respectively for predicting the presence of non-regional adenopathy. Conclusions: Routine abdominal sequences are of very low yield in routine prostate cancer MR staging, frequently resulting in incidental findings requiring further work-up and should be reserved for high-risk cases. Our experience supports the use of an abdominal staging sequence in high

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort.

    Science.gov (United States)

    Fortner, Renée T; Hüsing, Anika; Kühn, Tilman; Konar, Meric; Overvad, Kim; Tjønneland, Anne; Hansen, Louise; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Fournier, Agnès; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Orfanos, Philippos; Masala, Giovanna; Agnoli, Claudia; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H B As; Peeters, Petra H M; Weiderpass, Elisabete; Gram, Inger T; Gavrilyuk, Oxana; Quirós, J Ramón; Maria Huerta, José; Ardanaz, Eva; Larrañaga, Nerea; Lujan-Barroso, Leila; Sánchez-Cantalejo, Emilio; Butt, Salma Tunå; Borgquist, Signe; Idahl, Annika; Lundin, Eva; Khaw, Kay-Tee; Allen, Naomi E; Rinaldi, Sabina; Dossus, Laure; Gunter, Marc; Merritt, Melissa A; Tzoulaki, Ioanna; Riboli, Elio; Kaaks, Rudolf

    2017-03-15

    Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were selected into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including etiologic markers on independent pathways and genetic markers may further improve discrimination. © 2016 UICC.

  10. 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.

  11. How should clinical data be included in experimental studies of cancer immunology?

    Science.gov (United States)

    Gjertsen, Bjørn Tore; Bruserud, Øystein

    2004-08-01

    Patients diagnosed with the same malignant disease are often heterogeneous with regard to age, complications, malignant cell morphology and tumor histology, disease stage, prognostic parameters, and previous therapy. Many of these factors can affect immunocompetent cells or influence the malignant cell susceptibility to immunotherapy. Summaries of relevant clinical information should therefore be included in cancer immunology studies to increase the present as well as the future scientific impact. Guidelines for selection of relevant information are suggested in the article.

  12. 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

  13. Prevalence of Telomerase Activity in Human Cancer

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    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.

  14. Cancer Metabolomics and the Human Metabolome Database

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    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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease

    NARCIS (Netherlands)

    Collaborative Group on Hormona, l Factors; van den Brandt, P.A.; Goldbohm, R.A.

    2001-01-01

    Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Collaborative Group on Hormonal Factors in Breast Cancer. BACKGROUND: Women with a family history of breast cancer are

  1. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease

    NARCIS (Netherlands)

    Collaborative Group on Hormona, l Factors; van den Brandt, P.A.; Goldbohm, R.A.

    2001-01-01

    Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Collaborative Group on Hormonal Factors in Breast Cancer. BACKGROUND: Women with a family history of breast cancer are

  2. 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.

  3. Cancer risks related to low-level RF/MW exposures, including cell phones.

    Science.gov (United States)

    Szmigielski, Stanislaw

    2013-09-01

    For years, radiofrequency (RF) and microwave (MW) radiations have been applied in the modern world. The rapidly increasing use of cellular phones called recent attention to the possible health risks of RF/MW exposures. In 2011, a group of international experts organized by IARC (International Agency for Research on Cancer in Lyon) concluded that RF/MW radiations should be listed as a possible carcinogen (group 2B) for humans. Three meta-analyses of case-control studies have concluded that using cell phones for more than ten years was associated with an increase in the overall risk of developing a brain tumor. The Interphone Study, the largest health-related case-control international study of use of cell phones and head and neck tumors, showed no statistically significant increases in brain cancers related to higher amounts of cell phone use, but excess risk in a small subgroup of more heavily exposed users associated with latency and laterality was reported. So far, the published studies do not show that mobile phones could for sure increase the risk of cancer. This conclusion is based on the lack of a solid biological mechanism, and the fact that brain cancer rates are not going up significantly. However, all of the studies so far have weaknesses, which make it impossible to entirely rule out a risk. Mobile phones are still a new technology and there is little evidence about effects of long-term use. For this reason, bioelectromagnetic experts advise application of a precautionary resources. It suggests that if people want to use a cell phone, they can choose to minimize their exposure by keeping calls short and preferably using hand-held sets. It also advises discouraging children from making non essential calls as well as also keeping their calls short.

  4. S5-4: Formal Modeling of Affordance in Human-Included Systems

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    Namhun Kim

    2012-10-01

    Full Text Available In spite of it being necessary for humans to consider modeling, analysis, and control of human-included systems, it has been considered a challenging problem because of the critical role of humans in complex systems and of humans' capability of executing unanticipated actions–both beneficial and detrimental ones. Thus, to provide systematic approaches to modeling human actions as a part of system behaviors, a formal modeling framework for human-involved systems in which humans play a controlling role based on their perceptual information is presented. The theory of affordance provides definitions of human actions and their associated properties; Finite State Automata (FSA based modeling is capable of mapping nondeterministic humans into computable components in the system representation. In this talk, we investigate the role of perception in human actions in the system operation and examine the representation of perceptual elements in affordance-based modeling formalism. The proposed framework is expected to capture the natural ways in which humans participate in the system as part of its operation. A human-machine cooperative manufacturing system control example and a human agent simulation example will be introduced for the illustrative purposes at the end of the presentation.

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

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    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.

  6. 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.

  7. Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer.

    Science.gov (United States)

    Komiyama, Shinichi; Katabuchi, Hidetaka; Mikami, Mikio; Nagase, Satoru; Okamoto, Aikou; Ito, Kiyoshi; Morishige, Kenichiro; Suzuki, Nao; Kaneuchi, Masanori; Yaegashi, Nobuo; Udagawa, Yasuhiro; Yoshikawa, Hiroyuki

    2016-06-01

    The fourth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer was published in 2015. The guidelines contain seven chapters and six flow charts. The major changes in this new edition are as follows-(1) the format has been changed from reviews to clinical questions (CQ), and the guidelines for optimal clinical practice in Japan are now shown as 41 CQs and answers; (2) the 'flow charts' have been improved and placed near the beginning of the guidelines; (3) the 'basic points', including tumor staging, histological classification, surgical procedures, chemotherapy, and palliative care, are described before the chapter; (4) the FIGO surgical staging of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was revised in 2014 and the guideline has been revised accordingly to take the updated version of this classification into account; (5) the procedures for examination and management of hereditary breast and ovarian cancer are described; (6) information on molecular targeting therapy has been added; (7) guidelines for the treatment of recurrent cancer based on tumor markers alone are described, as well as guidelines for providing hormone replacement therapy after treatment.

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    Sharon J Pitteri

    Full Text Available The complexity of the human plasma proteome represents a substantial challenge for biomarker discovery. Proteomic analysis of genetically engineered mouse models of cancer and isolated cancer cells and cell lines provide alternative methods for identification of potential cancer markers that would be detectable in human blood using sensitive assays. The goal of this work is to evaluate the utility of an integrative strategy using these two approaches for biomarker discovery.We investigated a strategy that combined quantitative plasma proteomics of an ovarian cancer mouse model with analysis of proteins secreted or shed by human ovarian cancer cells. Of 106 plasma proteins identified with increased levels in tumor bearing mice, 58 were also secreted or shed from ovarian cancer cells. The remainder consisted primarily of host-response proteins. Of 25 proteins identified in the study that were assayed, 8 mostly secreted proteins common to mouse plasma and human cancer cells were significantly upregulated in a set of plasmas from ovarian cancer patients. Five of the eight proteins were confirmed to be upregulated in a second independent set of ovarian cancer plasmas, including in early stage disease.Integrated proteomic analysis of cancer mouse models and human cancer cell populations provides an effective approach to identify potential circulating protein biomarkers.

  10. Including Antenna Models in Microwave Imaging for Breast-Cancer Screening

    DEFF Research Database (Denmark)

    Rubæk, Tonny; Meincke, Peter

    2006-01-01

    Microwave imaging is emerging as a tool for screening for breast cancer, but the lack of methods for including the characteristics of the antennas of the imaging systems in the imaging algorithms limits their performance. In this paper, a method for incorporating the full antenna characteristics......, in terms of the transmission-matrix representation, in a frequency-domain imaging algorithm is presented. The algorithm is tested on a simulation of the Physical-Anomaly Tomography (PAT) scanner imaging system developed at the Technical University of Denmark and is shown to have superior performance when...

  11. 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

  12. 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.

  13. 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

  14. Differential network analysis in human cancer research.

    Science.gov (United States)

    Gill, Ryan; Datta, Somnath; Datta, Susmita

    2014-01-01

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

  15. Associations of Filaggrin Gene Loss-of-Function Variants and Human Papillomavirus-Related Cancer and PreCancer in Danish Adults

    DEFF Research Database (Denmark)

    Skaaby, Tea; Husemoen, Lise Lotte N; Jørgensen, Torben

    2014-01-01

    to human papillomavirus (HPV) infection and thus a higher risk of HPV-related cancer and pre-cancer. We investigated the association of the FLG genotype with incidence of HPV-related cancer of cervix, vagina, vulva, penis, anus and head and neck, and pre-cancer of the cervix. METHODS: We included 13...

  16. Associations of Filaggrin Gene Loss-of-Function Variants and Human Papillomavirus-Related Cancer and Pre-Cancer in Danish Adults

    DEFF Research Database (Denmark)

    Skaaby, Tea; Husemoen, Lise Lotte N; Jørgensen, Torben;

    2014-01-01

    to human papillomavirus (HPV) infection and thus a higher risk of HPV-related cancer and pre-cancer. We investigated the association of the FLG genotype with incidence of HPV-related cancer of cervix, vagina, vulva, penis, anus and head and neck, and pre-cancer of the cervix. METHODS: We included 13...

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

    Directory of Open Access Journals (Sweden)

    Jennifer S Myers

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

  18. 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.

  19. Including Secular Philosophies Such as Humanism in Locally Agreed Syllabuses for Religious Education

    Science.gov (United States)

    Watson, Jacqueline

    2010-01-01

    The 2004 "National Framework for Religious Education" (NFRE) innovatively recommended that secular philosophies such as humanism, or secular worldviews, be included in locally agreed syllabuses for religious education (RE) in England. However, the NFRE is a non-statutory document, and Agreed Syllabus Conferences (ASCs) and Standing…

  20. Intestinal fermentation of lactose and prebiotic lactose derivatives, including human milk oligosaccharides

    NARCIS (Netherlands)

    Venema, K.

    2012-01-01

    This review describes the recent advances in technology to study fermentation of lactose and its prebiotic derivatives, including human milk oligosaccharides. Novel molecular tools to identify members of the microbiota that ferment these substrates are highlighted, as well as the use of stable isoto

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. MicroRNA Regulation of Human Breast Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yohei Shimono

    2015-12-01

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

  7. 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.

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

    Science.gov (United States)

    Ding, Lin; El Zaatari, Mohamad

    2017-01-01

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

  9. 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.

  10. 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.

  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. Nomogram including pretherapeutic parameters for prediction of survival after SIRT of hepatic metastases from colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fendler, Wolfgang Peter [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Klinik und Poliklinik fuer Nuklearmedizin, Munich (Germany); Ilhan, Harun [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Paprottka, Philipp M. [Ludwig-Maximilians-University of Munich, Department of Clinical Radiology, Munich (Germany); Jakobs, Tobias F. [Hospital Barmherzige Brueder, Department of Diagnostic and Interventional Radiology, Munich (Germany); Heinemann, Volker [Ludwig-Maximilians-University of Munich, Department of Internal Medicine III, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Bartenstein, Peter; Haug, Alexander R. [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Khalaf, Feras [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Ezziddin, Samer [Saarland University Medical Center, Department of Nuclear Medicine, Homburg (Germany); Hacker, Marcus [Vienna General Hospital, Department of Nuclear Medicine, Vienna (Austria)

    2015-09-15

    Pre-therapeutic prediction of outcome is important for clinicians and patients in determining whether selective internal radiation therapy (SIRT) is indicated for hepatic metastases of colorectal cancer (CRC). Pre-therapeutic characteristics of 100 patients with colorectal liver metastases (CRLM) treated by radioembolization were analyzed to develop a nomogram for predicting survival. Prognostic factors were selected by univariate Cox regression analysis and subsequent tested by multivariate analysis for predicting patient survival. The nomogram was validated with reference to an external patient cohort (n = 25) from the Bonn University Department of Nuclear Medicine. Of the 13 parameters tested, four were independently associated with reduced patient survival in multivariate analysis. These parameters included no liver surgery before SIRT (HR:1.81, p = 0.014), CEA serum level ≥ 150 ng/ml (HR:2.08, p = 0.001), transaminase toxicity level ≥2.5 x upper limit of normal (HR:2.82, p = 0.001), and summed computed tomography (CT) size of the largest two liver lesions ≥10 cm (HR:2.31, p < 0.001). The area under the receiver-operating characteristic curve for our prediction model was 0.83 for the external patient cohort, indicating superior performance of our multivariate model compared to a model ignoring covariates. The nomogram developed in our study entailing four pre-therapeutic parameters gives good prediction of patient survival post SIRT. (orig.)

  13. Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14

    Science.gov (United States)

    Ruark, Elise; Seal, Sheila; McDonald, Heather; Zhang, Feng; Elliot, Anna; Lau, KingWai; Perdeaux, Elizabeth; Rapley, Elizabeth; Eeles, Rosalind; Peto, Julian; Kote-Jarai, Zsofia; Muir, Kenneth; Nsengimana, Jeremie; Shipley, Janet; Bishop, D. Timothy; Stratton, Michael R; Easton, Douglas F; Huddart, Robert A; Rahman, Nazneen; Turnbull, Clare

    2013-01-01

    Testicular germ cell tumor (TGCT) is the most common cancer in young men and is notable for its high familial risks1,2. To date, six loci associated with TGCT have been reported3-7. From GWAS analysis of 307,291 SNPs in 986 cases and 4,946 controls, we selected for follow-up 694 SNPs, which we genotyped in a further 1,064 TGCT cases and 10,082 controls from the UK. We identified SNPs at nine new loci showing association with TGCT (P<5×10−8), at 1q22, 1q24.1, 3p24.3, 4q24, 5q31.1, 8q13.3, 16q12.1, 17q22 and 21q22.3, which together account for an additional 4-6% of the familial risk of TGCT. The loci include genes plausibly related to TGCT development. PRDM14, at 8q13.3, is essential for early germ cell specification8 whilst DAZL, at 3p24.3, is required for regulation of germ cell development9. Furthermore, PITX1, at 5q31.1 regulates TERT expression, and is the third TGCT locus implicated in telomerase regulation10. PMID:23666240

  14. 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...

  15. Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions

    Directory of Open Access Journals (Sweden)

    Eugene B. Chang

    2013-01-01

    Full Text Available Compound K (20-O-beta-D-glucopyranosyl-20(S-protopanaxadiol, CK, an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to inhibit cell growth in a variety of cancers. However, the mechanisms are not completely understood, especially in colorectal cancer (CRC. A xenograft tumor model was used first to examine the anti-CRC effect of CK in vivo. Then, multiple in vitro assays were applied to investigate the anticancer effects of CK including antiproliferation, apoptosis and cell cycle distribution. In addition, a qPCR array and western blot analysis were executed to screen and validate the molecules and pathways involved. We observed that CK significantly inhibited the growth of HCT-116 tumors in an athymic nude mouse xenograft model. CK significantly inhibited the proliferation of human CRC cell lines HCT-116, SW-480, and HT-29 in a dose- and time-dependent manner. We also observed that CK induced cell apoptosis and arrested the cell cycle in the G1 phase in HCT-116 cells. The processes were related to the upregulation of p53/p21, FoxO3a-p27/p15 and Smad3, and downregulation of cdc25A, CDK4/6 and cyclin D1/3. The major regulated targets of CK were cyclin dependent inhibitors, including p21, p27, and p15. These results indicate that CK inhibits transcriptional activation of multiple tumor-promoting pathways in CRC, suggesting that CK could be an active compound in the prevention or treatment of CRC.

  16. 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.

  17. 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

  18. 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.

  19. Complex pattern of colon cancer recurrence including a kidney metastasis: A case report

    Institute of Scientific and Technical Information of China (English)

    Helfried Waleczek; Moritz N Wente; Jürgen Kozianka

    2005-01-01

    We report a case of a 77-year-old female with a local recurrence of cancer after right hemicolectomy which infiltrated the pancreatic head affording pancreatoduodenectomy, who developed 3 years later recurrent tumor masses localized in the mesentery of the jejunum and in the lower pole of the left kidney. Partial nephrectomy and a segment resection of the small bowel were performed. Histological examination of both specimens revealed a necrotic metastasis of the primary carcinoma of the colon. Although intraluminal implantation of colon cancer cells in the renal pelvic mucosa from ureteric metastasis has been described, metastasis of a colorectal cancer in the kidney parenchyma is extremely rare and can be treated in an organ preserving manner. A complex pattern of colon cancer recurrence with unusual and rare sites of metastasis is reported.

  20. Alterations of 5-Hydroxymethylcytosine in Human Cancers

    Directory of Open Access Journals (Sweden)

    Ali Yesilkanal

    2013-06-01

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

  1. 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.

  2. Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including 1 family with male breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sruewing, J.P.; Brody, L.C.; Erdos, M.R. [National Institute of Health, Bethesda, MD (United States)] [and others

    1995-07-01

    Genetic epidemiological evidence suggests that mutations in BRCA1 may be responsible for approximately one half of early onset familial breast cancer and the majority of familial breast/ovarian cancer. The recent cloning of BRCA1 allows for the direct detection of mutations, but the feasibility of presymptomatic screening for cancer susceptibility is unknown. We analyzed genomic DNA from one affected individual from each of 24 families with at least three cases of ovarian or breast cancer, using SSCP assays. Variant SSCP bands were subcloned and sequenced. Allele-specific oligonucleotide hybridization was used to verify sequence changes and to screen DNA from control individuals. Six frameshift and two missense mutations were detected in 10 different families. A frameshift mutation was detected in a male proband affected with both breast and prostate cancer. A 40-bp deletion was detected in a patient who developed intra-abdominal carcinomatosis 1 year after prophylactic oophorectomy. Mutations were detected throughout the gene, and only one was detected in more than a single family. These results provide further evidence that inherited breast and ovarian cancer can occur as a consequence of a wide array of BRCA1 mutations. These results suggests that development of a screening test for BRCA1 mutations will be technically challenging. The finding of a mutation in a family with male breast cancer, not previously thought to be related to BRCA1, also illustrates the potential difficulties of genetic counseling for individuals known to carry mutations. 37 refs., 1 fig., 1 tab.

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

    Science.gov (United States)

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

    2017-06-15

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

  4. 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

  5. Genomics of Ovarian Cancer Progression Reveals Diverse Metastatic Trajectories Including Intraepithelial Metastasis to the Fallopian Tube.

    Science.gov (United States)

    Eckert, Mark A; Pan, Shawn; Hernandez, Kyle M; Loth, Rachel M; Andrade, Jorge; Volchenboum, Samuel L; Faber, Pieter; Montag, Anthony; Lastra, Ricardo; Peter, Marcus E; Yamada, S Diane; Lengyel, Ernst

    2016-12-01

    Accumulating evidence has supported the fallopian tube rather than the ovary as the origin for high-grade serous ovarian cancer (HGSOC). To understand the relationship between putative precursor lesions and metastatic tumors, we performed whole-exome sequencing on specimens from eight HGSOC patient progression series consisting of serous tubal intraepithelial carcinomas (STIC), invasive fallopian tube lesions, invasive ovarian lesions, and omental metastases. Integration of copy number and somatic mutations revealed patient-specific patterns with similar mutational signatures and copy-number variation profiles across all anatomic sites, suggesting that genomic instability is an early event in HGSOC. Phylogenetic analyses supported STIC as precursor lesions in half of our patient cohort, but also identified STIC as metastases in 2 patients. Ex vivo assays revealed that HGSOC spheroids can implant in the fallopian tube epithelium and mimic STIC lesions. That STIC may represent metastases calls into question the assumption that STIC are always indicative of primary fallopian tube cancers. We find that the putative precursor lesions for HGSOC, STIC, possess most of the genomic aberrations present in advanced cancers. In addition, a proportion of STIC represent intraepithelial metastases to the fallopian tube rather than the origin of HGSOC. Cancer Discov; 6(12); 1342-51. ©2016 AACR.See related commentary by Swisher et al., p. 1309This article is highlighted in the In This Issue feature, p. 1293. ©2016 American Association for Cancer Research.

  6. A human in vitro whole blood assay to predict the systemic cytokine response to therapeutic oligonucleotides including siRNA.

    Directory of Open Access Journals (Sweden)

    Christoph Coch

    Full Text Available Therapeutic oligonucleotides including siRNA and immunostimulatory ligands of Toll-like receptors (TLR or RIG-I like helicases (RLH are a promising novel class of drugs. They are in clinical development for a broad spectrum of applications, e.g. as adjuvants in vaccines and for the immunotherapy of cancer. Species-specific immune activation leading to cytokine release is characteristic for therapeutic oligonucleotides either as an unwanted side effect or intended pharmacology. Reliable in vitro tests designed for therapeutic oligonucleotides are therefore urgently needed in order to predict clinical efficacy and to prevent unexpected harmful effects in clinical development. To serve this purpose, we here established a human whole blood assay (WBA that is fast and easy to perform. Its response to synthetic TLR ligands (R848: TLR7/8, LPS: TLR4 was on a comparable threshold to the more time consuming peripheral blood mononuclear cell (PBMC based assay. By contrast, the type I IFN profile provoked by intravenous CpG-DNA (TLR9 ligand in humans in vivo was more precisely replicated in the WBA than in stimulated PBMC. Since Heparin and EDTA, but not Hirudin, displaced oligonucleotides from their delivery agent, only Hirudin qualified as the anticoagulant to be used in the WBA. The Hirudin WBA exhibited a similar capacity as the PBMC assay to distinguish between TLR7-activating and modified non-stimulatory siRNA sequences. RNA-based immunoactivating TLR7/8- and RIG-I-ligands induced substantial amounts of IFN-α in the Hirudin-WBA dependent on delivery agent used. In conclusion, we present a human Hirudin WBA to determine therapeutic oligonucleotide-induced cytokine release during preclinical development that can readily be performed and offers a close reflection of human cytokine response in vivo.

  7. 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.

  8. Intravenous phentolamine infusion alleviates the pain of abdominal visceral cancer, including pancreatic carcinoma.

    Science.gov (United States)

    Yasukawa, Masako; Yasukawa, Ken'ichi; Kamiizumi, You; Yokoyama, Ryouji

    2007-01-01

    This case report series describes eight patients (four patients with pancreatic carcinoma, one patient with hepatocellular carcinoma, one patient with gastric and rectal carcinoma, one with sigmoid colon cancer, and one with rectal cancer), whose abdominal cancer pain was treated with intravenous phentolamine infusion at 80 mg x day(-1) for 2 days. All but one of the patients had already been treated with opioids. All eight patients complained of severe abdominal pain; in five patients the pain radiated to the back, and there was associated anal pain in two patients. Analgesia was achieved in three patients; pain alleviation was obtained in four patients, but was not sustained in two of these four patients; and the treatment in one patient could not be judged for efficacy because epidural morphine was used together with the phentolamine. Adverse effects of phentolamine were tachycardia and/or hypotension.

  9. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses

    Science.gov (United States)

    Chiappinelli, Katherine B.; Strissel, Pamela L.; Desrichard, Alexis; Li, Huili; Henke, Christine; Akman, Benjamin; Hein, Alexander; Rote, Neal S.; Cope, Leslie M.; Snyder, Alexandra; Makarov, Vladimir; Buhu, Sadna; Slamon, Dennis J.; Wolchok, Jedd D.; Pardoll, Drew M.; Beckmann, Matthias W.; Zahnow, Cynthia A.; Mergoub, Taha; Chan, Timothy A.; Baylin, Stephen B.; Strick, Reiner

    2015-01-01

    Summary We show that DNA methyltransferase inhibitors (DNMTis) upregulate immune signaling in cancer through the viral defense pathway. In ovarian cancer (OC), DNMTis trigger cytosolic sensing of double-stranded RNA (dsRNA) causing a Type I Interferon response and apoptosis. Knocking down dsRNA sensors TLR3 and MAVS reduces this response twofold, and blocking interferon beta or its receptor abrogates it. Upregulation of hypermethylated endogenous retrovirus (ERV) genes accompanies the response and ERV overexpression activates the response. Basal levels of ERV and viral defense gene expression significantly correlate in primary OC and the latter signature separates primary samples for multiple tumor types from The Cancer Genome Atlas into low versus high expression groups. In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model. PMID:26317466

  10. FGFR4 transmembrane domain polymorphism and cancer risk: a meta-analysis including 8555 subjects.

    Science.gov (United States)

    Xu, Wei; Li, Yan; Wang, Xueli; Chen, Bo; Wang, Yan; Liu, Shifeng; Xu, Jijun; Zhao, Weihong; Wu, Jianqing

    2010-12-01

    Fibroblast growth factor receptor 4 (FGFR4), belonging to the receptor tyrosine kinase family, is involved in cancer initiation and progression. The FGFR4 Gly388Arg polymorphism in the transmembrane domain of the receptor was shown to contribute to genetic susceptibility to cancer but the results were inconsistent. We performed a meta-analysis using 12 eligible case-control studies with a total of 4892 patients and 3663 controls to summarise the data on the association between the FGFR4 Gly388Arg polymorphism and cancer risks. The overall odds ratio (OR) with a 95% confidence interval (CI) showed statistical association between the FGFR4 Gly388Arg polymorphism and cancer risks under homozygote comparison, allele contrast and the recessive genetic model. In the subgroup analysis by ethnicity, statistically significantly increased cancer risks were found among Asians for homozygote comparison (OR = 1.43, 95% CI = 1.13-1.80, P(heterogeneity)=0.24), allele contrast (OR = 1.16, 95% CI = 1.04-1.29, P(heterogeneity) = 0.25) and the recessive genetic model (OR = 1.47, 95% CI = 1.19-1.81, P(heterogeneity) = 0.15). In the subgroup analysis for different tumour types, Arg(388) allele had an effect of increasing the risks of breast (homozygote comparison OR = 1.57, 95% CI = 1.04-2.37, P(heterogeneity) = 0.83 and the recessive model OR = 1.51, 95% CI = 1.02-2.24, P(heterogeneity) = 0.80) and prostate cancer (Gly/Arg versus Gly/Gly: OR = 1.16, 95% CI = 1.02-1.32, P(heterogeneity)=0.74; Arg versus Gly: OR = 1.17, 95% CI = 1.07-1.29, P(heterogeneity) = 0.18 and the dominant model: OR = 1.20, 95% CI = 1.06-1.35, P(heterogeneity) = 0.89). Our meta-analysis suggests that the FGFR4 Gly388Arg polymorphism most likely contributes to susceptibility to cancer, especially in Asians. Besides, the Arg(388) allele might be associated with increased risks of breast and prostate cancer.

  11. 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.

  12. 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.

  13. 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

  14. 42 CFR 81.25 - Guidelines for claims including two or more primary cancers.

    Science.gov (United States)

    2010-10-01

    ... the probability of causation for a second primary cancer identified in the claim, and PCn is the... estimated for the claim when Equation 1 is evaluated based on the joint distribution of PC1, . . ., PCn.4... Evaluating Equation 1 based on the individual upper 99th percentiles of PC1, . . ., PCn approximates...

  15. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

    OpenAIRE

    Zhao, Bing; HU, MENGCAI

    2013-01-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa...

  16. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells

    OpenAIRE

    Reyhan Akhtar; Mohd Ali; Safrannisa Mahmood; Sankar Nath Sanyal

    2014-01-01

    Background: Silibinin a flavonoid from milk thistle (Silybum marianum) exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml) for 24, 48 or 72 h showed a progressive decline in cell viability. Res...

  17. HABP2 is a novel regulator of hyaluronan-mediated human lung cancer progression

    OpenAIRE

    Tamara eMirzapoiazova; Nurbek eMambetsariev; Frances E Lennon; Bolot eMambetsariev; Joshua E. Berlind; Ravi eSalgia; Singleton, Patrick A.

    2015-01-01

    Background: Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA), which we have previously demonstrated can regulate the activity of the extracellular serine protease, Hyaluronan Binding Protein 2 (HABP2). This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics.Methods: Immunohistochemical analysis was...

  18. HABP2 is a Novel Regulator of Hyaluronan-Mediated Human Lung Cancer Progression

    OpenAIRE

    Mirzapoiazova, Tamara; Mambetsariev, Nurbek; Frances E Lennon; Mambetsariev, Bolot; Joshua E. Berlind; Salgia, Ravi; Singleton, Patrick A.

    2015-01-01

    Background Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA), which we have previously demonstrated can regulate the activity of the extracellular serine protease, hyaluronan binding protein 2 (HABP2). This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics. Methods Immunohistochemical an...

  19. Curability of cancer by radiotherapy and chemotherapy, including in neuraxial neoplasms

    Directory of Open Access Journals (Sweden)

    Jalali Rakesh

    2009-01-01

    Full Text Available In the October of 1996, Lance Armstrong, celebrated cyclist and one of the greatest athletes the world has ever seen, at the age of 24, was diagnosed with metastatic testicular cancer with disease having already spread to his abdomen, lungs and brain. Lance underwent four cycles of chemotherapy, actually the pretty standard one, pioneered at the Indiana University and not only did he get completely cured of his cancer, he remains extremely well till date, 12 years later. He sure did have a few adverse effects during those cycles of chemotherapy in the form of nausea, vomiting, weakness and fall in blood count but he knew and experienced them only for a short transient time and emerged triumphant and strong. In fact, he went on to win six awe-inspiring and incredible successive Tours de France victories from 1999-2005, one of the most grueling sporting events testing the endurance of the very fittest. After his retirement, he has been so inspired that he has completely devoted himself to educate people about the common myths about cancer, and promised to raise awareness and generate money for furthering research into surgery, radiation therapy and chemotherapy for cancer through his foundation. He says "I am indebted to the doctors, nurses and medicine and would want to pay them back for all their energy and caring." In his successful journey of overcoming cancer, he captures the essence of its treatment so well by declaring "Pain is temporary, it may last a minute, or an hour, or a day, or a year, but eventually, it will subside and something else will take its place. If I quit, however, it will last forever".

  20. 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

  1. 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.

  2. Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review.

    Science.gov (United States)

    Volkow, Nora D; Swanson, James M; Evins, A Eden; DeLisi, Lynn E; Meier, Madeline H; Gonzalez, Raul; Bloomfield, Michael A P; Curran, H Valerie; Baler, Ruben

    2016-03-01

    With a political debate about the potential risks and benefits of cannabis use as a backdrop, the wave of legalization and liberalization initiatives continues to spread. Four states (Colorado, Washington, Oregon, and Alaska) and the District of Columbia have passed laws that legalized cannabis for recreational use by adults, and 23 others plus the District of Columbia now regulate cannabis use for medical purposes. These policy changes could trigger a broad range of unintended consequences, with profound and lasting implications for the health and social systems in our country. Cannabis use is emerging as one among many interacting factors that can affect brain development and mental function. To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis.

  3. Risk of Cancer in relation to Natural Radiation, including Radon: Evidence from Epidemiological Studies

    Science.gov (United States)

    Baysson, Hélène; Tirmarche, Margot; Laurier, Dominique

    2008-08-01

    A review of recently published epidemiological studies on populations exposed to natural background ionizing radiation is proposed. The advantages and disadvantages of different types of epidemiological studies as well as the uncertainty linked to multiple exposures are discussed. As radon is the greatest source of natural radiation, particular attention is given to quantification of risk obtained through cohort studies of uranium miners and after joint analysis of case-control studies on lung cancer and residential radon.

  4. Numerical Analysis of Induced Current in Human Head Exposed to Nonuniform Magnetic Field Including Harmonics

    Science.gov (United States)

    Tarao, Hiroo; Hayashi, Noriyuki; Isaka, Katsuo

    In this paper, induced currents in an anatomical head model exposed to a non-uniform ELF magnetic field (B-field) including harmonics are numerically calculated, and are discussed based on the basic restriction established by International Commission on Non-Ionizing Radiation Protection (ICNIRP). A casual hair dryer of 100V and 1.2kW is chosen as a typical source of the non-uniform B-field including both the fundamental and second harmonic components. The B-field distribution around the hair dryer is estimated by using the 3-orthogonal magnetic dipole moments, which are derived from a couple of measured values around it. The high-resolution human head model used is constructed based on the MRI images of a real human, and consists of six kinds of tissues (bone, brain, eyeballs, muscle, skin and blood). So-called impedance method is used for the numerical calculation of the induced current. The numerical results show that the maximum values of the induced current of 17µA/m2, for the 60Hz component, which is about 1/120 of the ICNIRP basic restriction appear in the muscle near the eyeball when the hair dryer is used from the side of the head model, and the averaged current in the eyeballs that have the highest conductivity is the highest among the six tissues. It is also demonstrated that the induced current due to the 120Hz B-field becomes comparable to the 60Hz current although the magnitude of the 120Hz B-field is much smaller than that of the 60Hz B-field.

  5. A new prognostic model for cancer-specific survival after radical cystectomy including pretreatment thrombocytosis and standard pathological risk factors.

    Science.gov (United States)

    Todenhöfer, Tilman; Renninger, Markus; Schwentner, Christian; Stenzl, Arnulf; Gakis, Georgios

    2012-12-01

    Study Type - Prognosis (cohort series) Level of Evidence 2a What's known on the subject? and What does the study add? Preoperative thrombocytosis has been identified as a predictor of poor outcome in various cancer types. However, the prognostic role of platelet count in patients with invasive bladder cancer undergoing radical cystectomy is unknown. The present study demonstrates that preoperative thrombocytosis is an independent risk factor for decreased cancer-specific survival after radical treatment of invasive bladder cancer. We developed a new prognostic scoring model for cancer-specific outcomes after radical cystectomy including platelet count and established pathological risk factors. Consideration of platelet count in the final model increased its predictive accuracy significantly. Thrombocytosis may be a useful parameter to include within established international bladder cancer nomograms. •  To investigate the oncological significance of preoperative thrombocytosis in patients with invasive bladder cancer undergoing radical cystectomy, as it has been reported as a marker for aggressive tumour biology in a variety of solid tumours. •  The series comprised 258 patients undergoing radical cystectomy between 1999 and 2010 in whom different clinical and histopathological parameters were assessed. •  Elevated platelet count was defined as >450 × 10(9) /L. •  Based on regression estimates of significant parameters in multivariable analysis a new weighted scoring model was developed to predict cancer-specific outcomes. •  The median follow-up was 30 months (6-116). •  Of the 258 patients, 26 (10.1%) had elevated and 232 (89.9%) had normal platelet count. The 3-year cancer-specific survival in patients with normal and elevated platelet count was 61.5% and 32.7%, respectively (P thrombocytosis (2.68, 1.26-5.14; P= 0.011). •  The 3-year cancer-specific survival in patients with a score 0 (low risk), 1-2 (intermediate risk) and 3

  6. 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.

  7. Effective treatment of glioblastoma requires crossing the blood-brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine.

    Science.gov (United States)

    Kim, Sang-Soo; Harford, Joe B; Pirollo, Kathleen F; Chang, Esther H

    2015-12-18

    Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor. Both therapeutic resistance and restricted permeation of drugs across the blood-brain barrier (BBB) play a major role in the poor prognosis of GBM patients. Accumulated evidence suggests that in many human cancers, including GBM, therapeutic resistance can be attributed to a small fraction of cancer cells known as cancer stem cells (CSCs). CSCs have been shown to have stem cell-like properties that enable them to evade traditional cytotoxic therapies, and so new CSC-directed anti-cancer therapies are needed. Nanoparticles have been designed to selectively deliver payloads to relevant target cells in the body, and there is considerable interest in the use of nanoparticles for CSC-directed anti-cancer therapies. Recent advances in the field of nanomedicine offer new possibilities for overcoming CSC-mediated therapeutic resistance and thus significantly improving management of GBM. In this review, we will examine the current nanomedicine approaches for targeting CSCs and their therapeutic implications. The inhibitory effect of various nanoparticle-based drug delivery system towards CSCs in GBM tumors is the primary focus of this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. A melanoma immune response signature including Human Leukocyte Antigen-E.

    Science.gov (United States)

    Tremante, Elisa; Ginebri, Agnese; Lo Monaco, Elisa; Benassi, Barbara; Frascione, Pasquale; Grammatico, Paola; Cappellacci, Sandra; Catricalà, Caterina; Arcelli, Diego; Natali, Pier Giorgio; Di Filippo, Franco; Mottolese, Marcella; Visca, Paolo; Benevolo, Maria; Giacomini, Patrizio

    2014-01-01

    Paired cultures of early-passage melanoma cells and melanocytes were established from metastatic lesions and the uninvolved skin of five patients. In this stringent autologous setting, cDNA profiling was used to analyze a subset of 1477 genes selected by the Gene Ontology term 'immune response'. Human Leukocyte Antigen E (HLA-E) was ranked 19th among melanoma-overexpressed genes and was embedded in a transformation signature including its preferred peptide ligand donors HLA-A, HLA-B, HLA-C, and HLA-G. Mostly undetectable in normal skin and 39 nevi (including rare and atypical lesions), HLA-E was detected by immunohistochemistry in 17/30 (57%) and 32/48 (67%) primary and metastatic lesions, respectively. Accordingly, surface HLA-E was higher on melanoma cells than on melanocytes and protected the former (6/6 cell lines) from lysis by natural killer (NK) cells, functionally counteracting co-expressed triggering ligands. Although lacking HLA-E, melanocytes (4/4 cultures) were nevertheless (and surprisingly) fully protected from NK cell lysis.

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

    Directory of Open Access Journals (Sweden)

    Arul eNarayanasamy

    2013-08-01

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

  10. 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

  11. Effects of black grape extract on activities of DNA turn-over enzymes in cancerous and non cancerous human colon tissues.

    Science.gov (United States)

    Durak, Ilker; Cetin, Recep; Devrim, Erdinç; Ergüder, Imge B

    2005-05-06

    Effects of extract of dried whole black grape including seed on adenosine deaminase (ADA), 5' nucleotidase (5'NT) and xanthine oxidase (XO) enzymes were investigated in cancerous and non-cancerous human colon tissues. Enzyme activities were measured in 20 colon tissues, 10 from cancerous region and 10 from non cancerous region with and without pre incubation with black grape extract. ADA and 5'NT activities were found increased and that of the XO decreased in the cancerous tissues relative to non cancerous ones. After incubation period with black grape extract for 12 h, ADA and 5'NT activities were found to be significantly lowered but that of XO unchanged in both cancerous and non cancerous tissues. Results suggest that ADA and 5'NT activities increase but XO activity decreases in cancerous human colon tissues, which may provide advantage to the cancerous tissues in obtaining new nucleotides for rapid DNA synthesis through accelerated salvage pathway activity. Black grape extract makes significant inhibition on the ADA and 5'NT activities of cancerous and non cancerous colon tissues, thereby eliminating this advantage of cancer cells, which might be the basis for the beneficial effect of black grape in some kinds of human cancers.

  12. 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

  13. 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.

  14. 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.

  15. Integrative Analysis of Gene Expression Data Including an Assessment of Pathway Enrichment for Predicting Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Pingzhao Hu

    2006-01-01

    Full Text Available Background: Microarray technology has been previously used to identify genes that are differentially expressed between tumour and normal samples in a single study, as well as in syntheses involving multiple studies. When integrating results from several Affymetrix microarray datasets, previous studies summarized probeset-level data, which may potentially lead to a loss of information available at the probe-level. In this paper, we present an approach for integrating results across studies while taking probe-level data into account. Additionally, we follow a new direction in the analysis of microarray expression data, namely to focus on the variation of expression phenotypes in predefined gene sets, such as pathways. This targeted approach can be helpful for revealing information that is not easily visible from the changes in the individual genes. Results: We used a recently developed method to integrate Affymetrix expression data across studies. The idea is based on a probe-level based test statistic developed for testing for differentially expressed genes in individual studies. We incorporated this test statistic into a classic random-effects model for integrating data across studies. Subsequently, we used a gene set enrichment test to evaluate the significance of enriched biological pathways in the differentially expressed genes identified from the integrative analysis. We compared statistical and biological significance of the prognostic gene expression signatures and pathways identified in the probe-level model (PLM with those in the probeset-level model (PSLM. Our integrative analysis of Affymetrix microarray data from 110 prostate cancer samples obtained from three studies reveals thousands of genes significantly correlated with tumour cell differentiation. The bioinformatics analysis, mapping these genes to the publicly available KEGG database, reveals evidence that tumour cell differentiation is significantly associated with many

  16. Overview of gene therapy clinical progress including cancer treatment with gene-modified T cells.

    Science.gov (United States)

    Brenner, Malcolm K; Okur, Fatma V

    2009-01-01

    It is now twenty years since the first legal gene transfer studies were approved, and there has been considerable disappointment in the slow rate of progress that followed the initial studies. Gradually, however, as the limitations of available vectors are acknowledged and overcome, and with advances in our understanding of the molecular and cell biology of genetic diseases and of cancer, unequivocal successes are now being reported. In this paper we describe the remaining major roadblocks to successful gene therapy and outline approaches to overcome them. We also illustrate how genetically modified immune system cells are already being used for the effective treatment of hematological and other malignancies, and how these approaches are being modified so that they can be effective in treating a broader range of malignancies.

  17. Clinicopathologic characteristics of anterior prostate cancer (APC), including correlation with previous biopsy pathology.

    Science.gov (United States)

    Magers, Martin J; Zhan, Tianyu; Udager, Aaron M; Wei, John T; Tomlins, Scott A; Wu, Angela J; Kunju, Lakshmi P; Lew, Madelyn; Feng, Felix Y; Hamstra, Daniel A; Siddiqui, Javed; Chinnaiyan, Arul M; Montgomery, Jeffrey S; Weizer, Alon Z; Morgan, Todd M; Hollenbeck, Brent K; Miller, David C; Palapattu, Ganesh S; Jiang, Hui; Mehra, Rohit

    2015-11-01

    Anterior-predominant prostate cancer (APC) is an incompletely understood entity which can be difficult to sample via transrectal biopsy. Seemingly favorable biopsy results may belie the potential aggressiveness of these tumors. Here, we attempt to characterize APC by retrospectively examining the clinicopathologic features of APC at radical prostatectomy and comparing our findings with prior biopsy information. We found that 17.4 % of patients in our study had APC. APC demonstrated a significantly lower (P value biopsy than non-transperineal saturation (i.e., transrectal ultrasound guided) biopsy strategies. Four patients (7 %) without transperineal saturation biopsy exhibited a significantly worse GS at RP than biopsy, compared to five patients (36 %) with transperineal saturation biopsy. Our findings corroborate the difficulty in detecting APC and suggest that APC is not a uniform disease with a wholly indolent phenotype. Dedicated long-term outcome data are needed in these patients. Additionally, alternative pathologic staging parameters may be necessary.

  18. Broader prevalence of Wolbachia in insects including potential human disease vectors.

    Science.gov (United States)

    de Oliveira, C D; Gonçalves, D S; Baton, L A; Shimabukuro, P H F; Carvalho, F D; Moreira, L A

    2015-06-01

    Wolbachia are intracellular, maternally transmitted bacteria considered the most abundant endosymbionts found in arthropods. They reproductively manipulate their host in order to increase their chances of being transmitted to the offspring, and currently are being used as a tool to control vector-borne diseases. Studies on distribution of Wolbachia among its arthropod hosts are important both for better understanding why this bacterium is so common, as well as for its potential use as a biological control agent. Here, we studied the incidence of Wolbachia in a broad range of insect species, collected from different regions of Brazil, using three genetic markers (16S rRNA, wsp and ftsZ), which varied in terms of their sensitivity to detect this bacterium. The overall incidence of Wolbachia among species belonging to 58 families and 14 orders was 61.9%. The most common positive insect orders were Coleoptera, Diptera, Hemiptera and Hymenoptera, with Diptera and Hemiptera having the highest numbers of Wolbachia-positive families. They included potential human disease vectors whose infection status has never been reported before. Our study further shows the importance of using quantitative polymerase chain reaction for high-throughput and sensitive Wolbachia screening.

  19. Including limitations in news coverage of cancer research: effects of news hedging on fatalism, medical skepticism, patient trust, and backlash.

    Science.gov (United States)

    Jensen, Jakob D; Carcioppolo, Nick; King, Andy J; Bernat, Jennifer K; Davis, LaShara; Yale, Robert; Smith, Jessica

    2011-05-01

    Past research has demonstrated that news coverage of cancer research, and scientific research generally, rarely contains discourse-based hedging, including caveats, limitations, and uncertainties. In a multiple message experiment (k = 4 news stories, N = 1082), the authors examined whether hedging shaped the perceptions of news consumers. The results revealed that participants were significantly less fatalistic about cancer (p = .039) and marginally less prone to nutritional backlash (p = .056) after exposure to hedged articles. Participants exposed to articles mentioning a second researcher (unaffiliated with the present study) exhibited greater trust in medical professions (p = .001). The findings provide additional support for the inclusion of discourse-based hedging in cancer news coverage and suggest that news consumers will use scientific uncertainty in illness representations.

  20. 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.

  1. Intracellular actions of steroid hormones and their therapeutic value, including the potential of radiohalosteroids against ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Holt, J.A. (Chicago Univ. (United States). Dept. of Obstetrics and Gynecology); Scharl, A. (Koeln Univ., Cologne (Germany). Frauen-Klinik); Kullander, S. (Lund Univ. (Sweden). Womens Hospital Malmoe); Beckmann, M.W. (Johann Wolfgang von Goethe Univ., Frankfurt am Main (Germany). Zentrum fuer Frauenheilkunde und Geburtshilfe)

    1992-01-01

    With recombinant cDNA technology, yeast and cultured animal cells can be made to express mammalian cDNA steroid receptors from cDNA clones that contain deletions and substitutions. Among the leading problems addressed in these models is the characterization of sequences that promote association or interaction with other transcription regulating molecules, including oncogene products. Recently it has been found that heat shock proteins may serve not only to stabilize the receptor proteins but also to precondition the activation imparted by ligand binding. Aberrant receptor proteins can be found in ovarian cancer. Whether aberrant receptor proteins are associated with transformation in general or with a variable clinical response to steroidal or anti-steroidal therapy is not known. Even after chemotherapy, steroid receptors are expressed in the metastases of ovarian cancers seen clinically, and they may have potential use for localization and treatment of receptor-rich cancers. Radioligand pharmaceuticals appropriate for imaging or for site-directed radiocytotoxicity can be sequestered to the nuclei of receptor-rich cancers. Initial clinical imaging and therapy trials with such pharmaceuticals have been approved and begun. In the use of halogenated estrogen radiopharmaceuticals, liver metabolism and enterohepatic recirculation are important considerations. Ascites prolongs retention of radiohalogenated estrogen in the abdominal cavity. Distant metastases have been localized with [[sup 123]I]-estrogen in breast cancer patients in pre-operative procedures. Receptor-mediated cytotoxicity occurs when estrogen receptor radioligand pharmaceuticals that are Auger electron emitters are used in vitro. (au) (119 refs., 3 figs.).

  2. Earliest Detection of Oral Cancer Using Non-Invasive Brush Biopsy Including DNA-Image-Cytometry: Report on Four Cases

    Directory of Open Access Journals (Sweden)

    Torsten W. Remmerbach

    2003-01-01

    Full Text Available Objective: We describe four patients presenting early oral cancers, detected cytologically on non‐invasive brush biopsies including DNA‐image cytometry as an adjunctive method before histology on scalpel biopsies confirmed the evidence of malignancy. Methods: Brush biopsies were performed and smears thereof investigated cytologically. After Feulgen restaining, DNA‐measurements were performed using a DNA‐Image‐Cytometer. Case reports: Oral squamous cell carcinomas were diagnosed cytologically in macroscopically suspicious lesions and malignancy confirmed by DNA‐cytometry. The initially performed scalpel biopsies did neither supply evidence of oral cancer nor of severe dysplasia. After at least one to 15 months the occurrence of cancer was finally proven histologically on a second scalpel biopsy each (three microinvasive and one in situ carcinoma. Conclusion: Non‐invasive brush biopsies are a suitable instrument for early cytologic detection of cancer of the mouth. DNA‐image‐cytometry, as an adjunctive method, can be used to confirm the cytologic diagnosis or suspicion of cancer in patients with doubtful lesions (dysplasias. DNA‐aneuploidy is a marker for (prospective malignancy in smears of the oral cavity, which may detect malignancy months prior to histology. In future this method could be used as a mass screening tool in dentists practise. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐4/remmerbach.htm.

  3. Perfluorooctanesulfonate and related fluorochemicals in several organisms including humans from Italy

    Energy Technology Data Exchange (ETDEWEB)

    Corsolini, S. [Siena Univ. (Italy); Kannan, K. [New York State Univ., Albany, NY (United States)

    2004-09-15

    Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant, extremely resistant to environmental degradation and is ubiquitous in the environment. Traditional monitoring studies for persistent chemicals failed to identify this contaminant for a long time because of its unique physicochemical properties and its tendency to bind to proteins instead of accumulating in fatty tissues. PFOS is known to be toxic in laboratory animals (rats, mice, monkeys) at levels close to the range already found in organisms and people. PFOS has been commercially produced by an electrochemical fluorination process for over 40 years. Perfluorooctane sulfonylfluoride (POSF; C{sub 8}F{sub 17}SO{sub 2}F) is used as a building block for further reactions that produce several other sulfonated fluorinated compounds, including perfluorooctane sulfonate (C{sub 8}F{sub 17}SO{sub 3}{sup -}) and other precursor molecules such as n-ethyl or n-methyl perfluorooctanesulfonamidoethanol. POSF-based fluorochemicals have been used in a wide variety of industrial and consumer products, including protective coatings for carpets and apparel, paper coatings, insecticide formulations, and surfactants. These compounds repel water and oil, reduce surface tension, catalyze oligomerization and polymerization, and maintain their properties under extreme conditions. Depending upon the specific functional derivatization or the degree of polymerization, POSF-based chemicals may degrade or metabolize to PFOS, which is known to be the final metabolite of POSF-based fluorochemicals. PFOS is stable, chemically inert, and non-reactive and has the potential to bioaccumulate. It has been found in polar bears from the Arctic, albatross and other fish-eating water birds in the mid-Pacific, and aquatic organisms11 and people world-wide. PFOS and other perfluorinated chemicals such as perfluorooctanesulfonamide (PFOSA), perfluorohexanesulfonate (PFHxS), and perfluorooctanoate (PFOA) have been detected in human blood. In

  4. Human papillomavirus and gastrointestinal cancer in Iranian population: A systematic review and meta-analysis.

    Science.gov (United States)

    Omrani-Navai, Versa; Alizadeh-Navaei, Reza; Yahyapour, Yousef; Hedayatizadeh-Omran, Akbar; Abediankenari, Saeid; Janbabaei, Ghasem; Toghani, Fatima

    2017-01-01

    Gastrointestinal (GI) malignancies are the most common cancers and account for nearly half of all cancer-related deaths in Iran. There was a strong association between human papillomavirus (HPV) infection and urogenital cancers, in particular the cervix. However, there is no clear causal relationship in all types of cancers, including gastrointestinal cancers. Therefore, the present study as a systematic review and meta-analysis was designed to evaluate the prevalence and relation of HPV in GI cancers. This systematic review and meta-analysis study assess the prevalence of human papillomavirus in GI cancers in Iran. Data were collected by searching electronic databases, including PubMed, Google Scholar, Scopus, SID and Iranmedex by English and Persian key words up to August 2016. Key words included: Human Papillomavirus, HPV, Cancer, Neoplasm, Carcinoma, Esophageal, colorectal, Gastrointestinal and Iran articles were entered in the EndNote software and duplicate papers were excluded. Data were extracted and analyzed by comprehensive meta-analysis software, Version 2 (CMA.V2) and random effects model. Finally, we included 17 studies in this meta-analysis. The prevalence of HPV in Iranian patients with GI cancers was 16.4% (CI95%: 10.4-24.9). Considering all HPV types, the odds ratio of GI cancers in positive patients was 3.03 (CI95%: 1.42-6.45) while in patients with HPV-16 was 3.62 (CI: 1.43-4.82). The results show a strong relationship between HPV infection especially high-risk HPV type 16 and GI cancers in Iranian population.

  5. 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.

  6. The radiobiology of prostate cancer including new aspects of fractionated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, Jack F. [Medical School of Wisconsin Univ., Madison (United States). Dept. of Human Oncology

    2005-05-01

    Total radiation dose is not a reliable measure of biological effect when dose-per-fraction or dose-rate is changed. Large differences in biological effectiveness (per gray) are seen between the 2 Gy doses of external beam radiotherapy and the large boost doses given at high dose-rate from afterloading sources. The effects are profoundly different in rapidly or slowly proliferating tissues, that is for most tumors versus late complications. These differences work the opposite way round for prostate tumors versus late complications compared with most other types of tumor. Using the Linear-Quadratic formula it is aimed to explain these differences, especially for treatments of prostate cancer. The unusually slow growth rate of prostate cancers is associated with their high sensitivity to increased fraction size, so a large number of small fractions, such as 35 or 40 'daily' doses of 2 Gy, is not an optimum treatment. Theoretical modeling shows a stronger enhancement of tumor effect than of late complications for larger (and fewer) fractions, in prostate tumors uniquely. Biologically Effective Doses and Normalized Total Doses (in 2 Gy fraction equivalents) are given for prostate tumor, late rectal reactions, and - a new development - acute rectal mucosa. Tables showing the change of fraction-size sensitivity (the alpha/beta ratio) with proliferation rates of tissues lead to the association of slow cell doubling times in prostate tumors with small alpha/beta ratios. Clinical evidence to confirm this biological expectation is reviewed. The alpha/beta ratios of prostate tumors appear to be as low as 1.5 Gy (95% confidence interval 1.3-1.8 Gy), in contrast with the value of about 10 Gy for most other types of tumor. The important point is that alpha/beta ratio=1.5 Gy appears to be significantly less than the alpha/beta ratio=3 Gy for late complications in rectal tissues. Such differences are also emerging from recent clinical results. From this important

  7. Dosimetric evaluation of three adaptive strategies for prostate cancer treatment including pelvic lymph nodes irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cantin, Audrey; Gingras, Luc; Archambault, Louis, E-mail: louis.archambault@phy.ulaval.ca [Département de Physique, de génie Physique et d’optique et Centre de Recherche sur le Cancer, Université Laval, Québec, Québec G1V 0A6, Canada and Département de Radio-Oncologie et Centre de Recherche du CHU de Québec, CHU de Québec—Université Laval, 11 côte du Palais, Québec, Québec G1R 2J6 (Canada); Lachance, Bernard; Foster, William [Département de Radio-Oncologie et Centre de Recherche du CHU de Québec, CHU de Québec—Université Laval, 11 côte du Palais, Québec, Québec G1R 2J6 (Canada); Goudreault, Julie [Département de Radio-Oncologie et Centre de Recherche du CHU de Québec, CHU de Québec—Université Laval, 11 côte du Palais, Québec, Québec G1R 2J6, Canada and Département de Radio-Oncologie, CSSS de Gatineau–Hôpital de Gatineau, 909 Boulevard La Vérendrye, Gatineau, Québec J8P 7H2 (Canada)

    2015-12-15

    Purpose: The movements of the prostate relative to the pelvic lymph nodes during intensity-modulated radiation therapy treatment can limit margin reduction and affect the protection of the organs at risk (OAR). In this study, the authors performed an analysis of three adaptive treatment strategies that combine information from both bony and gold marker registrations. The robustness of those treatments against the interfraction prostate movements was evaluated. Methods: A retrospective study was conducted on five prostate cancer patients with 7–13 daily cone-beam CTs (CBCTs). The clinical target volumes (CTVs) consisting of pelvic lymph nodes, prostate, and seminal vesicles as well as the OARs were delineated on each CBCT and the initial CT. Three adaptive strategies were analyzed. Two of these methods relied on a two-step patient positioning at each fraction. First step: a bony registration was used to deliver the nodal CTV prescription. Second step: a gold marker registration was then used either to (1) complete the dose delivered to the prostate (complement); (2) or give almost the entire prescription to the prostate with a weak dose gradient between the targets to compensate for possible motions (gradient). The third method (COR) used a pool of precalculated plans based on images acquired at previous treatment fractions. At each new fraction, a plan is selected from that pool based on the daily position of prostate center-of-mass. The dosimetric comparison was conducted and results are presented with and without the systematic shift in the prostate position on the CT planning. The adaptive strategies were compared to the current clinical standard where all fractions are treated with the initial nonadaptive plan. Results: The minimum daily prostate D{sub 95%} is improved by 2%, 9%, and 6% for the complement, the gradient, and the COR approaches, respectively, compared to the nonadaptive method. The average nodal CTV D{sub 95%} remains constant across the

  8. 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.

  9. Collaborative Group on Hormonal Factors in Breast cancer: Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83000 women with breast cancer from 16 countries

    NARCIS (Netherlands)

    Beral, V.; Bull, D.; Doll, R.; Peto, R.; Reeves, G.; van den Brandt, P.A.; Goldbohm, R.A.

    2004-01-01

    Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83?000 women with breast cancer from 16 countries. Beral V, Bull D, Doll R, Peto R, Reeves G; Collaborative Group on Hormonal Factors in Breast Cancer. BACKGROUND: The Collaborative Group on Hormo

  10. Collaborative Group on Hormonal Factors in Breast cancer: Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83000 women with breast cancer from 16 countries

    NARCIS (Netherlands)

    Beral, V.; Bull, D.; Doll, R.; Peto, R.; Reeves, G.; van den Brandt, P.A.; Goldbohm, R.A.

    2004-01-01

    Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83?000 women with breast cancer from 16 countries. Beral V, Bull D, Doll R, Peto R, Reeves G; Collaborative Group on Hormonal Factors in Breast Cancer. BACKGROUND: The Collaborative Group on

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

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    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

  12. Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

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    Kazuyoshi Shiga

    2016-01-01

    Full Text Available Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6 in colorectal cancer (CRC. Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS and disease-free survival (DFS rates according to IL-6 status were calculated for all patients and according to disease stage. Results. The mean IL-6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients. Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence.

  13. HUMAN DNA QUANTIFICATION IN THE STOOLS OF PATIENTS WITH COLORECTAL CANCER

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    Yolanda TEIXEIRA

    2015-12-01

    Full Text Available Background - Colorectal cancer is one of the main cause of cancer in the world. Colonoscopy is the best screen method, however the compliance is less than 50%. Quantification of human DNA (hDNA in the feces may be a possible screen non-invasive method that is a consequence of the high proliferation and exfoliation of cancer cells. Objective - To quantify the human DNA in the stools of patients with colorectal cancer or polyps. Methods - Fifty patients with CRC, 26 polyps and 53 with normal colonoscopy were included. Total and human DNA were analyzed from the frozen stools. Results - An increased concentration of hDNA in the stools was observed in colorectal cancer patients compared to controls and polyps. Tumors localized in the left side of the colon had higher concentrations of hDNA. There were no difference between polyps and controls. A cut off of 0.87 ng/mL of human DNA was determined for colorectal cancer patients by the ROC curve, with a sensitivity of 66% and a specificity of 86.8%. For polyps the cut off was 0.41, the sensitivity was 41% and the specificity 77.4%. Conclusion - A higher concentration of hDNA had been found in colorectal cancer patients The quantification of hDNA from the stools can be a trial method for the diagnosis of colorectal cancer.

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

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    Fabien J Cousin

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

  15. [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.

  16. Towards the human colorectal cancer microbiome.

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    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.

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

    Science.gov (United States)

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

    2005-01-20

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

  18. 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.

  19. Role of ARPC2 in Human Gastric Cancer

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    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.

  20. Oncogenic functions of IGF1R and INSR in prostate cancer include enhanced tumor growth, cell migration and angiogenesis.

    Science.gov (United States)

    Heidegger, Isabel; Kern, Johann; Ofer, Philipp; Klocker, Helmut; Massoner, Petra

    2014-05-15

    We scrutinized the effect of insulin receptor (INSR) in addition to IGF1R in PCa using in vitro and in vivo models. In-vitro overexpression of IGF1R and INSRA, but not INSRB increased cell proliferation, colony formation, migration, invasion and resistance to apoptosis in prostate cancer cells (DU145, LNCaP, PC3). Opposite effects were induced by downregulation of IGF1R and total INSR, but not INSRB. In contrast to tumor cells, non-cancerous epithelial cells of the prostate (EP156T, RWPE-1) were inhibited on overexpression and stimulated by knockdown of receptors. In-vivo analyses using the chicken allantoic membrane assay confirmed the tumorigenic effects of IGF1R and INSR. Apart of promoting tumor growth, IGF1R and INSR overexpression also enhanced angiogenesis indicated by higher vessel density and increased number of desmin-immunoreactive pericytes. Our study underscores the oncogenic impact of IGF1R including significant effects on tumor growth, cell migration, sensitivity to apoptotic/chemotherapeutic agents and angiogenesis, and characterizes the INSR, in particular the isoform INSRA, as additional cancer-promoting receptor in prostate cancer. Both, the insulin-like growth factor receptor 1 and the insulin receptor exert oncogenic functions, thus proposing that both receptors need to be considered in therapeutic settings.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Whole body MRI, including diffusion-weighted imaging in follow-up of patients with testicular cancer.

    Science.gov (United States)

    Mosavi, Firas; Laurell, Anna; Ahlström, Håkan

    2015-11-01

    Whole body (WB) magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) has become increasingly utilized in cancer imaging, yet the clinical utility of these techniques in follow-up of testicular cancer patients has not been evaluated. The purpose of this study was to evaluate the feasibility of WB MRI with continuous table movement (CTM) technique, including multistep DWI in follow-up of patients with testicular cancer. WB MRI including DWI was performed in follow-up of 71 consecutive patients (median age, 37 years; range 19-84) with histologically confirmed testicular cancer. WB MRI protocol included axial T1-Dixon and T2-BLADE sequences using CTM technique. Furthermore, multi-step DWI was performed using b-value 50 and 1000 s/mm(2). One criterion for feasibility was patient tolerance and satisfactory image quality. Another criterion was the accuracy in detection of any pathological mass, compared to standard of reference. Signal intensity in DWI was used for evaluation of residual mass activity. Clinical, laboratory and imaging follow-up were applied as standard of reference for the evaluation of WB MRI. WB MRI was tolerated in nearly all patients (69/71 patients, 97%) and the image quality was satisfactory. Metal artifacts deteriorated the image quality in six patients, but it did not influence the overall results. No case of clinical relapse was observed during the follow-up time. There was a good agreement between conventional WB MRI and standard of reference in all patients. Three patients showed residual masses and DWI signal was not restricted in these patients. Furthermore, DWI showed abnormally high signal intensity in a normal-sized retroperitoneal lymph node indicating metastasis. The subsequent (18)F-FDG PET/CT could verify the finding. WB MRI with CTM technique including multi-step DWI is feasible in follow-up of patients with testicular cancer. DWI may contribute to important added-value data to conventional MRI sequences

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

    Science.gov (United States)

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

    1995-05-01

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

  7. Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway.

    Science.gov (United States)

    Zhang, Xiang-An; Zhang, Shuangxi; Yin, Qing; Zhang, Jing

    2015-01-01

    Quercetin can inhibit the growth of cancer cells with the ability to act as chemopreventers. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. Nuclear factor kappa-B (NF-κB) is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Inhibitors of NF-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in colon cancer. In this study, we demonstrate that quercetin induces apoptosis in human colon cancer CACO-2 and SW-620 cells through inhibiting NF-κB pathway, as well as down-regulation of B-cell lymphoma 2 and up-regulation of Bax, thus providing basis for clinical application of quercetin in colon cancer cases.

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

    Science.gov (United States)

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

    2012-11-01

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

  9. Elevation of sulfatides in ovarian cancer: An integrated transcriptomic and lipidomic analysis including tissue-imaging mass spectrometry

    Directory of Open Access Journals (Sweden)

    McDonald John F

    2010-07-01

    Full Text Available Abstract Background Sulfatides (ST are a category of sulfated galactosylceramides (GalCer that are elevated in many types of cancer including, possibly, ovarian cancer. Previous evidence for elevation of ST in ovarian cancer was based on a colorimetric reagent that does not provide structural details and can also react with other lipids. Therefore, this study utilized mass spectrometry for a structure-specific and quantitative analysis of the types, amounts, and tissue localization of ST in ovarian cancer, and combined these findings with analysis of mRNAs for the relevant enzymes of ST metabolism to explore possible mechanisms. Results Analysis of 12 ovarian tissues graded as histologically normal or having epithelial ovarian tumors by liquid chromatography electrospray ionization-tandem mass spectrometry (LC ESI-MS/MS established that most tumor-bearing tissues have higher amounts of ST. Because ovarian cancer tissues are comprised of many different cell types, histological tissue slices were analyzed by matrix-assisted laser desorption ionization-tissue-imaging MS (MALDI-TIMS. The regions where ST were detected by MALDI-TIMS overlapped with the ovarian epithelial carcinoma as identified by H & E staining and histological scoring. Furthermore, the structures for the most prevalent species observed via MALDI-TIMS (d18:1/C16:0-, d18:1/C24:1- and d18:1/C24:0-ST were confirmed by MALDI-TIMS/MS, whereas, a neighboring ion(m/z 885.6 that was not tumor specific was identified as a phosphatidylinositol. Microarray analysis of mRNAs collected using laser capture microdissection revealed that expression of GalCer synthase and Gal3ST1 (3'-phosphoadenosine-5'-phosphosulfate:GalCer sulfotransferase were approximately 11- and 3.5-fold higher, respectively, in the ovarian epithelial carcinoma cells versus normal ovarian stromal tissue, and they were 5- and 2.3-fold higher in comparison with normal surface ovarian epithelial cells, which is a likely

  10. 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

  11. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells.

    Science.gov (United States)

    Zhao, Bing; Hu, Mengcai

    2013-12-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer.

  12. Long interspersed element-1 protein expression is a hallmark of many human cancers.

    Science.gov (United States)

    Rodić, Nemanja; Sharma, Reema; Sharma, Rajni; Zampella, John; Dai, Lixin; Taylor, Martin S; Hruban, Ralph H; Iacobuzio-Donahue, Christine A; Maitra, Anirban; Torbenson, Michael S; Goggins, Michael; Shih, Ie-Ming; Duffield, Amy S; Montgomery, Elizabeth A; Gabrielson, Edward; Netto, George J; Lotan, Tamara L; De Marzo, Angelo M; Westra, William; Binder, Zev A; Orr, Brent A; Gallia, Gary L; Eberhart, Charles G; Boeke, Jef D; Harris, Chris R; Burns, Kathleen H

    2014-05-01

    Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1-encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1-encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen.

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

    Science.gov (United States)

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

    2015-01-01

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

  14. 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

  15. Human cancer cells express Slug-based epithelial-mesenchymal transition gene expression signature obtained in vivo

    Directory of Open Access Journals (Sweden)

    Anastassiou Dimitris

    2011-12-01

    Full Text Available Abstract Background The biological mechanisms underlying cancer cell motility and invasiveness remain unclear, although it has been hypothesized that they involve some type of epithelial-mesenchymal transition (EMT. Methods We used xenograft models of human cancer cells in immunocompromised mice, profiling the harvested tumors separately with species-specific probes and computationally analyzing the results. Results Here we show that human cancer cells express in vivo a precise multi-cancer invasion-associated gene expression signature that prominently includes many EMT markers, among them the transcription factor Slug, fibronectin, and α-SMA. We found that human, but not mouse, cells express the signature and Slug is the only upregulated EMT-inducing transcription factor. The signature is also present in samples from many publicly available cancer gene expression datasets, suggesting that it is produced by the cancer cells themselves in multiple cancer types, including nonepithelial cancers such as neuroblastoma. Furthermore, we found that the presence of the signature in human xenografted cells was associated with a downregulation of adipocyte markers in the mouse tissue adjacent to the invasive tumor, suggesting that the signature is triggered by contextual microenvironmental interactions when the cancer cells encounter adipocytes, as previously reported. Conclusions The known, precise and consistent gene composition of this cancer mesenchymal transition signature, particularly when combined with simultaneous analysis of the adjacent microenvironment, provides unique opportunities for shedding light on the underlying mechanisms of cancer invasiveness as well as identifying potential diagnostic markers and targets for metastasis-inhibiting therapeutics.

  16. 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.

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

    Schiffman, Joshua D; Breen, Matthew

    2015-07-19

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

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

    Science.gov (United States)

    Schiffman, Joshua D.; Breen, Matthew

    2015-01-01

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

  20. 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.

  1. Human calcium metabolism including bone resorption measured with {sup 41}Ca tracer

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, S.P.H.T. [Lawrence Livermore National Lab., CA (United States); King, J.C. [California Univ., Berkeley, CA (United States). Dept. of Nutritional Science; Vieira, N.E. [National Inst. of Child Health and Human Development, Bethesda, MD (United States); Woodhouse, L.R. [California Univ., Berkeley, CA (United States). Dept. of Nutritional Science; Yergey, A.L. [National Inst. of Child Health and Human Development, Bethesda, MD (United States)

    1996-08-01

    Accelerator mass spectrometry is so sensitive to small quantities of {sup 41}Ca that it might be used as a tracer in the study of human calcium kinetics to generate unique kinds of data. In contrast with the use of other Ca isotopic tracers, {sup 41}Ca tracer can be so administered that the tracer movements between the various body pools achieve a quasi steady state. Resorbing bone may thus be directly measured. We have tested such a protocol against a conventional stable isotope experiment with good agreement.

  2. 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...

  3. 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.

  4. 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.

  5. Cross-cancer profiling of molecular alterations within the human autophagy interaction network.

    Science.gov (United States)

    Lebovitz, Chandra B; Robertson, A Gordon; Goya, Rodrigo; Jones, Steven J; Morin, Ryan D; Marra, Marco A; Gorski, Sharon M

    2015-01-01

    Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumor-related alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium. We found 3 (RB1CC1/FIP200, ULK4, WDR45/WIPI4) and one (ATG7) core autophagy genes to be under positive selection for somatic mutations in endometrial carcinoma and clear cell renal carcinoma, respectively, while 29 autophagy regulators and pathway interactors, including previously identified KEAP1, NFE2L2, and MTOR, were significantly mutated in 6 of the 11 cancer types examined. Gene expression analyses revealed that GABARAPL1 and MAP1LC3C/LC3C transcripts were less abundant in breast cancer and non-small cell lung cancers than in matched normal tissue controls; ATG4D transcripts were increased in lung squamous cell carcinoma, as were ATG16L2 transcripts in kidney cancer. Unsupervised clustering of autophagy-associated mRNA levels in tumors stratified patient overall survival in 3 of 9 cancer types (acute myeloid leukemia, clear cell renal carcinoma, and head and neck cancer). These analyses provide the first comprehensive resource of recurrently altered autophagy-associated genes in human tumors, and highlight cancer types and subtypes where perturbed autophagy may be relevant to patient overall survival.

  6. Specification of Region-Specific Neurons Including Forebrain Glutamatergic Neurons from Human Induced Pluripotent Stem Cells

    Science.gov (United States)

    Martins-Taylor, Kristen; Wang, Xiaofang; Zhang, Zheng; Park, Jung Woo; Zhan, Shuning; Kronenberg, Mark S.; Lichtler, Alexander; Liu, Hui-Xia; Chen, Fang-Ping; Yue, Lixia; Li, Xue-Jun; Xu, Ren-He

    2010-01-01

    Background Directed differentiation of human induced pluripotent stem cells (hiPSC) into functional, region-specific neural cells is a key step to realizing their therapeutic promise to treat various neural disorders, which awaits detailed elucidation. Methodology/Principal Findings We analyzed neural differentiation from various hiPSC lines generated by others and ourselves. Although heterogeneity in efficiency of neuroepithelial (NE) cell differentiation was observed among different hiPSC lines, the NE differentiation process resembles that from human embryonic stem cells (hESC) in morphology, timing, transcriptional profile, and requirement for FGF signaling. NE cells differentiated from hiPSC, like those from hESC, can also form rostral phenotypes by default, and form the midbrain or spinal progenitors upon caudalization by morphogens. The rostrocaudal neural progenitors can further mature to develop forebrain glutamatergic projection neurons, midbrain dopaminergic neurons, and spinal motor neurons, respectively. Typical ion channels and action potentials were recorded in the hiPSC-derived neurons. Conclusions/Significance Our results demonstrate that hiPSC, regardless of how they were derived, can differentiate into a spectrum of rostrocaudal neurons with functionality, which supports the considerable value of hiPSC for study and treatment of patient-specific neural disorders. PMID:20686615

  7. Specification of region-specific neurons including forebrain glutamatergic neurons from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Hui Zeng

    Full Text Available BACKGROUND: Directed differentiation of human induced pluripotent stem cells (hiPSC into functional, region-specific neural cells is a key step to realizing their therapeutic promise to treat various neural disorders, which awaits detailed elucidation. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed neural differentiation from various hiPSC lines generated by others and ourselves. Although heterogeneity in efficiency of neuroepithelial (NE cell differentiation was observed among different hiPSC lines, the NE differentiation process resembles that from human embryonic stem cells (hESC in morphology, timing, transcriptional profile, and requirement for FGF signaling. NE cells differentiated from hiPSC, like those from hESC, can also form rostral phenotypes by default, and form the midbrain or spinal progenitors upon caudalization by morphogens. The rostrocaudal neural progenitors can further mature to develop forebrain glutamatergic projection neurons, midbrain dopaminergic neurons, and spinal motor neurons, respectively. Typical ion channels and action potentials were recorded in the hiPSC-derived neurons. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that hiPSC, regardless of how they were derived, can differentiate into a spectrum of rostrocaudal neurons with functionality, which supports the considerable value of hiPSC for study and treatment of patient-specific neural disorders.

  8. The Role of Merkel Cell Polyomavirus and Other Human Polyomaviruses in Emerging Hallmarks of Cancer

    Directory of Open Access Journals (Sweden)

    Ugo Moens

    2015-04-01

    Full Text Available Polyomaviruses are non-enveloped, dsDNA viruses that are common in mammals, including humans. All polyomaviruses encode the large T-antigen and small t-antigen proteins that share conserved functional domains, comprising binding motifs for the tumor suppressors pRb and p53, and for protein phosphatase 2A, respectively. At present, 13 different human polyomaviruses are known, and for some of them their large T-antigen and small t-antigen have been shown to possess oncogenic properties in cell culture and animal models, while similar functions are assumed for the large T- and small t-antigen of other human polyomaviruses. However, so far the Merkel cell polyomavirus seems to be the only human polyomavirus associated with cancer. The large T- and small t-antigen exert their tumorigenic effects through classical hallmarks of cancer: inhibiting tumor suppressors, activating tumor promoters, preventing apoptosis, inducing angiogenesis and stimulating metastasis. This review elaborates on the putative roles of human polyomaviruses in some of the emerging hallmarks of cancer. The reciprocal interactions between human polyomaviruses and the immune system response are discussed, a plausible role of polyomavirus-encoded and polyomavirus-induced microRNA in cancer is described, and the effect of polyomaviruses on energy homeostasis and exosomes is explored. Therapeutic strategies against these emerging hallmarks of cancer are also suggested.

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

    Science.gov (United States)

    McKiernan, Janet; Thom, Bridgette

    2016-08-01

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

  10. 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 ...

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. Modelling of safety barriers including human and organisational factors to improve process safety

    DEFF Research Database (Denmark)

    Markert, Frank; Duijm, Nijs Jan; Thommesen, Jacob

    2013-01-01

    explosion, and the Mont Blanc Tunnel Fire, such an approach may have helped to maintain the integrity of the designed provisions against major deviations resulting in these disasters. In order to make this paradigm operational, safety management and in particular risk assessment tools need to be refined....... A valuable approach is the inclusion of human and organisational factors into the simulation of the reliability of the technical system using event trees and fault trees and the concept of safety barriers. This has been demonstrated e.g. in the former European research project ARAMIS (Accidental Risk...... Assessment Methodology for IndustrieS, see Salvi et al 2006). ARAMIS employs the bow-tie approach to modelling hazardous scenarios, and it suggests the outcome of auditing safety management to be connected to a semi-quantitative assessment of the quality of safety barriers. ARAMIS discriminates a number...

  16. Human Gait Feature Extraction Including a Kinematic Analysis Toward Robotic Power Assistance

    Directory of Open Access Journals (Sweden)

    Mario I. Chacon-Murguia

    2012-09-01

    Full Text Available The present work proposes a method for human gait and kinematic analysis. Gait analysis consists of the determination of hip, knee and ankle positions through video analysis. Gait kinematic for the thigh and knee is then generated from this data. Evaluations of the gait analysis method indicate an acceptable performance of 86.66% for hip and knee position estimation, and comparable findings with other reported works for gait kinematic. A coordinate systems assignment is performed according to the DH algorithm and a direct kinematic model of the legs is obtained. The legs’ angles obtained from the video analysis are applied to the kinematic model in order to revise the application of this model to robotic legs in a power assisted system.

  17. Microscopic age determination of human skeletons including an unknown but calculable variable

    DEFF Research Database (Denmark)

    Wallin, Johan Albert; Tkocz, Izabella; Kristensen, Gustav

    1994-01-01

    estimation, which includes the covariance matrix of four single equation residuals, improves the accuracy of age determination. The standard deviation, however, of age prediction remains 12.58 years. An experimental split of the data was made in order to demonstrate that the use of subgroups gives a false...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-15

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

  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. Multistate Statistical Modeling: A Tool to Build a Lung Cancer Microsimulation Model That Includes Parameter Uncertainty and Patient Heterogeneity.

    Science.gov (United States)

    Bongers, Mathilda L; de Ruysscher, Dirk; Oberije, Cary; Lambin, Philippe; Uyl-de Groot, Carin A; Coupé, V M H

    2016-01-01

    With the shift toward individualized treatment, cost-effectiveness models need to incorporate patient and tumor characteristics that may be relevant to treatment planning. In this study, we used multistate statistical modeling to inform a microsimulation model for cost-effectiveness analysis of individualized radiotherapy in lung cancer. The model tracks clinical events over time and takes patient and tumor features into account. Four clinical states were included in the model: alive without progression, local recurrence, metastasis, and death. Individual patients were simulated by repeatedly sampling a patient profile, consisting of patient and tumor characteristics. The transitioning of patients between the health states is governed by personalized time-dependent hazard rates, which were obtained from multistate statistical modeling (MSSM). The model simulations for both the individualized and conventional radiotherapy strategies demonstrated internal and external validity. Therefore, MSSM is a useful technique for obtaining the correlated individualized transition rates that are required for the quantification of a microsimulation model. Moreover, we have used the hazard ratios, their 95% confidence intervals, and their covariance to quantify the parameter uncertainty of the model in a correlated way. The obtained model will be used to evaluate the cost-effectiveness of individualized radiotherapy treatment planning, including the uncertainty of input parameters. We discuss the model-building process and the strengths and weaknesses of using MSSM in a microsimulation model for individualized radiotherapy in lung cancer.

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

    Science.gov (United States)

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

    2010-08-01

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

  2. Multiplex characterization of human pathogens including species and antibiotic-resistance gene identification.

    Science.gov (United States)

    Barisˇ ić, Ivan; Petzka, Josefine; Schoenthaler, Silvia; Vierlinger, Klemens; Noehammer, Christa; Wiesinger-Mayr, Herbert

    2016-01-01

    The efficient medical treatment of infections requires detailed information about the pathogens involved and potential antibiotic-resistance mechanisms. The dramatically increasing incidence of multidrug-resistant bacteria especially highlights the importance of sophisticated diagnostic tests enabling a fast patient-customized therapy. However, the current molecular detection methods are limited to either the detection of species or only a few antibiotic-resistance genes.In this work, we present a human pathogen characterization assay using a rRNA gene microarray identifying 75 species comprising bacteria and fungi. A statistical classifier was developed to facilitate the automated species identification. Additionally, the clinically most important β-lactamases were identified simultaneously in a 100-plex reaction using padlock probes and the same microarray. The specificity and sensitivity of the combined assay was determined using clinical isolates. The detection limit was 10(5) c.f.u. ml(-1), recovering 89 % of the detectable β-lactamase-encoding genes specifically. The total assay time was less than 7 hand the modular character of the antibiotic-resistance detection allows the easy integration of further genetic targets. In summary, we present a fast, highly specific and sensitive multiplex pathogen characterization assay.

  3. 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.

  4. 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.

  5. [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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Richard Simon

    2008-01-01

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

  8. Human epididymis protein 4 immunostaining of malignant ascites differentiates cancer of Müllerian origin from gastrointestinal cancer.

    Science.gov (United States)

    Stiekema, Anna; Van de Vijver, Koen K; Boot, Henk; Broeks, Annegien; Korse, Catharina M; van Driel, Willemien J; Kenter, Gemma G; Lok, Christianne A R

    2017-03-01

    An accurate diagnosis of cancer of Müllerian origin is required before the initiation of treatment. An overlap in clinical presentation and cytological, histological, or imaging studies with other nongynecological tumors does occur. Therefore, immunocytochemistry markers are used to determine tumor origin. Human epididymis protein 4 (HE4) is overexpressed in tissue of epithelial ovarian cancer (EOC). It has shown to be a sensitive and specific serum marker for EOC and to be of value for the differentiation between EOC and ovarian metastases of gastrointestinal origin. The objective of the current study was to evaluate HE4 immunocytochemistry in malignant ascites for differentiation between cancer of Müllerian origin, including EOC, and adenocarcinomas of the gastrointestinal tract. Cytological specimens of 115 different adenocarcinomas (45 EOCs, 46 cases of gastric cancer, and 24 cases of colorectal cancer) were stained for HE4, paired box 8 (PAX8), and other specific markers. 91% of the ascites samples from patients with EOC stained for both HE4 and PAX8. The 4 samples without HE4 staining were a clear cell carcinoma, a low-grade serous adenocarcinoma, an undifferentiated adenocarcinoma, and a neuroendocrine carcinoma. All high-grade serous adenocarcinomas (n = 37, 100%) stained with HE4, compared with 94% that stained positively for PAX8. In cases of gastric or colorectal cancer, 25% and 21% of cases, respectively, stained positive for HE4. No PAX8 staining was observed in colorectal or gastric adenocarcinomas. HE4 staining in ascites is feasible and appears to have a high sensitivity for high-grade serous ovarian cancer. HE4 is a useful addition to the current panel of immunocytochemistry markers for the diagnosis of EOC and for differentiation with gastrointestinal adenocarcinomas. Cancer Cytopathol 2017;125:197-204. © 2016 American Cancer Society. © 2017 American Cancer Society.

  9. Anticancer Effects of Different Seaweeds on Human Colon and Breast Cancers

    Directory of Open Access Journals (Sweden)

    Ghislain Moussavou

    2014-09-01

    Full Text Available Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality in men and women. It also describes various compounds extracted from a range of seaweeds that have been shown to eradicate or slow the progression of cancer. Fucoidan extracted from the brown algae Fucus spp. has shown activity against both colorectal and breast cancers. Furthermore, we review the mechanisms through which these compounds can induce apoptosis in vitro and in vivo. By considering the ability of compounds present in seaweeds to act against colorectal and breast cancers, this review highlights the potential use of seaweeds as anticancer agents.

  10. CE: Human Papillomavirus-Related Oral Cancers: The Nurse's Role in Mitigating Stigma and Dispelling Myths.

    Science.gov (United States)

    Katz, Anne

    2017-01-01

    : The prevalence of human papillomavirus (HPV)-related oral cancers has been rising, the cancers occurring in adults at a younger age than HPV-negative oral cancers typically do and in men more often than women. Patients who are diagnosed often don't understand the disease's etiology. Because HPV is sexually transmitted, diagnosis with an HPV-related oral cancer may prompt feelings of shame, embarrassment, and guilt. There are currently three vaccines for HPV. It's essential for nurses to educate patients on HPV transmission and HPV-related oral cancer, thus helping to mitigate the stigma and dispel myths, and to promote vaccination in at-risk populations, including children and young adults.

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

    Science.gov (United States)

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

    2015-02-01

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

  12. Human papillomavirus-associated cancers as acquired immunodeficiency syndrome defining illnesses

    Directory of Open Access Journals (Sweden)

    Shohreh Shahabi

    2013-04-01

    Full Text Available The Centers for Disease Control currently report cervical, vulvar, vaginal, anal and some head and neck cancers as human papillomavirus (HPV-associated cancers. Only cervical cancer is listed amongst acquired immunodeficiency syndrome (AIDS defining illnesses. All of these cancers may represent progression of the immunocompromised state with the inability to eradicate viral infection. This study reports the case of a 27-year old HIV positive female presenting with a persistent right vulvar exophytic lesion. High-risk HPV analysis and immunostaining for P16 were both positive. A biopsy of the lesion revealed invasive squamous cell carcinoma. The patient underwent neoadjuvant radiation and chemotherapy followed by a radical vulvectomy. During treatment, her CD4 T-lymphocyte count decreased to 120 advancing her condition from HIV to AIDS. This case suggests that all HPV-associated cancers should be included as AIDS defining illnesses.

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

    Institute of Scientific and Technical Information of China (English)

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

    2001-01-01

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

  14. 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)

  15. ADH IB expression, but not ADH III, is decreased in human lung cancer.

    Science.gov (United States)

    Mutka, Sarah C; Green, Lucia H; Verderber, Evie L; Richards, Jane P; Looker, Doug L; Chlipala, Elizabeth A; Rosenthal, Gary J

    2012-01-01

    Endogenous S-nitrosothiols, including S-nitrosoglutathione (GSNO), mediate nitric oxide (NO)-based signaling, inflammatory responses, and smooth muscle function. Reduced GSNO levels have been implicated in several respiratory diseases, and inhibition of GSNO reductase, (GSNOR) the primary enzyme that metabolizes GSNO, represents a novel approach to treating inflammatory lung diseases. Recently, an association between decreased GSNOR expression and human lung cancer risk was proposed in part based on immunohistochemical staining using a polyclonal GSNOR antibody. GSNOR is an isozyme of the alcohol dehydrogenase (ADH) family, and we demonstrate that the antibody used in those studies cross reacts substantially with other ADH proteins and may not be an appropriate reagent. We evaluated human lung cancer tissue arrays using monoclonal antibodies highly specific for human GSNOR with minimal cross reactivity to other ADH proteins. We verified the presence of GSNOR in ≥85% of specimens examined, and extensive analysis of these samples demonstrated no difference in GSNOR protein expression between cancerous and normal lung tissues. Additionally, GSNOR and other ADH mRNA levels were evaluated quantitatively in lung cancer cDNA arrays by qPCR. Consistent with our immunohistochemical findings, GSNOR mRNA levels were not changed in lung cancer tissues, however the expression levels of other ADH genes were decreased. ADH IB mRNA levels were reduced (>10-fold) in 65% of the lung cancer cDNA specimens. We conclude that the previously reported results showed an incorrect association of GSNOR and human lung cancer risk, and a decrease in ADH IB, rather than GSNOR, correlates with human lung cancer.

  16. ADH IB expression, but not ADH III, is decreased in human lung cancer.

    Directory of Open Access Journals (Sweden)

    Sarah C Mutka

    Full Text Available Endogenous S-nitrosothiols, including S-nitrosoglutathione (GSNO, mediate nitric oxide (NO-based signaling, inflammatory responses, and smooth muscle function. Reduced GSNO levels have been implicated in several respiratory diseases, and inhibition of GSNO reductase, (GSNOR the primary enzyme that metabolizes GSNO, represents a novel approach to treating inflammatory lung diseases. Recently, an association between decreased GSNOR expression and human lung cancer risk was proposed in part based on immunohistochemical staining using a polyclonal GSNOR antibody. GSNOR is an isozyme of the alcohol dehydrogenase (ADH family, and we demonstrate that the antibody used in those studies cross reacts substantially with other ADH proteins and may not be an appropriate reagent. We evaluated human lung cancer tissue arrays using monoclonal antibodies highly specific for human GSNOR with minimal cross reactivity to other ADH proteins. We verified the presence of GSNOR in ≥85% of specimens examined, and extensive analysis of these samples demonstrated no difference in GSNOR protein expression between cancerous and normal lung tissues. Additionally, GSNOR and other ADH mRNA levels were evaluated quantitatively in lung cancer cDNA arrays by qPCR. Consistent with our immunohistochemical findings, GSNOR mRNA levels were not changed in lung cancer tissues, however the expression levels of other ADH genes were decreased. ADH IB mRNA levels were reduced (>10-fold in 65% of the lung cancer cDNA specimens. We conclude that the previously reported results showed an incorrect association of GSNOR and human lung cancer risk, and a decrease in ADH IB, rather than GSNOR, correlates with human lung cancer.

  17. HABP2 is a novel regulator of hyaluronan-mediated human lung cancer progression

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    Tamara eMirzapoiazova

    2015-07-01

    Full Text Available Background: Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA, which we have previously demonstrated can regulate the activity of the extracellular serine protease, Hyaluronan Binding Protein 2 (HABP2. This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics.Methods: Immunohistochemical analysis was performed on lung cancer patient samples using anti-HABP2 antibody. Stable control, shRNA and HABP2 overexpressing human lung adenocarcinoma cells were evaluated using immunoblot analysis, migration, extravasation and urokinase plasminogen activator (uPA activation assays with or without high molecular weight HA (HMW-HA or low molecular weight HA (LMW-HA. In human lung cancer xenograft models, primary tumor growth rates and lung metastasis were analyzed using consecutive tumor volume measurements and nestin immunoreactivity in nude mouse lungs.Results: We provide evidence that HABP2 is an important regulator of lung cancer progression. HABP2 expression was increased in several subtypes of patient non-small cell lung cancer samples. Further, HABP2 overexpression increased LMW-HA-induced uPA activation, migration and extravasation in human lung adenocarcinoma cells. In vivo, overexpression of HABP2 in human lung adenocarcinoma cells increased primary tumor growth rates in nude mice by ~2 fold and lung metastasis by ~10 fold compared to vector control cells (n=5 per condition.Conclusions: Our data suggests a possible direct effect of HABP2 on uPA activation and lung cancer progression. Our observations suggest that exploration of HABP2 in non-small cell lung carcinoma merits further study both as a diagnostic and therapeutic option.

  18. Human blood basophils display a unique phenotype including activation linked membrane structures.

    Science.gov (United States)

    Stain, C; Stockinger, H; Scharf, M; Jäger, U; Gössinger, H; Lechner, K; Bettelheim, P

    1987-12-01

    To evaluate the membrane marker profile of human basophils a panel of well-established monoclonal antibodies (MoAbs, n = 60) was used for a combined toluidine/immunofluorescence staining procedure. Myeloid-associated MoAbs (particularly MoAbs against the LFA-1 family (CD11, CDw18), MoAbs directed against lactosylceramide (CDw17), anti-glycoprotein (gp) 150 MoAbs MCS 2 and MY 7 (CDw13), anti-gp 67 MoAb MY 9, anti Fc gamma-receptor (mol wt 40 kd) MoAb CIKM5, anti-CR 1 MoAb E 11, and the antiglycolipid MoAb VIM-2) were reactive with basophils, indicating a close relationship to other mature myeloid cells. Under normal conditions, basophils surprisingly express at least three activation-linked structures not detectable on mature neutrophils, ie, the p45 structure defined by MoAbs OKT-10 and VIP-2b, the p24 structure identified by the CD9 MoAb BA-2, and the receptor for interleukin 2 (IL 2) recognized by three different MoAbs (anti-TAC, IL2RI, anti-IL 2). Moreover, under short-term culture conditions basophils both in mononuclear cell (MNC) suspension and as purified fractions display the HLA-DR and T4 antigens. The neutrophilic/eosinophilic structure 3-fucosyl-N-acetyllactosamine is expressed on basophils only after neuraminidase treatment. Basophils were not stained at all by CD 16 MoAbs directed against the Fc gamma-receptor (mol wt 50 to 70 kd) of neutrophils, by the MoAb 63D3 (CDw12) recognizing the monocyte/granulocyte-associated p 200 antigen, and by the CDw 14 antibodies (VIM-13, Mo 2) defining the monocyte-specific structure p 55. Enriched basophils freshly obtained from chronic granulocytic leukemia (CGL) patients yielded identical results in FACS analyses. In summary, these data indicate that basophils generate a unique combination of surface determinants and possibly represent an activated cell population.

  19. Role of ARPC2 in Human Gastric Cancer

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

    2017-01-01

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

  20. Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

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    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.

  1. 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.

  2. Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research.

    Science.gov (United States)

    Lee, Sung Jong; Yang, Andrew; Wu, T C; Hung, Chien Fu

    2016-09-01

    Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.

  3. Evaluation of trace element concentration in cancerous and non-cancerous tissues of human stomach.

    Science.gov (United States)

    Kohzadi, Shadi; Sheikhesmaili, Farshad; Rahehagh, Ramesh; Parhizkar, Baran; Ghaderi, Ebrahim; Loqmani, Hozan; Shahmoradi, Behzad; Mohammadi, Ebrahim; Maleki, Afshin

    2017-10-01

    Gastric cancer has a high mortality rate in west of Iran. Various environmental elements are proposed as cancer risk factors including trace elements. Trace elements can induce initiation or progression of carcinogenesis via oxidative stress and DNA injury. The aim of this study was to measure and compare some trace element concentration (Ca, Cu, Fe, As, Mg, Ni, Cd and Cr) in gastric cancer tissues and normal tissues. For this purpose, 35 patients with gastric cancer and 30 without any cancer were biopsied. Biopsies were taken from cancerous tissue and non-cancerous tissue of gastric cancer patients and gastric tissue of normal patients. The analysis of trace elements was performed using Inductively coupled plasma mass spectrometry (ICP-MS). Data analysis was carried out using SPSS and STATA 12 software. The research found that the concentrations of Fe, Mg, and As were higher in cancerous tissues compared with non-cancerous tissues whereas Cr, Cu, Ca, and Ni concentrations were higher in non-cancerous tissues of cancerous patients. When comparisons were made for cancer and normal samples, copper was the only metal, which was significantly higher in cancerous samples (p tissues was significantly higher compared with cancerous tissues (P = 0.02). Chi-Square test showed that there was no significant relationship in the demographic information between cancerous and normal patients except for location with K(2) = 7.604. Increased Cu and As concentration in gastric patients (both tissues) propose that these elements may have carcinogenic effects, although further study is suggested. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Anti-proliferation Effect of Polypeptide Extracted from Scorpion Venom on Human Prostate Cancer Cells in vitro

    OpenAIRE

    Zhang, Yue Ying; Wu, Li Cun; Wang, Zhao Peng; Wang, Zhao Xia; Jia, Qing; Jiang, Guo Sheng; Zhang, Wei Dong

    2009-01-01

    Background Prostate cancer is a major cause of cancer-related death in men. Therefore there has been considerable interest to explore neoadjuvant therapy. Polypeptide extracted from scorpion venom (PESV), originally obtained from the East-Asian scorpion Buthus martensi Karsch (BmK), is being studied for both prevention and treatment of various human malignancies including prostate cancer. Methods The present study was to investigate the effect of PESV on cell proliferation, cell cycle, and ap...

  5. Hispolon inhibits the growth of estrogen receptor positive human breast cancer cells through modulation of estrogen receptor alpha

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    Jang, Eun Hyang; Jang, Soon Young; Cho, In-Hye [Department of Pharmacy, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Hong, Darong [Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Jung, Bom; Park, Min-Ju [Department of Pharmacy, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Kim, Jong-Ho, E-mail: jonghokim@khu.ac.kr [Department of Pharmacy, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of)

    2015-08-07

    Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated the effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy. - Highlights: • Hispolon decreased ERα expression at both mRNA and protein levels. • Hispolon decreased ERα transcriptional activity. • Hispolon treatment inhibited expression of ERα target gene pS2. • Shikonin is a candidate chemotherapeutic target in the treatment of human breast cancer.

  6. 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

  7. 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

  8. Comparative oncogenomic analysis of copy number alterations in human and zebrafish tumors enables cancer driver discovery.

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    GuangJun Zhang

    2013-08-01

    Full Text Available The identification of cancer drivers is a major goal of current cancer research. Finding driver genes within large chromosomal events is especially challenging because such alterations encompass many genes. Previously, we demonstrated that zebrafish malignant peripheral nerve sheath tumors (MPNSTs are highly aneuploid, much like human tumors. In this study, we examined 147 zebrafish MPNSTs by massively parallel sequencing and identified both large and focal copy number alterations (CNAs. Given the low degree of conserved synteny between fish and mammals, we reasoned that comparative analyses of CNAs from fish versus human MPNSTs would enable elimination of a large proportion of passenger mutations, especially on large CNAs. We established a list of orthologous genes between human and zebrafish, which includes approximately two-thirds of human protein-coding genes. For the subset of these genes found in human MPNST CNAs, only one quarter of their orthologues were co-gained or co-lost in zebrafish, dramatically narrowing the list of candidate cancer drivers for both focal and large CNAs. We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers.

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

    Science.gov (United States)

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

    2013-10-01

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

  10. Outcome of combined modality treatment including neoadjuvant chemotherapy of 128 cases of locally advanced breast cancer: Data from a tertiary cancer center in northern India

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    V Raina

    2011-01-01

    Full Text Available Background: Breast cancer is now the most common cancer in many parts of India and the incidence varies from 12 to 31/100000, and is rising. Locally advanced breast cancer (LABC accounts for 30 - 35% of all cases of breast cancers in India. LABC continues to present a challenge and imposes a major health impact in our country. Materials and Methods: We carried out a analysis of our LABC patients who received neoadjuvant chemotherapy (NACT at our hospital over a 10-year period, from January 1995 to December 2004. We analyzed the response to NACT, disease-free survival (DFS, and overall survival (OS. Results: Patients with stages IIIA, IIIB, and IIIC were included. LABC comprised of 26.24% (609 patients of new patients. One hundred and twenty-eight (31.1% patients received NACT. Median age was 48 years and estrogen receptor was positive in 64%. Chemotherapy protocol was an FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide regimen in the following doses: Cyclophosphamide 600 mg/m2, 5-FU 600 mg/m2, and Epirubicin 75 mg/m2 given every three weeks, six doses, followed by modified radical mastectomy (MRM and locoregional radiotherapy. The overall response rate (complete response (CR + partial response (PR was 84.4%, clinical CR (cCR was 13.3% and pathological CR (pCR was 7.8%. Median DFS and OS were 33 and 101 months, respectively. The disease-free survival (DFS and overall survival (OS at five years were 41 and 58%, respectively. Conclusions: This study analyzes the outcome in patients who received NACT, in the largest number of LABC patients from a single center in India, and our results are comparable to the results reported from other centers.

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

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    Takayuki Ueno

    2015-01-01

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

  12. Identification of Claudin 1 Transcript Variants in Human Invasive Breast Cancer

    Science.gov (United States)

    Zelinski, Teresa; Xie, Jiuyong; Cooper, Steven; Penner, Carla; Leygue, Etienne; Myal, Yvonne

    2016-01-01

    Background The claudin 1 tight junction protein, solely responsible for the barrier function of epithelial cells, is frequently down regulated in invasive human breast cancer. The underlying mechanism is largely unknown, and no obvious mutations in the claudin 1 gene (CLDN1) have been identified to date in breast cancer. Since many genes have been shown to undergo deregulation through splicing and mis-splicing events in cancer, the current study was undertaken to investigate the occurrence of transcript variants for CLDN1 in human invasive breast cancer. Methods RT-PCR analysis of CLDN1 transcripts was conducted on RNA isolated from 12 human invasive breast tumors. The PCR products from each tumor were resolved by agarose gel electrophoresis, cloned and sequenced. Genomic DNA was also isolated from each of the 12 tumors and amplified using PCR CLDN1 specific primers. Sanger sequencing and single nucleotide polymorphism (SNP) analyses were conducted. Results A number of CLDN1 transcript variants were identified in these breast tumors. All variants were shorter than the classical CLDN1 transcript. Sequence analysis of the PCR products revealed several splice variants, primarily in exon 1 of CLDN1; resulting in truncated proteins. One variant, V1, resulted in a premature stop codon and thus likely led to nonsense mediated decay. Interestingly, another transcript variant, V2, was not detected in normal breast tissue samples. Further, sequence analysis of the tumor genomic DNA revealed SNPs in 3 of the 4 coding exons, including a rare missense SNP (rs140846629) in exon 2 which represents an Ala124Thr substitution. To our knowledge this is the first report of CLDN1 transcript variants in human invasive breast cancer. These studies suggest that alternate splicing may also be a mechanism by which claudin 1 is down regulated at both the mRNA and protein levels in invasive breast cancer and may provide novel insights into how CLDN1 is reduced or silenced in human breast

  13. 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 ...

  14. Transduction motif analysis of gastric cancer based on a human signaling network

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    Liu, G.; Li, D.Z.; Jiang, C.S.; Wang, W. [Fuzhou General Hospital of Nanjing Command, Department of Gastroenterology, Fuzhou, China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou (China)

    2014-04-04

    To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

  15. Transduction motif analysis of gastric cancer based on a human signaling network

    Directory of Open Access Journals (Sweden)

    G. Liu

    2014-05-01

    Full Text Available To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

  16. Associations of filaggrin gene loss-of-function variants and human papillomavirus-related cancer and pre-cancer in Danish adults.

    Directory of Open Access Journals (Sweden)

    Tea Skaaby

    Full Text Available Filaggrin proteins are expressed in the skin, oral cavity, oesophagus, and cervical mucose. Loss-of-function mutations in the filaggrin gene (FLG reduce filaggrin expression and cause an impaired skin barrier function. We hypothesized that FLG mutation carriers would be more susceptible to human papillomavirus (HPV infection and thus a higher risk of HPV-related cancer and pre-cancer. We investigated the association of the FLG genotype with incidence of HPV-related cancer of cervix, vagina, vulva, penis, anus and head and neck, and pre-cancer of the cervix.We included 13,376 persons from four population-based studies conducted in the same background population in Copenhagen, Denmark. Participants were genotyped for the most common FLG mutations in Europeans. Information on cancer was obtained from The Danish Cancer Registry until 11 July 2011.There were 489 cases of prevalent and 97 cases of incident HPV-related cancer and pre-cancer (median follow-up 11.5 years. There was a statistically significant association between FLG genotype and incident HPV-related cancer and pre-cancer with a hazard ratio, HR = 2.1 (95% confidence intervals, CI: 1.2, 3.7 for FLG mutation carriers vs. wild types.FLG loss-of-function mutations were associated with higher incidence of HPV-related cancers and pre-cancers that are potentially screening and vaccine preventable.

  17. 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.

  18. 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.

  19. CERVICAL CANCER AND THE HUMAN IMMUNODEFICIENCY ...

    African Journals Online (AJOL)

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

  20. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Christopher M. Fulkerson

    2017-01-01

    Full Text Available Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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...

  10. 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.

  11. 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.

  12. Molecular and Cellular Effects of Hydrogen Peroxide on Human Lung Cancer Cells: Potential Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Gabriela Vilema-Enríquez

    2016-01-01

    Full Text Available Lung cancer has a very high mortality-to-incidence ratio, representing one of the main causes of cancer mortality worldwide. Therefore, new treatment strategies are urgently needed. Several diseases including lung cancer have been associated with the action of reactive oxygen species (ROS from which hydrogen peroxide (H2O2 is one of the most studied. Despite the fact that H2O2 may have opposite effects on cell proliferation depending on the concentration and cell type, it triggers several antiproliferative responses. H2O2 produces both nuclear and mitochondrial DNA lesions, increases the expression of cell adhesion molecules, and increases p53 activity and other transcription factors orchestrating cancer cell death. In addition, H2O2 facilitates the endocytosis of oligonucleotides, affects membrane proteins, induces calcium release, and decreases cancer cell migration and invasion. Furthermore, the MAPK pathway and the expression of genes related to inflammation including interleukins, TNF-α, and NF-κB are also affected by H2O2. Herein, we will summarize the main effects of hydrogen peroxide on human lung cancer leading to suggesting it as a potential therapeutic tool to fight this disease. Because of the multimechanistic nature of this molecule, novel therapeutic approaches for lung cancer based on the use of H2O2 may help to decrease the mortality from this malignancy.

  13. Association between matrix metalloproteinase 1 -1607 1G>2G polymorphism and cancer risk: a meta-analysis including 19706 subjects.

    Science.gov (United States)

    Han, Guoda; Wei, Zhijiang; Lu, Zhiliang; Cui, Haibin; Bai, Xiyong; Ge, Huai'e; Zhang, Wei

    2014-01-01

    The association between MMP1 -1607 1G>2G polymorphism and cancer risk has been reported, but results remained controversial and ambiguous. To assess the association between MMP1 -1607 1G>2G polymorphism and cancer risk, a meta-analysis was performed. Based on comprehensive searches of the PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase), and Chinese Biomedical Literature Database (CBM), we identified outcome data from all articles estimating the association between MMP1 -1607 1G>2G polymorphism and cancer risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Thirty-eight studies involving 10178 cases and 9528 controls were included. Overall, significant association between MMP1 -1607 1G>2G polymorphism and cancer susceptibility was observed for additive model (OR = 1.21, 95% CI 1.09-1.35), for codominant model (OR = 1.34, 95% CI 1.10-1.63), for dominant model (OR = 1.17, 95% CI 1.01-1.34), for recessive model (OR = 1.31, 95% CI 1.14-1.52). In the subgroup analysis by ethnicity, the significant association was found among Asians but not among Caucasians. In the subgroup analysis by site of cancer, significant associations were found among lung cancer, colorectal cancer, head and neck cancer and bladder cancer. This meta-analysis demonstrated that the MMP1 -1607 1G>2G polymorphism was significantly associated with cancer risk.

  14. 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.

  15. Influence of the chopped frequency of light on optical transport characteristics of human skin including at acupuncture points

    Science.gov (United States)

    Yang, Hong-qin; Xie, Shu-sen; Liu, Song-hao; Li, Hui; Wang, Yu-hua; Guo, Zhou-yi

    2007-11-01

    An experimental protocol was established for noninvasively measuring the optical transport characteristics of skin tissue along human meridian direction over body surface including at acupuncture points. The diffuse remittance for 658 nm light radiation along the pericardium meridian and non-meridian directions were measured respectively. The influence of the chopped frequency of light on the detected light signal was investigated. It is shown that the optical transport characteristics of skin tissue accords with the Beer's exponential attenuation law along the meridian including at acupuncture points and non-median directions. However there is an obvious difference between the propagations along the meridian direction and non-meridian direction (P<0.05). Furthermore, the chopped frequency can affect the detected signal. The diffuse remittance signal decreased with the chopped frequency's increase and it was different between the meridian and non-meridian directions. These findings are important and meaningful for interpreting the human meridian phenomena by biomedical optics.

  16. Characterization of the Usage of the Serine Metabolic Network in Human Cancer

    Directory of Open Access Journals (Sweden)

    Mahya Mehrmohamadi

    2014-11-01

    Full Text Available The serine, glycine, one-carbon (SGOC metabolic network is implicated in cancer pathogenesis, but its general functions are unknown. We carried out a computational reconstruction of the SGOC network and then characterized its expression across thousands of cancer tissues. Pathways including methylation and redox metabolism exhibited heterogeneous expression indicating a strong context dependency of their usage in tumors. From an analysis of coexpression, simultaneous up- or downregulation of nucleotide synthesis, NADPH, and glutathione synthesis was found to be a common occurrence in all cancers. Finally, we developed a method to trace the metabolic fate of serine using stable isotopes, high-resolution mass spectrometry, and a mathematical model. Although the expression of single genes didn’t appear indicative of flux, the collective expression of several genes in a given pathway allowed for successful flux prediction. Altogether, these findings identify expansive and heterogeneous functions for the SGOC metabolic network in human cancer.

  17. An approach to including protein quality when assessing the net contribution of livestock to human food supply.

    Science.gov (United States)

    Ertl, P; Knaus, W; Zollitsch, W

    2016-11-01

    The production of protein from animal sources is often criticized because of the low efficiency of converting plant protein from feeds into protein in the animal products. However, this critique does not consider the fact that large portions of the plant-based proteins fed to animals may be human-inedible and that the quality of animal proteins is usually superior as compared with plant proteins. The aim of the present study was therefore to assess changes in protein quality in the course of the transformation of potentially human-edible plant proteins into animal products via livestock production; data from 30 Austrian dairy farms were used as a case study. A second aim was to develop an approach for combining these changes with quantitative aspects (e.g. with the human-edible feed conversion efficiency (heFCE), defined as kilogram protein in the animal product divided by kilogram potentially human-edible protein in the feeds). Protein quality of potentially human-edible inputs and outputs was assessed using the protein digestibility-corrected amino acid score and the digestible indispensable amino acid score, two methods proposed by the Food and Agriculture Organization of the United Nations to describe the nutritional value of proteins for humans. Depending on the method used, protein scores were between 1.40 and 1.87 times higher for the animal products than for the potentially human-edible plant protein input on a barn-gate level (=protein quality ratio (PQR)). Combining the PQR of 1.87 with the heFCE for the same farms resulted in heFCE×PQR of 2.15. Thus, considering both quantity and quality, the value of the proteins in the animal products for human consumption (in this case in milk and beef) is 2.15 times higher than that of proteins in the potentially human-edible plant protein inputs. The results of this study emphasize the necessity of including protein quality changes resulting from the transformation of plant proteins to animal proteins when

  18. Synthesis of Chromonylthiazolidines and Their Cytotoxicity to Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Hoang Le Tuan Anh

    2015-01-01

    Full Text Available Nine new chromonylthiazolidine derivatives were successfully semi-synthesized from paeonol. All of the compounds, including starting materials, the intermediate compound and products, were evaluated for their cytotoxic effects toward eight human cancer cell lines. The synthesized chromonylthiazolidines displayed weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed. Compounds 3a and 3b showed the most selective cytotoxic effects against human epidermoid carcinoma (IC50 44.1 ± 3.6 μg/mL and breast cancer (IC50 32.8 ± 1.4 μg/mL cell lines, respectively. The results suggest that chromoylthiazolidines are potential low-cost, and selective anticancer agents.

  19. Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45

    Institute of Scientific and Technical Information of China (English)

    Hai-hong ZHANG; Ai-zhen CAI; Xue-ming WEI; Li DING; Feng-zhi LI; Ai-ming ZHENG; Da-jiang DAI

    2013-01-01

    Objective:Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer.Many kinds of cell lines and tissues have demonstrated the presence of SP cells,including several gastric cancer cell lines.This study is aimed to identify the cancer stem-like cells in the SP of gastric cancer cell line MKN-45.Methods:We used fluorescence activated cell sorting (FACS) to sort SP cells in the human gastric carcinoma cell line MKN-45 (cells labeled with Hoechst 33342) and then characterized the cancer stem-like properties of SP cells.Results:This study found that the SP cells had higher clone formation efficiency than major population (MP) cells.Five stemness-related gene expression profiles,including OCT-4,SOX-2,NANOG,CD44,and adenosine triphosphate (ATP)-binding cassette transporters gene ABCG2,were tested in SP and MP cells using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).Western blot was used to show the difference of protein expression between SP and MP cells.Both results show that there was significantly higher protein expression in SP cells than in MP cells.When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice,SP cells show higher tumorigenesis tendency than MP cells.Conclusions:These results indicate that SP cells possess cancer stem cell properties and prove that SP cells from MKN-45 are gastric cancer stem-like cells.

  20. Transcriptional and epigenetic regulation of KIAA1199 gene expression in human breast cancer.

    Directory of Open Access Journals (Sweden)

    Cem Kuscu

    Full Text Available Emerging evidence has demonstrated that upregulated expression of KIAA1199 in human cancer bodes for poor survival. The regulatory mechanism controlling KIAA1199 expression in cancer remains to be characterized. In the present study, we have isolated and characterized the human KIAA1199 promoter in terms of regulation of KIAA1199 gene expression. A 3.3 kb fragment of human genomic DNA containing the 5'-flanking sequence of the KIAA1199 gene possesses both suppressive and activating elements. Employing a deletion mutagenesis approach, a 1.4 kb proximal region was defined as the basic KIAA1199 promoter containing a TATA-box close to the transcription start site. A combination of 5'-primer extension study with 5'RACE DNA sequencing analysis revealed one major transcription start site that is utilized in the human KIAA1199 gene. Bioinformatics analysis suggested that the 1.4 kb KIAA1199 promoter contains putative activating regulatory elements, including activator protein-1(AP-1, Twist-1, and NF-κB sites. Sequential deletion and site-direct mutagenesis analysis demonstrated that the AP-1 and distal NF-κB sites are required for KIAA1199 gene expression. Further analyses using an electrophoretic mobility-shift assay and chromatin immunoprecipitation confirmed the requirement of these cis- and trans-acting elements in controlling KIAA1199 gene expression. Finally, we found that upregulated KIAA1199 expression in human breast cancer specimens correlated with hypomethylation of the regulatory region. Involvement of DNA methylation in regulation of KIAA1199 expression was recapitulated in human breast cancer cell lines. Taken together, our study unraveled the regulatory mechanisms controlling KIAA1199 gene expression in human cancer.

  1. Chromatin Memory in the Development of Human Cancers

    OpenAIRE

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

    2014-01-01

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

  2. Prognostic values of tissue factor and its alternatively splice transcripts in human gastric cancer tissues.

    Science.gov (United States)

    Wu, Min; Chen, Lujun; Xu, Ting; Xu, Bin; Jiang, Jingting; Wu, Changping

    2017-08-08

    We have previously reported that the higher expression of TF in human esophageal cancer tissues was significantly associated with tumor invasion, intratumoral microvessel density and patients' postoperative prognoses. Besides its trans-membranous form, TF also has alternatively spliced transcripts. In the present study, the transcripts of the two TF isoforms, flTF and asTF, in human gastric cancer tissues were determined by real-time PCR, and the correlation between the expression of TF isoforms and patient's clinicopathological features was also analyzed. Our results showed that the relative mRNA expression levels of flTF and asTF in human gastric cancer tissues was significantly higher than those in normal tissues (P=0.035 and P=0.006, respectively). The relative mRNA expression level of asTF was significantly associated with age (P=0.018), meanwhile, we could not find that flTF or asTF expression level was correlated with any other characteristics of the patients, including gender, TNM stage, pathological grade, tumor size, histological type, or chemotherapy sensitivity. Univariate analysis demonstrated that the overall survival rate of gastric cancer patients with lower flTF or asTF expression level was greater than those with higher expression level (P=0.018 and =0.038, respectively). Multivariate COX model analysis also demonstrated that flTF expression (P=0.048) or asTF expression (P=0.002) could be used as independent prognostic predictors in human gastric cancer. Thus, both flTF and asTF mRNA expression levels in cancer tissues could be used as useful risk factors for evaluating the prognoses of patients suffering from gastric cancer.

  3. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis.

    Science.gov (United States)

    Higdon, Jane V; Delage, Barbara; Williams, David E; Dashwood, Roderick H

    2007-03-01

    Cruciferous vegetables are a rich source of glucosinolates and their hydrolysis products, including indoles and isothiocyanates, and high intake of cruciferous vegetables has been associated with lower risk of lung and colorectal cancer in some epidemiological studies. Glucosinolate hydrolysis products alter the metabolism or activity of sex hormones in ways that could inhibit the development of hormone-sensitive cancers, but evidence of an inverse association between cruciferous vegetable intake and breast or prostate cancer in humans is limited and inconsistent. Organizations such as the National Cancer Institute recommend the consumption of five to nine servings of fruits and vegetables daily, but separate recommendations for cruciferous vegetables have not been established. Isothiocyanates and indoles derived from the hydrolysis of glucosinolates, such as sulforaphane and indole-3-carbinol (I3C), have been implicated in a variety of anticarcinogenic mechanisms, but deleterious effects also have been reported in some experimental protocols, including tumor promotion over prolonged periods of exposure. Epidemiological studies indicate that human exposure to isothiocyanates and indoles through cruciferous vegetable consumption may decrease cancer risk, but the protective effects may be influenced by individual genetic variation (polymorphisms) in the metabolism and elimination of isothiocyanates from the body. Cooking procedures also affect the bioavailability and intake of glucosinolates and their derivatives. Supplementation with I3C or the related dimer 3,3'-diindolylmethane (DIM) alters urinary estrogen metabolite profiles in women, but the effects of I3C and DIM on breast cancer risk are not known. Small preliminary trials in humans suggest that I3C supplementation may be beneficial in treating conditions related to human papilloma virus infection, such as cervical intraepithelial neoplasia and recurrent respiratory papillomatosis, but larger randomized

  4. 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.

  5. 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.

  6. Induction of dormancy in hypoxic human papillomavirus-positive cancer cells

    Science.gov (United States)

    Hoppe-Seyler, Karin; Bossler, Felicitas; Lohrey, Claudia; Bulkescher, Julia; Rösl, Frank; Jansen, Lars; Mayer, Arnulf; Vaupel, Peter; Dürst, Matthias; Hoppe-Seyler, Felix

    2017-01-01

    Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and head and neck cancers, enable HPV-positive cancer cells to escape from these regulatory principles: E6/E7 is efficiently repressed, yet, p53 levels do not increase. Moreover, E6/E7 repression under hypoxia does not result in cellular senescence, owing to hypoxia-associated impaired mechanistic target of rapamycin (mTOR) signaling via the inhibitory REDD1/TSC2 axis. Instead, a reversible growth arrest is induced that can be overcome by reoxygenation. Impairment of mTOR signaling also interfered with the senescence response of hypoxic HPV-positive cancer cells toward prosenescent chemotherapy in vitro. Collectively, these findings indicate that hypoxic HPV-positive cancer cells can induce a reversible state of dormancy, with decreased viral antigen synthesis and increased therapeutic resistance, and may serve as reservoirs for tumor recurrence on reoxygenation. PMID:28115701

  7. ANTI-TUMOR ACTIVITY AND IMMUNE RESPONSES INDUCED BY HUMAN CANCER-ASSOCIATED MUCIN CORE PEPTIDE

    Institute of Scientific and Technical Information of China (English)

    Ma Yunguo; Yuan Mei; Fei Lihua; Li Li

    1998-01-01

    Objective: To investigate the immune responses induced by apomucin which is a mixture of mucin core peptide, in mice for elucidating the role of mucin core peptide in the modulation of cancers. Methods:Apomucin was isolated from human pancreatic cancer cell line SW1990. The mice were immunized with this apomucin (10μg/time×6) plus DETOX. Results: When immunized, all mice developed delayed-type hypersensitivity (DTH) after challenged with apomucin or synthetic peptide MUC-2 or MUC-3, while the mice immunized with apomucin alone did not develop DTH.No antibodies were detected by ELISA after immunization. When the spleen cells of vaccinated mice were cocultured with this apomucin (10-50μg/ml) and rhIL-2(50U/ml) in vitro, the proliferated lymphocytes showed cytotoxicity against human cancer cells, including colon cancer, gastric cancer, pancreatic cancer and leukemia as measured by Cr-51 release assay. Antibodies against MUC-2 and MUC-3 could block the cytotoxicity. Conclusion: It was identified that a vaccine combined of apomucin and immune adjuvant DETOX can induce cellular immune response and anti-tumor cytotoxicity in mice.

  8. Validation of the Turkish Cervical Cancer and Human Papilloma Virus Awareness Questionnaire.

    Science.gov (United States)

    Özdemir, E; Kısa, S

    2016-09-01

    The aim of this study was to determine the validity and reliability of the 'Cervical Cancer and Human Papilloma Virus Awareness Questionnaire' among fertility age women by adapting the scale into Turkish. Cervical cancer is the fourth most commonly form seen among women. Death from cervical cancer ranks third among causes and is one of the most preventable forms of cancer. This cross-sectional study included 360 women from three family health centres between January 5 and June 25, 2014. Internal consistency showed that the Kuder-Richardson 21 reliability coefficient in the first part was 0.60, Cronbach's alpha reliability coefficient was 0.61 in the second part. The Kaiser-Meyer-Olkin value of the items on the scale was 0.712. The Barlett test was significant. The confirmatory factor analysis indicated that the model matched the data adequately. This study shows that the Turkish version of the instrument is a valid and reliable tool to evaluate knowledge, perceptions and preventive behaviours of women regarding human papilloma virus and cervical cancer. Nurses who work in the clinical and primary care settings need to screen, detect and refer women who may be at risk from cervical cancer. © 2016 International Council of Nurses.

  9. A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs

    Directory of Open Access Journals (Sweden)

    Maria Isabel Carvalho

    2016-01-01

    Full Text Available Infiltrating cells of the immune system are widely accepted to be generic constituents of tumor microenvironment. It has been well established that the development of mammary cancer, both in humans and in dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cells seem to exhibit exclusive phenotypic and functional characteristics and mammary cancer cells can take advantage of signaling molecules released by them. Cancer related inflammation has an important role in mammary carcinogenesis, contributing to the acquisition of core hallmark capabilities that allow cancer cells to survive, proliferate, and disseminate. Indeed, recent studies in human breast cancer and in canine mammary tumors have identified a growing list of signaling molecules released by inflammatory cells that serve as effectors of their tumor-promoting actions. These include the COX-2, the tumor EGF, the angiogenic VEGF, other proangiogenic factors, and a large variety of chemokines and cytokines that amplify the inflammatory state. This review describes the intertwined signaling pathways shared by T-lymphocytic/macrophage infiltrates and important tissue biomarkers in both human and dog mammary carcinogenesis.

  10. A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs.

    Science.gov (United States)

    Carvalho, Maria Isabel; Silva-Carvalho, Ricardo; Pires, Isabel; Prada, Justina; Bianchini, Rodolfo; Jensen-Jarolim, Erika; Queiroga, Felisbina L

    2016-01-01

    Infiltrating cells of the immune system are widely accepted to be generic constituents of tumor microenvironment. It has been well established that the development of mammary cancer, both in humans and in dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cells seem to exhibit exclusive phenotypic and functional characteristics and mammary cancer cells can take advantage of signaling molecules released by them. Cancer related inflammation has an important role in mammary carcinogenesis, contributing to the acquisition of core hallmark capabilities that allow cancer cells to survive, proliferate, and disseminate. Indeed, recent studies in human breast cancer and in canine mammary tumors have identified a growing list of signaling molecules released by inflammatory cells that serve as effectors of their tumor-promoting actions. These include the COX-2, the tumor EGF, the angiogenic VEGF, other proangiogenic factors, and a large variety of chemokines and cytokines that amplify the inflammatory state. This review describes the intertwined signaling pathways shared by T-lymphocytic/macrophage infiltrates and important tissue biomarkers in both human and dog mammary carcinogenesis.

  11. Serological proteome analysis of dogs with breast cancer unveils common serum biomarkers with human counterparts.

    Science.gov (United States)

    Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi; Rahbarghazi, Reza

    2014-03-01

    Canine mammary tumor is being touted as a model for investigating the human breast cancer. Breast cancer of the both species has similar biological behavior, histopathologic characteristics, and metastatic pattern. In this study, we used the serological proteome analysis to detect autoantigens that elicit a humoral response in dogs with mammary tumor in order to identify serum biomarkers with potential usefulness as diagnostic markers and to better understand molecular mechanisms underlying canine breast cancer development. Protein extract from a cell line was subject to 2DE followed by Western blotting using sera from 15 dogs with mammary tumor and sera from 15 healthy control dogs. Immunoreactive autoantigens were subsequently identified by the MALDI-TOF MS. Four autoantigens, including manganese-superoxide dismutase, triose phosphate isomerase, alpha-enolase, and phosphoglycerate mutase1, with significantly higher immunoreactivity in the tumor samples than in the normal samples were identified as biomarker candidates. Immunohistochemistry and Western blotting revealed higher expression of these biomarkers in the malignant tumors than in the normal or benign tumors. The autoantigens found in this study have been reported to elicit autoantibody response in the human breast cancer, indicating the similarity of breast cancer proteome profile in dogs with that in human beings.

  12. The spectrum of SWI/SNF mutations, ubiquitous in human cancers.

    Directory of Open Access Journals (Sweden)

    A Hunter Shain

    Full Text Available SWI/SNF is a multi-subunit chromatin remodeling complex that uses the energy of ATP hydrolysis to reposition nucleosomes, thereby modulating gene expression. Accumulating evidence suggests that SWI/SNF functions as a tumor suppressor in some cancers. However, the spectrum of SWI/SNF mutations across human cancers has not been systematically investigated. Here, we mined whole-exome sequencing data from 24 published studies representing 669 cases from 18 neoplastic diagnoses. SWI/SNF mutations were widespread across diverse human cancers, with an excess of deleterious mutations, and an overall frequency approaching TP53 mutation. Mutations occurred most commonly in the SMARCA4 enzymatic subunit, and in subunits thought to confer functional specificity (ARID1A, ARID1B, PBRM1, and ARID2. SWI/SNF mutations were not mutually-exclusive of other mutated cancer genes, including TP53 and EZH2 (both previously linked to SWI/SNF. Our findings implicate SWI/SNF as an important but under-recognized tumor suppressor in diverse human cancers, and provide a key resource to guide future investigations.

  13. 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.

  14. [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.

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. 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

  20. 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 ...

  1. 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

  2. Prevalence of Arcobacter spp. in humans, animals and foods of animal origin including sea food from India.

    Science.gov (United States)

    Patyal, A; Rathore, R S; Mohan, H V; Dhama, K; Kumar, A

    2011-10-01

    The present study reports the prevalence of Arcobacter, an emerging pathogen in human, animals and foods of animal origin in India. A total of 600 samples from various sources, viz. diarrhoeal stools of humans and dogs, faecal swabs of animals (pig, poultry), preputial washings of breeding bulls and food samples (chicken, pork, fish) were examined for presence of Arcobacter spp. Using cultural methods, a total of 63 Arcobacter spp. were isolated of 600 (10.50%) samples with highest isolation rate were from pig faeces (21.33%) followed by sea foods (17.33%), poultry faeces (14.67%), pork (16.00%), chicken meat (12.00%) and human stools (2.67%). The isolates were confirmed as arcobacters by genus-based PCR. PCR screening of all the enriched samples revealed the overall prevalence of Arcobacter spp. to be 12.00% with highest in pig (25.33%), followed by sea food (21.33%), poultry (17.33%), pork (16%), chicken meat (12%) and human stools (4.00%). No Arcobacter spp. was isolated or detected from diarrhoeal faecal samples of dogs and preputial washings. With multiplex PCR, three different species were detected (A. butzleri, A. cryaerophilus and A. skirrowii) with most of the samples showing mixed infections. There are only two recent reports from India; one with cultural isolation and another with PCR detection of Arcobacter spp. in stool samples of humans with clinical diarrhoea. In this context, our present report is the first report of isolation and detection of Arcobacter spp. from various sources of animals and foods including diarrhoeic human stool samples, utilizing both cultural and molecular tools identifying arcobacters at genus and species level. These results support the importance of arcobacters as an emerging food-borne pathogen, possessing zoonotic potential.

  3. 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.

  4. HIF induces human embryonic stem cell markers in cancer cells.

    Science.gov (United States)

    Mathieu, Julie; Zhang, Zhan; Zhou, Wenyu; Wang, Amy J; Heddleston, John M; Pinna, Claudia M A; Hubaud, Alexis; Stadler, Bradford; Choi, Michael; Bar, Merav; Tewari, Muneesh; Liu, Alvin; Vessella, Robert; Rostomily, Robert; Born, Donald; Horwitz, Marshall; Ware, Carol; Blau, C Anthony; Cleary, Michele A; Rich, Jeremy N; Ruohola-Baker, Hannele

    2011-07-01

    Low oxygen levels have been shown to promote self-renewal in many stem cells. In tumors, hypoxia is associated with aggressive disease course and poor clinical outcomes. Furthermore, many aggressive tumors have been shown to display gene expression signatures characteristic of human embryonic stem cells (hESC). We now tested whether hypoxia might be responsible for the hESC signature observed in aggressive tumors. We show that hypoxia, through hypoxia-inducible factor (HIF), can induce an hESC-like transcriptional program, including the induced pluripotent stem cell (iPSC) inducers, OCT4, NANOG, SOX2, KLF4, cMYC, and microRNA-302 in 11 cancer cell lines (from prostate, brain, kidney, cervix, lung, colon, liver, and breast tumors). Furthermore, nondegradable forms of HIFα, combined with the traditional iPSC inducers, are highly efficient in generating A549 iPSC-like colonies that have high tumorigenic capacity. To test potential correlation between iPSC inducers and HIF expression in primary tumors, we analyzed primary prostate tumors and found a significant correlation between NANOG-, OCT4-, and HIF1α-positive regions. Furthermore, NANOG and OCT4 expressions positively correlated with increased prostate tumor Gleason score. In primary glioma-derived CD133 negative cells, hypoxia was able to induce neurospheres and hESC markers. Together, these findings suggest that HIF targets may act as key inducers of a dynamic state of stemness in pathologic conditions.

  5. Telomerase efficiently elongates highly transcribing telomeres in human cancer cells.

    Directory of Open Access Journals (Sweden)

    Benjamin O Farnung

    Full Text Available RNA polymerase II transcribes the physical ends of linear eukaryotic chromosomes into a variety of long non-coding RNA molecules including telomeric repeat-containing RNA (TERRA. Since TERRA discovery, advances have been made in the characterization of TERRA biogenesis and regulation; on the contrary its associated functions remain elusive. Most of the biological roles so far proposed for TERRA are indeed based on in vitro experiments carried out using short TERRA-like RNA oligonucleotides. In particular, it has been suggested that TERRA inhibits telomerase activity. We have exploited two alternative cellular systems to test whether TERRA and/or telomere transcription influence telomerase-mediated telomere elongation in human cancer cells. In cells lacking the two DNA methyltransferases DNMT1 and DNMT3b, TERRA transcription and steady-state levels are greatly increased while telomerase is able to elongate telomeres normally. Similarly, telomerase can efficiently elongate transgenic inducible telomeres whose transcription has been experimentally augmented. Our data challenge the current hypothesis that TERRA functions as a general inhibitor of telomerase and suggest that telomere length homeostasis is maintained independently of TERRA and telomere transcription.

  6. Neoplastic human embryonic stem cells as a model of radiation resistance of human cancer stem cells.

    Science.gov (United States)

    Dingwall, Steve; Lee, Jung Bok; Guezguez, Borhane; Fiebig, Aline; McNicol, Jamie; Boreham, Douglas; Collins, Tony J; Bhatia, Mick

    2015-09-08

    Studies have implicated that a small sub-population of cells within a tumour, termed cancer stem cells (CSCs), have an enhanced capacity for tumour formation in multiple cancers and may be responsible for recurrence of the disease after treatment, including radiation. Although comparisons have been made between CSCs and bulk-tumour, the more important comparison with respect to therapy is between tumour-sustaining CSC versus normal stem cells that maintain the healthy tissue. However, the absence of normal known counterparts for many CSCs has made it difficult to compare the radiation responses of CSCs with the normal stem cells required for post-radiotherapy tissue regeneration and the maintenance of tissue homeostasis. Here we demonstrate that transformed human embryonic stem cells (t-hESCs), showing features of neoplastic progression produce tumours resistant to radiation relative to their normal counterpart upon injection into immune compromised mice. We reveal that t-hESCs have a reduced capacity for radiation induced cell death via apoptosis and exhibit altered cell cycle arrest relative to hESCs in vitro. t-hESCs have an increased expression of BclXL in comparison to their normal counterparts and re-sensitization of t-hESCs to radiation upon addition of BH3-only mimetic ABT737, suggesting that overexpression of BclXL underpins t-hESC radiation insensitivity. Using this novel discovery platform to investigate radiation resistance in human CSCs, our study indicates that chemotherapy targeting Bcl2-family members may prove to be an adjuvant to radiotherapy capable of targeting CSCs.

  7. VI-14, a novel flavonoid derivative, inhibits migration and invasion of human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fanni; Li, Chenglin; Zhang, Haiwei; Lu, Zhijian [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China); Li, Zhiyu; You, Qidong [Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Lu, Na [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China); Guo, Qinglong, E-mail: anticancer_drug@yahoo.com.cn [State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009 (China)

    2012-06-01

    It has been well characterized that flavonoids possess pronounced anticancer potentials including anti-angiogenesis, anti-metastasis, and pro-apoptosis. Herein, we report, for the first time, that VI-14, a novel flavonoid derivative, possesses anti-cancer properties. The purpose of this study is to investigate the anti-migration and anti-invasion activities of VI-14 in breast cancer cells. Our data indicate that VI-14 inhibits adhesion, migration and invasion of MDA-MB-231 and MDA-MB-435 human breast cancer cells. MDA-MB-231 cells treated with VI-14 display reduced activities and expressions of ECM degradation-associated proteins including matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) at both the protein and mRNA levels. Meanwhile, VI-14 treatment induces an up-regulated expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and 2 (TIMP-2) in MDA-MB-231 cells. Western blotting results show that phosphorylation levels of critical components of the MAPK signaling pathway, including ERK, JNK and P38, are dramatically decreased in VI-14-treated MDA-MB-231 cells. Furthermore, treatment of VI-14 significantly decreases the nuclear levels and the binding ability of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). Taken together, our data suggest that VI-14 treatment suppresses migration and motility of breast cancer cells, and VI-14 may be a potential compound for cancer therapy. Highlights: ► We report for the first time that VI-14 possesses anti-cancer properties. ► VI-14 weakens the adhesion, migration and invasion of human breast cancer cells. ► VI-14 decreases the activities and expressions of MMP-2/9. ► VI-14 suppresses the phosphorylation levels of the MAPK signaling pathway. ► VI-14 decreases the nuclear levels and the binding ability of NF-κB and AP-1.

  8. Effects of ovarian cancer G protein coupled receptor 1 on the proliferation, migration, and adhesion of human ovarian cancer cells

    Institute of Scientific and Technical Information of China (English)

    REN Juan; ZHANG Long

    2011-01-01

    Background OGR1 was found as a G-protein coupled receptor (GPCR) and proton sensor. Our previous studies have found that OGR1 has inhibitory effect on the metastasis of prostate cancer. In order to investigate the roles of OGR1 gene in the biological activities of ovarian cancer, we studied the OGR1 effects on ovarian cancer cells, HEY cells.Methods OGR1 gene was transfected into HEY cell, in which endogenous expression is low. OGR1-overxepressed cells and vector-transfected cells were compared in different assays. Western blotting was employed to confirm the high expression level of OGR1. Cell proliferation was determined by MTT assay and cell doubling time assay. Cell migration assay (transwell assay) and cell adhesion assay were performed to determine the migration and adhesion potential of cells. Student's t test was employed for statistical analysis.Results Proliferation of OGR1-overexpressed cells was significantly reduced (P <0.01); cell migration was significantly inhibited in the OGR1-transfected cells (P <0.01); cell adhesion to extracellular matrix including fibronectin, vitronectin,collagen Ⅰ/Ⅳ was significantly increased (P <0.01).Conclusions OGR1 expression in human ovarian cancer cells significantly inhibited the cell proliferation and migration,but significantly enhanced cell adhesion to the extracellular matrix. It indicated that OGR1 may be a tumor suppressor gene for ovarian cancer.

  9. 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.

  10. Mutations of p53 gene exons 4-8 in human esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Li-Ya Li; Jin-Tian Tang; Li-Qun Jia; Pei-Wen Li

    2005-01-01

    AIM: To characterize the tumor suppressor gene p53 mutations in exon 4, esophageal cancer and adjacent noncancerous tissues.METHODS: We performed p53 (exons 4-8) gene mutation analysis on 24 surgically resected human esophageal cancer specimens by PCR, single-strand conformation polymorphism, and DNA sequencing. RESULTS: p53 gene mutations were detected in 9 of 22 (40.9%) esophageal cancer specimens and 10 of 17 (58.8%) adjacent non-cancerous tissues. Eight of sixteen (50.0%) point mutations detected were G-A transitions and 9 of 18 (50.0%) p53 gene mutations occurred in exon 4 in esophageal cancer specimens. Only 1 of 11 mutations detected was G-A transition and 4 of 11 (36.4%) p53 gene mutations occurred in exon 4 in adjacent non-cancerous tissues.CONCLUSION: Mutation of p53 gene in exon 4 may play an important role in development of esophageal cancer. The observation of p53 gene mutation in adjacent noncancerous tissues suggests that p53 gene mutation may be an early event in esophageal carcinogenesis. Some clinical factors, including age, sex, pre-operation therapy and location of tumors, do not influence p53 gene mutation rates.

  11. Activation of miR-9 by human papillomavirus in cervical cancer.

    Science.gov (United States)

    Liu, Weijun; Gao, Ge; Hu, Xiaoxia; Wang, Yuhui; Schwarz, Julie K; Chen, Jason J; Grigsby, Perry W; Wang, Xiaowei

    2014-11-30

    Cervical cancer is the third most common cancer in women worldwide, leading to about 300,000 deaths each year. Most cervical cancers are caused by human papillomavirus (HPV) infection. However, persistent transcriptional activity of HPV oncogenes, which indicates active roles of HPV in cervical cancer maintenance and progression, has not been well characterized. Using our recently developed assays for comprehensive profiling of HPV E6/E7 transcripts, we have detected transcriptional activities of 10 high-risk HPV strains from 87 of the 101 cervical tumors included in the analysis. These HPV-positive patients had significantly better survival outcome compared with HPV-negative patients, indicating HPV transcriptional activity as a favorable prognostic marker for cervical cancer. Furthermore, we have determined microRNA (miRNA) expression changes that were correlated with tumor HPV status. Our profiling and functional analyses identified miR-9 as the most activated miRNA by HPV E6 in a p53-independent manner. Further target validation and functional studies showed that HPV-induced miR-9 activation led to significantly increased cell motility by downregulating multiple gene targets involved in cell migration. Thus, our work helps to understand the molecular mechanisms as well as identify potential therapeutic targets for cervical cancer and other HPV-induced cancers.

  12. Optical redox imaging indices discriminate human breast cancer from normal tissues

    Science.gov (United States)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2016-11-01

    Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (pcancerous tissues (pcancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients.

  13. RELATIONSHIP BETWEEN TELOMERE LENGTH AND RADIOSENSITIVITY IN VARIOUS HUMAN CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    CAO Zhen; ZHOU Yun-feng; LUO Zhi-guo; XIAO Chuang-ying; DAI Jing; PAN Dong-feng; ZHOU Fu-xiang; XIE Cong-hua; ZHANG Gong; LIU Shi-quan

    2005-01-01

    Objective: To investigate the relationship between telomere length and radiosensitivity in various human cancer cell lines with the expectation to find a valid and common predictor of radiosensitivity for different cancers. Methods: Eight human cancer cell lines were used, including five human breast cancer cell lines (ZR-75-30, MCF-7, MDA-MB-435S, T-47-D,F539-1590), two human larynx squamous carcinoma cell lines (Hep-2 and Hep-2R) and a human malignant glioma cell line(U251). Among them, the radioresistant cell line Hep-2R was isolated and established from a radiosensitive human larynx squamous carcinoma cell line Hep-2 by our center. The radiobiological characteristics of the eight lines were analyzed by the method of colony-forming assay and the radiosensitivity parameters were calculated. Telomere length was analyzed by TRF(mean Telomere Restriction Fragments) length assay. Results: The radioresistance of Hep-2R cell line proved to be stable in long-term passaged cultures as well as in frozen samples. Radiosensitivity parameters are different among those lines. The SF2 values of Hep-2 and U251 are 0.4148 and 0.7520, respectively; The SF2 values of breast cancer cell lines are between those of Hep-2 and U251. The TRF of Hep-2R is 11.12Kb, longer than three times that of its parental counterpart. There is a positive correlation both between SF2 and TRF (r=0.786, P<0.05), and between Do and TRF (r=0.905, P<0.01). Conclusion:It is concluded that radiosensitivity and telomere length (TRF) are negatively correlated, TRF could be a valid predictor for radiosensitivity.

  14. Increased expression of class III β-tubulin in castration-resistant human prostate cancer

    OpenAIRE

    Terry, S; Ploussard, G.; Allory, Y; Nicolaiew, N; Boissière-Michot, F; Maillé, P; Kheuang, L; Coppolani, E; Ali, A.; Bibeau, F; Culine, S; Buttyan, R; de la Taille, A; Vacherot, F

    2009-01-01

    Background: Class III β-tubulin (βIII-tubulin) is expressed in tissues of neuronal lineage and also in several human malignancies, including non-small-cell lung carcinoma, breast and ovarian cancer. Overexpression of βIII-tubulin in these tumours is associated with an unfavourable outcome and resistance to taxane-based therapies. At present, βIII-tubulin expression remains largely uncharacterised in prostate cancer. Methods: In this report, we evaluated the expression of βIII-tubulin in 138 d...

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

    Directory of Open Access Journals (Sweden)

    MUÑOZ NUBIA

    1997-01-01

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

  16. Effects of ambient particulate matter on human breast cancer: is xenogenesis responsible?

    Directory of Open Access Journals (Sweden)

    Qiang Huo

    Full Text Available BACKGROUND: Recently, evidence from several studies has revealed that air pollution is associated with the increased morbidity and mortality of breast cancer patients. However, to date, the underlying mechanism remains largely unclear. Considering the high prevalence of air pollution and breast cancer in China, it is necessary to understand how air pollution may affect breast cancer. METHODS: We analyzed 1,832 female patients who had resided in the same cities for at least 10 years prior to their diagnosis. Variables including demographic data as well as clinical and tumor characteristics, including the patient's age at menarche, family history of breast cancer, tumor histopathological type, tumor size, lymph node metastasis, distant metastasis, histological grade, estrogen receptor (ER status, progesterone receptor (PR status and human epidermal growth factor receptor 2 (HER-2 status at the time of diagnosis were analyzed. RESULTS: Compared to patients residing in low-pollution areas, patients living in high-pollution areas demonstrated a younger age at menarche (p<0.001, a greater family history of breast cancer (p = 0.034 and more invasive cancers (p = 0.028 with higher tumor grades (p = 0.028 and estrogen receptor (ER-positive status (p = 0.022. Differences in tumor grade were only found in ER-positive cases. CONCLUSIONS: Our findings and clinical data indicate that long-term air pollution exposure may contribute to the development of breast cancer by playing the role of a xenoestrogen, and also provides new insight into the association between air pollution and the morbidity and mortality of breast cancer patients. Furthermore, it is urgently necessary to study the association between air pollution and breast cancer to improve the living quality and health of females, and applicable public health strategies may need to be established or modified as soon as possible.

  17. Human papillomavirus types detected in skin warts and cancer differ in their transforming properties but commonly counteract UVB induced protective responses in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Shterzer, Naama; Heyman, Dariya; Shapiro, Beny; Yaniv, Abraham; Jackman, Anna [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Serour, Francis [Department of Pediatric Surgery, The E. Wolfson Medical Center, Holon (Israel); Chaouat, Malka [Laboratory of Experimental Surgery, Hadassah University Hospital, Ein Karem, Jerusalem (Israel); Gonen, Pinhas [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Tommasino, Massimo [International Agency for Research on Cancer, World Health Organization, Lyon (France); Sherman, Levana [Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv (Israel)

    2014-11-15

    In the present study, E6E7 and E6 proteins of human papillomaviruses (HPVs) associated with skin warts and cancer were compared for their transforming and carcinogenic abilities in primary human keratinocytes (PHKs). We show that E6E7 of cancer associated beta HPV types, notably 49 and 24, were able to extend the life span and enhance the clonogenic efficiency of PHKs when maintained in serum free/low calcium medium. Activities of the beta HPV E6E7 were lower than those of HPV16 E6E7. In contrast, E6 proteins from HPV types detected in skin warts or cancer, notably 10, 49 and 38, attenuated UVB induced protective responses in PHKs including cell death, proliferation arrest and accumulation of the proapoptotic proteins, p53, bax or bak. Together, this investigation revealed functional differences and commonalities between HPVs associated with skin warts and cancer, and allowed the identification of specific properties of beta HPVs supporting their involvement in skin carcinogenesis. - Highlights: • Primary keratinocytes were used to evaluate transforming and carcinogenic abilities of cutaneous HPVs. • E6E7 of cancer associated β HPV types transform primary human keratinocytes. • E6 proteins of cancer and wart associated HPVs inhibit UVB induced cell death. • E6s of cancer and wart associated HPVs attenuate UVB induced proliferation arrest. • E6s of cancer and wart associated HPVs attenuate UVB induced apoptosis signaling.

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

    Directory of Open Access Journals (Sweden)

    Shinya Akatsuka

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

  19. Multiple primary malignancies including colon, stomach, lung, breast, and liver cancer: a case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Nien-Chih Hu; Shih-Chung Hsieh; Tong-Jong Chen; Jun-Yih Chang

    2009-01-01

    @@ Multiple primary malignancies in a single patient are relatively rare but have increase in frequency in recent decades. This may be a result of medical advancements in diagnostic and therapeutic strategies, a possible effect of new carcinogens in the industrial environment, and longer life span allowing another primary cancer to develop. Among those with multiple primary malignancies, double cancer is commonly seen, while triple cancers occur in 0.5% of patients, and quadruple or quintuple cancers occur in only less than 0.1% of the population.~1 This report describes a rare case of a patient with five metachronous primary malignancies. The time interval between each of the malignancies is more than 2 years. Literatures about at least four primary malignancies are also discussed.

  20. Compound MMH01 possesses toxicity against human leukemia and pancreatic cancer cells.

    Science.gov (United States)

    Chen, Yu-Jen; Chou, Cheng-Jen; Chang, Tun-Tschu

    2009-04-01

    MMH01 is a compound isolated from Antrodia cinnamomea. MMH01 markedly inhibited growth of human leukemia U937 and pancreatic cancer BxPC3 cells. It resulted in distinct patterns of cell cycle distribution in U937 (G2/M, sub-G1 and polyploidy) and BxPC3 cells (G0/G1 and sub-G1). The modes of cell death in U937 cells include apoptosis and mitotic catastrophe, whereas apoptosis-associated events or necrosis in BxPC3 cells. Neither mitochondrial membrane permeabilization nor caspase dependence was noted. Proteins involving mitotic catastrophe-associated cell death such as cyclin B1 and checkpoint kinase 2 were activated in U937 cells. Only slight to moderate viability inhibition was noted to human monocytes, the normal counterpart of these myeloid leukemic cells. In conclusion, MMH01 possesses cytotoxicity against human leukemia and pancreatic cancer cells.

  1. Anticancer actions of PPARγ ligands:Current state and future perspectives in human lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jesse; Roman

    2010-01-01

    Peroxisome proliferator-activated receptors(PPARs) are ligand-dependent nuclear transcription factors and members of the nuclear receptor superfamily.Of the three PPARs identified to date(PPARγ,PPARβ/δ,and PPARα),PPARγ has been studied the most,in part because of the availability of PPARγagonists(also known as PPARγ ligands)and its significant effects on the management of several human diseases including type 2 diabetes,metabolic syndrome,cardiovascular disease and cancers.PPARγ is expressed in many tumors including lung cancer,and its function has been linked to the process of lung cancer development, progression and metastasis.Studies performed in gynogenic and xenograft models of lung cancer showed decreased tumor growth and metastasis in animals treated with PPARγ ligands.Furthermore,data are emerging from retrospective clinical studies that suggest a protective role for PPARγ ligands on the incidence of lung cancer.This review summarizes the research being conducted in this area and focuses on the mechanisms and potential therapeutic effects of PPARγ ligands as a novel anti-lung cancer treatment strategy.

  2. Study protocol: rehabilitation including social and physical activity and education in children and teenagers with cancer (RESPECT)

    OpenAIRE

    Thorsteinsson, Troels; Helms, Anne Sofie; Adamsen, Lis; Andersen, Lars Bo; Andersen, Karen Vitting; Christensen, Karl Bang; Halse, Henrik; Heilmann, Carsten; Hejgaard, Nete; Johansen, Christoffer; Madsen, Marianne; Madsen, Svend Aage; Simovska, Venka; Strange, Birgit; Thing, Lone Friis

    2013-01-01

    Background During cancer treatment children have reduced contact with their social network of friends, and have limited participation in education, sports, and leisure activities. During and following cancer treatment, children describe school related problems, reduced physical fitness, and problems related to interaction with peers. Methods/design The RESPECT study is a nationwide population-based prospective, controlled, mixed-methods intervention study looking at children aged 6-18 years n...

  3. Regulation of the Proliferation of Colon Cancer Cells by Compounds that Affect Glycolysis, Including 3-Bromopyruvate, 2-Deoxyglucose and Biguanides

    OpenAIRE

    Lea, Michael A.; Qureshi, Mehreen S.; Buxhoeveden, Michael; Gengel, Nicolette; Kleinschmit, Jessica; desBordes, Charles

    2013-01-01

    In previous studies we observed that 2-deoxyglucose blocked the acidification of the medium used for culture of colon cancer cells caused by incubation with biguanides and had an additive inhibitory effect on growth. In the present work, we found that 3-bromopyruvate can also prevent the lowering of pH caused by biguanide treatment. 3-Bromopyruvate inhibited colonic cancer cell proliferation but the effect was not always additive to that of biguanides and an additive effect was more notable i...

  4. 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.

  5. Human breast biomonitoring and environmental chemicals: use of breast tissues and fluids in breast cancer etiologic research.

    Science.gov (United States)

    LaKind, Judy S; Wilkins, Amy A; Bates, Michael N

    2007-09-01

    Extensive research indicates that the etiology of breast cancer is complex and multifactorial and may include environmental risk factors. Breast cancer etiology and exposure to xenobiotic compounds, diet, electromagnetic fields, and lifestyle have been the subject of numerous scientific inquiries, but research has yielded inconsistent results. Biomonitoring has been used to explore associations between breast cancer and levels of environmental chemicals in the breast. Research using breast tissues and fluids to cast light on the etiology of breast cancer is, for the most part, predicated on the assumption that the tissue or fluid samples either contain measurable traces of the environmental agent(s) associated with the cancer or that they retain biological changes that are biomarkers of such exposure or precursors of carcinogenic effect. In this paper, we review breast cancer etiology research utilizing breast biomonitoring. We first provide a brief synopsis of the current state of understanding of associations between exposure to environmental chemicals and breast cancer etiology. We then describe the published breast cancer research on tissues and fluids, which have been used for biomonitoring, specifically human milk and its components, malignant and benign breast tissue, nipple aspirate fluid (NAF) and breast cyst fluid. We conclude with a discussion on recommendations for biomonitoring of breast tissues and fluids in future breast cancer etiology research. Both human milk and NAF fluids, and the cells contained therein, hold promise for future biomonitoring research into breast cancer etiology, but must be conducted with carefully delineated hypotheses and a scientifically supportable epidemiological approach.

  6. 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.

  7. Cancer genes hypermethylated in human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Vincenzo Calvanese

    Full Text Available Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation.

  8. Value of the small cohort study including a physical examination for minor structural defects in identifying new human teratogens.

    Science.gov (United States)

    Chambers, Christina D

    2011-03-01

    Most known human teratogens are associated with a unique or characteristic pattern of major and minor malformations and this pattern helps to establish the causal link between the teratogenic exposure and the outcome. Although traditional case-control and cohort study designs can help identify potential teratogens, there is an important role for small cohort studies that include a dysmorphological examination of exposed and unexposed infants for minor structural defects. In combination with other study design approaches, the small cohort study with a specialized physical examination fulfills a necessary function in screening for new potential teratogens and can help to better delineate the spectrum and magnitude of risk for known teratogens.

  9. Benzyl isothiocyanate inhibits epithelial-mesenchymal transition in cultured and xenografted human breast cancer cells.

    Science.gov (United States)

    Sehrawat, Anuradha; Singh, Shivendra V

    2011-07-01

    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 show, for the first time, that BITC inhibits epithelial-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 line (PL-45) to BITC resulted in upregulation of epithelial markers (e.g., E-cadherin and/or occludin) with a concomitant decrease in protein levels of mesenchymal markers, including vimentin, fibronectin, snail, and/or c-Met. The BITC-mediated induction of E-cadherin protein was accompanied by an increase in its transcription, whereas BITC-treated MDA-MB-231 cells exhibited suppression of vimentin, snail, and slug mRNA levels. Experimental EMT induced by exposure to TGFβ and TNFα or Rb knockdown in a spontaneously immortalized nontumorigenic human mammary epithelial cell line (MCF-10A) was also partially reversed by BITC treatment. The TGFβ-/TNFα-induced migration of MCF-10A cells was inhibited in the presence of BITC, which was partially attenuated by RNA interference of E-cadherin. Inhibition of MDA-MB-231 xenograft growth in vivo in female athymic mice by BITC administration was associated with an increase in protein level of E-cadherin and suppression of vimentin and fibronectin protein expression. In conclusion, this study reports a novel anticancer effect of BITC involving inhibition of EMT, a process triggered during progression of cancer to invasive state.

  10. 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...

  11. 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 ...

  12. A meta-analysis of the relationship between glutathione S-transferase T1 null/presence gene polymorphism and the risk of lung cancer including 31802 subjects.

    Science.gov (United States)

    Zhou, Hua-Fu; Feng, Xu; Zheng, Bao-Shi; Qian, Jun; He, Wei

    2013-10-01

    The relationship between glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between GSTT1 null/presence gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on July 1, 2012, and eligible investigations were included and synthesized using meta-analysis method. 51 reports were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 15,140 patients with lung cancer and 16,662 controls. There was a marked association between GSTT1 null genotype and lung cancer risk in overall populations (OR = 1.15, 95 % CI 1.04-1.27, P = 0.007). Furthermore, GSTT1 null genotype was associated with the lung cancer risk in Asians (OR = 1.47, 95 % CI 1.23-1.76, P null genotype was not associated with the risk of lung cancer in Caucasians, Brazilian population and Africans. In conclusion, GSTT1 null genotype is associated with the lung cancer in overall populations and in Asians.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Gene Therapy of Human Breast Cancer

    Science.gov (United States)

    1996-10-01

    1987. Partial characterization of chicken spleen cell culture supernatants stimulated with Staphylococcus aureus. Developmental & Comparative...Immunology 1 1: 191. 8. Schoof, D. D., and C. H. Tempelis. 1 986. The role of soluble protein A in chicken spleen cell activation. Developmental...promoter upstream of the neomycin phosphotransferase gene. No other eukarjotic genes are expressed. Other sequences include an intron and poly(A) site

  18. Prevention of HPV-related cancers in Norway: cost-effectiveness of expanding the HPV vaccination program to include pre-adolescent boys.

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    Emily A Burger

    Full Text Available BACKGROUND: Increasingly, countries have introduced female vaccination against human papillomavirus (HPV, causally linked to several cancers and genital warts, but few have recommended vaccination of boys. Declining vaccine prices and strong evidence of vaccine impact on reducing HPV-related conditions in both women and men prompt countries to reevaluate whether HPV vaccination of boys is warranted. METHODS: A previously-published dynamic model of HPV transmission was empirically calibrated to Norway. Reductions in the incidence of HPV, including both direct and indirect benefits, were applied to a natural history model of cervical cancer, and to incidence-based models for other non-cervical HPV-related diseases. We calculated the health outcomes and costs of the different HPV-related conditions under a gender-neutral vaccination program compared to a female-only program. RESULTS: Vaccine price had a decisive impact on results. For example, assuming 71% coverage, high vaccine efficacy and a reasonable vaccine tender price of $75 per dose, we found vaccinating both girls and boys fell below a commonly cited cost-effectiveness threshold in Norway ($83,000/quality-adjusted life year (QALY gained when including vaccine benefit for all HPV-related diseases. However, at the current market price, including boys would not be considered 'good value for money.' For settings with a lower cost-effectiveness threshold ($30,000/QALY, it would not be considered cost-effective to expand the current program to include boys, unless the vaccine price was less than $36/dose. Increasing vaccination coverage to 90% among girls was more effective and less costly than the benefits achieved by vaccinating both genders with 71% coverage. CONCLUSIONS: At the anticipated tender price, expanding the HPV vaccination program to boys may be cost-effective and may warrant a change in the current female-only vaccination policy in Norway. However, increasing coverage in girls is

  19. Differentiation of human influenza A viruses including the pandemic subtype H1N1/2009 by conventional multiplex PCR.

    Science.gov (United States)

    Furuse, Yuki; Odagiri, Takashi; Okada, Takashi; Khandaker, Irona; Shimabukuro, Kozue; Sawayama, Rumi; Suzuki, Akira; Oshitani, Hitoshi

    2010-09-01

    April 2009 witnessed the emergence of a novel H1N1 influenza A virus infecting the human population. Currently, pandemic and seasonal influenza viruses are co-circulating in human populations. Understanding the course of the emerging pandemic virus is important. It is still unknown how the novel virus co-circulates with or outcompetes seasonal viruses. Sustainable and detailed influenza surveillance is required throughout the world including developing countries. In the present study, a multiplex PCR using four primers was developed, which was designed to differentiate the pandemic H1N1 virus from the seasonal H1N1 and H3N2 viruses, to obtain amplicons of different sizes. Multiplex PCR analysis could clearly differentiate the three subtypes of human influenza A virus. This assay was performed using 206 clinical samples collected in 2009 in Japan. Between February and April, four samples were subtyped as seasonal H1N1 and four as seasonal H3N2. All samples collected after July were subtyped as pandemic H1N1. Currently, pandemic viruses seem to have replaced seasonal viruses almost completely in Japan. This is a highly sensitive method and its cost is low. Influenza surveillance using this assay would provide significant information on the epidemiology of both pandemic and seasonal influenza.

  20. 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.

  1. Predicting the Peritoneal Absorption of Icodextrin in Rats and Humans Including the Effect of α-Amylase Activity in Dialysate.

    Science.gov (United States)

    Akonur, Alp; Holmes, Clifford J; Leypoldt, John K

    2015-01-01

    Contrary to ultrafiltration, the three-pore model predictions of icodextrin absorption from the peritoneal cavity have not yet been reported likely, in part, due to difficulties in estimating the degradation of glucose-polymer chains by α-amylase activity in dialysate. We incorporated this degradation process in a modified three-pore model of peritoneal transport to predict ultrafiltration and icodextrin absorption simultaneously in rats and humans. Separate three-pore models were constructed for humans and rats. The model for humans was adapted from PD Adequest 2.0 including a clearance term out of the peritoneal cavity to account for the absorption of large molecules to the peritoneal tissues, and considering patients who routinely used icodextrin by establishing steady-state plasma concentrations. The model for rats employed a standard three-pore model in which human kinetic parameters were scaled for a rat based on differences in body weight. Both models described the icodextrin molecular weight (MW) distribution as five distinct MW fractions. First order kinetics was applied using degradation rate constants obtained from previous in-vitro measurements using gel permeation chromatography. Ultrafiltration and absorption were predicted during a 4-hour exchange in rats, and 9 and 14-hour exchanges in humans with slow to fast transport characteristics with and without the effect of amylase activity. In rats, the icodextrin MW profile shifted towards the low MW fractions due to complete disappearance of the MW fractions greater than 27.5 kDa. Including the effect of amylase activity (60 U/L) resulted in 21.1% increase in ultrafiltration (UF) (7.6 mL vs 6.0 mL) and 7.1% increase in icodextrin absorption (CHO) (62.5% with vs 58.1%). In humans, the shift in MW profile was less pronounced. The fast transport (H) patient absorbed more icodextrin than the slow transport (L) patient during both 14-hour (H: 47.9% vs L: 40.2%) and 9-hour (H: 37.4% vs L: 31.7%) exchanges

  2. 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.

  3. Clinical and functional aspects of microRNA regulation in human cancers

    OpenAIRE

    Caramuta, Stefano

    2012-01-01

    miRNAs are short single-stranded non-coding RNAs which regulate gene expression at the posttranscriptional level in many biological processes, including proliferation, apoptosis and differentiation. A number of studies have shown the importance of miRNAs in carcinogenesis and accumulating evidence supports their role as diagnostic and prognostic biomarkers in human cancers. Moreover, dysregulation of miRNA processing factors, which are needed for miRNA maturation, have been ...

  4. Derailing the UPS of Protein Turnover in Cancer and other Human Diseases

    Directory of Open Access Journals (Sweden)

    Jit Kong Cheong

    2013-01-01

    Full Text Available Protein modifications by the covalent linkage of ubiquitin have significant involvement in many cellular processes, including stress response, oncogenesis, viral infection, transcription, protein turnover, organelle biogenesis, DNA repair, cellular differentiation, and cell cycle control. We provide a brief overview of the fundamentals of the regulation of protein turnover by the ubiquitin-proteasome pathway and discuss new therapeutic strategies that aim to mitigate the deleterious effects of its dysregulation in cancer and other human disease pathophysiology.

  5. Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

    OpenAIRE

    Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-Hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

    2012-01-01

    Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 μM) for 24 hr induced...

  6. Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

    OpenAIRE

    Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

    2012-01-01

    Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 μM) for 24 hr induced...

  7. 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.

  8. Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites

    Directory of Open Access Journals (Sweden)

    Hofmann Alan F

    2010-05-01

    Full Text Available Abstract Background Bile salts are the major end-metabolites of cholesterol and are also important in lipid and protein digestion and in influencing the intestinal microflora. We greatly extend prior surveys of bile salt diversity in both reptiles and mammals, including analysis of 8,000 year old human coprolites and coprolites from the extinct Shasta ground sloth (Nothrotherium shastense. Results While there is significant variation of bile salts across species, bile salt profiles are generally stable within families and often within orders of reptiles and mammals, and do not directly correlate with differences in diet. The variation of bile salts generally accords with current molecular phylogenies of reptiles and mammals, including more recent groupings of squamate reptiles. For mammals, the most unusual finding was that the Paenungulates (elephants, manatees, and the rock hyrax have a very different bile salt profile from the Rufous sengi and South American aardvark, two other mammals classified with Paenungulates in the cohort Afrotheria in molecular phylogenies. Analyses of the approximately 8,000 year old human coprolites yielded a bile salt profile very similar to that found in modern human feces. Analysis of the Shasta ground sloth coprolites (approximately 12,000 years old showed the predominant presence of glycine-conjugated bile acids, similar to analyses of bile and feces of living sloths, in addition to a complex mixture of plant sterols and stanols expected from an herbivorous diet. Conclusions The bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution, with some bile salt modifications only found within single groups such as marsupials. Analysis of the evolution of bile salt structures in different species provides a potentially rich model system for the evolution of a complex biochemical pathway in vertebrates. Our results also demonstrate the stability of bile salts in coprolites

  9. Growth inhibition of pancreatic cancer cells by histone deacetylase inhibitor belinostat through suppression of multiple pathways including HIF, NFkB, and mTOR signaling in vitro and in vivo.

    Science.gov (United States)

    Chien, Wenwen; Lee, Dhong Hyun; Zheng, Yun; Wuensche, Peer; Alvarez, Rosie; Wen, Ding Ling; Aribi, Ahmed M; Thean, Su Ming; Doan, Ngan B; Said, Jonathan W; Koeffler, H Phillip

    2014-09-01

    Pancreatic ductal adenocarcinoma is a devastating disease with few therapeutic options. Histone deacetylase inhibitors are a novel therapeutic approach to cancer treatment; and two new pan-histone deacetylase inhibitors (HDACi), belinostat and panobinostat, are undergoing clinical trials for advanced hematologic malignancies, non-small cell lung cancers and advanced ovarian epithelial cancers. We found that belinostat and panobinostat potently inhibited, in a dose-dependent manner, the growth of six (AsPc1, BxPc3, Panc0327, Panc0403, Panc1005, MiaPaCa2) of 14 human pancreatic cancer cell lines. Belinostat increased the percentage of apoptotic pancreatic cancer cells and caused prominent G2 /M growth arrest of most pancreatic cancer cells. Belinostat prominently inhibited PI3K-mTOR-4EBP1 signaling with a 50% suppression of phorphorylated 4EBP1 (AsPc1, BxPc3, Panc0327, Panc1005 cells). Surprisingly, belinostat profoundly blocked hypoxia signaling including the suppression of hypoxia response element reporter activity; as well as an approximately 10-fold decreased transcriptional expression of VEGF, adrenomedullin, and HIF1α at 1% compared to 20% O2 . Treatment with this HDACi decreased levels of thioredoxin mRNA associated with increased levels of its endogenous inhibitor thioredoxin binding protein-2. Also, belinostat alone and synergistically with gemcitabine significantly (P = 0.0044) decreased the size of human pancreatic tumors grown in immunodeficiency mice. Taken together, HDACi decreases growth, increases apoptosis, and is associated with blocking the AKT/mTOR pathway. Surprisingly, it blocked hypoxic growth related signals. Our studies of belinostat suggest it may be an effective drug for the treatment of pancreatic cancers when used in combination with other drugs such as gemcitabine. © 2014 Wiley Periodicals, Inc.

  10. Regulation of the proliferation of colon cancer cells by compounds that affect glycolysis, including 3-bromopyruvate, 2-deoxyglucose and biguanides.

    Science.gov (United States)

    Lea, Michael A; Qureshi, Mehreen S; Buxhoeveden, Michael; Gengel, Nicolette; Kleinschmit, Jessica; Desbordes, Charles

    2013-02-01

    In previous studies performed by our group, we observed that 2-deoxyglucose blocked the acidification of the medium used for culture of colon cancer cells caused by incubation with biguanides and it had an additive inhibitory effect on growth. In the present work, we found that 3-bromopyruvate can also prevent the lowering of pH caused by biguanide treatment. 3-Bromopyruvate inhibited colonic cancer cell proliferation, but the effect was not always additive to that of biguanides and an additive effect was more notable in combined treatment with 3-bromopyruvate and 2-deoxyglucose. The induction of alkaline phosphatase activity by butyrate was not consistently affected by combination with other agents that modified glucose metabolism. The drug combinations that were examined inhibited proliferation of wild-type and p53-null cells and affected colonic cancer lines with different growth rates.

  11. An in vitro model that recapitulates the epithelial to mesenchymal transition (EMT in human breast cancer.

    Directory of Open Access Journals (Sweden)

    Elad Katz

    Full Text Available The epithelial to mesenchymal transition (EMT is a developmental program in which epithelial cells down-regulate their cell-cell junctions, acquire spindle cell morphology and exhibit cellular motility. In human breast cancer, invasion into surrounding tissue is the first step in metastatic progression. Here, we devised an in vitro model using selected cell lines, which recapitulates many features of EMT as observed in human breast cancer. By comparing the gene expression profiles of claudin-low breast cancers with the experimental model, we identified a 9-gene signature characteristic of EMT. This signature was found to distinguish a series of breast cancer cell lines that have demonstrable, classical EMT hallmarks, including loss of E-cadherin protein and acquisition of N-cadherin and vimentin expression. We subsequently developed a three-dimensional model to recapitulate the process of EMT with these cell lines. The cells maintain epithelial morphology when encapsulated in a reconstituted basement membrane, but undergo spontaneous EMT and invade into surrounding collagen in the absence of exogenous cues. Collectively, this model of EMT in vitro reveals the behaviour of breast cancer cells beyond the basement membrane breach and recapitulates the in vivo context for further investigation into EMT and drugs that may interfere with it.

  12. In vitro spontaneous differentiation of human breast cancer stem cells and methods to control this process

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    Phuc Van Pham

    2015-06-01

    Full Text Available Breast cancer stem cells were considered as origins of breast cancer. Previously published studies showed that breast cancer stem cells exhibited high multi-drug resistance. This study aimed to evaluate the spontaneous differentiation of human breast cancer stem cells and investigate some in vitro conditions to control this process. Human breast cancer stem cells (BCSCs were sorted from primary culture of breast malignant tumors based on expression of CD44 and CD24. The in vitro spontaneous differentiation of BCSCs was evaluated in the popular culture medium DMEM/F12 supplemented with 10% fetal bovine serum (FBS, 1% antibiotic-antimycotic. There were some different methods to control the spontaneous differentiation of BCSCs included free serum culture, mammosphere culture, basic fibroblast growth factor and epidermal growth factor supplement to serum medium, and hypoxia culture. The results showed that BCSCs always were spontaneously differentiated in vitro in the popular culture medium DMEM/F12 plus 10% FBS. The percentage of BCSCs gradually decreased according to sub-culture times and became stable after 20 sub-culture times. All investigated methods could not completely inhibit the spontaneous differentiation of BCSCs. Serum-free culture combined with hypoxia condition had strongest inhibition of this process. These results demonstrated that the spontaneous differentiation is nature process of BCSCs; therefore this process should be determined and suitably controlled depending on different experiments. [Biomed Res Ther 2015; 2(6.000: 290-296

  13. 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…

  14. 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…

  15. Predicting human genetic interactions from cancer genome evolution.

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    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.

  16. 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...

  17. Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers.

    Science.gov (United States)

    Shen, Yao; Kim, Arianna L; Du, Rong; Liu, Liang

    2016-01-01

    Exposure to ultraviolet radiation (UVR) is a major risk factor for both melanoma and non-melanoma skin cancers. In addition to its mutagenic effect, UVR can also induce substantial transcriptional instability in skin cells affecting thousands of genes, including many cancer genes, suggesting that transcriptional instability may be another important etiological factor in skin photocarcinogenesis. In this study, we performed detailed transcriptomic profiling studies to characterize the kinetic changes in global gene expression in human keratinocytes exposed to different UVR conditions. We identified a subset of UV-responsive genes as UV signature genes (UVSGs) based on 1) conserved UV-responsiveness of this subset of genes among different keratinocyte lines; and 2) UV-induced persistent changes in their mRNA levels long after exposure. Interestingly, 11 of the UVSGs were shown to be critical to skin cancer cell proliferation and survival. Through computational Gene Set Enrichment Analysis, we demonstrated that a significant portion of the UVSGs were dysregulated in human skin squamous cell carcinomas, but not in other human malignancies. This highlights the potential and specificity of the UVSGs in clinical diagnosis of UV damage and stratification of skin cancer risk.

  18. Tanshinone IIA Induces Apoptosis in Human Oral Cancer KB Cells through a Mitochondria-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Pao-Yu Tseng

    2014-01-01

    Full Text Available Tanshinone IIA (Tan IIA, an active phytochemical in the dried root of Salvia miltiorrhiza Bunge, has shown an antiproliferative activity on various human cancer cell lines including nasopharyngeal carcinoma cells. However, the effects of Tan IIA on human oral cancer cells are still unknown. This study aimed to investigate the antiproliferative effects of Tan IIA on human oral cancer KB cells and explored the possible underlying mechanism. Treatment of KB cells with Tan IIA suppressed cell proliferation/viability and induced cell death in a dose-dependent manner through sulforhodamine B colorimetric assay. Observation of cell morphology revealed the involvement of apoptosis in the Tan IIA-induced growth inhibition on KB cells. Cell cycle analysis showed a cell cycle arrest in G2/M phase on Tan IIA-treated cells. The dissipation of mitochondrial membrane potential observed by flow cytometry and the expression of activated caspases with the cleaved poly (ADP-ribose polymerase under immunoblotting analysis indicated that Tan IIA-induced apoptosis in KB cells was mediated through the mitochondria-dependent caspase pathway. These observations suggested that Tan IIA could be a potential anticancer agent for oral cancer.

  19. Salidroside inhibits the growth of human breast cancer in vitro and in vivo.

    Science.gov (United States)

    Zhao, Gang; Shi, Aiping; Fan, Zhimin; Du, Ye

    2015-05-01

    Salidroside has been identified as one of the most potent compounds isolated from the plant Rhodiola rosea, and was found to have several important biological properties, including antioxidant and anti-inflammatory activity; however, its anticancer effects are poorly understood. Thus, the present study focused on evaluating the effects of purified salidroside on the growth of human breast cancer in vitro and in vivo, and on further investigating its possible molecular mechanisms. The human breast cancer cell line, MCF-7, was incubated with various concentrations of salidroside, and cell proliferation, colony formation, cell cycle distribution, apoptosis, migration and invasion were assayed by several in vitro approaches. As a result, it was found that salidroside treatment significantly inhibited cell proliferation, colony formation, migration and invasion, as well as induced cell apoptosis and cell cycle arrest at the G0/G1 phase in vitro. In addition, we also evaluated the effect of salidroside on tumor growth in a nude mouse model, and found that salidroside treatment significantly suppressed tumor growth in vivo. We also further disclosed that salidroside treatment significantly inhibited the intracellular reactive oxygen species (ROS) formation and MAPK pathway activation, which may contribute to the inhibition of tumor growth of breast cancer and reduction of oxidative stress. In conclusion, these findings suggest that salidroside may be a promising candidate target for the prevention and treatment of human breast cancer.

  20. Bio-luminescent imaging and characterization of organ-specific metastasis of human cancer in NOD/SCID mice

    Science.gov (United States)

    Chun, Nicole A. L.; Murakami, Takashi

    2010-02-01

    Many clinical evidences demonstrate that the sites of distant metastasis are not random and certain malignant tumors show a tendency to develop metastases in specific organs (e.g., brain, liver, and lungs). However, an appropriate animal model to characterize the metastatic nature of transplantable human cancer cell lines has not been reported well. Recent advances in bio-luminescent imaging (BLI) technologies have facilitated the quantitative analysis of various cellular processes in vivo. To visualize the fate of tumor progression in the living mice, we are constructing a luciferaseexpressing human cancer cell library (including melanoma, colon, breast, and prostate cancer). Herein we demonstrate that the BLI technology in couple with a fine ultrasonic guidance realizes cancer cell-type dependent metastasis to the specific organs. For example, some melanoma cell lines showed frequent metastasis to brain, lungs, and lymph nodes in the mouse model. Notably, reflecting the clinical features of melanoma, breast, and prostate cancer, some of the cell lines showed preferential metastasis to the brain. Moreover, these cellular resources for BLI allow a high throughput screening for potential anti-cancer drugs. Thus, this BLI-mediated additional strategy with the luciferase-expressing cancer cell resources should promote many translational studies for human cancer therapy.

  1. Comparison of treatment outcome in metastatic colorectal cancer patients included in a clinical trial versus daily practice in The Netherlands

    NARCIS (Netherlands)

    Mol, L.; Koopman, M.; Gils, C.W. van; Ottevanger, P.B.; Punt, C.J.A.

    2013-01-01

    Abstract The external validity of trial results is a matter of debate, and no strong evidence is available to support whether a trial may have a positive or a negative effect on the outcome of patients. Methods. We compared the results of stage IV colorectal cancer patients treated within a large

  2. Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shengzhang Lin

    2013-01-01

    Full Text Available Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990 with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153, a marker of the endoplasmic-reticulum-stress- (ERS- mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78, phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK, and phosphoeukaryotic initiation factor-2α (phospho-eIF2α, activating transcription factor 4 (ATF4 and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.

  3. Linking DNA adduct formation and human cancer risk in chemical carcinogenesis.

    Science.gov (United States)

    Poirier, Miriam C

    2016-08-01

    Over two centuries ago, Sir Percival Pott, a London surgeon, published a pioneering treatise showing that soot exposure was the cause of high incidences of scrotal cancers occurring in young men who worked as chimney sweeps. Practicing at a time when cellular pathology was not yet recognized, Sir Percival nonetheless observed that the high incidence and short latency of the chimney sweep cancers, was fundamentally different from the rare scrotal cancers typically found in elderly men. Furthermore, his diagnosis that the etiology of these cancers was related to chimney soot exposure, was absolutely accurate, conceptually novel, and initiated the field of "occupational cancer epidemiology." After many intervening years of research focused on mechanisms of chemical carcinogenesis, briefly described here, it is clear that DNA damage, or DNA adduct formation, is "necessary but not sufficient" for tumor induction, and that many additional factors contribute to carcinogenesis. This review includes a synopsis of carcinogen-induced DNA adduct formation in experimental models and in the human population, with particular attention paid to molecular dosimetry and molecular cancer epidemiology. Environ. Mol. Mutagen. 57:499-507, 2016. © 2016 Wiley Periodicals, Inc.

  4. 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.

  5. Effects of Antioxidants in Human Cancers: Differential Effects on Non-Coding Intronic RNA Expression

    Directory of Open Access Journals (Sweden)

    Shreya Menon

    2016-01-01

    Full Text Available The notion that dietary antioxidants can help fight cancer is popular. However, the mechanism(s behind the effect of antioxidants in cancer is still unclear. Previous studies indicate that supplements can influence gene expression; however, all of these studies were focused on the coding/exonic gene expression. Studies are now emerging to highlight critical functional roles for RNAs expressed from the non-coding regions. This project was designed to study the effect of antioxidant supplements on non-coding intronic RNA expression in human cancers. Vitamin E, N-Acetyl cysteine (NAC and Sulforaphane are commonly used supplements to prevent diseases including cancers. We studied the effect of these antioxidant supplements on the non-coding intronic RNA expression using publicly available datasets from a mouse model for lung cancer and prostate cancer cell lines. Although high throughput polyA-enriched RNA-Seq data characterize spliced coding mRNA regions, recent studies reveal the expression of reads from the non-coding intronic regions. Our analyses indicate that cancer cells have higher expression of introns compared to that of normal cells and that treatment with antioxidant supplements reduces the increased expression of introns of several genes. However, we did find high expression of introns of multiple genes including many oncogenes in the supplement treated groups compared to that of the control; this effect was distinct depending on the cell type and the supplement studied. Using RT-PCRs, we validated the expression of introns of two oncogenes, DLK1 and LRG1, known to be key players in lung cancer progression, and demonstrate changed intronic expression with supplement treatment in cancer cells. With regard to the antioxidant system, supplements did not change the intronic RNAs for endogenous antioxidant enzymes except for a significant decrease in the expression of superoxide dismutase (SOD intronic RNA. Concurrently, we also found that a

  6. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls

    DEFF Research Database (Denmark)

    Cancer, Collaborative Group on Epidemiological Studies of Ovarian; Beral, V.; Doll, R.

    2008-01-01

    BACKGROUND: Oral contraceptives were introduced almost 50 years ago, and over 100 million women currently use them. Oral contraceptives can reduce the risk of ovarian cancer, but the eventual public-health effects of this reduction will depend on how long the protection lasts after use ceases. We...... aimed to assess these effects. METHODS: Individual data for 23,257 women with ovarian cancer (cases) and 87,303 without ovarian cancer (controls) from 45 epidemiological studies in 21 countries were checked and analysed centrally. The relative risk of ovarian cancer in relation to oral contraceptive use...... was estimated, stratifying by study, age, parity, and hysterectomy. FINDINGS: Overall 7308 (31%) cases and 32,717 (37%) controls had ever used oral contraceptives, for average durations among users of 4.4 and 5.0 years, respectively. The median year of cancer diagnosis was 1993, when cases were aged an average...

  7. PREFACE: 9th International Fröhlich's Symposium: Electrodynamic Activity of Living Cells (Including Microtubule Coherent Modes and Cancer Cell Physics)

    Science.gov (United States)

    Cifra, Michal; Pokorný, Jirí; Kucera, Ondrej

    2011-12-01

    mechanisms of the harmony and order. But human knowledge about the electrodynamic and electromagnetic fields in biological systems is still at a low level. The Symposium continued in the series of international scientific meetings devoted to physical processes in living cells organized in Prague. The first meeting was entitled 'Biophysical Aspects of Cancer' (6-9 July 1987). On this occasion the Anglo-German physicist H Fröhlich presented a lecture 'Coherence in Biology'. The next meeting which was devoted to the Fröhlich coherent systems, information transfer, and neural activity was in 1993. The role of the Fröhlich coherence in the neural activity was included in the meeting 'Biophysical Aspects of Coherence' in 1995 too. The subsequent symposia were entitled 'Electromagnetic Fields in Biological Systems' (1998), 'Electromagnetic Aspects of Selforganization in Biology' (2000), 'Endogenous Physical Fields in Biology' (2002), 'Coherence and Electromagnetic Fields in Biological Systems' (2005), and 'Biophysical Aspects of Cancer - Electromagnetic Mechanisms' (2008). In 2008 a novel project for research of convergence of physics and oncology was triggered in the USA by the National Cancer Institute and the Institute of Public Health. This volume contains the a large number of the papers presented at the Symposium. The ideas presented at the Symposium might have impact on the future research of physical processes and mechanisms in biological systems. Experimental research may provide a background for understanding the neglected part of biological activity and reveal the physical mechanisms of the cancer transformation pathway. The Symposium and this volume were prepared by a scientific team whose members were M Cifra, D Havelka, A Jandová, F Jelínek, O Kucera, M Nedbalová, and F Šrobár. Jirí Pokorný A list of committees, sponsors, the list of talks and some photographs from the conference can be found in the PDF file.

  8. How important is Overdiagnosis to members of the public offered the chance to include it in an online multi-criteria decision aid for prostate cancer screening?

    DEFF Research Database (Denmark)

    Kaltoft, Mette Kjer; Nielsen, Jesper Bo; Salkeld, Glenn;

    Objectives To establish the proportion of men who chose to include Overdiagnosis as a criterion in an online multi-criteria decision aid for the prostate cancer screening decision; and to determine the relative importance assigned to Overdiagnosis by those who included it in their personalised aid...... was 33%. Conclusions Overdiagnosis was prominent among the criteria selected from a menu by male members of the public participating in a trial of online multi-criteria decision aids for prostate cancer. Notably, over 40% of those who excluded 4 to 6 of the 10 criteria included Overdiagnosis in their aid....... Methods The data are from the 'Pick Your Own' arm of an Australian community panel-based trial involving men aged 40-69 years without diagnosed prostate cancer. The 720 participants were asked to choose between 1 and 10 criteria for inclusion in their aid. With only Overdiagnosis spelled out here...

  9. N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori.

    Science.gov (United States)

    Ziebarth, D; Spiegelhalder, B; Bartsch, H

    1997-02-01

    Micro-organisms commonly present in human saliva and three DSM strains (Helicobacter pylori, Campylobacter jejuni and Neisseria cinerea), which can be isolated from the human gastro-intestinal tract, were assayed in vitro for their capacity to catalyse N-nitrosation of a series of medicinal drugs and other compounds. Following incubation at pH 7.2 in the presence of nitrate (or nitrite) for up to 24 (48) h, the yield of N-nitroso compounds (NOC) was quantified by HPLC equipped with a post-column derivatization device, allowing the sensitive detection of acid-labile and acid-stable NOC. Eleven out of the 23 test compounds underwent bacteria-catalysed nitrosation by salivary bacteria, the yield of the respective nitrosation products varying 800-fold. 4-(Methylamino)antipyrine exhibited the highest rate of nitrosation, followed by dichlofenac > metamizole > piperazine > five other drugs, whilst L-proline and L-thioproline had the lowest nitrosation rate. Ten drugs including aminophenazone, cimetidine and nicotine, did not inhibit bacterial growth, allowing transitory nitrite to be formed, but no N-nitroso derivatives were detected. Three drugs inhibited the proliferation of bacteria and neither nitrite nor any NOC were formed. Using metamizole as an easily nitrosatable precursor, two strains, Campylobacter jejuni and Helicobacter pylori, were shown to catalyse nitrosation in the presence of nitrite at pH 7.2. As compared to Neisseria cinerea used as a nitrosation-proficient control strain, H. pylori was 30-100 times less effective, whilst C. jejuni had intermediary activity. The results of our sensitive nitrosation assay further confirm that bacteria isolated from human sources, possessing nitrate reductase and/or nitrosating enzymes such as cytochrome cd1-nitrite reductase (Calmels et al., Carcinogenesis, 17, 533-536, 1996), can contribute to intragastric nitrosamine formation in the anacidic stomach when nitrosatable precursors from exogenous and endogenous sources

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Anti-cancer effect of Cordyceps militaris in human colorectal carcinoma RKO cells via cell cycle arrest and mitochondrial apoptosis

    OpenAIRE

    Lee, Hwan Hee; Lee, Seulki; Lee, Kanghyo; Shin, Yu Su; Kang, Hyojeung; Cho, Hyosun

    2015-01-01

    Background Cordyceps militaris has been used as a traditional medicine in Asian countries for a long time. Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris ethanol extract on a human colorectal cancer-derived cell line, RKO. Methods RKO cells were treated with various concentrations of nucleosides-enriched ethanol extract of Cordyceps militaris for 48 h an...

  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. 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.

  15. 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.

  16. 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.

  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. Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    William N. Rom

    2013-01-01

    Full Text Available Decreasing the risk of lung cancer, or preventing its development in high-risk individuals, would have a huge impact on public health. The most effective means to decrease lung cancer incidence is to eliminate exposure to carcinogens. However, with recent advances in the understanding of pulmonary carcinogenesis and the identification of intermediate biomarkers, the prospects for the field of chemoprevention research have improved dramatically. Here we review the most recent research in lung cancer chemoprevention—focusing on those agents that have been investigated in human clinical trials. These agents fall into three major categories. First, oxidative stress plays an important role in pulmonary carcinogenesis; and therefore, antioxidants (including vitamins, selenium, green tea extracts, and isothiocyanates may be particularly effective in preventing the development of lung cancer. Second, inflammation is increasingly accepted as a crucial factor in carcinogenesis, and many investigators have focused on anti-inflammatory agents, such as glucocorticoids, NSAIDs, statins, and PPARγ agonists. Finally, the PI3K/AKT/mTOR pathway is recognized to play a central role in tobacco-induced carcinogenesis, and inhibitors of this pathway, including myoinositol and metformin, are promising agents for lung cancer prevention. Successful chemoprevention will likely require targeting of multiple pathways to carcinogenesis—both to minimize toxicity and maximize efficacy.

  19. 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.

  20. Quality assessment of delineation and dose planning of early breast cancer patients included in the randomized Skagen Trial 1

    DEFF Research Database (Denmark)

    Francolini, Giulio; Thomsen, Mette S; Yates, Esben S

    2017-01-01

    Background and purpose: To report on a Quality assessment (QA) of Skagen Trial 1, exploring hypofractionation for breast cancer patients with indication for regional nodal radiotherapy. Material and methods: Deviations from protocol regarding target volume delineations and dose parameters (Dmin, ...... coverage in most patients. Inter-observer variability in contouring was low. Dose parameters were in harmony with protocol regardless original or GS segmentation.......Background and purpose: To report on a Quality assessment (QA) of Skagen Trial 1, exploring hypofractionation for breast cancer patients with indication for regional nodal radiotherapy. Material and methods: Deviations from protocol regarding target volume delineations and dose parameters (Dmin......, Dmax, D98%, D95% and D2%) from randomly selected dose plans were assessed. Target volume delineation according to ESTRO guidelines was obtained through atlas based automated segmentation and centrally approved as gold standard (GS). Dice similarity scores (DSC) with original delineations were measured...

  1. 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

  2. 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

  3. 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

  4. Results of extralevator abdominoperineal resection for low rectal cancer including quality of life and long-term wound complications.

    Science.gov (United States)

    Welsch, Thilo; Mategakis, Vyron; Contin, Pietro; Kulu, Yakup; Büchler, Markus W; Ulrich, Alexis

    2013-04-01

    Extralevator abdominoperineal resection (APR) for low rectal cancer has been adopted by centers to improve oncological outcome. The present study aimed to investigate oncological results, wound complications, and quality of life (QoL). Patients who underwent extralevator APR for rectal cancer between 2007 and 2011 were identified retrospectively. QoL status was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CR30 and CR29 questionnaires. Thirty laparoscopic (n = 7) or open (n = 23) extralevator APRs were performed in 17 male and 13 female patients. The mortality was zero; circumferential margin involvement occurred in two cases (6.7 %); and there was no bowel perforation. No local recurrence was noted after a median follow-up of 28.3 months; however, six patients died, and eight developed distant metastases. Perineal wound complications were found in 46.6 % of patients, and all were managed conservatively. Fifty percent of the patients reported persistent perineal pain at the follow-up exam. QoL was assessed 7 to 46 months after surgery, and the global health status (70.6) was comparable to the EORTC reference group and published conventional APR series. The QLQ-CR29 module revealed high mean symptom scores for urinary frequency (48.1), incontinence (30.5), and impotence (79.1). Extralevator APR can control local recurrence but not distant metastases of low rectal cancer. The extended perineal resection appears not to decrease general QoL, but it results in a high rate of perineal wound complications. Genitourinary functions are often impaired, even in the long term, and further improvements to the technique must seek to reduce genitourinary harm.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Gopal K. Singh, PhD

    2012-11-01

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

  7. 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....

  8. 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

  9. No role for human papillomavirus infection in oral cancers in a region in southern India.

    Science.gov (United States)

    Laprise, Claudie; Madathil, Sreenath A; Allison, Paul; Abraham, Priya; Raghavendran, Anantharam; Shahul, Hameed P; ThekkePurakkal, Akhil-Soman; Castonguay, Geneviève; Coutlée, François; Schlecht, Nicolas F; Rousseau, Marie-Claude; Franco, Eduardo L; Nicolau, Belinda

    2016-02-15

    Oral cancer is a major public health issue in India with ∼ 77,000 new cases and 52,000 deaths yearly. Paan chewing, tobacco and alcohol use are strong risk factors for this cancer in India. Human papillomaviruses (HPVs) are also related to a subset of head and neck cancers (HNCs). We examined the association between oral HPV and oral cancer in a sample of Indian subjects participating in a hospital-based case-control study. We recruited incident oral cancer cases (N = 350) and controls frequency-matched by age and sex (N = 371) from two main referral hospitals in Kerala, South India. Sociodemographic and behavioral data were collected by interviews. Epithelial cells were sampled using Oral CDx® brushes from the oral cancer site and the normal mucosa. Detection and genotyping of 36 HPV genotypes were done using a polymerase chain reaction protocol. Data collection procedures were performed by qualified dentists via a detailed protocol with strict quality control, including independent HPV testing in India and Canada. HPV DNA was detected in none of the cases or controls. Associations between oral cancer and risk factors usually associated with HPV infection, such as oral sex and number of lifetime sexual partners, were examined by logistic regression and were not associated with oral cancer. Lack of a role for HPV infection in this study may reflect cultural or religious characteristics specific to this region in India that are not conducive to oral HPV transmission. A nationwide representative prevalence study is needed to investigate HPV prevalence variability among Indian regions.

  10. Evaluating baculovirus as a vector for human prostate cancer gene therapy.

    Directory of Open Access Journals (Sweden)

    Stephanie L Swift

    Full Text Available Gene therapy represents an attractive strategy for the non-invasive treatment of prostate cancer, where current clinical interventions show limited efficacy. Here, we evaluate the use of the insect virus, baculovirus (BV, as a novel vector for human prostate cancer gene therapy. Since prostate tumours represent a heterogeneous environment, a therapeutic approach that achieves long-term regression must be capable of targeting multiple transformed cell populations. Furthermore, discrimination in the targeting of malignant compared to non-malignant cells would have value in minimising side effects. We employed a number of prostate cancer models to analyse the potential for BV to achieve these goals. In vitro, both traditional prostate cell lines as well as primary epithelial or stromal cells derived from patient prostate biopsies, in two- or three-dimensional cultures, were used. We also evaluated BV in vivo in murine prostate cancer xenograft models. BV was capable of preferentially transducing invasive malignant prostate cancer cell lines compared to early stage cancers and non-malignant samples, a restriction that was not a function of nuclear import. Of more clinical relevance, primary patient-derived prostate cancer cells were also efficiently transduced by BV, with robust rates observed in epithelial cells of basal phenotype, which expressed BV-encoded transgenes faster than epithelial cells of a more differentiated, luminal phenotype. Maximum transduction capacity was observed in stromal cells. BV was able to penetrate through three-dimensional structures, including in vitro spheroids and in vivo orthotopic xenografts. BV vectors containing a nitroreductase transgene in a gene-directed enzyme pro-drug therapy approach were capable of efficiently killing malignant prostate targets following administration of the pro-drug, CB1954. Thus, BV is capable of transducing a large proportion of prostate cell types within a heterogeneous 3-D prostate

  11. Accurate identification of the six human Plasmodium spp. causing imported malaria, including Plasmodium ovale wallikeri and Plasmodium knowlesi.

    Science.gov (United States)

    Calderaro, Adriana; Piccolo, Giovanna; Gorrini, Chiara; Rossi, Sabina; Montecchini, Sara; Dell'Anna, Maria Loretana; De Conto, Flora; Medici, Maria Cristina; Chezzi, Carlo; Arcangeletti, Maria Cristina

    2013-09-13

    Accurate identification of Plasmodium infections in non-endemic countries is of critical importance with regard to the administration of a targeted therapy having a positive impact on patient health and management and allowing the prevention of the risk of re-introduction of endemic malaria in such countries. Malaria is no longer endemic in Italy where it is the most commonly imported disease, with one of the highest rates of imported malaria among European non-endemic countries including France, the UK and Germany, and with a prevalence of 24.3% at the University Hospital of Parma. Molecular methods showed high sensitivity and specificity and changed the epidemiology of imported malaria in several non-endemic countries, highlighted a higher prevalence of Plasmodium ovale, Plasmodium vivax and Plasmodium malariae underestimated by microscopy and, not least, brought to light both the existence of two species of P. ovale (Plasmodium ovale curtisi and Plasmodium ovale wallikeri) and the infection in humans by Plasmodium knowlesi, otherwise not detectable by microscopy. In this retrospective study an evaluation of two real-time PCR assays able to identify P. ovale wallikeri, distinguishing it from P. ovale curtisi, and to detect P. knowlesi, respectively, was performed applying them on a subset of 398 blood samples belonging to patients with the clinical suspicion of malaria. These assays revealed an excellent analytical sensitivity and no cross-reactivity versus other Plasmodium spp. infecting humans, suggesting their usefulness for an accurate and complete diagnosis of imported malaria. Among the 128 patients with malaria, eight P. ovale curtisi and four P. ovale wallikeri infections were detected, while no cases of P. knowlesi infection were observed. Real-time PCR assays specific for P. ovale wallikeri and P. knowlesi were included in the panel currently used in the University Hospital of Parma for the diagnosis of imported malaria, accomplishing the goal of

  12. 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

  13. 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

  14. Modeling microRNA-mRNA Interactions Using PLS Regression in Human Colon Cancer

    Directory of Open Access Journals (Sweden)

    Li Xiaohong

    2011-05-01

    Full Text Available Abstract Background Changes in microRNA (miRNA expression patterns have been extensively characterized in several cancers, including human colon cancer. However, how these miRNAs and their putative mRNA targets contribute to the etiology of cancer is poorly understood. In this work, a bioinformatics computational approach with miRNA and mRNA expression data was used to identify the putative targets of miRNAs and to construct association networks between miRNAs and mRNAs to gain some insights into the underlined molecular mechanisms of human colon cancer. Method The miRNA and mRNA microarray expression profiles from the same tissues including 7 human colon tumor tissues and 4 normal tissues, collected by the Broad Institute, were used to identify significant associations between miRNA and mRNA. We applied the partial least square (PLS regression method and bootstrap based statistical tests to the joint expression profiles of differentially expressed miRNAs and mRNAs. From this analysis, we predicted putative miRNA targets and association networks between miRNAs and mRNAs. Pathway analysis was employed to identify biological processes related to these miRNAs and their associated predicted mRNA targets. Results Most significantly associated up-regulated mRNAs with a down-regulated miRNA identified by the proposed methodology were considered to be the miRNA targets. On average, approximately 16.5% and 11.0% of targets predicted by this approach were also predicted as targets by the common prediction algorithms TargetScan and miRanda, respectively. We demonstrated that our method detects more targets than a simple correlation based association. Integrative mRNA:miRNA predictive networks from our analysis were constructed with the aid of Cytoscape software. Pathway analysis validated the miRNAs through their predicted targets that may be involved in cancer-associated biological networks. Conclusion We have identified an alternative bioinformatics

  15. Drosophila caliban, a nuclear export mediator, can function as a tumor suppressor in human lung cancer cells.

    Science.gov (United States)

    Bi, Xiaolin; Jones, Tamara; Abbasi, Fatima; Lee, Heuijung; Stultz, Brian; Hursh, Deborah A; Mortin, Mark A

    2005-12-15

    We previously showed that the Drosophila DNA binding homeodomain of Prospero included a 28 amino-acid sequence (HDA) that functions as a nuclear export signal. We describe here the identification of a protein we named Caliban, which can directly interact with the HDA. Caliban is homologous to human Sdccag1, which has been implicated in colon and lung cancer. Here we show that Caliban and Sdccag1 are mediators of nuclear export in fly and human cells, as interference RNA abrogates export of EYFP-HDA in normal fly and human lung cells. Caliban functions as a bipartite mediator nuclear export as the carboxy terminus binds HDA and the amino terminus itself functions as an NES, which directly binds the NES receptor Exportin. Finally, while non-cancerous lung cells have functional Sdccag1, five human lung carcinoma cell lines do not, even though Exportin still functions in these cells. Expression of fly Caliban in these human lung cancer cells restores EYFP-HDA nuclear export, reduces a cell's ability to form colonies on soft agar and reduces cell invasiveness. We suggest that Sdccag1 inactivation contributes to the transformed state of human lung cancer cells and that Caliban should be considered a candidate for use in lung cancer gene therapy.

  16. 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.

  17. 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...

  18. 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.

  19. Human Papillomavirus and Tonsillar and Base of Tongue Cancer

    Directory of Open Access Journals (Sweden)

    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.

  20. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

    Science.gov (United States)

    Xin, Hong-Wu; Hari, Danielle M; Mullinax, John E; Ambe, Chenwi M; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J; Wiegand, Gordon W; Garfield, Susan H; Thorgeirsson, Snorri S; Avital, Itzhak

    2012-04-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. Copyright © 2012 AlphaMed Press.

  1. 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.

  2. 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...

  3. 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...

  4. 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...

  5. 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.

  6. Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines.

    Science.gov (United States)

    Souza, Raquel P; Bonfim-Mendonça, Patrícia de S; Gimenes, Fabrícia; Ratti, Bianca A; Kaplum, Vanessa; Bruschi, Marcos L; Nakamura, Celso V; Silva, Sueli O; Maria-Engler, Silvya S; Consolaro, Marcia E L

    2017-01-01

    Recently, the cytotoxic effects of apigenin (4',5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the Δψm, and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes.

  7. Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines

    Directory of Open Access Journals (Sweden)

    Raquel P. Souza

    2017-01-01

    Full Text Available Recently, the cytotoxic effects of apigenin (4′,5,7-trihydroxyflavone, particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive, SiHa (HPV 16-positive, CaSki (HPV 16 and HPV 18-positive, and C33A (HPV-negative cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT. Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells. Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the Δψm, and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes.

  8. Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines

    Science.gov (United States)

    Souza, Raquel P.; Gimenes, Fabrícia; Ratti, Bianca A.; Kaplum, Vanessa; Bruschi, Marcos L.; Nakamura, Celso V.; Maria-Engler, Silvya S.

    2017-01-01

    Recently, the cytotoxic effects of apigenin (4′,5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the Δψm, and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes. PMID:28191273

  9. Can we expand active surveillance criteria to include biopsy Gleason 3+4 prostate cancer? A multi-institutional study of 2,323 patients

    NARCIS (Netherlands)

    Ploussard, G.; Isbarn, H.; Briganti, A.; Sooriakumaran, P.; Surcel, C.I.; Salomon, L.; Freschi, M.; Mirvald, C.; Poel, H.G. van der; Jenkins, A.; Ost, P.; Oort, I.M. van; Yossepowitch, O.; Giannarini, G.; Bergh, R.C. van den

    2015-01-01

    OBJECTIVE: To test the expandability of active surveillance (AS) to Gleason score 3+4 cancers by assessing the unfavorable disease risk in a large multi-institutional cohort. MATERIALS AND METHODS: We performed a retrospective analysis including 2,323 patients with localized Gleason score 3+4 prosta

  10. Deciphering the colon cancer genes--report of the InSiGHT-Human Variome Project Workshop, UNESCO, Paris 2010

    DEFF Research Database (Denmark)

    Kohonen-Corish, Maija R J; Macrae, Finlay; Genuardi, Maurizio;

    2011-01-01

    The Human Variome Project (HVP) has established a pilot program with the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) to compile all inherited variation affecting colon cancer susceptibility genes. An HVP-InSiGHT Workshop was held on May 10, 2010, prior to the HVP...... Integration and Implementation Meeting at UNESCO in Paris, to review the progress of this pilot program. A wide range of topics were covered, including issues relating to genotype-phenotype data submission to the InSiGHT Colon Cancer Gene Variant Databases (chromium.liacs.nl/LOVD2/colon_cancer...

  11. Mutation and Expression of the DCC Gene in Human Lung Cancer

    Directory of Open Access Journals (Sweden)

    Takashi Kohno

    2000-07-01

    Full Text Available Chromosome 18q is frequently deleted in lung cancers, a common region of 18q deletions was mapped to chromosome 18g21. Since the DCC candidate tumor suppressor gene has been mapped in this region, mutation and expression of the DCC gene were examined in 46 lung cancer cell lines, consisting of 14 small cell lung carcinomas (SCLCs and 32 non-small cell lung carcinomas (NSCLCs, to elucidate the pathogenetic significance of DCC alterations in human lung carcinogenesis. A heterozygous missense mutation was detected in a NSCLC cell line, Ma26, while homozygous deletion was not detected in any of the cell lines. The DCC gene was expressed in 11 (24% of the 46 cell lines, the incidence of DCC expression was significantly higher in SCLCs (7/14, 50% than in NSCLCs (4/32, 13% (P = .01, Fisher's exact test. Therefore, genetic alterations of DCC are infrequent; however, the levels of DCC expression vary among lung cancer cells, in particular, between SCLCs and NSCLCs. The present result does not implicate DCC as a specific mutational target of 18q deletions in human lung cancer; however, it suggests that DCC is a potential target of inactivation by genetic defects including intron or promoter mutations and/or epigenetic alterations. The present result also suggests that DCC expression is associated with some properties of SCLCs, such as a neuroendocrine (NE feature.

  12. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models

    Science.gov (United States)

    Liu, Huiping; Patel, Manishkumar R.; Prescher, Jennifer A.; Patsialou, Antonia; Qian, Dalong; Lin, Jiahui; Wen, Susanna; Chang, Ya-Fang; Bachmann, Michael H.; Shimono, Yohei; Dalerba, Piero; Adorno, Maddalena; Lobo, Neethan; Bueno, Janet; Dirbas, Frederick M.; Goswami, Sumanta; Somlo, George; Condeelis, John; Contag, Christopher H.; Gambhir, Sanjiv Sam; Clarke, Michael F.

    2010-01-01

    To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44+ cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy. PMID:20921380

  13. Changes in knowledge of cervical cancer following introduction of human papillomavirus vaccine among women at high risk for cervical cancer

    Science.gov (United States)

    Stewart Massad, L.; Evans, Charlesnika T.; Weber, Kathleen M.; D'Souza, Gypsyamber; Hessol, Nancy A.; Wright, Rodney L.; Colie, Christine; Strickler, Howard D.; Wilson, Tracey E.

    2015-01-01

    Purpose To describe changes in knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination among women at high risk for cervical cancer in the first five years after introduction of HPV vaccination. Methods In 2007, 2008–9, and 2011, women in a multicenter U.S. cohort study completed 44-item self-report questionnaires assessing knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results across time were assessed for individuals, and three study enrollment cohorts were compared. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Associations were assessed in multivariable models. Results In all, 974 women completed three serial questionnaires; most were minority, low income, and current or former smokers. The group included 652 (67%) HIV infected and 322 (33%) uninfected. Summary knowledge scores (possible range 0–24) increased from 2007 (12.8, S.D. 5.8) to 2008–9 (13.9, S.D. 5.3, P < 0.001) and to 2011 (14.3, S.D. 5.2, P < 0.0001 vs 2007 and < 0.04 vs 2008–9). Higher knowledge scores at first and follow-up administration of questionnaires, higher income, and higher education level were associated with improved knowledge score at third administration. Women not previously surveyed had scores similar to those of the longitudinal group at baseline. Conclusion Substantial gaps in understanding of HPV and cervical cancer prevention exist despite years of health education. While more effective educational interventions may help, optimal cancer prevention may require opt-out vaccination programs that do not require nuanced understanding. PMID:25870859

  14. 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

  15. Automated adipose study for assessing cancerous human breast tissue using optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Gan, Yu; Yao, Xinwen; Chang, Ernest W.; Bin Amir, Syed A.; Hibshoosh, Hanina; Feldman, Sheldon; Hendon, Christine P.

    2017-02-01

    Breast cancer is the third leading cause of death in women in the United States. In human breast tissue, adipose cells are infiltrated or replaced by cancer cells during the development of breast tumor. Therefore, an adipose map can be an indicator of identifying cancerous region. We developed an automated classification method to generate adipose map within human breast. To facilitate the automated classification, we first mask the B-scans from OCT volumes by comparing the signal noise ratio with a threshold. Then, the image was divided into multiple blocks with a size of 30 pixels by 30 pixels. In each block, we extracted texture features such as local standard deviation, entropy, homogeneity, and coarseness. The features of each block were input to a probabilistic model, relevance vector machine (RVM), which was trained prior to the experiment, to classify tissue types. For each block within the B-scan, RVM identified the region with adipose tissue. We calculated the adipose ratio as the number of blocks identified as adipose over the total number of blocks within the B-scan. We obtained OCT images from patients (n = 19) in Columbia medical center. We automatically generated the adipose maps from 24 B-scans including normal samples (n = 16) and cancerous samples (n = 8). We found the adipose regions show an isolated pattern that in cancerous tissue while a clustered pattern in normal tissue. Moreover, the adipose ratio (52.30 ± 29.42%) in normal tissue was higher than the that in cancerous tissue (12.41 ± 10.07%).

  16. 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 ...

  17. Effects of environmental organochlorine pesticides on human breast cancer: putative involvement on invasive cell ability.

    Science.gov (United States)

    Pestana, Diogo; Teixeira, Diana; Faria, Ana; Domingues, Valentina; Monteiro, Rosário; Calhau, Conceição

    2015-02-01

    Human exposure to persistent organic pollutants (POPs) is a certainty, even to long banned pesticides like o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT), and its metabolites p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and p,p'-dichlorodiphenyldichloroethane (p,p'-DDD). POPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p'-DDT, p,p'-DDE, and p,p'-DDD (50-1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology. © 2013 Wiley Periodicals, Inc.

  18. Establishment and Analysis of Cancer Stem-Like and Non-Cancer Stem-Like Clone Cells from the Human Colon Cancer Cell Line SW480.

    Science.gov (United States)

    Takaya, Akari; Hirohashi, Yoshihiko; Murai, Aiko; Morita, Rena; Saijo, Hiroshi; Yamamoto, Eri; Kubo, Terufumi; Nakatsugawa, Munehide; Kanaseki, Takayuki; Tsukahara, Tomohide; Tamura, Yasuaki; Takemasa, Ichiro; Kondo, Toru; Sato, Noriyuki; Torigoe, Toshihiko

    2016-01-01

    Human cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be isolated as side population (SP) cells, aldehyde dehydrogenase high (ALDHhigh) cells or cell surface marker-positive cells including CD44+ cells and CD133+ cells. CSCs/CICs and non-CSCs/CICs are unstable in in vitro culture, and CSCs/CICs can differentiate into non-CSCs/CICs and some non-CSCs/CICs can dedifferentiate into CSCs/CICs. Therefore, experiments using a large amount of CSCs/CICs are technically very difficult. In this study, we isolated single cell clones from SP cells and main population (MP) cells derived from the human colon cancer cell line SW480. SP analysis revealed that SP clone cells had relatively high percentages of SP cells, whereas MP clone cells showed very few SP cells, and the phenotypes were sustainable for more than 2 months of in vitro culture. Xenograft transplantation revealed that SP clone cells have higher tumor-initiating ability than that of MP clone cells and SP clone cell showed higher chemo-resistance compared with MP clone cells. These results indicate that SP clone cells derived from SW480 cells are enriched with CSCs/CICs, whereas MP clone cells are pure non-CSCs/CICs. SP clone cells and MP clone cells are a very stable in vitro CSC/CIC-enriched and non-CSC/CIC model for further analysis.

  19. Red grape seed extract and its compound resveratrol exert cytotoxic effect to various human cancer lines.

    Science.gov (United States)

    Şahin, Fahri; Avcı, Çığır Biray; Avcu, Ferit; Ural, Ali Uğur; Sarper, Meral; Hışıl, Yaşar; Omay, Serdar Bedii; Saydam, Güray

    2007-09-05

    Modern medicinal agents currently available for treatment of cancers are very expensive, toxic, and less effective in treating some of the disease. Thus, one must investigate further in detail the agents derived from natural sources, such as grape seed, for the prevention and treatment of cancer and disease. In recent years interest of researchers has focused on grape seed and nowadays scientists have used extracts of grape seed to treat different health problems including cancer. We examined the cytotoxic effect of red grape seed extract (GSE) and its main compound resveratrol (RES) on different human cancer cell lines representing various solid tumors and hematological malignancies at the same time. Red GSE was prepared by using 1, 1, 1, 2- Tetrafluoroethane extraction method. Cytotoxicity of the extract and RES was evaluated by using trypan blue dye exclusion method and MTT assay. The results of our study show that GSE and RES have cytotoxic activities in varying degree in several cancer cell lines. There has not been any study evaluating the GES and RES in the same cell lines and in the same conditions. But, it is still needed to have more pre-clinical and laboratory studies to validate the usefulness of these agents either alone or in combination with existing therapy.

  20. Study on image feature extraction and classification for human colorectal cancer using optical coherence tomography

    Science.gov (United States)

    Huang, Shu-Wei; Yang, Shan-Yi; Huang, Wei-Cheng; Chiu, Han-Mo; Lu, Chih-Wei

    2011-06-01

    Most of the colorectal cancer has grown from the adenomatous polyp. Adenomatous lesions have a well-documented relationship to colorectal cancer in previous studies. Thus, to detect the morphological changes between polyp and tumor can allow early diagnosis of colorectal cancer and simultaneous removal of lesions. OCT (Optical coherence tomography) has been several advantages including high resolution and non-invasive cross-sectional image in vivo. In this study, we investigated the relationship between the B-scan OCT image features and histology of malignant human colorectal tissues, also en-face OCT image and the endoscopic image pattern. The in-vitro experiments were performed by a swept-source optical coherence tomography (SS-OCT) system; the swept source has a center wavelength at 1310 nm and 160nm in wavelength scanning range which produced 6 um axial resolution. In the study, the en-face images were reconstructed by integrating the axial values in 3D OCT images. The reconstructed en-face images show the same roundish or gyrus-like pattern with endoscopy images. The pattern of en-face images relate to the stages of colon cancer. Endoscopic OCT technique would provide three-dimensional imaging and rapidly reconstruct en-face images which can increase the speed of colon cancer diagnosis. Our results indicate a great potential for early detection of colorectal adenomas by using the OCT imaging.

  1. Molecular Mechanisms and Translational Therapies for Human Epidermal Receptor 2 Positive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Quanxia Lv

    2016-12-01

    Full Text Available Breast cancer is the second leading cause of cancer death among women. Human epidermal receptor 2 (HER2 positive breast cancer (HER2+ BC is the most aggressive subtype of breast cancer, with poor prognosis and a high rate of recurrence. About one third of breast cancer is HER2+ BC with significantly high expression level of HER2 protein compared to other subtypes. Therefore, HER2 is an important biomarker and an ideal target for developing therapeutic strategies for the treatment HER2+ BC. In this review, HER2 structure and physiological and pathological roles in HER2+ BC are discussed. Two diagnostic tests, immunohistochemistry (IHC and fluorescent in situ hybridization (FISH, for evaluating HER2 expression levels are briefly introduced. The current mainstay targeted therapies for HER2+ BC include monoclonal antibodies, small molecule tyrosine kinase inhibitors, antibody–drug conjugates (ADC and other emerging anti-HER2 agents. In clinical practice, combination therapies are commonly adopted in order to achieve synergistic drug response. This review will help to better understand the molecular mechanism of HER2+ BC and further facilitate the development of more effective therapeutic strategies against HER2+ BC.

  2. MUC1 selectively targets human pancreatic cancer in orthotopic nude mouse models.

    Directory of Open Access Journals (Sweden)

    Jeong Youp Park

    Full Text Available The goal of this study was to determine whether MUC1 antibody conjugated with a fluorophore could be used to visualize pancreatic cancer. Anti-MUC1 (CT2 antibody was conjugated with 550 nm or 650 nm fluorophores. Nude mouse were used to make subcutaneous and orthotopic models of pancreatic cancer. Western blot and flow cytometric analysis confirmed the expression of MUC1 in human pancreatic cancer cell lines including BxPC-3 and Panc-1. Immunocytochemistry with fluorophore conjugated anti-MUC1 antibody demonstrated fluorescent areas on the membrane of Panc-1 cancer cells. After injecting the conjugated anti-MUC1 antibodies via the tail vein, subcutaneously transplanted Panc-1 and BxPC-3 tumors emitted strong fluorescent signals. In the subcutaneous tumor models, the fluorescent signal from the conjugated anti-MUC1 antibody was noted around the margin of the tumor and space between the cells. The conjugated anti-MUC1 antibody bound the tumor in orthotopically-transplanted Panc-1 and BxPC-3 models enabling the tumors to be imaged. This study showed that fluorophore conjugated anti-MUC1 antibodies could visualize pancreatic tumors in vitro and in vivo and may help to improve the diagnosis and treatment of pancreatic cancer.

  3. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells

    Directory of Open Access Journals (Sweden)

    Reyhan Akhtar

    2014-02-01

    Full Text Available Background: Silibinin a flavonoid from milk thistle (Silybum marianum exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml for 24, 48 or 72 h showed a progressive decline in cell viability. Results: Loss of cell viability was time dependent and optimum inhibition of cell growth (78% was observed at 72 h. Under inverted microscope, the dead cells were seen as cell aggregates. IC50 (silibinin concentration killing 50% cells values were 180, 110 and 40μg/ml at 24, 48 and 72 h respectively. Conclusion: These findings re-enforce the anticancer potential of silibinin, as reported earlier for various other cancer cell lines (Ramasamy and Agarwal (2008, Cancer Letters, 269: 352-62.

  4. “An Environment Built to Include Rather than Exclude Me”: Creating Inclusive Environments for Human Well-Being

    Directory of Open Access Journals (Sweden)

    Natasha A. Layton

    2015-09-01

    Full Text Available Contemporary discourses which challenge the notion of health as the “absence of disease” are prompting changes in health policy and practice. People with disability have been influential in progressing our understanding of the impact of contextual factors in individual and population health, highlighting the impact of environmental factors on functioning and inclusion. The World Health Organization’s (WHO more holistic definition of health as “wellbeing” is now applied in frameworks and legislation, and has long been understood in occupational therapy theory. In practice, however, occupational therapists and other professionals often address only local and individual environmental factors to promote wellbeing, within systems and societies that limit equity in population health and restrict inclusion in communities. This paper presents an in-depth analysis of the supports and accommodations identified by a cohort of individuals (n-100 living with disability. A range of environmental facilitators and barriers were identified in peoples’ experience of “inclusive community environs” and found to influence inclusion and wellbeing. The roles and responsibilities of individuals, professionals, and society to enact change in environments are discussed in light of these findings. Recommendations include a focus on the subjective experience of environments, and application of theory from human rights and inclusive economics to address the multiple dimensions and levels of environments in working towards inclusion and wellbeing.

  5. "An Environment Built to Include Rather than Exclude Me": Creating Inclusive Environments for Human Well-Being.

    Science.gov (United States)

    Layton, Natasha A; Steel, Emily J

    2015-09-08

    Contemporary discourses which challenge the notion of health as the "absence of disease" are prompting changes in health policy and practice. People with disability have been influential in progressing our understanding of the impact of contextual factors in individual and population health, highlighting the impact of environmental factors on functioning and inclusion. The World Health Organization's (WHO) more holistic definition of health as "wellbeing" is now applied in frameworks and legislation, and has long been understood in occupational therapy theory. In practice, however, occupational therapists and other professionals often address only local and individual environmental factors to promote wellbeing, within systems and societies that limit equity in population health and restrict inclusion in communities. This paper presents an in-depth analysis of the supports and accommodations identified by a cohort of individuals (n-100) living with disability. A range of environmental facilitators and barriers were identified in peoples' experience of "inclusive community environs" and found to influence inclusion and wellbeing. The roles and responsibilities of individuals, professionals, and society to enact change in environments are discussed in light of these findings. Recommendations include a focus on the subjective experience of environments, and application of theory from human rights and inclusive economics to address the multiple dimensions and levels of environments in working towards inclusion and wellbeing.

  6. 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.

  7. 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.

  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. A taxonomy of epithelial human cancer and their metastases

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    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

  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. Cytotoxic Compounds from Juglans sinensis Dode Display Anti-Proliferative Activity by Inducing Apoptosis in Human Cancer Cells.

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    Lee, Yoo Jin; Cui, Jun; Lee, Jun; Han, Ah-Reum; Lee, Eun Byul; Jang, Ho Hee; Seo, Eun Kyoung

    2016-01-01

    Phytochemical investigation of the bark of Juglans sinensis Dode (Juglandaceae) led to the isolation of two active compounds, 8-hydroxy-2-methoxy-1,4-naphthoquinone (1) and 5-hydroxy-2-methoxy-1,4-naphthoquinone (2), together with 15 known compounds 3-17. All compounds were isolated from this plant for the first time. The structures of 1 and 2 were elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments. Compounds 1-17 were tested for their cytotoxicity against the A549 human lung cancer cell line; compounds 1 and 2 exhibited significant cytotoxicity and additionally had potent cytotoxicity against six human cancer cell lines, MCF7 (breast cancer), SNU423 (liver cancer), SH-SY5Y (neuroblastoma), HeLa (cervical cancer), HCT116 (colorectal cancer), and A549 (lung cancer). In particular, breast, colon, and lung cancer cells were more sensitive to the treatment using compound 1. In addition, compounds 1 and 2 showed strong cytotoxic activity towards human breast cancer cells MCF7, HS578T, and T47D, but not towards MCF10A normal-like breast cells. They also inhibited the colony formation of MCF7, A549, and HCT116 cells in a dose-dependent manner. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased in MCF7 cells upon the treatment with compounds 1 and 2. The mechanism of cell death caused by compounds 1 and 2 may be attributed to the upregulation of Bax and downregulation of Bcl2. These findings suggest that compounds 1 and 2 may be regarded as potential therapeutic agents against cancer.

  12. Preclinical models for interrogating drug action in human cancers using Stable Isotope Resolved Metabolomics (SIRM)

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    Lane, Andrew N.; Higashi, Richard M.; Fan, Teresa W-M.

    2016-01-01

    Aims In this review we compare the advantages and disadvantages of different model biological systems for determining the metabolic functions of cells in complex environments, how they may change in different disease states, and respond to therapeutic interventions. Background All preclinical drug-testing models have advantages and drawbacks. We compare and contrast established cell, organoid and animal models with ex vivo organ or tissue culture and in vivo human experiments in the context of metabolic readout of drug efficacy. As metabolism reports directly on the biochemical state of cells and tissues, it can be very sensitive to drugs and/or other environmental changes. This is especially so when metabolic activities are probed by stable isotope tracing methods, which can also provide detailed mechanistic information on drug action. We have developed and been applying Stable Isotope-Resolved Metabolomics (SIRM) to examine metabolic reprogramming of human lung cancer cells in monoculture, in mouse xenograft/explant models, and in lung cancer patients in situ (Lane et al. 2011; T. W. Fan et al. 2011; T. W-M. Fan et al. 2012; T. W. Fan et al. 2012; Xie et al. 2014b; Ren et al. 2014a; Sellers et al. 2015b). We are able to determine the influence of the tumor microenvironment using these models. We have now extended the range of models to fresh human tissue slices, similar to those originally described by O. Warburg (Warburg 1923), which retain the native tissue architecture and heterogeneity with a paired benign versus cancer design under defined cell culture conditions. This platform offers an unprecedented human tissue model for preclinical studies on metabolic reprogramming of human cancer cells in their tissue context, and response to drug treatment (Xie et al. 2014a). As the microenvironment of the target human tissue is retained and individual patient's response to drugs is obtained, this platform promises to transcend current limitations of drug selection

  13. The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein

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    Hur Soo

    2006-03-01

    Full Text Available Abstract Background Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of our study was to identify an unique gene that shows cancer-associated expression, and characterizes its function related to human carcinogenesis. Methods We used the differential display (DD RT-PCR method using normal cervical, cervical cancer, metastatic cervical tissues, and cervical cancer cell lines to identify genes overexpressed in cervical cancers and identified gremlin 1 which was overexpressed in cervical cancers. We determined expression levels of gremlin 1 using Northern blot analysis and immunohistochemical study in various types of human normal and cancer tissues. To understand the tumorigenesis pathway of identified gremlin 1 protein, we performed a yeast two-hybrid screen, GST pull down assay, and immunoprecipitation to identify gremlin 1 interacting proteins. Results DDRT-PCR analysis revealed that gremlin 1 was overexpressed in uterine cervical cancer. We also identified a human gremlin 1 that was overexpressed in various human tumors including carcinomas of the lung, ovary, kidney, breast, colon, pancreas, and sarcoma. PIG-2-transfected HEK 293 cells exhibited growth stimulation and increased telomerase activity. Gremlin 1 interacted with homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide (14-3-3 eta; YWHAH. YWHAH protein binding site for gremlin 1 was located between residues 61–80 and gremlin 1 binding site for YWHAH was found to be located between residues 1 to 67. Conclusion Gremlin 1 may play an oncogenic role especially in carcinomas of the uterine cervix, lung, ovary, kidney, breast, colon, pancreas, and sarcoma. Over-expressed gremlin 1 functions by interaction with YWHAH. Therefore, Gremlin 1 and its binding

  14. 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.

  15. Human breast cancer cell-mediated bone collagen degradation requires plasminogen activation and matrix metalloproteinase activity

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    Hill Peter A

    2005-02-01

    Full Text Available Abstract Background Breast cancer cells frequently metastasize to the skeleton and induce extensive bone destruction. Cancer cells produce proteinases, including matrix metalloproteinases (MMPs and the plasminogen activator system (PAS which promote invasion of extracellular matrices, but whether these proteinases degrade bone matrix is unclear. To characterize the role that breast cancer cell proteinases play in bone degradation we compared the effects of three human breast cancer cell lines, MDA-MB-231, ZR-75-1 and MCF-7 with those of a normal breast epithelial cell line, HME. The cell lines were cultured atop radiolabelled matrices of either mineralized or non-mineralized bone or type I collagen, the principal organic constituent of bone. Results The 3 breast cancer cell lines all produced significant degradation of the 3 collagenous extracellular matrices (ECMs whilst the normal breast cell line was without effect. Breast cancer cells displayed an absolute requirement for serum to dissolve collagen. Degradation of collagen was abolished in plasminogen-depleted serum and could be restored by the addition of exogenous plasminogen. Localization of plasmin activity to the cell surface was critical for the degradation process as aprotinin, but not α2 antiplasmin, prevented collagen dissolution. During ECM degradation breast cancer cell lines expressed urokinase-type plasminogen activator (u-PA and uPA receptor, and MMPs-1, -3, -9,-13, and -14. The normal breast epithelial cell line expressed low levels of MMPs-1, and -3, uPA and uPA receptor. Inhibitors of both the PAS (aprotinin and PA inhibitor-1 and MMPs (CT1166 and tisue inhibitor of metalloproteinase blocked collagen degradation, demonstrating the requirement of both plasminogen activation and MMP activity for degradation. The activation of MMP-13 in human breast cancer cells was prevented by plasminogen activator inhibitor-1 but not by tissue inhibitor of metalloproteinase-1, suggesting

  16. Accumulation and biological effects of cobalt ferrite nanoparticles in human pancreatic and ovarian cancer cells.

    Science.gov (United States)

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

    2014-01-01

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

  17. 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.

  18. 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.

  19. Curcumin and emodin down-regulate TGF-β signaling pathway in human cervical cancer cells.

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    Pooja Chandrakant Thacker

    Full Text Available Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer.

  20. Paeonol reverses paclitaxel resistance in human breast cancer cells by regulating the expression of transgelin 2.

    Science.gov (United States)

    Cai, Jiangxia; Chen, Siying; Zhang, Weipeng; Hu, Sasa; Lu, Jun; Xing, Jianfeng; Dong, Yalin

    2014-06-15

    Paclitaxel (PTX) is a first-line antineoplastic drug that is commonly used in clinical chemotherapy for breast cancer treatment. However, the occurrence of drug resistance in chemotherapeutic treatment has greatly restricted its use. There is thus an urgent need to find ways of reversing paclitaxel chemotherapy resistance in breast cancer. Plant-derived agents have great potential in preventing the onset of the carcinogenic process and enhancing the efficacy of mainstream antitumor drugs. Paeonol, a main compound derived from the root bark of Paeonia suffruticosa, has various biological activities, and is reported to have reversal drug resistance effects. This study established a paclitaxel-resistant human breast cancer cell line (MCF-7/PTX) and applied the dual-luciferase reporter gene assay, MTT assay, flow cytometry, transfection assay, Western blotting and the quantitative real-time polymerase chain reaction (qRT-PCR) to investigate the reversing effects of paeonol and its underlying mechanisms. It was found that transgelin 2 may mediate the resistance of MCF-7/PTX cells to paclitaxel by up-regulating the expressions of the adenosine-triphosphate binding cassette transporter proteins, including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), and breast cancer resistance protein (BCRP). Furthermore, the ability of paeonol to reverse paclitaxel resistance in breast cancer was confirmed, with a superior 8.2-fold reversal index. In addition, this study found that paeonol down-regulated the transgelin 2-mediated paclitaxel resistance by reducing the expressions of P-gp, MRP1, and BCRP in MCF-7/PTX cells. These results not only provide insight into the potential application of paeonol to the reversal of paclitaxel resistance, thus facilitating the sensitivity of breast cancer chemotherapy, but also highlight a potential role of transgelin 2 in the development of paclitaxel resistance in breast cancer.

  1. Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence.

    Science.gov (United States)

    Alsbeih, Ghazi A; Al-Harbi, Najla M; Bin Judia, Sara S; Khoja, Hatim A; Shoukri, Mohamed M; Tulbah, Asma M

    2017-07-01

    Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  2. On-chip immunoelectrophoresis of extracellular vesicles released from human breast cancer cells.

    Science.gov (United States)

    Akagi, Takanori; Kato, Kei; Kobayashi, Masashi; Kosaka, Nobuyoshi; Ochiya, Takahiro; Ichiki, Takanori

    2015-01-01

    Extracellular vesicles (EVs) including exosomes and microvesicles have attracted considerable attention in the fields of cell biology and medicine. For a better understanding of EVs and further exploration of their applications, the development of analytical methods for biological nanovesicles has been required. In particular, considering the heterogeneity of EVs, methods capable of measuring individual vesicles are desired. Here, we report that on-chip immunoelectrophoresis can provide a useful method for the differential protein expression profiling of individual EVs. Electrophoresis experiments were performed on EVs collected from the culture supernatant of MDA-MB-231 human breast cancer cells using a measurement platform comprising a microcapillary electrophoresis chip and a laser dark-field microimaging system. The zeta potential distribution of EVs that reacted with an anti-human CD63 (exosome and microvesicle marker) antibody showed a marked positive shift as compared with that for the normal immunoglobulin G (IgG) isotype control. Thus, on-chip immunoelectrophoresis could sensitively detect the over-expression of CD63 glycoproteins on EVs. Moreover, to explore the applicability of on-chip immunoelectrophoresis to cancer diagnosis, EVs collected from the blood of a mouse tumor model were analyzed by this method. By comparing the zeta potential distributions of EVs after their immunochemical reaction with normal IgG, and the anti-human CD63 and anti-human CD44 (cancer stem cell marker) antibodies, EVs of tumor origin circulating in blood were differentially detected in the real sample. The result indicates that the present method is potentially applicable to liquid biopsy, a promising approach to the low-invasive diagnosis of cancer.

  3. On-chip immunoelectrophoresis of extracellular vesicles released from human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Takanori Akagi

    Full Text Available Extracellular vesicles (EVs including exosomes and microvesicles have attracted considerable attention in the fields of cell biology and medicine. For a better understanding of EVs and further exploration of their applications, the development of analytical methods for biological nanovesicles has been required. In particular, considering the heterogeneity of EVs, methods capable of measuring individual vesicles are desired. Here, we report that on-chip immunoelectrophoresis can provide a useful method for the differential protein expression profiling of individual EVs. Electrophoresis experiments were performed on EVs collected from the culture supernatant of MDA-MB-231 human breast cancer cells using a measurement platform comprising a microcapillary electrophoresis chip and a laser dark-field microimaging system. The zeta potential distribution of EVs that reacted with an anti-human CD63 (exosome and microvesicle marker antibody showed a marked positive shift as compared with that for the normal immunoglobulin G (IgG isotype control. Thus, on-chip immunoelectrophoresis could sensitively detect the over-expression of CD63 glycoproteins on EVs. Moreover, to explore the applicability of on-chip immunoelectrophoresis to cancer diagnosis, EVs collected from the blood of a mouse tumor model were analyzed by this method. By comparing the zeta potential distributions of EVs after their immunochemical reaction with normal IgG, and the anti-human CD63 and anti-human CD44 (cancer stem cell marker antibodies, EVs of tumor origin circulating in blood were differentially detected in the real sample. The result indicates that the present method is potentially applicable to liquid biopsy, a promising approach to the low-invasive diagnosis of cancer.

  4. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies

    DEFF Research Database (Denmark)

    Beral, V.; Bull, D.; Pirie, K.

    2012-01-01

    Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected w...

  5. Clinical efficacy of including capecitabine in neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis of randomized controlled trials.

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    Qiuyun Li

    Full Text Available BACKGROUND: Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients. METHODS: The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1. RESULTS: Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87-1.40, p = 0.43, pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83-1.18, p = 0.90, overall response rate (ORR; RR = 1.00, 95% CI 0.94-1.07, p = 0.93, or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93-1.04, p = 0.49. CONCLUSIONS: Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.

  6. Establishment of highly tumorigenic human colorectal cancer cell line (CR4 with properties of putative cancer stem cells.

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    Rebecca A Rowehl

    Full Text Available BACKGROUND: Colorectal cancer (CRC has the third highest mortality rates among the US population. According to the most recent concept of carcinogenesis, human tumors are organized hierarchically, and the top of it is occupied by malignant stem cells (cancer stem cells, CSCs, or cancer-initiating cells, CICs, which possess unlimited self-renewal and tumor-initiating capacities and high resistance to conventional therapies. To reflect the complexity and diversity of human tumors and to provide clinically and physiologically relevant cancer models, large banks of characterized patient-derived low-passage cell lines, and especially CIC-enriched cell lines, are urgently needed. PRINCIPAL FINDINGS: Here we report the establishment of a novel CIC-enriched, highly tumorigenic and clonogenic colon cancer cell line, CR4, derived from liver metastasis. This stable cell line was established by combining 3D culturing and 2D culturing in stem cell media, subcloning of cells with particular morphology, co-culture with carcinoma associated fibroblasts (CAFs and serial transplantation to NOD/SCID mice. Using RNA-Seq complete transcriptome profiling of the tumorigenic fraction of the CR4 cells in comparison to the bulk tumor cells, we have identified about 360 differentially expressed transcripts, many of which represent stemness, pluripotency and resistance to treatment. Majority of the established CR4 cells express common markers of stemness, including CD133, CD44, CD166, EpCAM, CD24 and Lgr5. Using immunocytochemical, FACS and western blot analyses, we have shown that a significant ratio of the CR4 cells express key markers of pluripotency markers, including Sox-2, Oct3/4 and c-Myc. Constitutive overactivation of ABC transporters and NF-kB and absence of tumor suppressors p53 and p21 may partially explain exceptional drug resistance of the CR4 cells. CONCLUSIONS: The highly tumorigenic and clonogenic CIC-enriched CR4 cell line may provide an important new

  7. The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer

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    Erhong Meng

    2015-07-01

    Full Text Available Defined cellular mechanisms have evolved that recognize and repair DNA to protect the integrity of its structure and sequence when encountering assaults from endogenous and exogenous sources. There are five major DNA repair pathways: mismatch repair, nucleotide excision repair, direct repair, base excision repair and DNA double strand break repair (including non-homologous end joining and homologous recombination repair. Aberrant activation of the Hedgehog (Hh signaling pathway is a feature of many cancer types. The Hh pathway has been documented to be indispensable for epithelial-mesenchymal transition, invasion and metastasis, cancer stemness, and chemoresistance. The functional transcription activators of the Hh pathway include the GLI proteins. Inhibition of the activity of GLI can interfere with almost all DNA repair types in human cancer, indicating that Hh/GLI functions may play an important role in enabling tumor cells to survive lethal types of DNA damage induced by chemotherapy and radiotherapy. Thus, Hh signaling presents an important therapeutic target to overcome DNA repair-enabled multi-drug resistance and consequently increase chemotherapeutic response in the treatment of cancer.

  8. The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Erhong; Hanna, Ann; Samant, Rajeev S.; Shevde, Lalita A., E-mail: lsamant@uab.edu [Department of Pathology, Comprehensive Cancer Center, University of Alabama at Birmingham, WTI320D, 1824 6th Avenue South, Birmingham, AL 35233 (United States)

    2015-07-21

    Defined cellular mechanisms have evolved that recognize and repair DNA to protect the integrity of its structure and sequence when encountering assaults from endogenous and exogenous sources. There are five major DNA repair pathways: mismatch repair, nucleotide excision repair, direct repair, base excision repair and DNA double strand break repair (including non-homologous end joining and homologous recombination repair). Aberrant activation of the Hedgehog (Hh) signaling pathway is a feature of many cancer types. The Hh pathway has been documented to be indispensable for epithelial-mesenchymal transition, invasion and metastasis, cancer stemness, and chemoresistance. The functional transcription activators of the Hh pathway include the GLI proteins. Inhibition of the activity of GLI can interfere with almost all DNA repair types in human cancer, indicating that Hh/GLI functions may play an important role in enabling tumor cells to survive lethal types of DNA damage induced by chemotherapy and radiotherapy. Thus, Hh signaling presents an important therapeutic target to overcome DNA repair-enabled multi-drug resistance and consequently increase chemotherapeutic response in the treatment of cancer.

  9. Racial and Ethnic Group Knowledge, Perceptions and Behaviors about Human Papillomavirus, Human Papillomavirus Vaccination, and Cervical Cancer among Adolescent Females.

    Science.gov (United States)

    Bond, Sharon M; Cartmell, Kathleen B; Lopez, Cristina M; Ford, Marvella E; Brandt, Heather M; Gore, Elena I; Zapka, Jane G; Alberg, Anthony J

    2016-10-01

    Human papillomavirus (HPV) vaccines provide an opportunity to greatly reduce the burden of cervical cancer. Although there has been improvement in uptake, there are notable ethnic/racial disparities. This qualitative study was conducted to better understand factors related to vaccine uptake among female adolescents from 3 racial/ethnic groups: African American (AA), Hispanic, and Caucasian. Findings can inform the development of optimal messages and strategies for clinical and population-based interventions. This mixed-methods descriptive study included completion of a brief structured survey and focus group discussion. Six focus groups were conducted with female adolescents, 2 each in the AA, Hispanic, and Caucasian groups. Brief structured survey questions and the focus group protocol addressed knowledge, perceptions, and behaviors related to HPV, HPV vaccination, and cervical cancer. Participants were 60 female adolescents (ages 13-19, mean age = 16.6 years) recruited from high schools, public health clinics, and churches. Themes across questions were remarkably similar among AA, Hispanic, and Caucasian participants. Each group had high awareness of the terms HPV, HPV vaccination, and cervical cancer, but with little in-depth knowledge about these topics. There was a high acceptance of HPV vaccination. Misperceptions about optimal cervical cancer prevention strategies such as simply knowing one's partner and good hygiene were most common among Hispanic adolescents. Awareness about Pap testing was most common among Caucasian adolescents. Predominantly uniform perceptions of HPV vaccines across racial/ethnic groups suggest a "one size fits all" approach will likely have greater reach with cervical cancer prevention messaging than culturally tailored interventions. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  10. Myeloid-derived suppressor cell heterogeneity in human cancers.

    Science.gov (United States)

    Solito, Samantha; Marigo, Ilaria; Pinton, Laura; Damuzzo, Vera; Mandruzzato, Susanna; Bronte, Vincenzo

    2014-06-01

    The dynamic interplay between cancer and host immune system often affects the process of myelopoiesis. As a consequence, tumor-derived factors sustain the accumulation and functional differentiation of myeloid cells, including myeloid-derived suppressor cells (MDSCs), which can interfere with T cell-mediated responses. Since both the phenotype and mechanisms of action of MDSCs appear to be tumor-dependent, it is important not only to determine the presence of all MDSC subsets in each cancer patient, but also which MDSC subsets have clinical relevance in each tumor environment. In this review, we describe the differences between MDSC populations expanded within different tumor contexts and evaluate the prognostic significance of MDSC expansion in peripheral blood and within tumor masses of neoplastic patients.

  11. 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.

  12. 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)

  13. Brain metastases in women with epithelial ovarian cancer: multimodal treatment including surgery or gamma-knife radiation is associated with prolonged survival.

    Science.gov (United States)

    Niu, Xiaoyu; Rajanbabu, Anupama; Delisle, Megan; Peng, Feng; Vijaykumar, Dehannathuparambil K; Pavithran, Keechilattu; Feng, Yukuan; Lau, Susie; Gotlieb, Walter H; Press, Joshua Z

    2013-09-01

    To explore the impact of treatment modality on survival in patients with brain metastases from epithelial ovarian cancer. We conducted a retrospective review of cases of ovarian cancer with brain metastases treated at institutions in three countries (Canada, China, and India) and conducted a search for studies regarding brain metastases in ovarian cancer reporting survival related to treatment modality. Survival was analyzed according to treatment regimens involving (1) some form of surgical excision or gamma-knife radiation with or without other modalities, (2) other modalities without surgery or gamma-knife radiation, or (3) palliation only. Twelve patients (mean age 56 years) with detailed treatment/outcome data were included; five were from China, four from Canada, and three from India. Median time from diagnosis of ovarian cancer to brain metastasis was 19 months (range 10 to 37 months), and overall median survival time from diagnosis of ovarian cancer was 38 months (13 to 82 months). Median survival time from diagnosis of brain metastasis was 17 months (1 to 45 months). Among patients who had multimodal treatment including gamma-knife radiotherapy or surgical excision, the median survival time after the identification of brain metastasis was 25.6 months, compared with 6.0 months in patients whose treatment did not include this type of focused localized modality (P = 0.006). Analysis of 20 studies also indicated that use of gamma-knife radiotherapy and excisional surgery in multi-modal treatment resulted in improved median survival interval (25 months vs. 6.0 months, P gamma-knife radiotherapy and surgical excision.

  14. A further review of inhalation studies with cigarette smoke and lung cancer in experimental animals, including transgenic mice.

    Science.gov (United States)

    Coggins, C R E

    2010-10-01

    The lack of an effective animal model for pulmonary carcinogenesis in smokers is a continuing problem for researchers trying to design Potentially Reduced Risk Products for those smokers who are either unwilling or unable to quit smoking. The major failing of inhalation assays with cigarette smoke in laboratory animals is that these assays produce only small percentages of animals with pulmonary tumors (e.g. adenomas, with the occasional adenocarcinoma), as opposed to the highly invasive carcinomas (e.g. small cell and squamous cell) seen in smokers. To update previous reviews on animal models, and to add different types of transgenic (Tg) mice to the review. Reviews were made of articles retrieved from PubMed and elsewhere. The addition of Tg mice to the arsenal of tests used for the evaluation of the carcinogenic potential of cigarettes did not result in any better understanding of the inability of such testing to reflect the epidemiological evidence for lung cancer in smokers. As in previous reviews on the subject, the best assay providing support for the epidemiology data is still the 5-month whole-body exposure of male A/J mice to a combination of mainstream/sidestream smoke, followed by a 4-month recovery.

  15. Increased Mortality of Respiratory Diseases, Including Lung Cancer, in the Area with Large Amount of Ashfall from Mount Sakurajima Volcano

    Directory of Open Access Journals (Sweden)

    Kenta Higuchi

    2012-01-01

    Full Text Available Objectives. Mount Sakurajima in Japan is one of the most active volcanoes in the world. This work was conducted to examine the effect of volcanic ash on the chronic respiratory disease mortality in the vicinity of Mt. Sakurajima. Methods. The present work examined the standardized mortality ratios (SMRs of respiratory diseases during the period 1968–2002 in Sakurajima town and Tarumizu city, where ashfall from the volcano recorded more than 10.000 g/m2/yr on average in the 1980s. Results. The SMR of lung cancer in the Sakurajima-Tarumizu area was 1.61 (95% CI = 1.44–1.78 for men and 1.67 (95% CI = 1.39–1.95 for women while it was nearly equal to one in Kanoya city, which neighbors Tarumizu city but located at the further position from Mt. Sakurajima, and therefore has much smaller amounts of ashfall. Sakurajima-Tarumizu area had elevated SMRs for COPDs and acute respiratory diseases while Kanoya did not. Conclusions. Cristobalite is the most likely cause of the increased deaths from those chronic respiratory diseases since smoking is unlikely to explain the increased mortality of respiratory diseases among women since the proportion of smokers in Japanese women is less than 20%, and SPM levels in the Sakurajima-Tarumizu area were not high. Further studies seem warranted.

  16. Ligand structure-function relationships in the vitamin D endocrine system from the perspective of drug development (including cancer treatment).

    Science.gov (United States)

    Norman, Anthony W; Mizwicki, Mathew T; Okamura, William H

    2003-01-01

    It has become readily apparent to many scientists and pharmaceutical companies that the vitamin D endocrine system offers a wide array of drug development opportunities. There are already successes, as noted by 1alpha,25(OH)2D3 (Roche, and Abbott) for renal osteodystrophy and osteoporosis and 1alpha(OH)D3 (Leo, Chugai, Teijin) for renal osteodystrophy and (in Japan) osteoporosis, 1alpha,24(OH)2-24-cyclopropyl-D3 (Dovonex) and 1alpha,24(OH)2D3 (Teijin) for psoriasis, and 19-nor-1alpha,25(OH)2D2 (Abbott) for renal osteodystrophy, as well as drugs under active development. Yet there are still many important and challenging drug development frontiers, particularly in the area of cancer treatment and immune system disorders where exploration is only in the initial early stages. In addition, the application of vitamin D-related drugs in neurology and brain pathology should not be overlooked. It is to be hoped that the cellular and molecular basis for the vexing problem of analog-induced hypercalcemia will be elucidated. Given that there are believed to be over 2000 analogs of 1alpha,25(OH)2D3 already available for consideration, it is to be expected that over the next decade a significant number of new vitamin D structure-function drug development projects will be brought to conclusion.

  17. Modeling human papillomavirus and cervical cancer in the United States for analyses of screening and vaccination

    Directory of Open Access Journals (Sweden)

    Ortendahl Jesse

    2007-10-01

    Full Text Available Abstract Background To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. Methods We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN, HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Results Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69–82% and 69% (60–77%, respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter

  18. 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

  19. Siah1 proteins enhance radiosensitivity of human breast cancer cells

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    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.

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

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    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.

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

    Science.gov (United States)

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

    2013-08-28

    To identify the role of human development in t