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Sample records for solid human cancers

  1. Radiosensitivity and cell kinetics of the human solid cancer transplanted to nude mouse

    International Nuclear Information System (INIS)

    Ikeuchi, Shunji

    1983-01-01

    This study was undertaken to analyse the relationship between radiosensitivity and cell kinetics of human solid cancer in experimental nude mouse system. Four strains of tumors used for the experiment were poorly differentiated squamous cell carcinoma of the lung (Lu-9), oat cell carcinoma of the lung (Lu-24), well differentiated squamous cell carcinoma of the tongue (To-1) and moderately differentiated squamous cell carcinoma of the esophagus (Es-4) which were serially transplantable to BALB/c nude mice. Radiosensitivity was evaluated by tumor growth in terms of inhibition rate, histological change and host reaction after irradiation. Cell kinetics were studied by autoradiography with pulse administration of 3 H-thymidine to mice. Although Lu-24 was most radiosensitive, followed by To-1, Es-4 and Lu-9 in the order of sensitivity, it was suggested that they might be more radioresistant in nude mice without T-cell function than in human. Regarding squamous cell carcinomas, well differentiated type was more radiosensitive than poorly differentiated one. All of these tumors in nude mouse revealed distinct percent labeled mitosis curves with two clear peaks which were quite different from those in human body. Lu-24 showed a characteristic pattern with a long time lag before visible growth, short G 1 , and low growth fraction, compared to other three tumors. Three strains of squamous cell carcinoma demonstrated similar cell kinetic factors which were almost the same as those in human body reported previously. The differences in volume doubling time of tumor, growth fraction and cell loss factor were partially related to those of radiosensitivities among tumors except for Lu-24. The theoretical volume doubling time was proved to be most reliable for estimation of effectiveness of irradiation, but the labeling index was not a valuable indicator for it. (author)

  2. Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors

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    Brellier Florence

    2012-09-01

    Full Text Available Abstract Background Tenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues. Tenascin-C is a well-studied biomarker known for its high overexpression in the stroma of most solid cancers. Tenascin-W, the least studied member of the family, is highly expressed in the stroma of colon and breast tumors and in gliomas, but not in the corresponding normal tissues. Other solid tumors have not been analyzed. The present study was undertaken to determine whether tenascin-W could serve as a cancer-specific extracellular matrix protein in a broad range of solid tumors. Methods We analyzed the expression of tenascin-W and tenascin-C by immunoblotting and by immunohistochemistry on multiple frozen tissue microarrays of carcinomas of the pancreas, kidney and lung as well as melanomas and compared them to healthy tissues. Results From all healthy adult organs tested, only liver and spleen showed detectable levels of tenascin-W, suggesting that tenascin-W is absent from most human adult organs under normal, non-pathological conditions. In contrast, tenascin-W was detectable in the majority of melanomas and their metastases, as well as in pancreas, kidney, and lung carcinomas. Comparing lung tumor samples and matching control tissues for each patient revealed a clear overexpression of tenascin-W in tumor tissues. Although the number of samples examined is too small to draw statistically significant conclusions, there seems to be a tendency for increased tenascin-W expression in higher grade tumors. Interestingly, in most tumor types, tenascin-W is also expressed in close proximity to blood vessels, as shown by CD31 co-staining of the samples. Conclusions The present study extends the tumor biomarker potential of tenascin-W to a broad range of solid tumors and shows its accessibility from the blood stream for potential therapeutic strategies.

  3. The quaternary state of polymerized human hemoglobin regulates oxygenation of breast cancer solid tumors: A theoretical and experimental study

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    Ju, Julia A.; Baek, Jin Hyen; Yalamanoglu, Ayla; Buehler, Paul W.; Gilkes, Daniele M.; Palmer, Andre F.

    2018-01-01

    A major constraint in the treatment of cancer is inadequate oxygenation of the tumor mass, which can reduce chemotherapeutic efficacy. We hypothesize that polymerized human hemoglobin (PolyhHb) can be transfused into the systemic circulation to increase solid tumor oxygenation, and improve chemotherapeutic outcomes. By locking PolyhHb in the relaxed (R) quaternary state, oxygen (O2) offloading at low O2 tensions (20 mm Hg) is facilitated with tense (T) state PolyhHb. Therefore, R-state PolyhHb may deliver significantly more O2 to hypoxic tissues. Biophysical parameters of T and R-state PolyhHb were used to populate a modified Krogh tissue cylinder model to assess O2 transport in a tumor. In general, we found that increasing the volume of transfused PolyhHb decreased the apparent viscosity of blood in the arteriole. In addition, we found that PolyhHb transfusion decreased the wall shear stress at large arteriole diameters (>20 μm), but increased wall shear stress for small arteriole diameters (state PolyhHb may be more effective than T-state PolyhHb for O2 delivery at similar transfusion volumes. Reduction in the apparent viscosity resulting from PolyhHb transfusion may result in significant changes in flow distributions throughout the tumor microcirculatory network. The difference in wall shear stress implies that PolyhHb may have a more significant effect in capillary beds through mechano-transduction. Periodic top-load transfusions of PolyhHb into mice bearing breast tumors confirmed the oxygenation potential of both PolyhHbs via reduced hypoxic volume, vascular density, tumor growth, and increased expression of hypoxia inducible genes. Tissue section analysis demonstrated primary PolyhHb clearance occurred in the liver and spleen indicating a minimal risk for renal damage. PMID:29414985

  4. Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype.

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    Sánchez-Vega, Francisco; Gotea, Valer; Margolin, Gennady; Elnitski, Laura

    2015-01-01

    The term CpG island methylator phenotype (CIMP) has been used to describe widespread DNA hypermethylation at CpG-rich genomic regions affecting clinically distinct subsets of cancer patients. Even though there have been numerous studies of CIMP in individual cancer types, a uniform analysis across tissues is still lacking. We analyze genome-wide patterns of CpG island hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA and 23 cancer cell lines from ENCODE. We identify differentially methylated loci that define CIMP+ and CIMP- samples, and we use unsupervised clustering to provide a robust molecular stratification of tumor methylomes for 12 cancer types and all cancer cell lines. With a minimal set of 89 discriminative loci, we demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations, based on their average levels of methylation. Tumor samples in different CIMP subclasses show distinctive correlations with gene expression profiles and recurrence of somatic mutations, copy number variations, and epigenetic silencing. Enrichment analyses indicate shared canonical pathways and upstream regulators for CIMP-targeted regions across cancer types. Furthermore, genomic alterations showing consistent associations with CIMP+/- status include genes involved in DNA repair, chromatin remodeling genes, and several histone methyltransferases. Associations of CIMP status with specific clinical features, including overall survival in several cancer types, highlight the importance of the CIMP+/- designation for individual tumor evaluation and personalized medicine. We present a comprehensive computational study of CIMP that reveals pan-cancer commonalities and tissue-specific differences underlying concurrent hypermethylation of CpG islands across tumors. Our stratification of solid tumors and cancer cell lines based on CIMP status is data-driven and agnostic to tumor type by design, which protects against known biases that have hindered

  5. Modulation of butyrate anticancer activity by solid lipid nanoparticle delivery: an in vitro investigation on human breast cancer and leukemia cell lines.

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    Foglietta, Federica; Serpe, Loredana; Canaparo, Roberto; Vivenza, Nicoletta; Riccio, Giovanna; Imbalzano, Erica; Gasco, Paolo; Zara, Gian Paolo

    2014-01-01

    Histone modification has emerged as a promising approach to cancer therapy. The short-chain fatty acid, butyric acid, a histone deacetylase (HD) inhibitor, has shown anticancer activity. Butyrate transcriptional activation is indeed able to withdraw cancer cells from the cell cycle, leading to programmed cell death. Since butyrate's clinical use is hampered by unfavorable pharmacokinetic and pharmacodynamic properties, delivery systems, such as solid lipid nanoparticles (SLN), have been developed to overcome these constraints. In order to outline the influence of butyrate delivery on its anticancer activity, the effects of butyrate as a free (sodium butyrate, NB) or nanoparticle (cholesteryl butyrate solid lipid nanoparticles, CBSLN) formulation on the growth of different human cancer cell lines, such as the promyelocytic leukemia, HL-60, and the breast cancer, MCF-7 was investigated. A detailed investigation into the mechanism of the induced cytotoxicity was also carried out, with a special focus on the modulation of HD and cyclin-dependent kinase (CDK) mRNA gene expression by real time PCR analysis. In HL-60 cells, CBSLN induced a higher and prolonged expression level of the butyrate target genes at lower concentrations than NB. This led to a significant decrease in cell proliferation, along with considerable apoptosis, cell cycle block in the G0/G1 phase, significant inhibition of total HD activity and overexpression of the p21 protein. Conversely, in MCF-7 cells, CBSLN did not enhance the level of expression of the butyrate target genes, leading to the same anticancer activity as that of NB. Solid lipid nanoparticles were able to improve butyrate anticancer activity in HL-60, but not in MCF-7 cells. This is consistent with difference in properties of the cells under study, such as expression of the TP53 tumor suppressor, or the transporter for short-chain fatty acids, SLC5A8.

  6. Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro

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    Simona Serini

    2018-02-01

    Full Text Available New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC, one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA. These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.

  7. The synergistic effect between vanillin and doxorubicin in ehrlich ascites carcinoma solid tumor and MCF-7 human breast cancer cell line.

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    Elsherbiny, Nehal M; Younis, Nahla N; Shaheen, Mohamed A; Elseweidy, Mohamed M

    2016-09-01

    Despite the remarkable anti-tumor activity of doxorubicin (DOX), its clinical application is limited due to multiple organ toxicities. Products with less side effects are therefore highly requested. The current study investigated the anti-cancer activities of vanillin against breast cancer and possible synergistic potentiation of DOX chemotherapeutic effects by vanillin. Vanillin (100mg/kg), DOX (2mg/kg) and their combination were administered i.p. to solid Ehrlich tumor-bearing mice for 21days. MCF-7 human breast cancer cell line was treated with vanillin (1 and 2mM), DOX (100μM) or their combination. Protection against DOX-induced nephrotoxicity was studied in rats that received vanillin (100mg/kg, ip) for 10days with a single dose of DOX (15mg/kg) on day 6. Vanillin exerted anticancer effects comparable to DOX and synergesticlly potentiated DOX anticancer effects both in-vivo and in-vitro. The anticancer potency of vanillin in-vivo was mediated via apoptosis and antioxidant capacity. It also offered an in-vitro growth inhibitory effect and cytotoxicity mediated by apoptosis (increased caspase-9 and Bax:Bcl-2 ratio) along with anti-metasasis effect. Vanillin protected against DOX-induced nephrotoxicity in rats. In conclusion, vanillin can be a potential lead molecule for the development of non-toxic agents for the treatment of breast cancer either alone or combined with DOX. Copyright © 2016. Published by Elsevier GmbH.

  8. In vitro antitumor efficacy of berberine: solid lipid nanoparticles against human HepG2, Huh7 and EC9706 cancer cell lines

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    Meng, Xiang-Ping; Wang, Xiao; Wang, Huai-ling; Chen, Tong-sheng; Wang, Yi-fei; Wang, Zhi-ping

    2016-03-01

    Hepatocarcinoma and esophageal squamous cell carcinomas threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma and esophageal carcinoma to chemotherapy. Berberine (Ber), an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma and antiesophageal carcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Ber loaded solid lipid nanoparticles (Ber-SLN) was prepared by hot melting and then high pressure homogenization technique. The in vitro anti-hepatocarcinoma and antiesophageal carcinoma effects of Ber-SLN relative to efficacy of bulk Ber were evaluated. The particle size and zeta potential of Ber-SLN were 154.3 ± 4.1 nm and -11.7 ± 1.8 mV, respectively. MTT assay showed that Ber-SLN effectively inhibited the proliferation of human HepG2 and Huh7 and EC9706 cells, and the corresponding IC50 value was 10.6 μg/ml, 5.1 μg/ml, and 7.3 μg/ml (18.3μg/ml, 6.5μg/ml, and 12.4μg/ml μg/ml of bulk Ber solution), respectively. These results suggest that the delivery of Ber-SLN is a promising approach for treating tumors.

  9. Adaptive Evolution Coupled with Retrotransposon Exaptation Allowed for the Generation of a Human-Protein-Specific Coding Gene That Promotes Cancer Cell Proliferation and Metastasis in Both Haematological Malignancies and Solid Tumours: The Extraordinary Case of MYEOV Gene

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    Spyros I. Papamichos

    2015-01-01

    Full Text Available The incidence of cancer in human is high as compared to chimpanzee. However previous analysis has documented that numerous human cancer-related genes are highly conserved in chimpanzee. Till date whether human genome includes species-specific cancer-related genes that could potentially contribute to a higher cancer susceptibility remains obscure. This study focuses on MYEOV, an oncogene encoding for two protein isoforms, reported as causally involved in promoting cancer cell proliferation and metastasis in both haematological malignancies and solid tumours. First we document, via stringent in silico analysis, that MYEOV arose de novo in Catarrhini. We show that MYEOV short-isoform start codon was evolutionarily acquired after Catarrhini/Platyrrhini divergence. Throughout the course of Catarrhini evolution MYEOV acquired a gradually elongated translatable open reading frame (ORF, a gradually shortened translation-regulatory upstream ORF, and alternatively spliced mRNA variants. A point mutation introduced in human allowed for the acquisition of MYEOV long-isoform start codon. Second, we demonstrate the precious impact of exonized transposable elements on the creation of MYEOV gene structure. Third, we highlight that the initial part of MYEOV long-isoform coding DNA sequence was under positive selection pressure during Catarrhini evolution. MYEOV represents a Primate Orphan Gene that acquired, via ORF expansion, a human-protein-specific coding potential.

  10. Advanced Solid State Lighting for Human Evaluation

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    National Aeronautics and Space Administration — Lighting intensity and color have a significant impact on human circadian rhythms.  Advanced solid state lighting was developed for the Advanced Exploration System...

  11. Human Breast Cancer Histoid

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    Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R.; Ingram, Marylou

    2011-01-01

    Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue. PMID:22034518

  12. Radioimmunotherapy of solid cancers. A review

    International Nuclear Information System (INIS)

    Kairemo, K.J.A.

    1996-01-01

    Depending on radionuclide characteristics, radioimmunotherapy (RIT) relies on radioactivity to destroy cells distant from immunotargeted cells. Therefore, even heterogeneous tumors (for antigen recognition) can be treated, because not all cells have to be targeted. Substantial complete response rates have been reported in patients with non-Hodgkin's lymphoma. Much more modest results have been reported for patients iwth bulky solid tumors, e.g. adenocarcinomas. The radiation doses delivered by targeting antibodies are generally too low to achieve major therapeutic responses. Dose escalation is limited by myelotoxicity, and higher doses need to be delivered to neoplasmas less radiosensitive than lymphomas. Various trials for both systematic and regional RIT have been reported on. Intraperitoneal adminostration has been applied for colorectal and ovarian carcinomas. Our own results indicate that, e.g., intraperitoneal pseudomyxoma can be treated with RIT. Myelotoxicity can be reduced by anti-antibody-enhancement, 2- and 3-step strategies, bispecific monoclonal antibodies (MABs), and extracorporeal immunoadsorption. The radionuclide has to be selected properly for each purpose; it can be a β-emitter, e.g. I-131, Y-90, Re-188, Re-186, Lu-177 or Sm-153, an α-emitter At-211 or Bi-212 or an Auger-emitter, e.g. I-125, I-123. One major problem with RIT, besides slow penetration rate into tumor tissue and low tumor-to-normal tissue ratio, is the HAMA response, which can be partly avoided by the use of humanized MAbs and immunosuppression. However, RIT will be, because of all the recent developments, an important form of cancer management. (orig.)

  13. Human papillomaviruses and cancer

    International Nuclear Information System (INIS)

    Haedicke, Juliane; Iftner, Thomas

    2013-01-01

    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

  14. A Tumor-stroma Targeted Oncolytic Adenovirus Replicated in Human Ovary Cancer Samples and Inhibited Growth of Disseminated Solid Tumors in Mice

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    Lopez, M Veronica; Rivera, Angel A; Viale, Diego L; Benedetti, Lorena; Cuneo, Nicasio; Kimball, Kristopher J; Wang, Minghui; Douglas, Joanne T; Zhu, Zeng B; Bravo, Alicia I; Gidekel, Manuel; Alvarez, Ronald D; Curiel, David T; Podhajcer, Osvaldo L

    2012-01-01

    Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 1010 v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15–40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression. PMID:22948673

  15. Torrefaction Processing for Human Solid Waste Management

    Science.gov (United States)

    Serio, Michael A.; Cosgrove, Joseph E.; Wójtowicz, Marek A.; Stapleton, Thomas J.; Nalette, Tim A.; Ewert, Michael K.; Lee, Jeffrey; Fisher, John

    2016-01-01

    This study involved a torrefaction (mild pyrolysis) processing approach that could be used to sterilize feces and produce a stable, odor-free solid product that can be stored or recycled, and also to simultaneously recover moisture. It was demonstrated that mild heating (200-250 C) in nitrogen or air was adequate for torrefaction of a fecal simulant and an analog of human solid waste (canine feces). The net result was a nearly undetectable odor (for the canine feces), complete recovery of moisture, some additional water production, a modest reduction of the dry solid mass, and the production of small amounts of gas and liquid. The liquid product is mainly water, with a small Total Organic Carbon content. The amount of solid vs gas plus liquid products can be controlled by adjusting the torrefaction conditions (final temperature, holding time), and the current work has shown that the benefits of torrefaction could be achieved in a low temperature range (< 250 C). These temperatures are compatible with the PTFE bag materials historically used by NASA for fecal waste containment and will reduce the energy consumption of the process. The solid product was a dry material that did not support bacterial growth and was hydrophobic relative to the starting material. In the case of canine feces, the solid product was a mechanically friable material that could be easily compacted to a significantly smaller volume (approx. 50%). The proposed Torrefaction Processing Unit (TPU) would be designed to be compatible with the Universal Waste Management System (UWMS), now under development by NASA. A stand-alone TPU could be used to treat the canister from the UWMS, along with other types of wet solid wastes, with either conventional or microwave heating. Over time, a more complete integration of the TPU and the UWMS could be achieved, but will require design changes in both units.

  16. Thyroid Adenomas After Solid Cancer in Childhood

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    Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Adjadj, Elisabeth [Radiation Epidemiology Group, INSERM, Villejuif (France); Institut Gustave Roussy, Villejuif (France); Univ. Paris-Sud, Villejuif (France); Thomas-Teinturier, Cecile [Radiation Epidemiology Group, INSERM, Villejuif (France); Hopital Bicetre, Bicetre (France); Oberlin, Odile [Radiation Epidemiology Group, INSERM, Villejuif (France); Institut Gustave Roussy, Villejuif (France); Veres, Cristina [Radiation Epidemiology Group, INSERM, Villejuif (France); Institut Gustave Roussy, Villejuif (France); Univ. Paris-Sud, Villejuif (France); Pacquement, Helene [Institut Curie, Paris (France); Jackson, Angela [Radiation Epidemiology Group, INSERM, Villejuif (France); Institut Gustave Roussy, Villejuif (France); Univ. Paris-Sud, Villejuif (France); Munzer, Martine; N' Guyen, Tan Dat [Institut Jean Godinot, Reims (France); Bondiau, Pierre-Yves [Centre Antoine Lacassagne, Nice (France); Berchery, Delphine; Laprie, Anne [Centre Claudius Regaud, Toulouse (France); Bridier, Andre; Lefkopoulos, Dimitri [Institut Gustave Roussy, Villejuif (France); Schlumberger, Martin [Institut Gustave Roussy, Villejuif (France); Univ. Paris-Sud, Villejuif (France); Rubino, Carole; Diallo, Ibrahima [Radiation Epidemiology Group, INSERM, Villejuif (France); Institut Gustave Roussy, Villejuif (France); Univ. Paris-Sud, Villejuif (France); Vathaire, Florent de, E-mail: florent.devathaire@igr.fr [Radiation Epidemiology Group, INSERM, Villejuif (France); Institut Gustave Roussy, Villejuif (France); Univ. Paris-Sud, Villejuif (France)

    2012-10-01

    Purpose: Very few childhood cancer survivor studies have been devoted to thyroid adenomas. We assessed the role of chemotherapy and the radiation dose to the thyroid in the risk of thyroid adenoma after childhood cancer. Methods and Materials: A cohort of 3254 2-year survivors of a solid childhood cancer treated in 5 French centers before 1986 was established. The dose received by the isthmus and the 2 lobes of the thyroid gland during each course of radiation therapy was estimated after reconstruction of the actual radiation therapy conditions in which each child was treated as well as the dose received at other anatomical sites of interest. Results: After a median follow-up of 25 years, 71 patients had developed a thyroid adenoma. The risk strongly increased with the radiation dose to the thyroid up to a few Gray, plateaued, and declined for high doses. Chemotherapy slightly increased the risk when administered alone but also lowered the slope of the dose-response curve for the radiation dose to the thyroid. Overall, for doses up to a few Gray, the excess relative risk of thyroid adenoma per Gray was 2.8 (90% CI: 1.2-6.9), but it was 5.5 (90% CI: 1.9-25.9) in patients who had not received chemotherapy or who had received only 1 drug, and 1.1 (90% CI: 0.4-3.4) in the children who had received more than 1 drug (P=.06, for the difference). The excess relative risk per Gray was also higher for younger children at the time of radiation therapy than for their older counterparts and was higher before attaining 40 years of age than subsequently. Conclusions: The overall pattern of thyroid adenoma after radiation therapy for a childhood cancer appears to be similar to that observed for thyroid carcinoma.

  17. Thyroid Adenomas After Solid Cancer in Childhood

    International Nuclear Information System (INIS)

    Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Adjadj, Elisabeth; Thomas-Teinturier, Cécile; Oberlin, Odile; Veres, Cristina; Pacquement, Hélène; Jackson, Angela; Munzer, Martine; N'Guyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Bridier, André; Lefkopoulos, Dimitri; Schlumberger, Martin; Rubino, Carole; Diallo, Ibrahima; Vathaire, Florent de

    2012-01-01

    Purpose: Very few childhood cancer survivor studies have been devoted to thyroid adenomas. We assessed the role of chemotherapy and the radiation dose to the thyroid in the risk of thyroid adenoma after childhood cancer. Methods and Materials: A cohort of 3254 2-year survivors of a solid childhood cancer treated in 5 French centers before 1986 was established. The dose received by the isthmus and the 2 lobes of the thyroid gland during each course of radiation therapy was estimated after reconstruction of the actual radiation therapy conditions in which each child was treated as well as the dose received at other anatomical sites of interest. Results: After a median follow-up of 25 years, 71 patients had developed a thyroid adenoma. The risk strongly increased with the radiation dose to the thyroid up to a few Gray, plateaued, and declined for high doses. Chemotherapy slightly increased the risk when administered alone but also lowered the slope of the dose-response curve for the radiation dose to the thyroid. Overall, for doses up to a few Gray, the excess relative risk of thyroid adenoma per Gray was 2.8 (90% CI: 1.2-6.9), but it was 5.5 (90% CI: 1.9-25.9) in patients who had not received chemotherapy or who had received only 1 drug, and 1.1 (90% CI: 0.4-3.4) in the children who had received more than 1 drug (P=.06, for the difference). The excess relative risk per Gray was also higher for younger children at the time of radiation therapy than for their older counterparts and was higher before attaining 40 years of age than subsequently. Conclusions: The overall pattern of thyroid adenoma after radiation therapy for a childhood cancer appears to be similar to that observed for thyroid carcinoma.

  18. Colon cancer associated transcripts in human cancers.

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

    2017-10-01

    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.

  19. Advances in Cancer Immunotherapy in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Smitha Menon

    2016-11-01

    Full Text Available Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field.

  20. HUMAN PROSTATE CANCER RISK FACTORS

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

  1. Combination of Vaccine-Strain Measles and Mumps Viruses Enhances Oncolytic Activity against Human Solid Malignancies.

    Science.gov (United States)

    Son, Ho Anh; Zhang, LiFeng; Cuong, Bui Khac; Van Tong, Hoang; Cuong, Le Duy; Hang, Ngo Thu; Nhung, Hoang Thi My; Yamamoto, Naoki; Toan, Nguyen Linh

    2018-02-07

    Oncolytic measles and mumps viruses (MeV, MuV) have a potential for anti-cancer treatment. We examined the anti-tumor activity of MeV, MuV, and MeV-MuV combination (MM) against human solid malignancies (HSM). MeV, MuV, and MM targeted and significantly killed various cancer cell lines of HSM but not normal cells. MM demonstrated a greater anti-tumor effect and prolonged survival in a human prostate cancer xenograft tumor model compared to MeV and MuV. MeV, MuV, and MM significantly induced the expression of immunogenic cell death markers and enhanced spleen-infiltrating immune cells. In conclusion, MM combination significantly improves the treatment of human solid malignancies.

  2. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  3. Human papillomavirus associated oropharyngeal cancer

    International Nuclear Information System (INIS)

    Stefanicka, P.

    2015-01-01

    Recently, there is substantial epidemiological, molecular-pathological and experimental evidence indicating that some of the high-risk human papillomavirus (HR-HPV), especially HPV type 16, are etiologically related to a subset of head and neck squamous cell carcinomas, in particular, those arising from the oropharynx. Incidence of oropharyngeal cancer is increasing in direct opposition to a decreasing incidence of all other head and neck cancers. The prognosis of patients with HPV associated oropharyngeal cancer is significantly better compare to patients with non associated oropharyngeal cancers. Patients with HPV-positive oropharyngeal cancer respond better to radiotherapy, surgery, chemoradiotherapy. Therefore, the presence of HPV in tumor is the most important prognostic factor in patients with oropharyngeal cancers. These findings have prompted the need for change of treatment strategies in these patients. The goal is selective de-intensified treatment stratified for HPV status. (author)

  4. Palliative Care Use Among Patients With Solid Cancer Tumors: A National Cancer Data Base Study.

    Science.gov (United States)

    Osagiede, Osayande; Colibaseanu, Dorin T; Spaulding, Aaron C; Frank, Ryan D; Merchea, Amit; Kelley, Scott R; Uitti, Ryan J; Ailawadhi, Sikander

    2018-01-01

    Palliative care has been increasingly recognized as an important part of cancer care but remains underutilized in patients with solid cancers. There is a current gap in knowledge regarding why palliative care is underutilized nationwide. To identify the factors associated with palliative care use among deceased patients with solid cancer tumors. Using the 2016 National Cancer Data Base, we identified deceased patients (2004-2013) with breast, colon, lung, melanoma, and prostate cancer. Data were described as percentages. Associations between palliative care use and patient, facility, and geographic characteristics were evaluated through multivariate logistic regression. A total of 1 840 111 patients were analyzed; 9.6% received palliative care. Palliative care use was higher in the following patient groups: survival >24 months (17% vs 2%), male (54% vs 46%), higher Charlson-Deyo comorbidity score (16% vs 8%), treatment at designated cancer programs (74% vs 71%), lung cancer (76% vs 28%), higher grade cancer (53% vs 24%), and stage IV cancer (59% vs 13%). Patients who lived in communities with a greater percentage of high school degrees had higher odds of receiving palliative care; Central and Pacific regions of the United States had lower odds of palliative care use than the East Coast. Patients with colon, melanoma, or prostate cancer had lower odds of palliative care than patients with breast cancer, whereas those with lung cancer had higher odds. Palliative care use in solid cancer tumors is variable, with a preference for patients with lung cancer, younger age, known insurance status, and higher educational level.

  5. Human Prostate Cancer Hallmarks Map

    Science.gov (United States)

    Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-01-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

  6. HCSD: the human cancer secretome database

    DEFF Research Database (Denmark)

    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...... 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...

  7. Human papillomavirus and genital cancer

    Directory of Open Access Journals (Sweden)

    Rapose Alwyn

    2009-01-01

    Full Text Available Human papillomavirus (HPV is one of the most common sexually transmitted infections world-wide. Low-risk HPV-types are associated with genital warts. Persistent infection with high-risk HPV-types is associated with genital cancers. Smoking and HIV infection have consistently been associated with longer duration of HPV infection and risk for genital cancer. There is an increasing incidence of anal cancers, and a close association with HPV infection has been demonstrated. Receptive anal sex and HIV-positive status are associated with a high risk for anal cancer. Two HPV vaccines are now available and offer protection from infection by the HPV-types included in the vaccine. This benefit is maximally seen in young women who were uninfected prior to vaccination.

  8. Human antimicrobial peptides and cancer.

    Science.gov (United States)

    Jin, Ge; Weinberg, Aaron

    2018-05-30

    Antimicrobial peptides (AMPs) have long been a topic of interest for entomologists, biologists, immunologists and clinicians because of these agents' intriguing origins in insects, their ubiquitous expression in many life forms, their capacity to kill a wide range of bacteria, fungi and viruses, their role in innate immunity as microbicidal and immunoregulatory agents that orchestrate cross-talk with the adaptive immune system, and, most recently, their association with cancer. We and others have theorized that surveillance through epithelial cell-derived AMPs functions to keep the natural flora of microorganisms in a steady state in different niches such as the skin, the intestines, and the mouth. More recently, findings related to specific activation pathways of some of these AMPs have led investigators to associate them with pro-tumoral activity; i.e., contributing to a tumorigenic microenvironment. This area is still in its infancy as there are intriguing yet contradictory findings demonstrating that while some AMPs have anti-tumoral activity and are under-expressed in solid tumors, others are overexpressed and pro-tumorigenic. This review will introduce a new paradigm in cancer biology as it relates to AMP activity in neoplasia to address the following questions: Is there evidence that AMPs contribute to tumor promoting microenvironments? Can an anti-AMP strategy be of use in cancer therapy? Do AMPs, expressed in and released from tumors, contribute to compositional shifting of bacteria in cancerous lesions? Can specific AMP expression characteristics be used one day as early warning signs for solid tumors? Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. 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 PMID:26566288

  10. Development of curcumin-loaded solid lipid nanoparticles utilizing glyceryl monostearate as single lipid using QbD approach: Characterization and Evaluation of anticancer activity against human breast cancer cell line.

    Science.gov (United States)

    Bhatt, Himanshu; Rompicharla, Sri Vishnu Kiran; Komanduri, Neeraja; Shah, Aashma; Paradkar, Sateja; Ghosh, Balaram; Biswas, Swati

    2018-05-03

    Solid lipid nanoparticles (SLNs) represent an affordable, easily scalable, stable and biocompatible drug delivery system with a high drug to lipid ratio which also improves solubility of poorly soluble drugs. SLNs were developed by using glyceryl monostearate as the single lipid in presence of surfactant Poloxamer 188 and evaluated the efficiency of the SLNs to load the therapeutic cargo, curcumin (CUR). The nano-formulation was optimized by Quality by Design approach to understand the effect of various process parameters on various quality attributes, including drug loadability, particle size and polydispersity. The nanoparticles were characterized using Differential scanning calorimetry (DSC), Fourier Transform Infra-red Spectroscopy (FT-IR) and X-Ray Diffraction (XRD) analysis. These novel SLNs were evaluated for in-vitro anticancer activity using breast adenocarcinoma cells (MDA-MB-231). The optimized formulation had particle size of 226.802±3.92 nm with low polydispersity index of 0.244±0.018. The % encapsulation of CUR into SLNs was found to be 67.88±2.08 %. DSC, FT-IR and XRD confirmed that the CUR was encapsulated stably into the lipid matrix, thereby improving the solubility of the drug. CUR-SLN showed sustained drug release in comparison to the free CUR solution. CUR-SLNs exhibited higher cellular uptake in human breast adenocarcinoma cells compared to free CUR at both 1 and 4 h time points. CUR-SLNs demonstrated decreased cell viability (43.97±1.53%) compared to free CUR (59.33±0.95%) at a concentration of 50 μg/mL after 24 h treatment. Further, treatment of MDA-MB-231 cells with CUR-SLNs for 24 h induced significantly higher apoptosis (37.28±5.3%) in cells compared to the free CUR (21.06±0.97%). The results provide strong rationale for further exploration of the newly developed CUR-SLN to be utilized as a potent chemotherapeutic agent in cancer therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Radiation risk models for all solid cancers other than those types of cancer requiring individual assessments after a nuclear accident

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Linda [Federal Office for Radiation Protection, Department ' ' Radiation Protection and Health' ' , Oberschleissheim (Germany); University of Zurich, Medical Physics Group, Institute of Physics, Zurich (Switzerland); Zhang, Wei [Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Oxford (United Kingdom)

    2016-03-15

    In the assessment of health risks after nuclear accidents, some health consequences require special attention. For example, in their 2013 report on health risk assessment after the Fukushima nuclear accident, the World Health Organisation (WHO) panel of experts considered risks of breast cancer, thyroid cancer and leukaemia. For these specific cancer types, use was made of already published excess relative risk (ERR) and excess absolute risk (EAR) models for radiation-related cancer incidence fitted to the epidemiological data from the Japanese A-bomb Life Span Study (LSS). However, it was also considered important to assess all other types of solid cancer together and the WHO, in their above-mentioned report, stated ''No model to calculate the risk for all other solid cancer excluding breast and thyroid cancer risks is available from the LSS data''. Applying the LSS models for all solid cancers along with the models for the specific sites means that some cancers have an overlap in the risk evaluations. Thus, calculating the total solid cancer risk plus the breast cancer risk plus the thyroid cancer risk can overestimate the total risk by several per cent. Therefore, the purpose of this paper was to publish the required models for all other solid cancers, i.e. all solid cancers other than those types of cancer requiring special attention after a nuclear accident. The new models presented here have been fitted to the same LSS data set from which the risks provided by the WHO were derived. Although it is known already that the EAR and ERR effect modifications by sex are statistically significant for the outcome ''all solid cancer'', it is shown here that sex modification is not statistically significant for the outcome ''all solid cancer other than thyroid and breast cancer''. It is also shown here that the sex-averaged solid cancer risks with and without the sex modification are very similar once breast and

  12. Radiation risk models for all solid cancers other than those types of cancer requiring individual assessments after a nuclear accident

    International Nuclear Information System (INIS)

    Walsh, Linda; Zhang, Wei

    2016-01-01

    In the assessment of health risks after nuclear accidents, some health consequences require special attention. For example, in their 2013 report on health risk assessment after the Fukushima nuclear accident, the World Health Organisation (WHO) panel of experts considered risks of breast cancer, thyroid cancer and leukaemia. For these specific cancer types, use was made of already published excess relative risk (ERR) and excess absolute risk (EAR) models for radiation-related cancer incidence fitted to the epidemiological data from the Japanese A-bomb Life Span Study (LSS). However, it was also considered important to assess all other types of solid cancer together and the WHO, in their above-mentioned report, stated ''No model to calculate the risk for all other solid cancer excluding breast and thyroid cancer risks is available from the LSS data''. Applying the LSS models for all solid cancers along with the models for the specific sites means that some cancers have an overlap in the risk evaluations. Thus, calculating the total solid cancer risk plus the breast cancer risk plus the thyroid cancer risk can overestimate the total risk by several per cent. Therefore, the purpose of this paper was to publish the required models for all other solid cancers, i.e. all solid cancers other than those types of cancer requiring special attention after a nuclear accident. The new models presented here have been fitted to the same LSS data set from which the risks provided by the WHO were derived. Although it is known already that the EAR and ERR effect modifications by sex are statistically significant for the outcome ''all solid cancer'', it is shown here that sex modification is not statistically significant for the outcome ''all solid cancer other than thyroid and breast cancer''. It is also shown here that the sex-averaged solid cancer risks with and without the sex modification are very similar once breast and thyroid cancers are factored out. Some other notable model

  13. Nanobodies As Novel Agents for Targeting Angiogenesis in Solid Cancers

    Directory of Open Access Journals (Sweden)

    Roghaye Arezumand

    2017-12-01

    Full Text Available Solid cancers are dependent on angiogenesis for sustenance. The FDA approval of Bevacizumab in 2004 inspired many scientists to develop more inhibitors of angiogenesis. Although several monoclonal antibodies (mAbs are being administered to successfully combat various pathologies, the complexity and large size of mAbs seem to narrow the therapeutic applications. To improve the performance of cancer therapeutics, including those blocking tumor angiogenesis, attractive strategies such as miniaturization of the antibodies have been introduced. Nanobodies (Nbs, small single-domain antigen-binding antibody fragments, are becoming promising therapeutic and diagnostic proteins in oncology due to their favorable unique structural and functional properties. This review focuses on the potential and state of the art of Nbs to inhibit the angiogenic process for therapy and the use of labeled Nbs for non-invasive in vivo imaging of the tumors.

  14. 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.

  15. 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...

  16. CUB-domain-containing protein 1 overexpression in solid cancers promotes cancer cell growth by activating Src family kinases.

    Science.gov (United States)

    Leroy, C; Shen, Q; Strande, V; Meyer, R; McLaughlin, M E; Lezan, E; Bentires-Alj, M; Voshol, H; Bonenfant, D; Alex Gaither, L

    2015-10-29

    The transmembrane glycoprotein, CUB (complement C1r/C1s, Uegf, Bmp1) domain-containing protein 1 (CDCP1) is overexpressed in several cancer types and is a predictor of poor prognosis for patients on standard of care therapies. Phosphorylation of CDCP1 tyrosine sites is induced upon loss of cell adhesion and is thought to be linked to metastatic potential of tumor cells. Using a tyrosine-phosphoproteomics screening approach, we characterized the phosphorylation state of CDCP1 across a panel of breast cancer cell lines. We focused on two phospho-tyrosine pTyr peptides of CDCP1, containing Tyr707 and Tyr806, which were identified in all six lines, with the human epidermal growth factor 2-positive HCC1954 cells showing a particularly high phosphorylation level. Pharmacological modulation of tyrosine phosphorylation indicated that, the Src family kinases (SFKs) were found to phosphorylate CDCP1 at Tyr707 and Tyr806 and play a critical role in CDCP1 activity. We demonstrated that CDCP1 overexpression in HEK293 cells increases global phosphotyrosine content, promotes anchorage-independent cell growth and activates several SFK members. Conversely, CDCP1 downregulation in multiple solid cancer cell lines decreased both cell growth and SFK activation. Analysis of primary human tumor samples demonstrated a correlation between CDCP1 expression, SFK and protein kinase C (PKC) activity. Taken together, our results suggest that CDCP1 overexpression could be an interesting therapeutic target in multiple solid cancers and a good biomarker to stratify patients who could benefit from an anti-SFK-targeted therapy. Our data also show that multiple tyrosine phosphorylation sites of CDCP1 are important for the functional regulation of SFKs in several tumor types.

  17. Prevalence of Human Papillomavirus in endometrial cancer

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  18. Human papilloma virus in oral cancer

    OpenAIRE

    Kim, Soung Min

    2016-01-01

    Cervical cancer is the second most prevalent cancer among women, and it arises from cells that originate in the cervix uteri. Among several causes of cervical malignancies, infection with some types of human papilloma virus (HPV) is well known to be the greatest cervical cancer risk factor. Over 150 subtypes of HPV have been identified; more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region and oral cavity. The recently introduced vaccine ...

  19. A Mouse Model for Human Anal Cancer

    Science.gov (United States)

    Stelzer, Marie K.; Pitot, Henry C.; Liem, Amy; Schweizer, Johannes; Mahoney, Charles; Lambert, Paul F.

    2010-01-01

    Human anal cancers are associated with high-risk human papillomaviruses (HPVs) that cause other anogenital cancers and head and neck cancers. As with other cancers, HPV16 is the most common high-risk HPV in anal cancers. We describe the generation and characterization of a mouse model for human anal cancer. This model makes use of K14E6 and K14E7 transgenic mice in which the HPV16 E6 and E7 genes are directed in their expression to stratified squamous epithelia. HPV16 E6 and E7 possess oncogenic properties including but not limited to their capacity to inactivate the cellular tumor suppressors p53 and pRb, respectively. Both E6 and E7 were found to be functionally expressed in the anal epithelia of K14E6/K14E7 transgenic mice. To assess the susceptibility of these mice to anal cancer, mice were treated topically with dimethylbenz[a]anthracene (DMBA), a chemical carcinogen that is known to induce squamous cell carcinomas in other sites. Nearly 50% of DMBA-treated HPV16 E6/E7 transgenic mice showed overt signs of tumors; whereas, none of the like treated non-transgenic mice showed tumors. Histopathological analyses confirmed that the HPV16 transgenic mice were increased in their susceptibility to anal cancers and precancerous lesions. Biomarker analyses demonstrated that these mouse anal cancers exhibit properties that are similar to those observed in HPV-positive precursors to human anal cancer. This is the first mouse model for investigating the contributions of viral and cellular factors in anal carcinogenesis, and should provide a platform for assessing new therapeutic modalities for treating and/or preventing this type of cancer. PMID:20947489

  20. Sustained Cytotoxicity of Wogonin on Breast Cancer Cells by Encapsulation in Solid Lipid Nanoparticles

    Directory of Open Access Journals (Sweden)

    Jong-Suep Baek

    2018-03-01

    Full Text Available While wogonin has been known to have cytotoxicity against various cancer cells, its bioavailability and cytotoxicity are low due to its low water solubility. Therefore, wogonin-loaded solid lipid nanoparticles were fabricated using a hot-melted evaporation technique. The highest solubility of wogonin was observed in stearic acid. Hence, wogonin-loaded solid lipid nanoparticles were composed of stearic acid as the lipid matrix. The physicochemical properties of the wogonin-loaded solid lipid nanoparticles were evaluated by dynamic laser scattering and scanning electron microscopy. The wogonin-loaded solid lipid nanoparticles exhibited sustained and controlled release up to 72 h. In addition, it was observed that the wogonin-loaded solid lipid nanoparticles exhibited enhanced cytotoxicity and inhibited poly (ADP-ribose polymerase in MCF-7 breast cancer cells. Overall, the results indicate that wogonin-loaded solid lipid nanoparticles could be an efficient delivery system for the treatment of breast cancer.

  1. Cancer stem cells in solid tumors: is 'evading apoptosis' a hallmark of cancer?

    Science.gov (United States)

    Enderling, Heiko; Hahnfeldt, Philip

    2011-08-01

    Conventional wisdom has long held that once a cancer cell has developed it will inevitably progress to clinical disease. Updating this paradigm, it has more recently become apparent that the tumor interacts with its microenvironment and that some environmental bottlenecks, such as the angiogenic switch, must be overcome for the tumor to progress. In parallel, attraction has been drawn to the concept that there is a minority population of cells - the cancer stem cells - bestowed with the exclusive ability to self-renew and regenerate the tumor. With therapeutic targeting issues at stake, much attention has shifted to the identification of cancer stem cells, the thinking being that the remaining non-stem population, already fated to die, will play a negligible role in tumor development. In fact, the newly appreciated importance of intercellular interactions in cancer development also extends in a unique and unexpected way to interactions between the stem and non-stem compartments of the tumor. Here we discuss recent findings drawn from a hybrid mathematical-cellular automaton model that simulates growth of a heterogeneous solid tumor comprised of cancer stem cells and non-stem cancer cells. The model shows how the introduction of cell fate heterogeneity paradoxically influences the tumor growth dynamic in response to apoptosis, to reveal yet another bottleneck to tumor progression potentially exploitable for disease control. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity

    Directory of Open Access Journals (Sweden)

    Yuan Q

    2014-10-01

    Full Text Available Qing Yuan,1 Jing Han,1,2 Wenshu Cong,1 Ying Ge,3 Dandan Ma,1,3,4 Zhaoxia Dai,3,4 Yaping Li,5 Xiaolin Bi1,3,4 1CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 2School of Life Sciences, Anhui University, Hefei, 3Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 4Graduate School, Dalian Medical University, Dalian, 5Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors; however, its toxicity and side effects limit its clinical efficacy. Herein, docetaxel-loaded solid lipid nanoparticles (DSNs were developed to reduce systemic toxicity of docetaxel while still keeping its anticancer activity. To evaluate its anticancer activity and toxicity, and to understand the molecular mechanisms of DSNs, different cellular, molecular, and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel (Taxotere® and induced more apoptosis at 24 hours after treatment in vitro. DSNs can cause the treated cancer cells to arrest in the G2/M phase in a dose-dependent manner similar to Taxotere. They can also suppress tumor growth very effectively in a mice model with human xenograft breast cancer. Systemic analysis of gene expression profiles by microarray and subsequent verification experiments suggested that both DSNs and Taxotere regulate gene expression and gene function, including DNA replication, DNA damage response, cell proliferation, apoptosis, and cell cycle regulation. Some of these genes expressed differentially at the protein level although their messenger RNA expression level was similar under Taxotere and DSN treatment. Moreover, DSNs improved the main side effect of Taxotere by greatly

  3. Solid cancer risks from radiation exposure for the Australian population

    International Nuclear Information System (INIS)

    Wise, K.N.

    2003-01-01

    Estimates are made of the risks to the Australian population as a function of age and gender for mortality or morbidity for all solid cancers after exposure to radiation. Excess relative risk (ERR) and excess absolute risk (EAR) models are used. The model coefficients are re-evaluated for radiation doses expressed as effective dose using data from the Japanese Life Span Study. Life-table methods are used throughout and the risk measures studied are: the risk of exposure related death, RERD and the risk of exposure related cancer, RERC. Australian life-table data and the age-specific cancer incidence and mortality rates of Australian males and females are taken from recent published tables. No dose and dose-rate effectiveness factor is applied. Sources of uncertainty used to calculate the confidence regions for the estimated risks include the statistical uncertainties of the model parameters and of the extrapolation of the risks beyond the period supported by the epidemiological data. Summary values of the risks are reported as averages of those calculated from the ERR and the EAR models. For males, the mortality risks per sievert range from 14% for 0-9 year age group, 7% at 30-39 years and 4% at 50-59 years. Corresponding values for females are 20%, 10% and 6%. Incidence risks are higher: for males the estimates are 32% for the 0-9 year group, 12% at 30-39 and 5% at 50-59. Corresponding values for females are 56%, 20% and 8%. The 90% confidence regions are about ± 50% of these values. Estimates are given for the risks from CT whole-body scanning or virtual colonoscopy which could be used for cancer screening. If used at 3 year intervals and the effective dose per procedure is 10 mSv, then the RERD for males beginning screening at 40, 50 and 60 years is 0.4%, 0.3% and 0.1%, respectively and for females, 0.6%, 0.4% and 0.2%, respectively. RERD estimates for a 5 year interval between screens are about one-third smaller. Copyright (2003) Australasian College of

  4. Environmental and genetic interactions in human cancer

    International Nuclear Information System (INIS)

    Paterson, M.C.

    Humans, depending upon their genetic make-up, differ in their susceptibility to the cancer-causing effects of extrinsic agents. Clinical and laboratory studies on the hereditary disorder, ataxia telangiectasia (AT) show that persons afflicted with this are cancer-prone and unusually sensitive to conventional radiotherapy. Their skin cells, when cultured, are hypersensitive to killing by ionizing radiation, being defective in the enzymatic repair of radiation-induced damange to the genetic material, deoxyribonucleic acid (DNA). This molecular finding implicates DNA damage and its imperfect repair as an early step in the induction of human cancer by radiation and other carcinogens. The parents of AT patients are clincally normal but their cultured cells are often moderately radiosensitive. The increased radiosensitivity of cultured cells offers a means of identifying a presumed cancer-prone subpopulation that should avoid undue exposure to certain carcinogens. The radioresponse of cells from patients with other cancer-associated genetic disorders and persons suspected of being genetically predisposed to radiation-induced cancer has also been measured. Increased cell killing by γ-rays appears in the complex genetic disease, tuberous sclerosis. Cells from cancer-stricken members of a leukemia-prone family are also radiosensitive, as are cells from one patient with radiation-associated breast cancer. These radiobiological data, taken together, strongly suggest that genetic factors can interact with extrinsic agents and thereby play a greater causative role in the development of common cancers in man than previously thought. (L.L.)

  5. Human pancreatic cancer xenografts recapitulate key aspects of cancer cachexia.

    Science.gov (United States)

    Delitto, Daniel; Judge, Sarah M; Delitto, Andrea E; Nosacka, Rachel L; Rocha, Fernanda G; DiVita, Bayli B; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Wallet, Shannon M; Judge, Andrew R; Trevino, Jose G

    2017-01-03

    Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia. Specifically, human PC xenografts were generated by implantation of pancreatic cancer cells, L3.6pl and PANC-1, either in the flank or orthotopically within the pancreas. Mice bearing orthotopic xenografts demonstrated significant muscle wasting and atrophy-associated gene expression changes compared to controls. Further, despite the absence of adaptive immunity, splenic tissue from orthotopically engrafted mice demonstrated elevations in several pro-inflammatory cytokines associated with cancer cachexia, including TNFα, IL1β, IL6 and KC (murine IL8 homologue), when compared to controls. Therefore, data presented here support further investigation into the complexity of cancer cachexia in PC to identify potential targets for this debilitating syndrome.

  6. Modeling Human Cancers in Drosophila.

    Science.gov (United States)

    Sonoshita, M; Cagan, R L

    2017-01-01

    Cancer is a complex disease that affects multiple organs. Whole-body animal models provide important insights into oncology that can lead to clinical impact. Here, we review novel concepts that Drosophila studies have established for cancer biology, drug discovery, and patient therapy. Genetic studies using Drosophila have explored the roles of oncogenes and tumor-suppressor genes that when dysregulated promote cancer formation, making Drosophila a useful model to study multiple aspects of transformation. Not limited to mechanism analyses, Drosophila has recently been showing its value in facilitating drug development. Flies offer rapid, efficient platforms by which novel classes of drugs can be identified as candidate anticancer leads. Further, we discuss the use of Drosophila as a platform to develop therapies for individual patients by modeling the tumor's genetic complexity. Drosophila provides both a classical and a novel tool to identify new therapeutics, complementing other more traditional cancer tools. © 2017 Elsevier Inc. All rights reserved.

  7. Human papilloma virus in oral cancer.

    Science.gov (United States)

    Kim, Soung Min

    2016-12-01

    Cervical cancer is the second most prevalent cancer among women, and it arises from cells that originate in the cervix uteri. Among several causes of cervical malignancies, infection with some types of human papilloma virus (HPV) is well known to be the greatest cervical cancer risk factor. Over 150 subtypes of HPV have been identified; more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region and oral cavity. The recently introduced vaccine for HPV infection is effective against certain subtypes of HPV that are associated with cervical cancer, genital warts, and some less common cancers, including oropharyngeal cancer. Two HPV vaccines, quadrivalent and bivalent types that use virus-like particles (VLPs), are currently used in the medical commercial market. While the value of HPV vaccination for oral cancer prevention is still controversial, some evidence supports the possibility that HPV vaccination may be effective in reducing the incidence of oral cancer. This paper reviews HPV-related pathogenesis in cancer, covering HPV structure and classification, trends in worldwide applications of HPV vaccines, effectiveness and complications of HPV vaccination, and the relationship of HPV with oral cancer prevalence.

  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. Solid phase radioimmunoassays for human C-reactive protein

    International Nuclear Information System (INIS)

    Shine, B.; Beer, F.C. de; Pepys, M.B.

    1981-01-01

    Two new, rapid and sensitive radioimmunoassays for human C-reactive protein (CRP) have been established using antiserum coupled to magnetizable cellulose particles, which facilitate phase separation. A single antibody method, using solid phase anti-CRP, provides a sensitivity of 50 μg/l with a 1-h incubation time and intra- and inter-assay coefficients of variation of 10%. A double antibody method, using fluid phase rabbit anti-CRP serum and solid phase sheep anti-rabbit IgG serum, provides a sensitivity of 3 μg/l with an overnight incubation and intra- and inter-assay coefficients of variation of 10%. Among 468 sera from normal adult volunteer blood donors the median CRP concentration was 800 μg/l, interquartile range 340-1700 μg/l and range 70-29,000 μg/l. Ninety percent of samples contained less than 3 mg/l and 99% less than 10 mg/l. Low levels (14-650 μg/l) of CRP were detected both in amniotic fluids and in cerebrospinal fluids. (Auth.)

  10. 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

  11. Prevalence of Telomerase Activity in Human Cancer

    Directory of Open Access Journals (Sweden)

    Chi-Hau Chen

    2011-05-01

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

  12. Radiobiology of human cancer radiotherapy

    International Nuclear Information System (INIS)

    Andrews, J.R.

    1978-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-09-10

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

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

    International Nuclear Information System (INIS)

    Uchino, Keita; Hirano, Gen; Hirahashi, Minako; Isobe, Taichi; Shirakawa, Tsuyoshi; Kusaba, Hitoshi; Baba, Eishi; Tsuneyoshi, Masazumi; Akashi, Koichi

    2012-01-01

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

  15. Human Papillomavirus and Vaccination in Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Kung-Liahng Wang

    2007-12-01

    Full Text Available Cervical cancer is not only the most frequently reported cancer among women, but also the most common female genital tract neoplasm in Taiwan. Early detection is effective, because the development, maintenance and progression of precursor lesions (cervical intraepithelial neoplasia [CIN] evolve slowly into invasive cancer, typically over a period of more than 10 years. It is now recognized that human papillomavirus (HPV infection is a necessary cause for over 99% of cervical cancer cases. Advances in the understanding of the causative role of HPV in the etiology of high-grade cervical lesions (CIN 2/3 and cervical cancer have led to the development, evaluation and recommendation of HPV-based technologies for cervical cancer prevention and control. The prevention of HPV infection before the onset of CIN is now possible with recently available prophylactic HPV vaccines, e.g. the quadrivalent Gardasil (Merck & Co., NJ, USA and bivalent Cervarix (GlaxoSmithKline, London, UK. This review article provides an up-to-date summary of recent studies and available information concerning HPV and vaccination in cervical cancer.

  16. Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors.

    Science.gov (United States)

    Zhang, Bing-Lan; Qin, Di-Yuan; Mo, Ze-Ming; Li, Yi; Wei, Wei; Wang, Yong-Sheng; Wang, Wei; Wei, Yu-Quan

    2016-04-01

    Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity. In this review, we discuss the obstacles imposed by solid tumors on CAR-T cell-based immunotherapy and strategies adopted to improve the therapeutic potential of this approach. Continued investigations are necessary to improve therapeutic outcomes and decrease the adverse effects of CAR-T cell therapy in patients with solid malignancies in the future.

  17. Evaluating the Needs of Patients Living With Solid Tumor Cancer: A Survey Design.

    Science.gov (United States)

    Schmidt, April L; Lorenz, Rebecca A; Buchanan, Paula M; McLaughlin, Laura

    2018-03-01

    To describe the unmet needs of adult patients living with solid tumor cancer. Survey design. Adult patients living with solid tumor cancer from two outpatient clinics were mailed the Sheffield Profile for Assessment and Referral to Care, a holistic screening questionnaire for assessing palliative care needs, and a demographics questionnaire. One hundred fifteen patients returned the instruments, corresponding to a 62% response rate. There were no significant differences by cancer type (breast, non-breast) or gender. However, Caucasians reported significantly more psychological issues, such as anxiety, than non-Caucasians ([ n = 101 (87.8%)] and [ n = 14 (12.2%)], respectively, p = .032). Older patients reported more concerns about loss of independence/activity ( p = .012) compared with younger age groups. Patients living with Stage III/IV cancer reported more distressed about independence/activity ( p = .034), family/social issues ( p = .007), and treatment side effects ( p = .027) than patients living with Stage I/II cancer. Patients living with solid tumor cancer have a myriad of unmet needs regardless of age, gender, cancer type, or cancer stage. There appears to be important differences by cancer stage. The Sheffield Profile for Assessment and Referral to Care questionnaire provides a holistic approach for nurses to identify unmet needs and concerns. Future research should explore the preferred methods of receiving support and information.

  18. Human papillomavirus-associated cancers: A growing global problem

    OpenAIRE

    Bansal, Anshuma; Singh, Mini P; Rai, Bhavana

    2016-01-01

    Human papillomavirus (HPV) infection is linked with several cancers such as cancer cervix, vagina, vulva, head and neck, anal, and penile carcinomas. Although there is a proven association of HPV with these cancers, questions regarding HPV testing, vaccination, and treatment of HPV-related cancers continue to remain unanswered. The present article provides an overview of the HPV-associated cancers.

  19. Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study.

    Science.gov (United States)

    Kulich, M; Reřicha, V; Reřicha, R; Shore, D L; Sandler, D P

    2011-04-01

    Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Příbram region, Czech Republic. A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. A transcriptome anatomy of human colorectal cancers

    International Nuclear Information System (INIS)

    Lü, Bingjian; Xu, Jing; Lai, Maode; Zhang, Hao; Chen, Jian

    2006-01-01

    Accumulating databases in human genome research have enabled integrated genome-wide study on complicated diseases such as cancers. A practical approach is to mine a global transcriptome profile of disease from public database. New concepts of these diseases might emerge by landscaping this profile. In this study, we clustered human colorectal normal mucosa (N), inflammatory bowel disease (IBD), adenoma (A) and cancer (T) related expression sequence tags (EST) into UniGenes via an in-house GetUni software package and analyzed the transcriptome overview of these libraries by GOTree Machine (GOTM). Additionally, we downloaded UniGene based cDNA libraries of colon and analyzed them by Xprofiler to cross validate the efficiency of GetUni. Semi-quantitative RT-PCR was used to validate the expression of β-catenin and. 7 novel genes in colorectal cancers. The efficiency of GetUni was successfully validated by Xprofiler and RT-PCR. Genes in library N, IBD and A were all found in library T. A total of 14,879 genes were identified with 2,355 of them having at least 2 transcripts. Differences in gene enrichment among these libraries were statistically significant in 50 signal transduction pathways and Pfam protein domains by GOTM analysis P < 0.01 Hypergeometric Test). Genes in two metabolic pathways, ribosome and glycolysis, were more enriched in the expression profiles of A and IBD than in N and T. Seven transmembrane receptor superfamily genes were typically abundant in cancers. Colorectal cancers are genetically heterogeneous. Transcription variants are common in them. Aberrations of ribosome and glycolysis pathway might be early indicators of precursor lesions in colon cancers. The electronic gene expression profile could be used to highlight the integral molecular events in colorectal cancers

  1. 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.

  2. First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors.

    Science.gov (United States)

    Stein, Mark N; Bertino, Joseph R; Kaufman, Howard L; Mayer, Tina; Moss, Rebecca; Silk, Ann; Chan, Nancy; Malhotra, Jyoti; Rodriguez, Lorna; Aisner, Joseph; Aiken, Robert D; Haffty, Bruce G; DiPaola, Robert S; Saunders, Tracie; Zloza, Andrew; Damare, Sherri; Beckett, Yasmeen; Yu, Bangning; Najmi, Saltanat; Gabel, Christian; Dickerson, Siobhan; Zheng, Ling; El-Deiry, Wafik S; Allen, Joshua E; Stogniew, Martin; Oster, Wolfgang; Mehnert, Janice M

    2017-08-01

    Purpose: ONC201 is a small-molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, pharmacokinetic, and pharmacodynamic information. Results: No grade >1 drug-related adverse events occurred, and the RP2D was defined as 625 mg. Pharmacokinetic analysis revealed a C max of 1.5 to 7.5 μg/mL (∼3.9-19.4 μmol/L), mean half-life of 11.3 hours, and mean AUC of 37.7 h·μg/L. Pharmacodynamic assays demonstrated induction of caspase-cleaved keratin 18 and prolactin as serum biomarkers of apoptosis and DRD2 antagonism, respectively. No objective responses by RECIST were achieved; however, radiographic regression of several individual metastatic lesions was observed along with prolonged stable disease (>9 cycles) in prostate and endometrial cancer patients. Conclusions: ONC201 is a selective DRD2 antagonist that is well tolerated, achieves micromolar plasma concentrations, and is biologically active in advanced cancer patients when orally administered at 625 mg every 3 weeks. Clin Cancer Res; 23(15); 4163-9. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Human retroviruses: their role in cancer.

    Science.gov (United States)

    Blattner, W A

    1999-01-01

    Viruses are etiologically linked to approximately 20% of all malignancies worldwide. Retroviruses account for approximately 8%-10% of the total. For human T-cell leukemia virus 1 (HTLV-I), the viral regulatory tax gene product is responsible for enhanced transcription of viral and cellular genes that promote cell growth by stimulating various growth factors and through dysregulation of cellular regulatory suppressor genes, such as p53. After a long latent period, adult T-cell leukemia/lymphoma (ATL) occurs in 1 per 1000 carriers per year, resulting in 2500-3000 cases per year worldwide and over half of the adult lymphoid malignancies in endemic areas. Human immunodeficiency virus 1 (HIV-1) accounts for a significant cancer burden, and its transactivating regulatory protein Tat enhances direct and indirect cytokine and immunological dysregulation to cause diverse cancers. Kaposi's sarcoma (KS) is a very rare tumor except after HIV-1 infection, when its incidence is greatly amplified reaching seventy thousand-fold in HIV-infected homosexual men. Human herpesvirus 8 (HHV-8), which is also known as Kaposi's sarcoma-associated virus (KSHV), is a necessary but not sufficient etiological factor in KS. The dramatic decline of KS since the introduction of highly active antiretroviral therapy (HAART) could be due to suppression of HIV-1 tat. B-cell non-Hodgkin's lymphoma occurs as their first acquired immunodeficiency syndrome-defining diagnosis in 3%-4% of HIV-infected patients. Hodgkin's lymphoma is also associated with HIV infection but at a lower risk. Human papillomaviruses are linked to invasive cervical cancer and anogenital cancers among HIV-infected patients. Human retroviruses cause malignancy via direct effects as well as through interactions with other oncogenic herpesviruses and other viruses.

  4. Incidence of non-lung solid cancers in Czech uranium miners: A case-cohort study

    International Nuclear Information System (INIS)

    Kulich, M.; Rericha, V.; Rericha, R.; Shore, D.L.; Sandler, D.P.

    2011-01-01

    Objectives: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Pribram region, Czech Republic. Methods: A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. Results: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. Conclusions: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. - Research highlights: → Uranium miners are chronically exposed to radon. → We evaluate risk of non-lung solid cancers among uranium miners. → No cancer type was significantly associated with radon exposure. → Malignant melanoma and gallbladder cancer showed non-significant elevated risk.

  5. Development of a new high-affinity human antibody with antitumor activity against solid and blood malignancies.

    Science.gov (United States)

    Sioud, Mouldy; Westby, Phuong; Vasovic, Vlada; Fløisand, Yngvar; Peng, Qian

    2018-04-16

    mAbs have emerged as a promising strategy for the treatment of cancer. However, in several malignancies, no effective antitumor mAbs are yet available. Identifying therapeutic mAbs that recognize common tumor antigens could render the treatment widely applicable. Here, a human single-chain variable fragment (scFv) antibody library was sequentially affinity selected against a panel of human cancer cell lines and an antibody fragment (named MS5) that bound to solid and blood cancer cells was identified. The MS5 scFv was fused to the human IgG1 Fc domain to generate an antibody (MS5-Fc fusion) that induced antibody-dependent cellular cytotoxicity and phagocytosis of cancer cells by macrophages. In addition, the MS5-Fc antibody bound to primary leukemia cells and induced antibody-dependent cellular cytotoxicity. In the majority of analyzed cancer cells, the MS5-Fc antibody induced cell surface redistribution of the receptor complexes, but not internalization, thus maximizing the accessibility of the IgG1 Fc domain to immune effector cells. In vitro stability studies showed that the MS5-Fc antibody was stable after 6 d of incubation in human serum, retaining ∼60% of its initial intact form. After intravenous injections, the antibody localized into tumor tissues and inhibited the growth of 3 different human tumor xenografts (breast, lymphoma, and leukemia). These antitumor effects were associated with tumor infiltration by macrophages and NK cells. In the Ramos B-cell lymphoma xenograft model, the MS5-Fc antibody exhibited a comparable antitumor effect as rituximab, a chimeric anti-CD20 IgG1 mAb. These results indicate that human antibodies with pan-cancer abilities can be generated from phage display libraries, and that the engineered MS5-Fc antibody could be an attractive agent for further clinical investigation.-Sioud, M., Westby, P., Vasovic, V., Fløisand, Y., Peng, Q. Development of a new high-affinity human antibody with antitumor activity against solid and

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

    International Nuclear Information System (INIS)

    Wang, Hongtao; Gao, Peng; Zheng, Jie

    2014-01-01

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

  7. BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

    Directory of Open Access Journals (Sweden)

    Cohn AL

    2017-02-01

    Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

  8. Molecular concept in human oral cancer.

    Science.gov (United States)

    Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U S

    2015-01-01

    The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of proto-oncogenes/oncogenes and tumor suppressor genes. Furthermore, these gene alterations can deregulate the normal activity such as increase in the production of growth factors (transforming growth factor-α [TGF-α], TGF-β, platelet-derived growth factor, etc.) or numbers of cell surface receptors (epidermal growth factor receptor, G-protein-coupled receptor, etc.), enhanced intracellular messenger signaling and mutated production of transcription factors (ras gene family, c-myc gene) which results disturb to tightly regulated signaling pathways of normal cell. Several oncogenes and tumor suppressor genes have been implicated in oral cancer especially cyclin family, ras, PRAD-1, cyclin-dependent kinase inhibitors, p53 and RB1. Viral infections, particularly with oncogenic human papilloma virus subtype (16 and 18) and Epstein-Barr virus have tumorigenic effect on oral epithelia. Worldwide, this is an urgent need to initiate oral cancer research programs at molecular and genetic level which investigates the causes of genetic and molecular defect, responsible for malignancy. This approach may lead to development of target dependent tumor-specific drugs and appropriate gene therapy.

  9. Evaluating human cancer cell metastasis in zebrafish

    International Nuclear Information System (INIS)

    Teng, Yong; Xie, Xiayang; Walker, Steven; White, David T; Mumm, Jeff S; Cowell, John K

    2013-01-01

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  10. Incidence of second solid cancer in patients after treatment of Hodgkin's disease

    International Nuclear Information System (INIS)

    Glanzmann, C.; Veraguth, A.; Luetolf, U.M.

    1994-01-01

    340 patients had curative treatment with mantle or paraaortic and pelvic radiotherapy (1964 to 1972) or mantle plus paraaortic and spleen or splenic pedicle or total nodal radiotherapy with or without chemotherapy (1973 to 1992). Since 1987, after chemotherapy only modified involved fields were irradiated. All seconds tumors have been histologically verified. The cumulative incidence of second solid cancer of the patients have been compared with the age and sex specific expected rates according to the ''Zuercher Krebsregister 1980 to 1990''. We observed seven patients with leucemia after radiotherapy plus chemotherapy, five patients with non-Hodgkin-lymphoma and 21 patients with solid cancers after radiotherapy or radiotherapy and chemotherapy with a cumulative risk of all second malignancies of 7,0% (ten years), 30.7% (20 years) and 40,5% (24 years). Cumulative risk of second solid cancer was 3,1% (ten years), 9,3% (15 years), 23,5% (20 years) and 34,3% (24 years). Cumulative risk of second solid cancer was significantly higher than expected with no decrease of the relative risk after more than 20 years of follow-up. We observed a significantly higher risk of breast cancer in women less than 30 years of age at treatment. Relative risk of second solid cancer was higher after radiotherapy plus chemotherapy compared to radiotherapy alone, but the difference was not statistically significant. Nearly all patients with radiotherapy plus chemotherapy and a follow-up of ten years or more had radiotherapy with large fields. (orig./MG) [de

  11. Human Papilloma Virus Vaccination for Control of Cervical Cancer ...

    African Journals Online (AJOL)

    Human Papilloma Virus Vaccination for Control of Cervical Cancer: A ... Primary HPV prevention may be the key to reducing incidence and burden of cervical cancer ... Other resources included locally-published articles and additional internet ...

  12. Effect of Training on Knowledge about Cervical Cancer and Human ...

    African Journals Online (AJOL)

    UNIBEN

    Effect of Training on Knowledge about Cervical Cancer and Human. Papiloma Virus Vaccine ... debut, multiple sexual partners, smoking, history of sexually ... prevent cervical cancer. These include ..... needed to understand and explain the.

  13. Therapy of solid cancers using T cells and running shoes

    DEFF Research Database (Denmark)

    Straten, Per Thor

    2017-01-01

    of tumor specific T cells at the tumor site, and underscores the need to define ways as how to increase immune cell infiltration to the tumor site. Regular exercise reduces the risk of cancer and disease recurrence, by largely unknown mechanisms. We recently demonstrated that voluntary wheel running showed...

  14. Evidence for widespread dysregulation of circadian clock progression in human cancer

    Directory of Open Access Journals (Sweden)

    Jarrod Shilts

    2018-01-01

    Full Text Available The ubiquitous daily rhythms in mammalian physiology are guided by progression of the circadian clock. In mice, systemic disruption of the clock can promote tumor growth. In vitro, multiple oncogenes can disrupt the clock. However, due to the difficulties of studying circadian rhythms in solid tissues in humans, whether the clock is disrupted within human tumors has remained unknown. We sought to determine the state of the circadian clock in human cancer using publicly available transcriptome data. We developed a method, called the clock correlation distance (CCD, to infer circadian clock progression in a group of samples based on the co-expression of 12 clock genes. Our method can be applied to modestly sized datasets in which samples are not labeled with time of day and coverage of the circadian cycle is incomplete. We used the method to define a signature of clock gene co-expression in healthy mouse organs, then validated the signature in healthy human tissues. By then comparing human tumor and non-tumor samples from twenty datasets of a range of cancer types, we discovered that clock gene co-expression in tumors is consistently perturbed. Subsequent analysis of data from clock gene knockouts in mice suggested that perturbed clock gene co-expression in human cancer is not caused solely by the inactivation of clock genes. Furthermore, focusing on lung cancer, we found that human lung tumors showed systematic changes in expression in a large set of genes previously inferred to be rhythmic in healthy lung. Our findings suggest that clock progression is dysregulated in many solid human cancers and that this dysregulation could have broad effects on circadian physiology within tumors. In addition, our approach opens the door to using publicly available data to infer circadian clock progression in a multitude of human phenotypes.

  15. Risk of Lymphoma and Solid Cancer among Patients with Rheumatoid Arthritis in a Primary Care Setting

    DEFF Research Database (Denmark)

    Andersen, Christen Bertel L; Lindegaard, Hanne Merete; Vestergaard, Hanne

    2014-01-01

    lymphoproliferative malignancies or solid cancers. These risk estimates did not change when eosinophilia, CRP, and comorbidities were included in the models. CONCLUSIONS: In this large cohort of patients with RA of short or long duration recruited from a primary care resource, RA was not associated with an increased...

  16. Linkage of DNA Methylation Quantitative Trait Loci to Human Cancer Risk

    Directory of Open Access Journals (Sweden)

    Holger Heyn

    2014-04-01

    Full Text Available Epigenetic regulation and, in particular, DNA methylation have been linked to the underlying genetic sequence. DNA methylation quantitative trait loci (meQTL have been identified through significant associations between the genetic and epigenetic codes in physiological and pathological contexts. We propose that interrogating the interplay between polymorphic alleles and DNA methylation is a powerful method for improving our interpretation of risk alleles identified in genome-wide association studies that otherwise lack mechanistic explanation. We integrated patient cancer risk genotype data and genome-scale DNA methylation profiles of 3,649 primary human tumors, representing 13 solid cancer types. We provide a comprehensive meQTL catalog containing DNA methylation associations for 21% of interrogated cancer risk polymorphisms. Differentially methylated loci harbor previously reported and as-yet-unidentified cancer genes. We suggest that such regulation at the DNA level can provide a considerable amount of new information about the biology of cancer-risk alleles.

  17. 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.

  18. Engineered Breast Cancer Cell Spheroids Reproduce Biologic Properties of Solid Tumors.

    Science.gov (United States)

    Ham, Stephanie L; Joshi, Ramila; Luker, Gary D; Tavana, Hossein

    2016-11-01

    Solid tumors develop as 3D tissue constructs. As tumors grow larger, spatial gradients of nutrients and oxygen and inadequate diffusive supply to cells distant from vasculature develops. Hypoxia initiates signaling and transcriptional alterations to promote survival of cancer cells and generation of cancer stem cells (CSCs) that have self-renewal and tumor-initiation capabilities. Both hypoxia and CSCs are associated with resistance to therapies and tumor relapse. This study demonstrates that 3D cancer cell models, known as tumor spheroids, generated with a polymeric aqueous two-phase system (ATPS) technology capture these important biological processes. Similar to solid tumors, spheroids of triple negative breast cancer cells deposit major extracellular matrix proteins. The molecular analysis establishes presence of hypoxic cells in the core region and expression of CSC gene and protein markers including CD24, CD133, and Nanog. Importantly, these spheroids resist treatment with chemotherapy drugs. A combination treatment approach using a hypoxia-activated prodrug, TH-302, and a chemotherapy drug, doxorubicin, successfully targets drug resistant spheroids. This study demonstrates that ATPS spheroids recapitulate important biological and functional properties of solid tumors and provide a unique model for studies in cancer research. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Tumor-Associated Neutrophils in Human Lung Cancer

    Science.gov (United States)

    2017-10-01

    markers in humans. The logistical, ethical , and regulatory difficulties in obtaining human tumor tissue for research also act to discourage such...Mouse models of cancer. Annu. Rev. Pathol 6, 95–119 52. Merlo, L.M. et al. (2006) Cancer as an evolutionary and ecological process. Nat. Rev. Cancer...some effect on the phenotype and function of TANs. The logistical, ethical , and regulatory difficulties in obtaining human tumor tissue for research

  20. 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.

  1. Human bladder cancer diagnosis using multiphoton microscopy

    Science.gov (United States)

    Mukherjee, Sushmita; Wysock, James S.; Ng, Casey K.; Akhtar, Mohammed; Perner, Sven; Lee, Ming-Ming; Rubin, Mark A.; Maxfield, Frederick R.; Webb, Watt W.; Scherr, Douglas S.

    2009-02-01

    At the time of diagnosis, approximately 75% of bladder cancers are non-muscle invasive. Appropriate diagnosis and surgical resection at this stage improves prognosis dramatically. However, these lesions, being small and/or flat, are often missed by conventional white-light cystoscopes. Furthermore, it is difficult to assess the surgical margin for negativity using conventional cystoscopes. Resultantly, the recurrence rates in patients with early bladder cancer are very high. This is currently addressed by repeat cystoscopies and biopsies, which can last throughout the life of a patient, increasing cost and patient morbidity. Multiphoton endoscopes offer a potential solution, allowing real time, noninvasive biopsies of the human bladder, as well as an up-close assessment of the resection margin. While miniaturization of the Multiphoton microscope into an endoscopic format is currently in progress, we present results here indicating that Multiphoton imaging (using a bench-top Multiphoton microscope) can indeed identify cancers in fresh, unfixed human bladder biopsies. Multiphoton images are acquired in two channels: (1) broadband autofluorescence from cells, and (2) second harmonic generation (SHG), mostly by tissue collagen. These images are then compared with gold standard hematoxylin/eosin (H&E) stained histopathology slides from the same specimen. Based on a "training set" and a very small "blinded set" of samples, we have found excellent correlation between the Multiphoton and histopathological diagnoses. A larger blinded analysis by two independent uropathologists is currently in progress. We expect that the conclusion of this phase will provide us with diagnostic accuracy estimates, as well as the degree of inter-observer heterogeneity.

  2. Different energy metabolism in two human small cell lung cancer subpopulations examined by 31P magnetic resonance spectroscopy and biochemical analysis in vivo and in vitro

    DEFF Research Database (Denmark)

    Kristjansen, P E; Spang-Thomsen, M; Quistorff, B

    1991-01-01

    Two human small cell lung cancer tumor lines, maintained as solid tumor xenografts on nude mice and as in vitro cell cultures, were studied by in vivo 31P magnetic resonance spectroscopy and by biochemical analysis of extracts of solid tumors and cell cultures. The tumor lines CPH SCCL 54A and CPH...

  3. A systematic atlas of chaperome deregulation topologies across the human cancer landscape.

    Directory of Open Access Journals (Sweden)

    Ali Hadizadeh Esfahani

    2018-01-01

    Full Text Available Proteome balance is safeguarded by the proteostasis network (PN, an intricately regulated network of conserved processes that evolved to maintain native function of the diverse ensemble of protein species, ensuring cellular and organismal health. Proteostasis imbalances and collapse are implicated in a spectrum of human diseases, from neurodegeneration to cancer. The characteristics of PN disease alterations however have not been assessed in a systematic way. Since the chaperome is among the central components of the PN, we focused on the chaperome in our study by utilizing a curated functional ontology of the human chaperome that we connect in a high-confidence physical protein-protein interaction network. Challenged by the lack of a systems-level understanding of proteostasis alterations in the heterogeneous spectrum of human cancers, we assessed gene expression across more than 10,000 patient biopsies covering 22 solid cancers. We derived a novel customized Meta-PCA dimension reduction approach yielding M-scores as quantitative indicators of disease expression changes to condense the complexity of cancer transcriptomics datasets into quantitative functional network topographies. We confirm upregulation of the HSP90 family and also highlight HSP60s, Prefoldins, HSP100s, ER- and mitochondria-specific chaperones as pan-cancer enriched. Our analysis also reveals a surprisingly consistent strong downregulation of small heat shock proteins (sHSPs and we stratify two cancer groups based on the preferential upregulation of ATP-dependent chaperones. Strikingly, our analyses highlight similarities between stem cell and cancer proteostasis, and diametrically opposed chaperome deregulation between cancers and neurodegenerative diseases. We developed a web-based Proteostasis Profiler tool (Pro2 enabling intuitive analysis and visual exploration of proteostasis disease alterations using gene expression data. Our study showcases a comprehensive profiling of

  4. A systematic atlas of chaperome deregulation topologies across the human cancer landscape

    Science.gov (United States)

    Sverchkova, Angelina

    2018-01-01

    Proteome balance is safeguarded by the proteostasis network (PN), an intricately regulated network of conserved processes that evolved to maintain native function of the diverse ensemble of protein species, ensuring cellular and organismal health. Proteostasis imbalances and collapse are implicated in a spectrum of human diseases, from neurodegeneration to cancer. The characteristics of PN disease alterations however have not been assessed in a systematic way. Since the chaperome is among the central components of the PN, we focused on the chaperome in our study by utilizing a curated functional ontology of the human chaperome that we connect in a high-confidence physical protein-protein interaction network. Challenged by the lack of a systems-level understanding of proteostasis alterations in the heterogeneous spectrum of human cancers, we assessed gene expression across more than 10,000 patient biopsies covering 22 solid cancers. We derived a novel customized Meta-PCA dimension reduction approach yielding M-scores as quantitative indicators of disease expression changes to condense the complexity of cancer transcriptomics datasets into quantitative functional network topographies. We confirm upregulation of the HSP90 family and also highlight HSP60s, Prefoldins, HSP100s, ER- and mitochondria-specific chaperones as pan-cancer enriched. Our analysis also reveals a surprisingly consistent strong downregulation of small heat shock proteins (sHSPs) and we stratify two cancer groups based on the preferential upregulation of ATP-dependent chaperones. Strikingly, our analyses highlight similarities between stem cell and cancer proteostasis, and diametrically opposed chaperome deregulation between cancers and neurodegenerative diseases. We developed a web-based Proteostasis Profiler tool (Pro2) enabling intuitive analysis and visual exploration of proteostasis disease alterations using gene expression data. Our study showcases a comprehensive profiling of chaperome shifts

  5. Torrefaction Processing for Human Solid Waste Management, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — New technology is needed to collect, stabilize, recover useful materials, and store human fecal waste for long duration missions, both for crew safety, comfort and...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-09

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

  7. Clinical Relevance of KRAS in Human Cancers

    Directory of Open Access Journals (Sweden)

    Sylwia Jančík

    2010-01-01

    Full Text Available The KRAS gene (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog is an oncogene that encodes a small GTPase transductor protein called KRAS. KRAS is involved in the regulation of cell division as a result of its ability to relay external signals to the cell nucleus. Activating mutations in the KRAS gene impair the ability of the KRAS protein to switch between active and inactive states, leading to cell transformation and increased resistance to chemotherapy and biological therapies targeting epidermal growth factor receptors. This review highlights some of the features of the KRAS gene and the KRAS protein and summarizes current knowledge of the mechanism of KRAS gene regulation. It also underlines the importance of activating mutations in the KRAS gene in relation to carcinogenesis and their importance as diagnostic biomarkers, providing clues regarding human cancer patients' prognosis and indicating potential therapeutic approaches.

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

    Science.gov (United States)

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

    2003-01-01

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

  9. 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

  10. Older age impacts on survival outcome in patients receiving curative surgery for solid cancer

    Directory of Open Access Journals (Sweden)

    Chang-Hsien Lu

    2018-07-01

    Full Text Available Summary: Background: Given the global increase in aging populations and cancer incidence, understanding the influence of age on postoperative outcome after cancer surgery is imperative. This study aimed to evaluate the impact of age on survival outcome in solid cancer patients receiving curative surgery. Methods: A total of 37,288 patients receiving curative surgeries for solid cancers between 2007 and 2012 at four affiliated Chang Gung Memorial Hospital were included in the study. All patients were categorized into age groups by decades for survival analysis. Results: The percentages of patient populations aged <40 years, 40–49 years, 50–59 years, 60–69 years, 70–79 years, and ≥80 years were 9.7%, 17.7%, 27.8%, 22.1%, 16.9%, and 5.7%, respectively. The median follow-up period was 38.9 months (range, 22.8–60.4 months and the overall, cancer-specific, and noncancer-specific mortality rates were 26.0%, 17.6%, and 8.5%, respectively. The overall mortality rate of patients in different age groups were 18.5%, 21.1%, 22.0%, 25.3%, 35.3%, and 49.0%, respectively. Compared to patients aged <40 years, more significant decrease in long-term survival were observed in aging patients. Multivariate analysis showed higher postoperative short-term mortality rates in patients older than 70 years, and the adjusted odds ratio of mortality risk ranged from 1.47 to 1.74 and 2.26 to 3.03 in patients aged 70–79 years and ≥80 years, respectively, compared to those aged <40 years. Conclusion: Aging was a negative prognostic factor of survival outcome in solid cancer patients receiving curative surgery. After adjustment of other clinicopathologic factors, the influence of age on survival outcome was less apparent in the elderly. Keywords: Age, Solid cancer, Surgical resection, Prognosis

  11. Occurrence of human bocaviruses and parvovirus 4 in solid tissues.

    Science.gov (United States)

    Norja, Päivi; Hedman, Lea; Kantola, Kalle; Kemppainen, Kaisa; Suvilehto, Jari; Pitkäranta, Anne; Aaltonen, Leena-Maija; Seppänen, Mikko; Hedman, Klaus; Söderlund-Venermo, Maria

    2012-08-01

    Human bocaviruses 1-4 (HBoV1-4) and parvovirus 4 (PARV4) are recently discovered human parvoviruses. HBoV1 is associated with respiratory infections of young children, while HBoV2-4 are enteric viruses. The clinical manifestations of PARV4 remain unknown. The objective of this study was to determine whether the DNAs of HBoV1-4 and PARV4 persist in human tissues long after primary infection. Biopsies of tonsillar tissue, skin, and synovia were examined for HBoV1-4 DNA and PARV4 DNA by PCR. Serum samples from the tissue donors were assayed for HBoV1 and PARV4 IgG and IgM antibodies. To obtain species-specific seroprevalences for HBoV1 and for HBoV2/3 combined, the sera were analyzed after virus-like particle (VLP) competition. While HBoV1 DNA was detected exclusively in the tonsillar tissues of 16/438 individuals (3.7%), all of them ≤8 years of age. HBoV2-4 and PARV4 DNAs were absent from all tissue types. HBoV1 IgG seroprevalence was 94.9%. No subject had HBoV1 or PARV4 IgM, nor did they have PARV4 IgG. The results indicate that HBoV1 DNA occurred in a small proportion of tonsils of young children after recent primary HBoV1 infection, but did not persist long in the other tissue types studied, unlike parvovirus B19 DNA. The results obtained by the PARV4 assays are in line with previous results on PARV4 epidemiology. Copyright © 2012 Wiley Periodicals, Inc.

  12. An early history of human breast cancer: West meets East.

    Science.gov (United States)

    Yan, Shou-He

    2013-09-01

    Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer.

  13. Transposable Elements in Human Cancer: Causes and Consequences of Deregulation

    Science.gov (United States)

    Anwar, Sumadi Lukman; Wulaningsih, Wahyu; Lehmann, Ulrich

    2017-01-01

    Transposable elements (TEs) comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers. PMID:28471386

  14. Transposable Elements in Human Cancer: Causes and Consequences of Deregulation

    Directory of Open Access Journals (Sweden)

    Sumadi Lukman Anwar

    2017-05-01

    Full Text Available Transposable elements (TEs comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers.

  15. Molecular concept in human oral cancer

    OpenAIRE

    Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U. S.

    2015-01-01

    The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-05

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

  17. miR-134: A Human Cancer Suppressor?

    Directory of Open Access Journals (Sweden)

    Jing-Yu Pan

    2017-03-01

    Full Text Available MicroRNAs (miRNAs are small noncoding RNAs approximately 20–25 nt in length, which play crucial roles through directly binding to corresponding 3′ UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis. Nevertheless, its roles in human cancer are still ambiguous, and its mechanisms are sophisticated as well, referring to a variety of targets and signal pathways, such as STAT5B, KRAS, MAPK/ERK signal pathway, Notch pathway, etc. Herein, we review the crucial roles of miR-134 in scores of human cancers via analyzing latest investigations, which might provide evidence for cancer diagnose, treatment, prognosis, or further investigations.

  18. The Relationship between TP53 Gene Status and Carboxylesterase 2 Expression in Human Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Momoko Ishimine

    2018-01-01

    Full Text Available Irinotecan (CPT-11 is an anticancer prodrug that is activated by the carboxylesterase CES2 and has been approved for the treatment of many types of solid tumors, including colorectal cancer. Recent studies with cell lines show that CES2 expression is regulated by the tumor suppressor protein p53. However, clinical evidence for this regulatory mechanism in cancer is lacking. In this study, we examined the relationship between TP53 gene status and CES2 expression in human colorectal cancer. Most colorectal cancer specimens (70%; 26 of 37 showed lower CES2 mRNA levels (≥1.5-fold lower than the adjacent normal tissue, and only 30% (12 of 37 showed similar (<1.5-fold lower or higher CES2 mRNA levels. However, TP53 gene sequencing revealed no relationship between CES2 downregulation and TP53 mutational status. Moreover, while colorectal cancer cells expressing wild-type p53 exhibited p53-dependent upregulation of CES2, PRIMA-1MET, a drug that restores the transcriptional activity of mutant p53, failed to upregulate CES2 expression in cells with TP53 missense mutations. These results, taken together, suggest that CES2 mRNA expression is decreased in human colorectal cancer independently of p53.

  19. REGγ is associated with multiple oncogenic pathways in human cancers

    International Nuclear Information System (INIS)

    He, Jing; Wang, Zhuo; Shi, Tieliu; Zhang, Pei; Chen, Rui; Li, Xiaotao; Cui, Long; Zeng, Yu; Wang, Guangqiang; Zhou, Ping; Yang, Yuanyuan; Ji, Lei; Zhao, Yanyan; Chen, Jiwu

    2012-01-01

    Recent studies suggest a role of the proteasome activator, REGγ, in cancer progression. Since there are limited numbers of known REGγ targets, it is not known which cancers and pathways are associated with REGγ. REGγ protein expressions in four different cancers were investigated by immunohistochemistry (IHC) analysis. Following NCBI Gene Expression Omnibus (GEO) database search, microarray platform validation, differential expressions of REGγ in corresponding cancers were statistically analyzed. Genes highly correlated with REGγ were defined based on Pearson's correlation coefficient. Functional links were estimated by Ingenuity Core analysis. Finally, validation was performed by RT-PCR analysis in established cancer cell lines and IHC in human colon cancer tissues Here, we demonstrate overexpression of REGγ in four different cancer types by micro-tissue array analysis. Using meta-analysis of publicly available microarray databases and biological studies, we verified elevated REGγ gene expression in the four types of cancers and identified genes significantly correlated with REGγ expression, including genes in p53, Myc pathways, and multiple other cancer-related pathways. The predicted correlations were largely consistent with quantitative RT-PCR analysis. This study provides us novel insights in REGγ gene expression profiles and its link to multiple cancer-related pathways in cancers. Our results indicate potentially important pathogenic roles of REGγ in multiple cancer types and implicate REGγ as a putative cancer marker

  20. Casein kinase II is elevated in solid human tumours and rapidly proliferating non-neoplastic tissue

    DEFF Research Database (Denmark)

    Münstermann, U; Fritz, G; Seitz, G

    1990-01-01

    Protein kinase CKII (i.e. casein kinase II, CKII, NII) is expressed at a higher level in rapidly proliferating tissues and in solid human tumours (e.g. colorectal carcinomas) when compared to the corresponding non-neoplastic colorectal mucosa. This could be shown by (a) Western blotting of cellular...

  1. Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

    Science.gov (United States)

    2018-05-15

    Adult Solid Neoplasm; Hormone-Resistant Prostate Carcinoma; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

  2. Human HRAD9B and testicular cancer

    International Nuclear Information System (INIS)

    Hopkins, K.M.; Wang, X.; Berlin, A.; Thaker, H.M.; Lieberman, H.B.

    2003-01-01

    Full text: The HRAD9 gene mediates radioresistance and regulates the G2/M cell cycle checkpoint induced by ionizing radiation. In this report, we describe the isolation of the human paralog of HRAD9, called HRAD9B. Furthermore, we demonstrate that, like HRAD9 protein, the HRAD9B gene product can coimmunoprecipitate with HRAD1, HRAD9, HHUS1 and HHUS1B proteins. However, HRAD9B is expressed predominantly in testis, whereas its paralog is expressed more universally in different tissues. And most notably, we demonstrate that HRAD9B exhibits markedly and consistently reduced expression in testicular seminomas, high levels of expression in normal adult testis, yet also shows expression in fetal testis cells where meiosis is not performed. These results suggest that HRAD9B could at the least serve as a marker for testicular cancer, and its expression may be causally related to the disease. Further studies are under way to determine the cause of the reduced expression of HRAD9B in germ cell tumors

  3. Towards the human colorectal cancer microbiome.

    Directory of Open Access Journals (Sweden)

    Julian R Marchesi

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

  4. Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

    Science.gov (United States)

    Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

    2003-10-01

    Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

  5. Digital Cellular Solid Pressure Vessels: A Novel Approach for Human Habitation in Space

    Science.gov (United States)

    Cellucci, Daniel; Jenett, Benjamin; Cheung, Kenneth C.

    2017-01-01

    It is widely assumed that human exploration beyond Earth's orbit will require vehicles capable of providing long duration habitats that simulate an Earth-like environment - consistent artificial gravity, breathable atmosphere, and sufficient living space- while requiring the minimum possible launch mass. This paper examines how the qualities of digital cellular solids - high-performance, repairability, reconfigurability, tunable mechanical response - allow the accomplishment of long-duration habitat objectives at a fraction of the mass required for traditional structural technologies. To illustrate the impact digital cellular solids could make as a replacement to conventional habitat subsystems, we compare recent proposed deep space habitat structural systems with a digital cellular solids pressure vessel design that consists of a carbon fiber reinforced polymer (CFRP) digital cellular solid cylindrical framework that is lined with an ultra-high molecular weight polyethylene (UHMWPE) skin. We use the analytical treatment of a linear specific modulus scaling cellular solid to find the minimum mass pressure vessel for a structure and find that, for equivalent habitable volume and appropriate safety factors, the use of digital cellular solids provides clear methods for producing structures that are not only repairable and reconfigurable, but also higher performance than their conventionally manufactured counterparts.

  6. Apoptosis induction of epifriedelinol on human cervical cancer cell line

    African Journals Online (AJOL)

    Background: Present investigation evaluates the antitumor activity of epifriedelinol for the management of cervical cancer by inducing process of apoptosis. Methods: Human Cervical Cancer Cell Line, C33A and HeLa were selected for study and treated with epifriedelinol at a concentration of (50-1000 μg/ml). Cytotoxicity of ...

  7. Identification of hormonal receptors in human breast cancer

    International Nuclear Information System (INIS)

    Rosa Pascual, M.; Lage, A.; Diaz, J.W.; Moreno, L.; Marta Diaz, T.

    1981-01-01

    The experience in the implementation of a technique for determining hormono-dependence of human breast cancer is presented. The results found with the use of the technique in 50 patients with malignant breast cancer treated at IOR are examined and discussed. (author)

  8. Acceptability of human papilloma virus vaccine and cervical cancer ...

    African Journals Online (AJOL)

    2012-07-14

    Jul 14, 2012 ... names in a prepared sampling frame of each group of workers, and thereafter ... Following individual counseling of eligible participants, .... Stanley M. Human Papilloma Virus Vaccines versus cervical cancer screening.

  9. Cloning of Novel Oncogenes Involved in Human Breast Cancer

    National Research Council Canada - National Science Library

    Clark, Geoffrey

    1998-01-01

    .... In order to identify genes which may play a role in breast cancer we have begun a process of manufacturing cDNA expression libraries derived from human breast tumor cell lines in retroviral vectors...

  10. Raman spectroscopy and imaging: applications in human breast cancer diagnosis.

    Science.gov (United States)

    Brozek-Pluska, Beata; Musial, Jacek; Kordek, Radzislaw; Bailo, Elena; Dieing, Thomas; Abramczyk, Halina

    2012-08-21

    The applications of spectroscopic methods in cancer detection open new possibilities in early stage diagnostics. Raman spectroscopy and Raman imaging represent novel and rapidly developing tools in cancer diagnosis. In the study described in this paper Raman spectroscopy has been employed to examine noncancerous and cancerous human breast tissues of the same patient. The most significant differences between noncancerous and cancerous tissues were found in regions characteristic for the vibrations of carotenoids, lipids and proteins. Particular attention was paid to the role played by unsaturated fatty acids in the differentiation between the noncancerous and the cancerous tissues. Comparison of Raman spectra of the noncancerous and the cancerous tissues with the spectra of oleic, linoleic, α-linolenic, γ-linolenic, docosahexaenoic and eicosapentaenoic acids has been presented. The role of sample preparation in the determination of cancer markers is also discussed in this study.

  11. Calorimetric signatures of human cancer cells and their nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Todinova, S. [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, Sofia 1113 (Bulgaria); Stoyanova, E. [Department of Molecular Immunology, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Tzarigradsko shose Blvd. 73, Sofia 1113 (Bulgaria); Krumova, S., E-mail: 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.

  12. Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer.

    Science.gov (United States)

    Ghaghada, Ketan B; Sato, Amy F; Starosolski, Zbigniew A; Berg, John; Vail, David M

    2016-01-01

    Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer. The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study. Liposomal-I resulted in significant (p contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan. The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of

  13. Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules.

    Science.gov (United States)

    Altorki, Nasser K; Yip, Rowena; Hanaoka, Takaomi; Bauer, Thomas; Aye, Ralph; Kohman, Leslie; Sheppard, Barry; Thurer, Richard; Andaz, Shahriyour; Smith, Michael; Mayfield, William; Grannis, Fred; Korst, Robert; Pass, Harvey; Straznicka, Michaela; Flores, Raja; Henschke, Claudia I

    2014-02-01

    A single randomized trial established lobectomy as the standard of care for the surgical treatment of early-stage non-small cell lung cancer. Recent advances in imaging/staging modalities and detection of smaller tumors have once again rekindled interest in sublobar resection for early-stage disease. The objective of this study was to compare lung cancer survival in patients with non-small cell lung cancer with a diameter of 30 mm or less with clinical stage 1 disease who underwent lobectomy or sublobar resection. We identified 347 patients diagnosed with lung cancer who underwent lobectomy (n = 294) or sublobar resection (n = 53) for non-small cell lung cancer manifesting as a solid nodule in the International Early Lung Cancer Action Program from 1993 to 2011. Differences in the distribution of the presurgical covariates between sublobar resection and lobectomy were assessed using unadjusted P values determined by logistic regression analysis. Propensity scoring was performed using the same covariates. Differences in the distribution of the same covariates between sublobar resection and lobectomy were assessed using adjusted P values determined by logistic regression analysis with adjustment for the propensity scores. Lung cancer-specific survival was determined by the Kaplan-Meier method. Cox survival regression analysis was used to compare sublobar resection with lobectomy, adjusted for the propensity scores, surgical, and pathology findings, when adjusted and stratified by propensity quintiles. Among 347 patients, 10-year Kaplan-Meier for 53 patients treated by sublobar resection compared with 294 patients treated by lobectomy was 85% (95% confidence interval, 80-91) versus 86% (confidence interval, 75-96) (P = .86). Cox survival analysis showed no significant difference between sublobar resection and lobectomy when adjusted for propensity scores or when using propensity quintiles (P = .62 and P = .79, respectively). For those with cancers 20 mm or less in

  14. Signatures of mutational processes in human cancer

    NARCIS (Netherlands)

    Alexandrov, L.B.; Nik-Zainal, S.; Wedge, D.C.; Aparicio, S.A.; Behjati, S.; Biankin, A.V.; Bignell, G.R.; Bolli, N.; Borg, A.; Borresen-Dale, A.L.; Boyault, S.; Burkhardt, B.; Butler, A.P.; Caldas, C.; Davies, H.R.; Desmedt, C.; Eils, R.; Eyfjord, J.E.; Foekens, J.A.; Greaves, M.; Hosoda, F.; Hutter, B.; Ilicic, T.; Imbeaud, S.; Imielinsk, M.; Jager, N.; Jones, D.T.; Knappskog, S.; Kool, M.; Lakhani, S.R.; Lopez-Otin, C.; Martin, S.; Munshi, N.C.; Nakamura, H.; Northcott, P.A.; Pajic, M.; Papaemmanuil, E.; Paradiso, A.; Pearson, J.V.; Puente, X.S.; Raine, K.; Ramakrishna, M.; Richardson, A.L.; Richter, J.; Rosenstiel, P.; Schlesner, M.; Schumacher, T.N.; Span, P.N.; Teague, J.W.; Totoki, Y.; Tutt, A.N.; Valdes-Mas, R.; Buuren, M.M. van; Veer, L. van 't; Vincent-Salomon, A.; Waddell, N.; Yates, L.R.; Zucman-Rossi, J.; Futreal, P.A.; McDermott, U.; Lichter, P.; Meyerson, M.; Grimmond, S.M.; Siebert, R.; Campo, E.; Shibata, T.; Pfister, S.M.; Campbell, P.J.; Stratton, M.R.; Schlooz-Vries, M.S.; Tol, J.J. van; Laarhoven, H.W. van; Sweep, F.C.; Bult, P.; et al.,

    2013-01-01

    All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362

  15. The detection, diagnosis and therapy of human lung cancer

    International Nuclear Information System (INIS)

    1978-01-01

    The Cancergram covers clinical aspects of cancers of the lung and tracheo-bronchial tree, i.e., the lower respiratory tract. This includes primary lung cancer in both early and advanced disease status. The topic includes clinically relevant aspects of the prevention, detection, diagnosis, evaluation, and therapy of lung cancer. Certain aspects of metastatic lung disease treatment or therapy which involve aspects of interest to primary lung cancer are included. With certain exceptions, general pre-clinical or animal studies not directly related to the primary human disease are excluded

  16. 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

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Evaluation of a new solid media specimen transport card for high risk HPV detection and cervical cancer prevention.

    Science.gov (United States)

    Maurer, Kathryn; Luo, Hongxue; Shen, Zhiyong; Wang, Guixiang; Du, Hui; Wang, Chun; Liu, Xiaobo; Wang, Xiamen; Qu, Xinfeng; Wu, Ruifang; Belinson, Jerome

    2016-03-01

    Solid media transport can be used to design adaptable cervical cancer screening programs but currently is limited by one card with published data. To develop and evaluate a solid media transport card for use in high-risk human papillomavirus detection (HR-HPV). The Preventative Oncology International (POI) card was constructed using PK 226 paper(®) treated with cell-lysing solution and indicating dye. Vaginal samples were applied to the POI card and the indicating FTA (iFTA) elute card. A cervical sample was placed in liquid media. All specimens were tested for HR-HPV. Color change was assessed at sample application and at card processing. Stability of the POI card and iFTA elute card was tested at humidity. 319 women were enrolled. Twelve women had at least one insufficient sample with no difference between media (p=0.36). Compared to liquid samples, there was good agreement for HR-HPV detection with kappa of 0.81 (95% CI 0.74-0.88) and 0.71 (95% CI 0.62-0.79) for the POI and iFTA elute card respectively. Sensitivity for ≥CIN2 was 100% (CI 100-100%), 95.1% (CI 92.7-97.6%), and 93.5% (CI 90.7-96.3%) for the HR-HPV test from the liquid media, POI card, and iFTA elute card respectively. There was no color change of the POI card noted in humidity but the iFTA elute card changed color at 90% humidity. The POI card is suitable for DNA transport and HR-HPV testing. This card has the potential to make cervical cancer screening programs more affordable worldwide. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Current understanding of mdig/MINA in human cancers.

    Science.gov (United States)

    Thakur, Chitra; Chen, Fei

    2015-07-01

    Mineral dust-induced gene, mdig has recently been identified and is known to be overexpressed in a majority of human cancers and holds predictive power in the poor prognosis of the disease. Mdig is an environmentally expressed gene that is involved in cell proliferation, neoplastic transformation and immune regulation. With the advancement in deciphering the prognostic role of mdig in human cancers, our understanding on how mdig renders a normal cell to undergo malignant transformation is still very limited. This article reviews the current knowledge of the mdig gene in context to human neoplasias and its relation to the clinico-pathologic factors predicting the outcome of the disease in patients. It also emphasizes on the promising role of mdig that can serve as a potential candidate for biomarker discovery and as a therapeutic target in inflammation and cancers. Considering the recent advances in understanding the underlying mechanisms of tumor formation, more preclinical and clinical research is required to validate the potential of using mdig as a novel biological target of therapeutic and diagnostic value. Expression level of mdig influences the prognosis of several human cancers especially cancers of the breast and lung. Evaluation of mdig in cancers can offer novel biomarker with potential therapeutic interventions for the early assessment of cancer development in patients.

  20. BMI-1, a promising therapeutic target for human cancer

    Science.gov (United States)

    WANG, MIN-CONG; LI, CHUN-LI; CUI, JIE; JIAO, MIN; WU, TAO; JING, LI; NAN, KE-JUN

    2015-01-01

    BMI-1 oncogene is a member of the polycomb-group gene family and a transcriptional repressor. Overexpression of BMI-1 has been identified in various human cancer tissues and is known to be involved in cancer cell proliferation, cell invasion, distant metastasis, chemosensitivity and patient survival. Accumulating evidence has revealed that BMI-1 is also involved in the regulation of self-renewal, differentiation and tumor initiation of cancer stem cells (CSCs). However, the molecular mechanisms underlying these biological processes remain unclear. The present review summarized the function of BMI-1 in different human cancer types and CSCs, and discussed the signaling pathways in which BMI-1 is potentially involved. In conclusion, BMI-1 may represent a promising target for the prevention and therapy of various cancer types. PMID:26622537

  1. Maintenance of prolactin receptors in human breast cancer

    International Nuclear Information System (INIS)

    Ben-David, M.; Dror, Y.; Biran, S.

    1981-01-01

    Breast tissue specimens of 110 women with various stages of breast cancer were tested in vitro to determine their specific binding sites for human prolactin. In contrast to the case of steroid receptors, binding sites for prolactin were found in the vast majority of breast cancer tissue. Distribution profiles giving amount of prolactin receptor and their affinity coefficients were found to be similar in the tissues of women whose ages, hormonal status, or stage of breast cancer varied. These findings show that in contrast to steroid receptors, human breast cancer tissue maintains binding sites for prolactin. The findings also indicate that there may be a higher dependency of breast cancer on prolactin than on steroids. Clinical trials must be carried out to determine the role of ''positive'' prolactin receptors in prognosis and prediction of response to future hormone therapy. (author)

  2. Rhein Induces Apoptosis in Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ching-Yao Chang

    2012-01-01

    Full Text Available Human breast cancers cells overexpressing HER2/neu are more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2 and control vector MCF-7 (MCF-7/VEC cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

  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. Technology and human purpose: the problem of solids transport on the Earth's surface

    Science.gov (United States)

    Haff, P. K.

    2012-11-01

    Displacement of mass of limited deformability ("solids") on the Earth's surface is opposed by friction and (the analog of) form resistance - impediments relaxed by rotational motion, self-powering of mass units, and transport infrastructure. These features of solids transport first evolved in the biosphere prior to the emergence of technology, allowing slope-independent, diffusion-like motion of discrete objects as massive as several tons, as illustrated by animal foraging and movement along game trails. However, high-energy-consumption technology powered by fossil fuels required a mechanism that could support fast advective transport of solids, i.e., long-distance, high-volume, high-speed, unidirectional, slope-independent transport across the land surface of materials like coal, containerized fluids, minerals, and economic goods. Pre-technology nature was able to sustain regional- and global-scale advection only in the limited form of piggybacking on geophysical flows of water (river sediment) and air (dust). The appearance of a mechanism for sustained advection of solids independent of fluid flows and gravity appeared only upon the emergence of human purpose. Purpose enables solids advection by, in effect, simulating a continuous potential gradient, otherwise lacking, between discrete and widely separated fossil-fuel energy sources and sinks. Invoking purpose as a mechanism in solids advection is an example of the need to import anthropic principles and concepts into the language and methodology of modern Earth system dynamics. As part of the emergence of a generalized solids advection mechanism, several additional transport requirements necessary to the function of modern large-scale technological systems were also satisfied. These include spatially accurate delivery of advected payload, targetability to essentially arbitrarily located destinations (such as cities), and independence of structure of advected payload from transport mechanism. The latter property

  5. Vaccines against human papilloma virus and cervical cancer: An overview

    Directory of Open Access Journals (Sweden)

    Sharma Savita

    2008-01-01

    Full Text Available The paradigm of preventing human papilloma virus (HPV infection through currently approved vaccines, namely, Gardasil, manufactured by Merck and Co., Inc. (Whitehouse Station, NJ and Cervarix, manufactured by GlaxoSmithKline (GSK, Philadelphia holds tremendous promise for the developing countries in decreasing the burden of HPV infection and its sequelae, such as cervical cancer, genital warts and anogenital cancers. Effective screening programs that have reduced the burden of this killer disease in the developed countries are still lacking in India, despite the high incidence of cervical cancer and the implementation of the National Cancer Control Programme since 1975. The recent breakthrough in the global war against cervical cancer will provide new insight for meeting the future challenge of the prevention of cervical cancer in India.

  6. KITENIN is associated with tumor progression in human gastric cancer.

    Science.gov (United States)

    Ryu, Ho-Seong; Park, Young-Lan; Park, Su-Jin; Lee, Ji-Hee; Cho, Sung-Bum; Lee, Wan-Sik; Chung, Ik-Joo; Kim, Kyung-Keun; Lee, Kyung-Hwa; Kweon, Sun-Seog; Joo, Young-Eun

    2010-09-01

    KAI1 COOH-terminal interacting tetraspanin (KITENIN) promotes tumor cell migration, invasion and metastasis in colon, bladder, head and neck cancer. The aims of current study were to evaluate whether KITENIN affects tumor cell behavior in human gastric cancer cell line and to document the expression of KITENIN in a well-defined series of gastric tumors, including complete long-term follow-up, with special reference to patient prognosis. To evaluate the impact of KITENIN knockdown on behavior of a human gastric cancer cell line, AGS, migration, invasion and proliferation assays using small-interfering RNA were performed. The expression of activator protein-1 (AP-1) target genes and AP-1 transcriptional activity were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and luciferase reporter assay. The expression of KITENIN and AP-1 target genes by RT-PCR and Western blotting or immunohistochemistry was also investigated in human gastric cancer tissues. The knockdown of KITENIN suppressed tumor cell migration, invasion and proliferation in AGS cells. The mRNA expression of matrix metalloproteinase-1 (MMP-1), MMP-3, cyclooxygenase-2 (COX-2), and CD44 was reduced by knockdown of KITENIN in AGS. AP-1 transcriptional activity was significantly decreased by knockdown of KITENIN in AGS cells. KITENIN expression was significantly increased in human cancer tissues at RNA and protein levels. Expression of MMP-1, MMP-3, COX-2 and CD44 were significantly increased in human gastric cancer tissues. Immunostaining of KITENIN was predominantly identified in the cytoplasm of cancer cells. Expression of KITENIN was significantly associated with tumor size, Lauren classification, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that KITENIN plays an important role in human gastric cancer progression by AP-1 activation.

  7. Human Papillomavirus Infections and Cancer Stem Cells of Tumors from the Uterine Cervix

    Science.gov (United States)

    López, Jacqueline; Ruíz, Graciela; Organista-Nava, Jorge; Gariglio, Patricio; García-Carrancá, Alejandro

    2012-01-01

    Different rate of development of productive infections (as low grade cervical intraepithelial neoplasias), or high grade lesions and cervical malignant tumors associated with infections of the Transformation zone (TZ) by High-Risk Human Papillomavirus (HR-HPV), could suggest that different epithelial host target cells could exist. If there is more than one target cell, their differential infection by HR-HPV may play a central role in the development of cervical cancer. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support in several solid tumors, including cervical cancer (CC). According to the cancer stem cell (CSC) hypothesis, CC can now be considered a disease in which stem cells of the TZ are converted to cervical cancer stem cells by the interplay between HR-HPV viral oncogenes and cellular alterations that are thought to be finally responsible for tumor initiation and maintenance. Current studies of CSC could provide novel insights regarding tumor initiation and progression, their relation with viral proteins and interplay with the tumor micro-environment. This review will focus on the biology of cervical cancer stem cells, which might contribute to our understanding of the mechanisms responsible for cervical tumor development. PMID:23341858

  8. 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...

  9. Environmental factors in causing human cancers: emphasis on tumorigenesis.

    Science.gov (United States)

    Sankpal, Umesh T; Pius, Hima; Khan, Moeez; Shukoor, Mohammed I; Maliakal, Pius; Lee, Chris M; Abdelrahim, Maen; Connelly, Sarah F; Basha, Riyaz

    2012-10-01

    The environment and dietary factors play an essential role in the etiology of cancer. Environmental component is implicated in ~80 % of all cancers; however, the causes for certain cancers are still unknown. The potential players associated with various cancers include chemicals, heavy metals, diet, radiation, and smoking. Lifestyle habits such as smoking and alcohol consumption, exposure to certain chemicals (e.g., polycyclic aromatic hydrocarbons, organochlorines), metals and pesticides also pose risk in causing human cancers. Several studies indicated a strong association of lung cancer with the exposure to tobacco products and asbestos. The contribution of excessive sunlight, radiation, occupational exposure (e.g., painting, coal, and certain metals) is also well established in cancer. Smoking, excessive alcohol intake, consumption of an unhealthy diet, and lack of physical activity can act as risk factors for cancer and also impact the prognosis. Even though the environmental disposition is linked to cancer, the level and duration of carcinogen-exposure and associated cellular and biochemical aspects determine the actual risk. Modulations in metabolism and DNA adduct formation are considered central mechanisms in environmental carcinogenesis. This review describes the major environmental contributors in causing cancer with an emphasis on molecular aspects associated with environmental disposition in carcinogenesis.

  10. Recurrently Mutated Genes Differ between Leptomeningeal and Solid Lung Cancer Brain Metastases.

    Science.gov (United States)

    Li, Yingmei; Liu, Boxiang; Connolly, Ian David; Kakusa, Bina Wasunga; Pan, Wenying; Nagpal, Seema; Montgomery, Stephen B; Hayden Gephart, Melanie

    2018-03-29

    When compared with solid brain metastases from NSCLC, leptomeningeal disease (LMD) has unique growth patterns and is rapidly fatal. Patients with LMD do not undergo surgical resection, limiting the tissue available for scientific research. In this study we performed whole exome sequencing on eight samples of LMD to identify somatic mutations and compared the results with those for 26 solid brain metastases. We found that taste 2 receptor member 31 gene (TAS2R31) and phosphodiesterase 4D interacting protein gene (PDE4DIP) were recurrently mutated among LMD samples, suggesting involvement in LMD progression. Together with a retrospective review of the charts of an additional 44 patients with NSCLC LMD, we discovered a surprisingly low number of KRAS mutations (n = 4 [7.7%]) but a high number of EGFR mutations (n = 33 [63.5%]). The median interval for development of LMD from NSCLC was shorter in patients with mutant EGFR (16.3 months) than in patients with wild-type EGFR (23.9 months) (p = 0.017). Targeted analysis of recurrent mutations thus presents a useful complement to the existing diagnostic tool kit, and correlations of EGFR in LMD and KRAS in solid metastases suggest that molecular distinctions or systemic treatment pressure underpin the differences in growth patterns within the brain. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  11. Human cancer protein-protein interaction network: a structural perspective.

    Directory of Open Access Journals (Sweden)

    Gozde Kar

    2009-12-01

    Full Text Available Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi-interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network. The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%. We illustrate the interface related affinity properties of two cancer-related hub

  12. Radiosensitizing effect of epothilone B on human epithelial cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Baumgart, T.; Kriesen, S.; Hildebrandt, G.; Manda, K. [Univ. of Rostock (Germany). Dept. of Radiotherapy and Radiation Oncology; Klautke, G.; Fietkau, R. [Friedrich-Alexander-Univ. Erlangen-Nuernberg, Erlangen (Germany). Dept. of Radiation Oncology; Kuznetsov, S.A.; Weiss, D.G. [Univ. of Rostock (Germany). Inst. of Biological Sciences, Cell Biology, and Biosystems Technology

    2012-02-15

    A combined modality treatment employing radiation and chemotherapy plays a central role in the management of solid tumors. In our study, we examined the cytotoxic and radiosensitive effect of the microtubule stabilizer epothilone B on two human epithelial tumor cell lines in vitro and its influence on the microtubule assembly. Cancer cells were treated with epothilone B in proliferation assays and in combination with radiation in colony-forming assays. For the analysis of ionizing radiation-induced DNA damage and the influence of the drug on its repair a {gamma}H2AX foci assay was used. To determine the effect of epothilone B on the microtubule assembly in cells and on purified tubulin, immunofluorescence staining and tubulin polymerization assay, respectively, were conducted. Epothilone B induced a concentration- and application-dependent antiproliferative effect on the cells, with IC{sub 50} values in the low nanomolar range. Colony forming assays showed a synergistic radiosensitive effect on both cell lines which was dependent on incubation time and applied concentration of epothilone B. The {gamma}H2AX assays demonstrated that ionizing radiation combined with the drug resulted in a concentration-dependent increase in the number of double-strand breaks and suggested a reduction in DNA repair capacity. Epothilone B produced enhanced microtubule bundling and abnormal spindle formation as revealed by immunofluorescence microscopy and caused microtubule formation from purified tubulin. The results of this study showed that epothilone B displays cytotoxic antitumor activity at low nanomolar concentrations and also enhances the radiation response in the tumor cells tested; this may be induced by a reduced DNA repair capacity triggered by epothilone B. It was also demonstrated that epothilone B in fact targets microtubules in a more effective manner than paclitaxel. (orig.)

  13. Endocrine Disruption and Human Prostate Cancer

    National Research Council Canada - National Science Library

    Risbridger, Gail

    2008-01-01

    .... In order to test the concept that Vinclozolin alters human prostate development and induces disease, we used our model system to study human prostate development and maturation over 8-12 weeks...

  14. Human Papillomavirus (HPV) and Oropharyngeal Cancer

    Science.gov (United States)

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Human papillomavirus (HPV) can cause serious health problems, including ... 6348 Email CDC-INFO U.S. Department of Health & Human Services HHS/Open USA.gov TOP

  15. 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

  16. Human tissue models in cancer research: looking beyond the mouse

    Directory of Open Access Journals (Sweden)

    Samuel J. Jackson

    2017-08-01

    Full Text Available Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of ‘non-animal human tissue’ models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models.

  17. Human tissue models in cancer research: looking beyond the mouse.

    Science.gov (United States)

    Jackson, Samuel J; Thomas, Gareth J

    2017-08-01

    Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of 'non-animal human tissue' models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models. © 2017. Published by The Company of Biologists Ltd.

  18. Implicating the H63D polymorphism in the HFE gene in increased incidence of solid cancers: a meta-analysis.

    Science.gov (United States)

    Shen, L L; Gu, D Y; Zhao, T T; Tang, C J; Xu, Y; Chen, J F

    2015-10-29

    A number of previous studies have demonstrated that the HFE H63D polymorphism is associated with increased risk of incidence multiple types of cancer, including colorectal cancer, breast cancer, liver cancer, pancreatic cancer, and gynecological malignant tumors. However, the clinical outcomes were inconsistent. Therefore, this meta-analysis was conducted to summarize the effect of the H63D variant on the incidence of solid tumor. PubMed and EMBASE databases were searched for articles associating the HFE H63D polymorphism with cancer risk. The relationships were evaluated by calculating the pooled odds ratios (ORs) with 95% confidence intervals (CIs). A total of 28 studies, including 7728 cancer cases and 11,895 controls, were identified. Statistically significant associations were identified between the HFE H63D polymorphism and solid cancer risk (CG vs CC, OR = 1.14, 95%CI = 1.07-1.23, P HFE H63D polymorphism may play a critical role in the increased aggressiveness of hepatocellular carcinoma and pancreatic cancer.

  19. Urinary acylcarnitines are altered in human kidney cancer.

    Science.gov (United States)

    Ganti, Sheila; Taylor, Sandra L; Kim, Kyoungmi; Hoppel, Charles L; Guo, Lining; Yang, Joy; Evans, Christopher; Weiss, Robert H

    2012-06-15

    Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at concentrations different from control patients. Here, we collected urine samples from kidney cancer patients and analyzed them by chromatography coupled to mass spectrometry. Once normalized to control for urinary concentration, samples were analyzed by two independent laboratories. After technical validation, we now show differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades. This finding was validated in a mouse xenograft model of human kidney cancer. Biological validation shows carbon chain length-dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher chain length acylcarnitines demonstrated inhibitory effects on NF-κB activation, suggesting an immune modulatory effect of these compounds. Thus, acylcarnitines in the kidney cancer urine may reflect alterations in metabolism, cell component synthesis and/or immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites which may lead to new therapeutic approaches for cancer and may prove useful in cancer biomarker studies. Furthermore, these findings open up a new area of investigation into the metabolic basis of kidney cancer. Copyright © 2011 UICC.

  20. 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.

  1. Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: A systematic expression analysis

    International Nuclear Information System (INIS)

    Hamm, Alexander; Knuechel, Ruth; Dahl, Edgar; Veeck, Juergen; Bektas, Nuran; Wild, Peter J; Hartmann, Arndt; Heindrichs, Uwe; Kristiansen, Glen; Werbowetski-Ogilvie, Tamra; Del Maestro, Rolando

    2008-01-01

    The inter-alpha-trypsin inhibitors (ITI) are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded by AMBP – and five homologous heavy chains (encoded by ITIH1, ITIH2, ITIH3, ITIH4, and ITIH5), contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis. We systematically investigated differential gene expression of the ITIH gene family, as well as AMBP and the interacting partner TNFAIP6 in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas) using cDNA dot blot analysis (Cancer Profiling Array, CPA), semiquantitative RT-PCR and immunohistochemistry. We found that ITIH genes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus, ITIH genes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we chose ITIH2 expression in human breast cancer. Loss of ITIH2 expression in 70% of cases (n = 50, CPA) could be confirmed by real-time PCR in an additional set of breast cancers (n = 36). Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p < 0.001) between ITIH2 expression and estrogen receptor (ER) expression indicating that ER may be involved in the regulation of this ECM molecule. Altogether, this is the first systematic analysis on the differential expression of ITIH genes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies

  2. Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH genes in multiple human solid tumors: A systematic expression analysis

    Directory of Open Access Journals (Sweden)

    Werbowetski-Ogilvie Tamra

    2008-01-01

    Full Text Available Abstract Background The inter-alpha-trypsin inhibitors (ITI are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded by AMBP – and five homologous heavy chains (encoded by ITIH1, ITIH2, ITIH3, ITIH4, and ITIH5, contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis. Methods We systematically investigated differential gene expression of the ITIH gene family, as well as AMBP and the interacting partner TNFAIP6 in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas using cDNA dot blot analysis (Cancer Profiling Array, CPA, semiquantitative RT-PCR and immunohistochemistry. Results We found that ITIH genes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus, ITIH genes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we chose ITIH2 expression in human breast cancer. Loss of ITIH2 expression in 70% of cases (n = 50, CPA could be confirmed by real-time PCR in an additional set of breast cancers (n = 36. Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p Conclusion Altogether, this is the first systematic analysis on the differential expression of ITIH genes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies.

  3. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Hao Hong

    Full Text Available New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM were then genetically modified to express an anti-L1-CAM CAR (CE7R, which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p. administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.

  4. 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.

  5. Mucous solids and liquid secretion by airways: studies with normal pig, cystic fibrosis human, and non-cystic fibrosis human bronchi

    Science.gov (United States)

    Martens, Chelsea J.; Inglis, Sarah K.; Valentine, Vincent G.; Garrison, Jennifer; Conner, Gregory E.

    2011-01-01

    To better understand how airways produce thick airway mucus, nonvolatile solids were measured in liquid secreted by bronchi from normal pig, cystic fibrosis (CF) human, and non-CF human lungs. Bronchi were exposed to various secretagogues and anion secretion inhibitors to induce a range of liquid volume secretion rates. In all three groups, the relationship of solids concentration (percent nonvolatile solids) to liquid volume secretion rate was curvilinear, with higher solids concentration associated with lower rates of liquid volume secretion. In contrast, the secretion rates of solids mass and water mass as functions of liquid volume secretion rates exhibited positive linear correlations. The y-intercepts of the solids mass-liquid volume secretion relationships for all three groups were positive, thus accounting for the higher solids concentrations in airway liquid at low rates of secretion. Predictive models derived from the solids mass and water mass linear equations fit the experimental percent solids data for the three groups. The ratio of solids mass secretion to liquid volume secretion was 5.2 and 2.4 times higher for CF bronchi than for pig and non-CF bronchi, respectively. These results indicate that normal pig, non-CF human, and CF human bronchi produce a high-percent-solids mucus (>8%) at low rates of liquid volume secretion (≤1.0 μl·cm−2·h−1). However, CF bronchi produce mucus with twice the percent solids (∼8%) of pig or non-CF human bronchi at liquid volume secretion rates ≥4.0 μl·cm−2·h−1. PMID:21622844

  6. Feasibility and accuracy evaluation of three human papillomavirus assays for FTA card-based sampling: a pilot study in cervical cancer screening

    OpenAIRE

    Wang, Shao-Ming; Hu, Shang-Ying; Chen, Wen; Chen, Feng; Zhao, Fang-Hui; He, Wei; Ma, Xin-Ming; Zhang, Yu-Qing; Wang, Jian; Sivasubramaniam, Priya; Qiao, You-Lin

    2015-01-01

    Background Liquid-state specimen carriers are inadequate for sample transportation in large-scale screening projects in low-resource settings, which necessitates the exploration of novel non-hazardous solid-state alternatives. Studies investigating the feasibility and accuracy of a solid-state human papillomavirus (HPV) sampling medium in combination with different down-stream HPV DNA assays for cervical cancer screening are needed. Methods We collected two cervical specimens from 396 women, ...

  7. Frequency of human papillomavirus infection in patients with gastrointestinal cancer.

    Science.gov (United States)

    Roesch-Dietlen, F; Cano-Contreras, A D; Sánchez-Maza, Y J; Espinosa-González, J M; Vázquez-Prieto, M Á; Valdés-de la O, E J; Díaz-Roesch, F; Carrasco-Arroniz, M Á; Cruz-Palacios, A; Grube-Pagola, P; Sumoza-Toledo, A; Vivanco-Cid, H; Mellado-Sánchez, G; Meixueiro-Daza, A; Silva-Cañetas, C S; Carrillo-Toledo, M G; Lagunes-Torres, R; Amieva-Balmori, M; Gómez-Castaño, P C; Reyes-Huerta, J U; Remes-Troche, J M

    2018-02-15

    Cancer is the result of the interaction of genetic and environmental factors. It has recently been related to viral infections, one of which is human papillomavirus. The aim of the present study was to describe the frequency of human papillomavirus infection in patients with digestive system cancers. A prospective, multicenter, observational study was conducted on patients with gastrointestinal cancer at 2public healthcare institutes in Veracruz. Two tumor samples were taken, one for histologic study and the other for DNA determination of human papillomavirus and its genotypes. Anthropometric variables, risk factors, sexual habits, tumor location, and histologic type of the cancer were analyzed. Absolute and relative frequencies were determined using the SPSS version 24.0 program. Fifty-three patients were studied. They had gastrointestinal cancer located in: the colon (62.26%), stomach (18.87%), esophagus (7.55%), rectum (7.55%), and small bowel (3.77%). Human papillomavirus was identified in 11.32% of the patients, 66.7% of which corresponded to squamous cell carcinoma and 33.3% to adenocarcinoma. Only genotype 18 was identified. Mean patient age was 61.8±15.2 years, 56.60% of the patients were men, and 43.40% were women. A total of 15.8% of the patients had a family history of cancer and 31.6% had a personal history of the disease, 38.6% were tobacco smokers, and 61.4% consumed alcohol. Regarding sex, 5.3% of the patients said they were homosexual, 3.5% were bisexual, 29.8% engaged in oral sex, and 24.6% in anal sex. Our study showed that human papillomavirus infection was a risk factor for the development of gastrointestinal cancer, especially of squamous cell origin. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  8. Foxp3 expression in human cancer cells

    Directory of Open Access Journals (Sweden)

    Gourgoulianis Konstantinos I

    2008-04-01

    Full Text Available Abstract Objective Transcription factor forkhead box protein 3 (Foxp3 specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs. Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types. Materials and methods Twenty five tumor cell lines of different tissue origins (lung cancer, colon cancer, breast cancer, melanoma, erythroid leukemia, acute T-cell leukemia were studied. Detection of Foxp3 mRNA was performed using both conventional RT-PCR and quantitative real-time PCR while protein expression was assessed by immunocytochemistry and flow cytometry, using different antibody clones. Results Foxp3 mRNA as well as Foxp3 protein was detected in all tumor cell lines, albeit in variable levels, not related to the tissue of origin. This expression correlated with the expression levels of IL-10 and TGFb1. Conclusion We offer evidence that Foxp3 expression, characterizes tumor cells of various tissue origins. The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.

  9. Fraction against Human Cancer Cell Lines

    African Journals Online (AJOL)

    fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and ... The morphology of the HepG2 cell nucleus was investigated by Hoechst 33342, ..... Gong F, Liang Y, Xie P, Chau F. Information theory.

  10. (Asteraceae) Fraction against Human Cancer Cell Lines

    African Journals Online (AJOL)

    Purpose: To investigate the anti-proliferative and apoptotic activity of crude and dichloromethane fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and L929). Methods: A. sieberi was extracted with methanol and further purification was carried out using liquidliquid extraction ...

  11. 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.

  12. Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yung-Lin Chu

    2013-07-01

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

  13. 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

  14. Concentration of uranium in human cancerous tissues of Southern Iraqi patients using fission track analysis

    International Nuclear Information System (INIS)

    Al-Hamzawi, A.A.; Al-Qadisiyah University, Qadisiyah; Jaafar, M.S.; Tawfiq, N.F.

    2015-01-01

    The technique of nuclear fission track analysis with solid state nuclear track detectors CR-39 has been applied to determine concentrations of uranium in cancerous samples of human tissues that excised from patients in the three key southern Iraqi governorates namely, Basrah, Dhi-Qar, and Muthanna. These provinces were the sites of intensive military events during the Gulf Wars in 1991 and 2003. The investigation was based on the study of 24 abnormal samples and 12 normal samples for comparing the results. These samples include four types of soft tissues (kidney, breast, stomach and uterus). The results show that uranium concentrations in the normal tissues ranged between (1.42-4.76 μg kg -1 ), whereas in the cancerous tissues ranged between (3.37-7.22 μg kg -1 ). The uranium concentrations in the normal tissues were significantly lower than in the abnormal tissues (P < 0.001). (author)

  15. Development of electrochemical biosensors and solid-phase amplification methods for the detection of human papillomavirus genes

    OpenAIRE

    Civit Pitarch, Laia

    2012-01-01

    A rapid, accurate and reliable diagnosis is crucial for the identification of a disease, like cancer, where an early detection can improve patient survival outcomes. Cervical cancer is the third most commonly diagnosed and the fourth leading cause of cancer death in women. It is well known that persistent infections with high-risk human papillomaviruses (HPV) are the primary cause of cervical cancer. Electrochemical DNA biosensors have received important attention owing to their characterist...

  16. Genetic and environmental factors in experimental and human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Takayama, S.; Takebe, H.; Gelboin, H.V.; MaChahon, B.; Matsushima, T.; Sugimura, T.

    1980-01-01

    Recently technological advances in assaying mutagenic principles have revealed that there are many mutagens in the environment, some of which might be carcinogenic to human beings. Other advances in genetics have shown that genetic factors might play an important role in the induction of cancer in human beings, e.g., the high incidence of skin cancers in patients with xeroderma pigmentosum. These proceedings deal with the relationships between genetic and environmental factors in carcinogenesis. The contributors cover mixed-function oxidases, pharmacogenetics, twin studies, DNA repair, immunology, and epidemiology.

  17. Solid-state NMR, electrophysiology and molecular dynamics characterization of human VDAC2

    International Nuclear Information System (INIS)

    Gattin, Zrinka; Schneider, Robert; Laukat, Yvonne; Giller, Karin; Maier, Elke; Zweckstetter, Markus; Griesinger, Christian; Benz, Roland; Becker, Stefan; Lange, Adam

    2015-01-01

    The voltage-dependent anion channel (VDAC) is the most abundant protein of the outer mitochondrial membrane and constitutes the major pathway for the transport of ADP, ATP, and other metabolites. In this multidisciplinary study we combined solid-state NMR, electrophysiology, and molecular dynamics simulations, to study the structure of the human VDAC isoform 2 in a lipid bilayer environment. We find that the structure of hVDAC2 is similar to the structure of hVDAC1, in line with recent investigations on zfVDAC2. However, hVDAC2 appears to exhibit an increased conformational heterogeneity compared to hVDAC1 which is reflected in broader solid-state NMR spectra and less defined electrophysiological profiles

  18. Solid-state NMR, electrophysiology and molecular dynamics characterization of human VDAC2

    Energy Technology Data Exchange (ETDEWEB)

    Gattin, Zrinka; Schneider, Robert; Laukat, Yvonne; Giller, Karin [Max Planck Institute for Biophysical Chemistry (Germany); Maier, Elke [Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Lehrstuhl für Biotechnologie (Germany); Zweckstetter, Markus; Griesinger, Christian [Max Planck Institute for Biophysical Chemistry (Germany); Benz, Roland [Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Lehrstuhl für Biotechnologie (Germany); Becker, Stefan; Lange, Adam, E-mail: alange@fmp-berlin.de [Max Planck Institute for Biophysical Chemistry (Germany)

    2015-04-15

    The voltage-dependent anion channel (VDAC) is the most abundant protein of the outer mitochondrial membrane and constitutes the major pathway for the transport of ADP, ATP, and other metabolites. In this multidisciplinary study we combined solid-state NMR, electrophysiology, and molecular dynamics simulations, to study the structure of the human VDAC isoform 2 in a lipid bilayer environment. We find that the structure of hVDAC2 is similar to the structure of hVDAC1, in line with recent investigations on zfVDAC2. However, hVDAC2 appears to exhibit an increased conformational heterogeneity compared to hVDAC1 which is reflected in broader solid-state NMR spectra and less defined electrophysiological profiles.

  19. Advancements in diagnosis and treatment of meningeal carcinomatosis in solid cancer

    Institute of Scientific and Technical Information of China (English)

    Jun-Zhao Cui; Ze-Yan Zhao; Yuan-Yuan Li; Ming-Ming Zheng; Ya-Juan Liu; Li-Tian Yan; Jun-Ying He; Qing Li; Xiao-Qing Li; Rui-Ping Gao; Hui Bu; Yue-Li Zou; Xiao-Su Guo; Wei-Xin Han

    2017-01-01

    Meningeal carcinomatosis (MC) is a disease that malignant tumor cells cultivate in the cerebrospinal fluid or meninges. With the development of therapy methods and new techniques, survival time of patients with tumor is prolonged, and the incidence of MC is increasing. Diagnosis is based on the evaluation of clinical manifestations, cerebrospinal fluid and neuroimaging findings. Furthermore, in recent years, the diagnostic value of the tumor-derived cell-free DNA in the cerebrospinal fluid (CSF) is promising and may improve the diagnostic yield of CSF analysis. Traditional treatments of MC include surgery, radiation therapy, systemic therapy, and intrathecal therapy. Recently, molecular targeted therapy and immunotherapy have received more and more attention. The authors review the epidemiology, pathogenesis, clinical manifestation, diagnosis and treatment of MC in solid cancer, and discuss the diagnosis and treatment options currently available as well as those under investigation.

  20. AR Signaling in Human Malignancies: Prostate Cancer and Beyond.

    Science.gov (United States)

    Antonarakis, Emmanuel S

    2018-01-18

    The notion that androgens and androgen receptor (AR) signaling are the hallmarks of prostate cancer oncogenesis and disease progression is generally well accepted. What is more poorly understood is the role of AR signaling in other human malignancies. This special issue of Cancers initially reviews the role of AR in advanced prostate cancer, and then explores the potential importance of AR signaling in other epithelial malignancies. The first few articles focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens, and they also outline the interaction between AR and other cellular pathways, including PI3 kinase signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt signaling, and epigenetic regulation in prostate cancer. The next several articles review the possible role of androgens and AR signaling in breast cancer, bladder cancer, salivary gland cancer, and hepatocellular carcinoma, as well as the potential treatment implications of using antiandrogen therapies in these non-prostatic malignancies.

  1. Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

    Energy Technology Data Exchange (ETDEWEB)

    Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Gilbert, Ethel; Curtis, Rochelle; Inskip, Peter; Kleinerman, Ruth; Morton, Lindsay; Rajaraman, Preetha; Little, Mark P. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-06-01

    Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.

  2. 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. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  4. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    International Nuclear Information System (INIS)

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

  5. Parallel recognition of cancer cells using an addressable array of solid-state micropores.

    Science.gov (United States)

    Ilyas, Azhar; Asghar, Waseem; Kim, Young-tae; Iqbal, Samir M

    2014-12-15

    Early stage detection and precise quantification of circulating tumor cells (CTCs) in the peripheral blood of cancer patients are important for early diagnosis. Early diagnosis improves the effectiveness of the therapy and results in better prognosis. Several techniques have been used for CTC detection but are limited by their need for dye tagging, low throughput and lack of statistical reliability at single cell level. Solid-state micropores can characterize each cell in a sample providing interesting information about cellular populations. We report a multi-channel device which utilized solid-state micropores array assembly for simultaneous measurement of cell translocation. This increased the throughput of measurement and as the cells passed the micropores, tumor cells showed distinctive current blockade pulses, when compared to leukocytes. The ionic current across each micropore channel was continuously monitored and recorded. The measurement system not only increased throughput but also provided on-chip cross-relation. The whole blood was lysed to get rid of red blood cells, so the blood dilution was not needed. The approach facilitated faster processing of blood samples with tumor cell detection efficiency of about 70%. The design provided a simple and inexpensive method for rapid and reliable detection of tumor cells without any cell staining or surface functionalization. The device can also be used for high throughput electrophysiological analysis of other cell types. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1

    OpenAIRE

    Harrison, Luke R.E.; Micha, Dimitra; Brandenburg, Martin; Simpson, Kathryn L.; Morrow, Christopher J.; Denneny, Olive; Hodgkinson, Cassandra; Yunus, Zaira; Dempsey, Clare; Roberts, Darren; Blackhall, Fiona; Makin, Guy; Dive, Caroline

    2011-01-01

    Solid tumors contain hypoxic regions in which cancer cells are often resistant to chemotherapy-induced apoptotic cell death. Therapeutic strategies that specifically target hypoxic cells and promote apoptosis are particularly appealing, as few normal tissues experience hypoxia. We have found that the compound ABT-737, a Bcl-2 homology domain 3 (BH-3) mimetic, promotes apoptotic cell death in human colorectal carcinoma and small cell lung cancer cell lines exposed to hypoxia. This hypoxic indu...

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

    DEFF Research Database (Denmark)

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

    1990-01-01

    Homeobox genes encode sequence-specific DNA-binding proteins that are involved in the regulation of gene expression during embryonic development. In this study, we examined the expression of homeobox proteins in human cancer. Antiserum was obtained against a synthetic peptide derived from...... was then isolated and used to elicit a rabbit antiserum. In immunostaining, both antisera reacted with the nuclei of cultured tumor cells. In tissue sections of human carcinoma, nuclear immunoreactivity was observed in the tumor cells in 40 of 42 cases examined. Adjacent normal epithelial tissue obtained from......, the presence of the homeobox transcript in human carcinoma was documented by in situ hybridization and RNase protection mapping. These results demonstrate that human cancer is associated with the expression of homeobox proteins. Such homeobox proteins, as well as other regulatory proteins, could be involved...

  8. Concepts in causality: chemically induced human urinary bladder cancer

    International Nuclear Information System (INIS)

    Lower, G.M. Jr.

    1982-01-01

    A significant portion of the incidence of human urinary bladder cancer can be attributed to occupational and cultural (tobacco smoking) situations associated with exposures to various arylamines, many of which represent established human carcinogens. A brief historical overview of research in bladder cancer causality indicates that the identification of causal agents and causal mechanism has been approached and rests upon information gathered at the organismal (geographical/historical), cellular, and molecular levels of biologic organization. This viewpoint speaks of a natural evolution within the biomedical sciences; a natural evolution from descriptive approaches to mechanistic approaches; and a natural evolution from more or less independent discipline-oriented approaches to hierarchically organized multidisciplinary approaches. Available information relevant to bladder cancer causality can be readily integrated into general conceptual frameworks to yield a hierarchial view of the natural history of urinary bladder cancer, a view consistent with contemporary natural systems and information theory and perhaps relevant also to other chemically induced epithelial cancers. Such frameworks are useful in appreciating the spatial and temporal boundaries and interrelationships in causality and the conceptual interrelationships within the biomedical sciences. Recent approaches in molecular epidemiology and the assessment of relative individual susceptibility to bladder cancer indicate that such frameworks are useful in forming hypotheses

  9. Characterization of human breast cancer by scanning acoustic microscopy

    Science.gov (United States)

    Chen, Di; Malyarenko, Eugene; Seviaryn, Fedar; Yuan, Ye; Sherman, Mark; Bandyopadhyay, Sudeshna; Gierach, Gretchen; Greenway, Christopher W.; Maeva, Elena; Strumban, Emil; Duric, Neb; Maev, Roman

    2013-03-01

    Objectives: The purpose of this study was to characterize human breast cancer tissues by the measurement of microacoustic properties. Methods: We investigated eight breast cancer patients using acoustic microscopy. For each patient, seven blocks of tumor tissue were collected from seven different positions around a tumor mass. Frozen sections (10 micrometer, μm) of human breast cancer tissues without staining and fixation were examined in a scanning acoustic microscope with focused transducers at 80 and 200 MHz. Hematoxylin and Eosin (H and E) stained sections from the same frozen breast cancer tissues were imaged by optical microscopy for comparison. Results: The results of acoustic imaging showed that acoustic attenuation and sound speed in cancer cell-rich tissue regions were significantly decreased compared with the surrounding tissue regions, where most components are normal cells/tissues, such as fibroblasts, connective tissue and lymphocytes. Our observation also showed that the ultrasonic properties were influenced by arrangements of cells and tissue patterns. Conclusions: Our data demonstrate that attenuation and sound speed imaging can provide biomechanical information of the tumor and normal tissues. The results also demonstrate the potential of acoustic microscopy as an auxiliary method for operative detection and localization of cancer affected regions.

  10. Alterations of MicroRNAs in Solid Cancers and Their Prognostic Value

    International Nuclear Information System (INIS)

    Chira, Panagiota; Vareli, Katerina; Sainis, Ioannis; Papandreou, Christos; Briasoulis, Evangelos

    2010-01-01

    MicroRNAs (miRNAs) are evolutionarily conserved, naturally abundant, small, regulatory non-coding RNAs that inhibit gene expression at the post-transcriptional level in a sequence-specific manner. Each miRNA represses the protein expression of several coding genes in a manner proportional to the sequence complementarity with the target transcripts. MicroRNAs play key regulatory roles in organismal development and homeostasis. They control fundamental biological processes, such as stem-cell regulation and cellular metabolism, proliferation, differentiation, stress resistance, and apoptosis. Differential miRNA expression is found in malignant tumors in comparison to normal tissue counterparts. This indicates that miRNA deregulation contributes to the initiation and progression of cancer. Currently, miRNA expression signatures are being rigorously investigated in various tumor types, with the aim of developing novel, efficient biomarkers that can improve clinical management of cancer patients. This review discusses deregulated miRNAs in solid tumors, and focuses on their emerging prognostic potential

  11. Management of Infection and Febrile Neutropenia in Patients with Solid Cancer.

    Science.gov (United States)

    Aguado, José María; Cruz, Juan Jesús; Virizuela, Juan Antonio; Aguilar, Manuela; Carmona, Alberto; Cassinello, Javier; Gudiol, Carlota; Jiménez Fonseca, Paula; Lizasoain, Manuel; Marco, Francesc; Ruiz, Isabel; Ruiz, Maribel; Salavert, Miguel; Vicente, David; Carratalà, Jordi

    A group of experts from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Medical Oncology (SEOM) have reviewed in this paper the main aspects to be considered in the evaluation of patients with solid cancer and infectious diseases. They have established a series of recommendations on the prevention of the most prevalent infections in these patients, the use of vaccines, the control measures of vascular catheter infection and prevention of infections before certain surgical procedures. Also the criteria for management of febrile neutropenia and the use of colony-stimulating factors were revised. Finally they provide a series of recommendations for the treatment of cancer patients with severe infection. The document is completed with a series of measures for the control of hospital infection. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  12. Ionizing radiation decreases human cancer mortality rates

    International Nuclear Information System (INIS)

    Luckey, T.D.

    1997-01-01

    Information from nine studies with exposed nuclear workers and military observers of atmospheric bomb explosions confirms the results from animal studies which showed that low doses of ionizing radiation are beneficial. The usual ''healthy worker effect'' was eliminated by using carefully selected control populations. The results from 13 million person-years show the cancer mortality rate of exposed persons is only 65.6% that of carefully selected unexposed controls. This overwhelming evidence makes it politically untenable and morally wrong to withhold public health benefits of low dose irradiation. Safe supplementation of ionizing radiation should become a public health service. (author)

  13. Artificial sweeteners and human bladder cancer.

    Science.gov (United States)

    Howe, G R; Burch, J D; Miller, A B; Morrison, B; Gordon, P; Weldon, L; Chambers, L W; Fodor, G; Winsor, G M

    1977-09-17

    A positive association between the use of artificial sweetners, particularly saccharin, and risk of bladder cancer in males has been observed in a case-control study of 480 men and 152 women in three Provinces in Canada. The risk ratio for ever versus never used is 1-6 for males (P=0-009, one-tailed test), and a significant dose-response relationship was obtained for both duration and frequency of use. The population attributable risk for males is estimated at 7%, though for diabetics, who have a similar risk ratio for artificial sweetner use as non-diabetics, the attributable risk is 33%.

  14. Excess relative risk of solid cancer mortality after prolonged exposure to naturally occurring high background radiation in Yangjiang, China

    Energy Technology Data Exchange (ETDEWEB)

    Sun Quanfu; Tao Zufan [Ministry of Health, Beijing (China). Lab. of Industrial Hygiene; Akiba, Suminori (and others)

    2000-10-01

    A study was made on cancer mortality in the high-background radiation areas of Yangjiang, China. Based on hamlet-specific environmental doses and sex- and age-specific occupancy factors, cumulative doses were calculated for each subject. In this article, we describe how the indirect estimation was made on individual dose and the methodology used to estimate radiation risk. Then, assuming a linear dose response relationship and using cancer mortality data for the period 1979-1995, we estimate the excess relative risk per Sievert for solid cancer to be -0.11 (95% CI, -0.67, 0.69). Also, we estimate the excess relative risks of four leading cancers in the study areas, i.e., cancers of the liver, nasopharynx, lung and stomach. In addition, we evaluate the effects of possible bias on our risk estimation. (author)

  15. Resveratrol: A review of preclinical studies for human cancer prevention

    International Nuclear Information System (INIS)

    Athar, Mohammad; Back, Jung Ho; Tang Xiuwei; Kim, Kwang Ho; Kopelovich, Levy; Bickers, David R.; Kim, Arianna L.

    2007-01-01

    The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds one of which is resveratrol (trans-3,4',5-trihydroxystilbene), a phytoalexin derived from the skin of grapes and other fruits. Resveratrol is known to have potent anti-inflammatory and antioxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells. Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis (initiation, promotion, and progression), in both chemically and UVB-induced skin carcinogenesis in mice, as well as in various murine models of human cancers. Evidence from numerous in vitro and in vivo studies has confirmed its ability to modulate various targets and signaling pathways. This review discusses the current preclinical and mechanistic data available and assesses resveratrol's anticancer effects to support its potential as an anticancer agent in human populations

  16. Sulphur XANES Analysis of Cultured Human Prostate Cancer Cells

    International Nuclear Information System (INIS)

    Kwiatek, W.M.; Podgorczyk, M.; Paluszkiewicz, Cz.; Balerna, A.; Kisiel, A.

    2008-01-01

    Prostate cancer is one of the most commonly diagnosed cancers in men throughout the world. It is believed that changes to the structure of protein binding sites, altering its metabolism, may play an important role in carcinogenesis. Sulphur, often present in binding sites, can influence such changes through its chemical speciation. Hence there is a need for precise investigation of coordination environment of sulphur. X-ray absorption near edge structure spectroscopy offers such possibility. Cell culture samples offer histologically well defined areas of good homogeneity, suitable for successful and reliable X-ray absorption near edge structure analysis. This paper presents sulphur speciation data collected from three different human prostate cancer cell lines (PC-3, LNCaP and DU-145). Sulphur X-ray absorption near edge structure analysis was performed on K-edge structure. The spectra of cells were compared with those of cancerous tissue and with organic substances as well as inorganic compounds. (authors)

  17. 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

  18. Knowledge and attitudes towards cervical cancer and human ...

    African Journals Online (AJOL)

    on respondents' biodata, knowledge of STIs, human papilloma virus and cervical cancer, health and communication resources in their communities. This was supplemented by focus group discussions among religious and tribal groups within the urban and rural communities. We found a low level of awareness about HPV ...

  19. Viruses and human cancers: challenges for preventive strategies.

    Science.gov (United States)

    de The, G

    1995-01-01

    Virus-associated human cancers provide unique opportunities for preventive strategies. The role of human papilloma viruses (HPV 16 and 18), hepatitis B virus (HBV), Epstein-Barr herpes virus (EBV), and retroviruses (human immunodeficiency virus [HIV] and human T-cell leukemia/lymphoma virus [HTLV]) in the development of common carcinomas and lymphomas represents a major cancer threat, particularly among individuals residing in developing countries, which account for 80% of the world's population. Even though these viruses are not the sole etiological agents of these cancers (as would be the case for infectious diseases), different approaches can be implemented to significantly decrease the incidence of virus-associated malignancies. The first approach is vaccination, which is available for HBV and possibly soon for EBV. The long delay between primary viral infection and development of associated tumors as well as the cost involved with administering vaccinations detracts from the feasibility of such an approach within developing countries. The second approach is to increase efforts to detect pre-cancerous lesions or early tumors using immunovirological means. This would allow early diagnosis and better treatment. The third strategy is linked to the existence of disease susceptibility genes, and suggests that counseling be provided for individuals carrying these genes to encourage them to modify their lifestyles and other conditions associated with increased cancer risks (predictive oncology). Specific recommendations include: a) increase international studies that explore the causes of the large variations in prevalence of common cancers throughout the world; b) conduct interdisciplinary studies involving laboratory investigation and social sciences, which may suggest hypotheses that may then be tested experimentally; and c) promote more preventive and health enhancement strategies in addition to curative and replacement therapies. PMID:8741797

  20. Identification of DNA methylation changes associated with human gastric cancer

    Directory of Open Access Journals (Sweden)

    Park Jung-Hoon

    2011-12-01

    Full Text Available Abstract Background Epigenetic alteration of gene expression is a common event in human cancer. DNA methylation is a well-known epigenetic process, but verifying the exact nature of epigenetic changes associated with cancer remains difficult. Methods We profiled the methylome of human gastric cancer tissue at 50-bp resolution using a methylated DNA enrichment technique (methylated CpG island recovery assay in combination with a genome analyzer and a new normalization algorithm. Results We were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands (CGIs, transcript bodies, and various repeat classes. We found that gastric cancer was associated with hypermethylation of 5' CGIs and the 5'-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA. Hypermethylation of 5' CGIs was significantly correlated with downregulation of associated genes, such as those in the HOX and histone gene families. We also discovered long-range epigenetic silencing (LRES regions in gastric cancer tissue and identified several hypermethylated genes (MDM2, DYRK2, and LYZ within these regions. The methylation status of CGIs and gene annotation elements in metastatic lymph nodes was intermediate between normal and cancerous tissue, indicating that methylation of specific genes is gradually increased in cancerous tissue. Conclusions Our findings will provide valuable data for future analysis of CpG methylation patterns, useful markers for the diagnosis of stomach cancer, as well as a new analysis method for clinical epigenomics investigations.

  1. Toxicity of diuron in human cancer cells.

    Science.gov (United States)

    Huovinen, Marjo; Loikkanen, Jarkko; Naarala, Jonne; Vähäkangas, Kirsi

    2015-10-01

    Diuron is a substituted phenylurea used as a herbicide to control broadleaf and grass weeds and as a biocidal antifouling agent. Diuron is carcinogenic in rat urinary bladder and toxic to the reproductive system of oysters, sea urchins and lizards. The few studies carried out in human cells do not include the genotoxicity of diuron. We have investigated the toxicity of diuron in human breast adenocarcinoma (MCF-7) and human placental choriocarcinoma (BeWo) cells. The production of reactive oxygen species (ROS) was statistically significantly increased in both cell lines but only at the highest 200 μM concentration. Diuron clearly reduced the viability of BeWo, but not MCF-7 cells. The relative cell number was decreased in both cell lines indicative of inhibition of cell proliferation. In the Comet assay, diuron increased DNA fragmentation in MCF-7 but not in BeWo cells. The expressions of p53 protein, a marker for cell stress, and p21 protein, a transcriptional target of p53, were increased, but only in MCF-7 cells. In conclusion, our results suggest that diuron is cytotoxic and potentially genotoxic in a tissue-specific manner and that ROS play a role in its toxicity. Thus, exposure to diuron may exert harmful effects on fetal development and damage human health. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Clinicopathological significance of PTPN12 expression in human breast cancer

    International Nuclear Information System (INIS)

    Yuan, Xunyi; Yuan, Zhentao; Jiang, Dandan; Li, Funian

    2012-01-01

    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

  3. Human cancers converge at the HIF-2alpha oncogenic axis.

    Science.gov (United States)

    Franovic, Aleksandra; Holterman, Chet E; Payette, Josianne; Lee, Stephen

    2009-12-15

    Cancer development is a multistep process, driven by a series of genetic and environmental alterations, that endows cells with a set of hallmark traits required for tumorigenesis. It is broadly accepted that growth signal autonomy, the first hallmark of malignancies, can be acquired through multiple genetic mutations that activate an array of complex, cancer-specific growth circuits [Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57-70; Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789-799]. The superfluous nature of these pathways is thought to severely limit therapeutic approaches targeting tumor proliferation, and it has been suggested that this strategy be abandoned in favor of inhibiting more systemic hallmarks, including angiogenesis (Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: Mechanisms of anti-tumor activity. Nat Rev Cancer 8:579-591; Stommel JM, et al. (2007) Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318:287-290; Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2:727-739; Kaiser J (2008) Cancer genetics: A detailed genetic portrait of the deadliest human cancers. Science 321:1280-1281]. Here, we report the unexpected observation that genetically diverse cancers converge at a common and obligatory growth axis instigated by HIF-2alpha, an element of the oxygen-sensing machinery. Inhibition of HIF-2alpha prevents the in vivo growth and tumorigenesis of highly aggressive glioblastoma, colorectal, and non-small-cell lung carcinomas and the in vitro autonomous proliferation of several others, regardless of their mutational status and tissue of origin. The concomitant deactivation of select receptor tyrosine kinases, including the EGFR and IGF1R, as well as downstream ERK/Akt signaling, suggests that HIF-2alpha exerts its proliferative effects by endorsing these major pathways. Consistently

  4. Development and evaluation of a magnetic solid-phase radioimmunoassay for total human thyroxine (T4)

    International Nuclear Information System (INIS)

    Abbas, S. H.; Hassan, A. M. E.; Abdalla, O. M.; Zahran, A. B.; Shabbo, N. M.; Ali, N. I.; Gubara, A.

    2009-02-01

    In this study a simple and rapid magnetic solid-phase radioimmunoassay (RIA) for human thyroxine (T4) was developed using locally raised sheep thyroxine antibody and radioiodinated thyroxine (T4) tracer by chloramine-T method. The assay involves two hours incubation at ambient temperature rang (30 to 35 o C ) associated with the antibody covalently linked by the easily performed carbonyldiimidazole (CDI) method to magnetic particles obtained from SIPAC. 0.1% triton with sodium azide used as a wash buffer. L-Thyroxine Na-salt peta hydrate from sigma was used for the preparation of standards and quality control sera. The coupled magnetic anti-T4 solid phase titrated in order to find out the suitable antibody concentration (titre) to be used in the assay. Optimizations followed by validation procedures were done. When correlated with kits imported from NETRIA and AMERSHAM, results were found to be highly comparable r=0.965 and p<0.05. Shelf life was also studied, so that the local prepared T4 RIA magnetic reagents can be used for the measurement of total human thyroxine with a very low cost compared to imported kits. (Author)

  5. [Soy isoflavones and human health: breast cancer and puberty timing].

    Science.gov (United States)

    Valladares, Luis; Garrido, Argelia; Sierralta, Walter

    2012-04-01

    Accumulated exposure to high levels of estrogen is associated with an increased incidence of breast cancer. Thus, factors such as early puberty, late menopause and hormone replacement therapy are considered to be risk factors, whereas early childbirth, breastfeeding and puberty at a later age are known to consistently decrease the lifetime breast cancer risk. Epidemiological studies suggest that consumption of isoflavones correlates with a lower incidence of breast cancer. Data from human intervention studies show that the effects of isoflavones on early breast cancer markers differ between pre- and post-menopausal women. The reports from experimental animals (rats and mice) on mammary tumors are variable. These results taken together with heterogeneous outcomes of human interventions, have led to a controversy surrounding the intake of isoflavones to reduce breast cancer risk. This review summarizes recent studies and analyzes factors that could explain the variability of results. In mammary tissue, from the cellular endocrine viewpoint, we analyze the effect of isoflavones on the estrogen receptor and their capacity to act as agonists or antagonists. On the issue of puberty timing, we analyze the mechanisms by which girls, but not boys, with higher prepuberal isoflavone intakes appear to enter puberty at a later age.

  6. Human cancer stem cells are a target for cancer prevention using (-)-epigallocatechin gallate.

    Science.gov (United States)

    Fujiki, Hirota; Sueoka, Eisaburo; Rawangkan, Anchalee; Suganuma, Masami

    2017-12-01

    Our previous experiments show that the main constituent of green-tea catechins, (-)-epigallocatechin gallate (EGCG), completely prevents tumor promotion on mouse skin initiated with 7,12-dimethylbenz(a)anthracene followed by okadaic acid and that EGCG and green tea extract prevent cancer development in a wide range of target organs in rodents. Therefore, we focused our attention on human cancer stem cells (CSCs) as targets of cancer prevention and treatment with EGCG. The numerous reports concerning anticancer activity of EGCG against human CSCs enriched from cancer cell lines were gathered from a search of PubMed, and we hope our review of the literatures will provide a broad selection for the effects of EGCG on various human CSCs. Based on our theoretical study, we discuss the findings as follows: (1) Compared with the parental cells, human CSCs express increased levels of the stemness markers Nanog, Oct4, Sox2, CD44, CD133, as well as the EMT markers, Twist, Snail, vimentin, and also aldehyde dehydrogenase. They showed decreased levels of E-cadherin and cyclin D1. (2) EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs. (3) EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs. (4) The inhibition of EGCG of the stemness of CSCs was weaker compared with parental cells. (5) The weak inhibitory activity of EGCG increased synergistically in combination with anticancer drugs. Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.

  7. [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. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  8. 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.

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    Cegolon Luca

    2013-01-01

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

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

    Science.gov (United States)

    Cegolon, Luca; Salata, Cristiano; Weiderpass, Elisabete; Vineis, Paolo; Palù, Giorgio; Mastrangelo, Giuseppe

    2013-01-03

    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. 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 as other tumors like sarcoma, lymphoma, bladder and

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

    International Nuclear Information System (INIS)

    Cegolon, Luca; Salata, Cristiano; Weiderpass, Elisabete; Vineis, Paolo; Palù, Giorgio; Mastrangelo, Giuseppe

    2013-01-01

    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. 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 as other tumors like sarcoma, lymphoma, bladder

  13. Human Cell Line-Derived Monoclonal IgA Antibodies for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Felix Hart

    2017-05-01

    Full Text Available IgA antibodies have great potential to improve the functional diversity of current IgG antibody-based cancer immunotherapy options. However, IgA production and purification is not well established, which can at least in part be attributed to the more complex glycosylation as compared to IgG antibodies. IgA antibodies possess up to five N-glycosylation sites within their constant region of the heavy chain as compared to one site for IgG antibodies. The human GlycoExpress expression system was developed to produce biotherapeutics with optimized glycosylation and used here to generate a panel of IgA isotype antibodies directed against targets for solid (TA-mucin 1, Her2, EGFR, Thomsen–Friedenreich and hematological (CD20 cancer indications. The feasibility of good manufacturing practice was shown by the production of 11 g IgA within 35 days in a one liter perfusion bioreactor, and IgA antibodies in high purity were obtained after purification. The monoclonal IgA antibodies possessed a high sialylation degree, and no non-human glycan structures were detected. Kinetic analysis revealed increased avidity antigen binding for IgA dimers as compared to monomeric antibodies. The IgA antibodies exhibited potent Fab- and Fc-mediated functionalities against cancer cell lines, whereby especially granulocytes are recruited. Therefore, for patients who do not sufficiently benefit from therapeutic IgG antibodies, IgA antibodies may complement current regiment options and represent a promising strategy for cancer immunotherapy. In conclusion, a panel of novel biofunctional IgA antibodies with human glycosylation was successfully generated.

  14. Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers

    International Nuclear Information System (INIS)

    Li, Zhaomin; Dong, Zizheng; Myer, David; Yip-Schneider, Michele; Liu, Jianguo; Cui, Ping; Schmidt, C Max; Zhang, Jian-Ting

    2010-01-01

    Pancreatic cancer is the fourth leading cause of death in the US. Unlike other solid tumors such as testicular cancer which are now curable, more than 90% of pancreatic cancer patients die due to lack of response to therapy. Recently, the level of 14-3-3σ mRNA was found to be increased in pancreatic cancers and this increased expression may contribute to the failure in treatment of pancreatic cancers. In the present study, we tested this hypothesis. Western blot analysis was used to determine 14-3-3σ protein level in fresh frozen tissues and was correlated to clinical outcome. A stable cell line expressing 14-3-3σ was established and the effect of 14-3-3σ over-expression on cellular response to radiation and anticancer drugs were tested using SRB assay and clonogenic assays. Cell cycle distribution and apoptosis analyses were performed using propidium iodide staining and PARP cleavage assays. We found that 14-3-3σ protein level was increased significantly in about 71% (17 of 24) of human pancreatic cancer tissues and that the 14-3-3σ protein level in cancers correlated with lymph node metastasis and poor prognosis. Furthermore, we demonstrated that over-expression of 14-3-3σ in a pancreatic cancer cell line caused resistance to γ-irradiation as well as anticancer drugs by causing resistance to treatment-induced apoptosis and G2/M arrest. The increased level of 14-3-3σ protein likely contributes to the poor clinical outcome of human pancreatic cancers by causing resistance to radiation and anticancer drugs. Thus, 14-3-3σ may serve as a prognosis marker predicting survival of pancreatic cancer patients and guide the clinical treatment of these patients

  15. Mortality from solid cancers other than lung, liver, and bone in relation to external dose among plutonium and non-plutonium workers in the Mayak Worker Cohort

    Energy Technology Data Exchange (ETDEWEB)

    Sokolnikov, Mikhail [Southern Urals Biophysics Institute, Ozyorsk (Russian Federation); Preston, Dale [Hirosoft International Corporation, Eureka, CA (United States); Stram, Daniel O. [University of Southern California, Keck School of Medicine, Los Angeles, CA (United States)

    2017-03-15

    Exposure to ionizing radiation has well-documented long-term effects on cancer rates and other health outcomes in humans. While in vitro experimental studies had demonstrated that the nature of some radiation effects depend on both total dose of the radiation and the dose rate (i.e., the pattern of dose distribution over time), the question of whether or not the carcinogenic effect of radiation exposure depends on the dose rate remains unanswered. Another issue of interest concerns whether or not concomitant exposure to external gamma rays and inhaled plutonium aerosols has any effect on the external exposure effects. The analyses of the present paper focus on the risk of solid cancers at sites other than lung, liver, and bone in Mayak workers. Recent findings are reviewed indicating that there is no evidence of plutonium dose response for these cancers in the Mayak worker cohort. Then the evidence for differences in the external dose effects among workers with and without the potential for exposure to alpha particles from inhaled plutonium is examined. It is found that there is no evidence that exposure to plutonium aerosols significantly affects the risk associated with external exposure. While the Mayak external dose risk estimate of an excess relative risk of 0.16 per Gy is somewhat lower than an appropriately normalized risk estimate from the Life Span Study of Japanese atomic bomb survivors, the uncertainties in these estimates preclude concluding that the external dose excess relative risks of this group of solid cancers differ in the two cohorts. (orig.)

  16. Mortality from solid cancers other than lung, liver, and bone in relation to external dose among plutonium and non-plutonium workers in the Mayak Worker Cohort

    International Nuclear Information System (INIS)

    Sokolnikov, Mikhail; Preston, Dale; Stram, Daniel O.

    2017-01-01

    Exposure to ionizing radiation has well-documented long-term effects on cancer rates and other health outcomes in humans. While in vitro experimental studies had demonstrated that the nature of some radiation effects depend on both total dose of the radiation and the dose rate (i.e., the pattern of dose distribution over time), the question of whether or not the carcinogenic effect of radiation exposure depends on the dose rate remains unanswered. Another issue of interest concerns whether or not concomitant exposure to external gamma rays and inhaled plutonium aerosols has any effect on the external exposure effects. The analyses of the present paper focus on the risk of solid cancers at sites other than lung, liver, and bone in Mayak workers. Recent findings are reviewed indicating that there is no evidence of plutonium dose response for these cancers in the Mayak worker cohort. Then the evidence for differences in the external dose effects among workers with and without the potential for exposure to alpha particles from inhaled plutonium is examined. It is found that there is no evidence that exposure to plutonium aerosols significantly affects the risk associated with external exposure. While the Mayak external dose risk estimate of an excess relative risk of 0.16 per Gy is somewhat lower than an appropriately normalized risk estimate from the Life Span Study of Japanese atomic bomb survivors, the uncertainties in these estimates preclude concluding that the external dose excess relative risks of this group of solid cancers differ in the two cohorts. (orig.)

  17. Radiation sensitivity of human lung cancer cell lines

    International Nuclear Information System (INIS)

    Carmichael, J.; Degraff, W.G.; Gamson, J.; Russo, G.; Mitchell, J.B.; Gazdar, A.F.; Minna, J.D.; Levitt, M.L.

    1989-01-01

    X-Ray survival curves were determined using a panel of 17 human lung cancer cell lines, with emphasis on non-small cell lung cancer (NSCLC). In contrast to classic small cell lung cancer (SCLC) cell lines, NSCLC cell lines were generally less sensitive to radiation as evidenced by higher radiation survival curve extrapolation numbers, surviving fraction values following a 2Gy dose (SF2) and the mean inactivation dose values (D) values. The spectrum of in vitro radiation responses observed was similar to that expected in clinical practice, although mesothelioma was unexpectedly sensitive in vitro. Differences in radiosensitivity were best distinguished by comparison of SF2 values. Some NSCLC lines were relatively sensitive, and in view of this demonstrable variability in radiation sensitivity, the SF2 value may be useful for in vitro predictive assay testing of clinical specimens. (author)

  18. Epidermal growth factor receptor in primary human lung cancer

    International Nuclear Information System (INIS)

    Yu Xueyan; Hu Guoqiang; Tian Keli; Wang Mingyun

    1996-01-01

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

  19. Distribution of Human papilloma virus genotypes in cervical cancer tissues

    Directory of Open Access Journals (Sweden)

    Stamenković M.

    2014-01-01

    Full Text Available Cervical cancer incidence and mortality rates in Serbia are among the highest in Europe and data on Human papilloma virus (HPV type distribution are scarce. The aim of this study was to determine the prevalence of HPV types in archival specimens of cervical cancer tissues of women in the Serbian population. A total of 45 paraffin-embedded tissue samples of cervical carcinoma were used in this study. The procedure included deparaffinization of tissue samples, DNA extraction, PCR, gel electrophoresis and HPV genotyping by direct sequencing. HPV was detected in 32 samples (71%. Genotyping revealed the presence of 6 high-risk HPV types 16, 18, 33, 45, 53 and 58, where HPV type 16 was the most prevalent type (73.7%. The results of this study and further studies will provide more detailed information about HPV genotype distribution and may contribute to the formulation of national guidelines for the prevention of cervical cancer. [175073

  20. Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype.

    Science.gov (United States)

    Kristiansen, G; Rose, M; Geisler, C; Fritzsche, F R; Gerhardt, J; Lüke, C; Ladhoff, A-M; Knüchel, R; Dietel, M; Moch, H; Varga, Z; Theurillat, J-P; Gorr, T A; Dahl, E

    2010-06-08

    We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-alpha (ERalpha)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1alpha (HIF-1alpha), HIF-2alpha, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERalpha or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2alpha and CAIX, but not to HIF-1alpha or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERalpha or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. We conclude that in breast cancer, Mb is co-expressed with ERalpha and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours.

  1. Serological analysis of human IgG and IgE anti-insulin antibodies by solid-phase radioimmunoassays

    International Nuclear Information System (INIS)

    Hamilton, R.G.; Rendell, M.; Adkinson, N.F. Jr.

    1980-01-01

    A single solid-phase assay system which is useful for quantitative measurement of both IgG and IgE anti-insulin antibodies in human serum has been developed. Insulin-specific immunoglobulins are absorbed from human serum by excess quantities of insulin-agarose. After washes to remove unbound immunoglobulins, radioiodinated Staph A or rabbit anti-human IgE is added to detect bound IgG or IgE anbitodies, respectively

  2. Epidemiological survey of radiation workers. Risk of leukemia and solid cancer by low level radiation exposure

    International Nuclear Information System (INIS)

    Tatsumi, Kouichi

    2011-01-01

    An interim report on the epidemiological survey of cohort involving radiation workers in the nuclear power plants in Japan was introduced. It consists of eight chapters such as introduction, the objects of mortality rate survey from death causes and creating a cohort, the method of tracking the life and death, analytical methods of mortality rate, analytical results, confounded effects of life style, discussion: contrast the report on the mortality rate of solid cancer except leukemia in Japan and other countries and the conclusions. The subjects of mortality rate of the forth survey were about 277,000 workers including from the first to the third survey. In a prospective cohort study, 203,904 workers were screened for analytical study, and they included 14,224 deaths (5,711 from malignant neoplasm, 6,310 from nonmalignant neoplasm and 1,995 from extrinsic death). The analytical results were shown by three types of death caused from leukemia, malignant neoplasm except for leukemia and nonmalignant neoplasm. Analytical results of the mortality rate from death caused in third and forth study, change of analytical results from the first to the forth observation period were illustrated. (S.Y.)

  3. 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.

  4. 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.

  5. Prevention of human cancer by modulation of chronic inflammatory processes

    Energy Technology Data Exchange (ETDEWEB)

    Ohshima, Hiroshi [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France)]. E-mail: ohshima@iarc.fr; Tazawa, Hiroshi [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France); Sylla, Bakary S. [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France); Sawa, Tomohiro [International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08 (France)

    2005-12-11

    Chronic inflammation induced by biological, chemical and physical factors has been associated with increased risk of human cancer at various sites. Inflammation facilitates the initiation of normal cells and their growth and progression to malignancy through production of pro-inflammatory cytokines and diverse reactive oxygen and nitrogen species. These also activate signaling molecules involved in inflammation and carcinogenesis such as nuclear transcription factor (NF-{kappa}B), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Several chemopreventive agents act through inhibition of signaling pathways (e.g. NF-{kappa}B), inhibition of oxidant-generating enzymes (e.g. iNOS) and mediators of inflammation (e.g. COX-2), scavenging reactive oxygen and nitrogen species, and modulation of xenobiotic-metabolizing enzymes (especially phase II enzyme induction). Some anti-inflammatory drugs have been tested in clinical trials to prevent human cancer at several sites. Better understanding of the molecular mechanisms by which chronic inflammation increases cancer risk will lead to further development of new strategies for cancer prevention at many sites.

  6. Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

    Directory of Open Access Journals (Sweden)

    Chui-Mian Zeng

    2018-05-01

    Full Text Available Frizzled receptors (FZDs are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs that serve as receptors for secreted Wingless-type (WNT ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

  7. Studies of rhodamine-123: effect on rat prostate cancer and human prostate cancer cells in vitro.

    Science.gov (United States)

    Arcadi, J A; Narayan, K S; Techy, G; Ng, C P; Saroufeem, R M; Jones, L W

    1995-06-01

    The effect of the lipophilic, cationic dye, Rhodamine-123 (Rh-123), on prostate cancer in rats, and on three tumor cell lines in vitro is reported here. The general toxicity of Rh-123 in mice has been found to be minimal. Lobund-Wistar (L-W) rats with the autochthonous prostate cancer of Pollard were treated for six doses with Rh-123 at a dose of 15 mg/kg subcutaneously every other day. Microscopic examination of the tumors revealed cellular and acinar destruction. The effectiveness of Rh-123 as a cytotoxic agent was tested by clonogenic and viability assays in vitro with three human prostate cancer cell lines. Severe (60-95%) growth inhibition was observed following Rh-123 exposure for 2-5 days at doses as low as 1.6 micrograms/ml in all three prostate cancer cell lines.

  8. 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. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Resources for Precision Analysis of Human Breast Cancer

    Science.gov (United States)

    2000-08-01

    correlation chemistry are necessary to confirm this observation, the, is different between the in vitro and in vivo situations, pattern of expression is...Feunteun 44. Mandinova A, Atar D, Schafer BW, Spiess M, Aebi U, Heizmann C1 J, Schnitt S, Livingston DM: Location of BRCA1 in human breast and Distinct...with progression-free survival, in prostate cancer [20]. expression but strong staining by immunohisto-S • chemistry were positive by western blot

  10. EMT is the dominant program in human colon cancer

    Directory of Open Access Journals (Sweden)

    Tollenaar Rob AEM

    2011-01-01

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

  11. Human Papillomavirus Genome Integration and Head and Neck Cancer.

    Science.gov (United States)

    Pinatti, L M; Walline, H M; Carey, T E

    2018-06-01

    We conducted a critical review of human papillomavirus (HPV) integration into the host genome in oral/oropharyngeal cancer, reviewed the literature for HPV-induced cancers, and obtained current data for HPV-related oral and oropharyngeal cancers. In addition, we performed studies to identify HPV integration sites and the relationship of integration to viral-host fusion transcripts and whether integration is required for HPV-associated oncogenesis. Viral integration of HPV into the host genome is not required for the viral life cycle and might not be necessary for cellular transformation, yet HPV integration is frequently reported in cervical and head and neck cancer specimens. Studies of large numbers of early cervical lesions revealed frequent viral integration into gene-poor regions of the host genome with comparatively rare integration into cellular genes, suggesting that integration is a stochastic event and that site of integration may be largely a function of chance. However, more recent studies of head and neck squamous cell carcinomas (HNSCCs) suggest that integration may represent an additional oncogenic mechanism through direct effects on cancer-related gene expression and generation of hybrid viral-host fusion transcripts. In HNSCC cell lines as well as primary tumors, integration into cancer-related genes leading to gene disruption has been reported. The studies have shown that integration-induced altered gene expression may be associated with tumor recurrence. Evidence from several studies indicates that viral integration into genic regions is accompanied by local amplification, increased expression in some cases, interruption of gene expression, and likely additional oncogenic effects. Similarly, reported examples of viral integration near microRNAs suggest that altered expression of these regulatory molecules may also contribute to oncogenesis. Future work is indicated to identify the mechanisms of these events on cancer cell behavior.

  12. Solid cancer mortality associated with chronic external radiation exposure at the French atomic energy commission and nuclear fuel company.

    Science.gov (United States)

    Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

    2011-07-01

    Studies of nuclear workers make it possible to directly quantify the risks associated with ionizing radiation exposure at low doses and low dose rates. Studies of the CEA (Commissariat à l'Energie Atomique) and AREVA Nuclear Cycle (AREVA NC) cohort, currently the most informative such group in France, describe the long-term risk to nuclear workers associated with external exposure. Our aim is to assess the risk of mortality from solid cancers among CEA and AREVA NC nuclear workers and its association with external radiation exposure. Standardized mortality ratios (SMRs) were calculated and internal Poisson regressions were conducted, controlling for the main confounding factors [sex, attained age, calendar period, company and socioeconomic status (SES)]. During the period 1968-2004, there were 2,035 solid cancers among the 36,769 CEA-AREVA NC workers. Cumulative external radiation exposure was assessed for the period 1950-2004, and the mean cumulative dose was 12.1 mSv. Mortality rates for all causes and all solid cancers were both significantly lower in this cohort than in the general population. A significant excess of deaths from pleural cancer, not associated with cumulative external dose, was observed, probably due to past asbestos exposure. We observed a significant excess of melanoma, also unassociated with dose. Although cumulative external dose was not associated with mortality from all solid cancers, the central estimated excess relative risk (ERR) per Sv of 0.46 for solid cancer mortality was higher than the 0.26 calculated for male Hiroshima and Nagasaki A-bomb survivors 50 years or older and exposed at the age of 30 years or older. The modification of our results after stratification for SES demonstrates the importance of this characteristic in occupational studies, because it makes it possible to take class-based lifestyle differences into account, at least partly. These results show the great potential of a further joint international study of

  13. Radiation?induced mesothelioma among long?term solid cancer survivors: a longitudinal analysis of SEER database

    OpenAIRE

    Farioli, Andrea; Ottone, Marta; Morganti, Alessio G.; Compagnone, Gaetano; Romani, Fabrizio; Cammelli, Silvia; Mattioli, Stefano; Violante, Francesco S.

    2016-01-01

    Abstract We investigated the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long?term (>5?years) solid cancer survivors. We analyzed data from the US Surveillance, Epidemiology, and End Results (SEER) program (1973?2012). We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure). We estimated hazard ratios [HR] with re...

  14. Headspace Solid Phase Micro Extraction Gas Chromatographic Determination of Fenthion in Human Serum

    Directory of Open Access Journals (Sweden)

    Kyriaki Machera

    2008-05-01

    Full Text Available A simple and effective analytical procedure was developed for the determination of fenthion residues in human serum samples. The sample treatment was performed using the headspace solid-phase micro extraction with polyacrylate fiber, which has the advantage to require low amount of serum (1 mL without tedious pre-treatment. The quantification of fenthion was carried out by gas chromatography-mass spectrometry and the recoveries ranged from 79 to 104% at two spiking levels for 6 replicates. Detection and quantification limits were calculated as 1.51 and 4.54 ng/mL of serum respectively. Two fenthion metabolites − fenoxon and fenthion–sulfoxide − were also identified.

  15. Quantitation of complement factor D in human serum by a solid-phase radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Barnum, S R; Niemann, M A; Kearney, J F; Volanakis, J E [Alabama Univ., Birmingham (USA)

    1984-03-16

    A sensitive solid-phase radioimmunoassay is described which quantitates human D to 1-2 ng/ml. The assay was used to measure the concentration of D in normal and acute-phase sera and sera from individuals with systemic lupus erythematosus. All 3 groups of sera had comparable levels of D with mean values of 1.8, 2.3 and 2.5 ..mu..g/ml, respectively. Also tested were sera decomplemented in vitro by activators of the classical and alternative pathways. The results indicated that D is not depleted by alternative or classical pathway activation. However, heat inactivation (56/sup 0/C, 30 min) of serum resulted in almost complete loss of antigenic D.

  16. Induction of apoptosis by eugenol in human breast cancer cells

    International Nuclear Information System (INIS)

    Vidhya, N.; Niranjali Devaraj, S.

    2011-01-01

    In the present study, potential anticancer effect of eugenol on inhibition of cell proliferation and induction of apoptosis in human MCF-7 breast cancer cells was investigated. Induction of cell death by eugenol was evaluated following MTT assay and monitoring lactate dehydrogenase released into the culture medium for cell viability and cytotoxicity, giemsa staining for morphological alterations, fluorescence microscopy analysis of cells using ethidium bromide and acridine orange and quantitation of DNA fragments for induction of apoptosis. Effect of eugenol on intracellular redox status of the human breast cancer cells was assessed by determining the level of glutathione and lipid peroxidation products (TBARS). Eugenol treatment inhibited the growth and proliferation of human MCF-7 breast cancer cells through induction of cell death, which was dose and time dependent. Microscopic examination of eugenol treated cells showed cell shrinkage, membrane blebbing and apoptotic body formation. Further, eugenol treatment also depleted the level of intracellular glutathione and increased the level of lipid peroxidation. The dose dependent increase in the percentage of apoptotic cells and DNA fragments suggested that apoptosis was involved in eugenol induced cell death and apoptosis might have played a role in the chemopreventive action of eugenol. (author)

  17. Imaging Proteolysis by Living Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mansoureh Sameni

    2000-01-01

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

  18. EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

    Science.gov (United States)

    Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

    2011-03-01

    Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

  19. Transit of solids through the human colon: Regional quantification in the unprepared bowel

    International Nuclear Information System (INIS)

    Proano, M.; Camilleri, M.; Phillips, S.F.; Brown, M.L.; Thomforde, G.M.

    1990-01-01

    We used a noninvasive method to label the solid phase of contents in the unprepared human colon. 111 In-labeled Amberlite pellets (0.5-1.8 mm diam) were placed in a gelatin capsule that was then coated with a pH-sensitive polymer (methacrylate). In vitro, the capsules disintegrated in simulated small bowel contents within 1-2 h; when ingested by healthy subjects, capsules released radiolabel in the distal ileum or proximal colon in 13 of 15 subjects. Transit of 111 In-pellets through the unprepared colon could then be quantitated radioscintigraphically. Segmental transit was defined in the ascending (AC), transverse (TC), descending (DC), and rectosigmoid (RS) colon. Radioactivity was also quantitated in stools. At 12 h, radioactivity was most obvious in the AC (59 +/- 11%, mean +/- SE) and the TC (21 +/- 6%); at 24 h, counts were distributed equally between AC, TC, and stools (P greater than 0.05); by 48 h, 56 +/- 11% counts had been excreted, although 30 +/- 10% remained in the TC. At 24 and 48 h, the amount in DC or RS was lower (P less than 0.05) than in the TC or in stools. Emptying of the AC was characterized by an initial lag period, when no counts emptied into the TC, followed by a period of emptying that was approximately linear. Thus this simple approach is able to label contents in the healthy human colon. The ascending and transverse colon appear to be sites of storage of solid residue, whereas the left colon and rectosigmoid function mainly as conduits

  20. Study of miRNA Based Gene Regulation, Involved in Solid Cancer, by the Assistance of Argonaute Protein

    Directory of Open Access Journals (Sweden)

    Surya Narayan Rath

    2016-09-01

    Full Text Available Solid tumor is generally observed in tissues of epithelial or endothelial cells of lung, breast, prostate, pancreases, colorectal, stomach, and bladder, where several genes transcription is regulated by the microRNAs (miRNAs. Argonaute (AGO protein is a family of protein which assists in miRNAs to bind with mRNAs of the target genes. Hence, study of the binding mechanism between AGO protein and miRNAs, and also with miRNAs-mRNAs duplex is crucial for understanding the RNA silencing mechanism. In the current work, 64 genes and 23 miRNAs have been selected from literatures, whose deregulation is well established in seven types of solid cancer like lung, breast, prostate, pancreases, colorectal, stomach, and bladder cancer. In silico study reveals, miRNAs namely, miR-106a, miR-21, and miR-29b-2 have a strong binding affinity towards PTEN, TGFBR2, and VEGFA genes, respectively, suggested as important factors in RNA silencing mechanism. Furthermore, interaction between AGO protein (PDB ID-3F73, chain A with selected miRNAs and with miRNAs-mRNAs duplex were studied computationally to understand their binding at molecular level. The residual interaction and hydrogen bonding are inspected in Discovery Studio 3.5 suites. The current investigation throws light on understanding miRNAs based gene silencing mechanism in solid cancer.

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

    Science.gov (United States)

    Koç, Zeliha

    2015-01-01

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

  2. Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base.

    Science.gov (United States)

    Cheraghlou, Shayan; Yu, Phoebe K; Otremba, Michael D; Park, Henry S; Bhatia, Aarti; Zogg, Cheryl K; Mehra, Saral; Yarbrough, Wendell G; Judson, Benjamin L

    2018-02-15

    The growing epidemic of human papillomavirus-positive (HPV+) oropharyngeal cancer and the favorable prognosis of this disease etiology have led to a call for deintensified treatment for some patients with HPV+ cancers. One of the proposed methods of treatment deintensification is the avoidance of chemotherapy concurrent with definitive/adjuvant radiotherapy. To the authors' knowledge, the safety of this form of treatment de-escalation is unknown and the current literature in this area is sparse. The authors investigated outcomes after various treatment combinations stratified by American Joint Committee on Cancer (AJCC) eighth edition disease stage using patients from the National Cancer Data Base. A retrospective study of 4443 patients with HPV+ oropharyngeal cancer in the National Cancer Data Base was conducted. Patients were stratified into AJCC eighth edition disease stage groups. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted. For patients with stage I disease, treatment with definitive radiotherapy was associated with diminished survival compared with chemoradiotherapy (hazard ratio [HR], 1.798; P = .029), surgery with adjuvant radiotherapy (HR, 2.563; P = .002), or surgery with adjuvant chemoradiotherapy (HR, 2.427; P = .001). For patients with stage II disease, compared with treatment with chemoradiotherapy, patients treated with a single-modality (either surgery [HR, 2.539; P = .009] or radiotherapy [HR, 2.200; P = .030]) were found to have poorer survival. Among patients with stage III disease, triple-modality therapy was associated with improved survival (HR, 0.518; P = .024) compared with treatment with chemoradiotherapy. Deintensification of treatment from chemoradiotherapy to radiotherapy or surgery alone in cases of HPV+ AJCC eighth edition stage I or stage II disease may compromise patient safety. Treatment intensification to triple-modality therapy for patients with stage III disease may improve survival in

  3. Autophagy sustains the survival of human pancreatic cancer PANC-1 cells under extreme nutrient deprivation conditions.

    Science.gov (United States)

    Kim, Sang Eun; Park, Hye-Jin; Jeong, Hye Kyoung; Kim, Mi-Jung; Kim, Minyeong; Bae, Ok-Nam; Baek, Seung-Hoon

    2015-07-31

    Pancreatic ductal adenocarcinomas are an extremely aggressive and devastating type of cancer with high mortality. Given the dense stroma and poor vascularization, accessibility to nutrients is limited in the tumor microenvironment. Here, we aimed to elucidate the role of autophagy in promoting the survival of human pancreatic cancer PANC-1 cells exposed to nutrient-deprived media (NDM) lacking glucose, amino acids, and serum. NDM inhibited Akt activity and phosphorylation of p70 S6K, and induced AMPK activation and mitochondrial depolarization. NDM also time-dependently increased LC3-II accumulation, number of GFP-LC3 puncta, and colocalization between GFP-LC3 and lysosomes. These results suggested that autophagy was progressively activated through Akt- and AMPK-mTOR pathway in nutrient-deficient PANC-1 cells. Autophagy inhibitors (chloroquine and wortmannin) or silencing of Atg5 augmented PANC-1 cell death in NDM. In cells exposed to NDM, chloroquine and wortmannin induced apoptosis and Z-VAD-fmk inhibited cytotoxicity of these inhibitors. These data demonstrate that autophagy is anti-apoptotic and sustains the survival of PANC-1 cells following extreme nutrient deprivation. Autophagy modulation may be a viable therapeutic option for cancer cells located in the core of solid tumors with a nutrient-deficient microenvironment. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Association of Sirolimus Use With Risk for Skin Cancer in a Mixed-Organ Cohort of Solid-Organ Transplant Recipients With a History of Cancer.

    Science.gov (United States)

    Karia, Pritesh S; Azzi, Jamil R; Heher, Eliot C; Hills, Victoria M; Schmults, Chrysalyne D

    2016-05-01

    Solid-organ transplant recipients (OTRs) are at an increased risk for skin cancer. Prior studies have demonstrated a reduced incidence of skin cancer in renal OTRs treated with sirolimus. However, little information exists on the use of sirolimus for the prevention of skin cancer in nonrenal OTRs or those already diagnosed as having a posttransplant cancer. To compare subsequent skin cancer formation in a mixed-organ cohort of OTRs who were or were not treated with sirolimus after developing a posttransplant index cancer of any type. A 9-year retrospective cohort study at 2 academic tertiary care centers. Electronic medical records were reviewed for OTRs diagnosed as having a posttransplant cancer of any type to determine the type of organ transplanted, pretransplant and posttransplant cancer, and immunosuppressive medications. Patients underwent transplant from January 1, 2000, to December 31, 2008. Data were collected from July 30, 2011, to December 31, 2012, when follow-up was completed, and analyzed from April 28, 2013, to October 4, 2014. Factors associated with subsequent skin cancer development were evaluated via multivariate Cox regression analysis. Of 329 OTRs with an index posttransplant cancer (100 women and 229 men; mean [SD] age, 56 [19] years), 177 (53.8%) underwent renal transplant; 58 (17.6%), heart transplant; 54 (16.4%), lung transplant; 34 (10.3%), liver transplant; and 6 (1.8%), mixed-organ transplant. Ninety-seven OTRs (29.5%) underwent conversion to sirolimus therapy after diagnosis. One hundred thirty OTRs (39.5%) developed second posttransplant cancers, of which 115 cases (88.5%) were skin cancers. An 11.6% reduction in skin cancer risk was observed in the sirolimus-treated vs non-sirolimus-treated groups overall (26 of 97 [26.8%] vs 89 of 232 [38.4%]; P = .045) and among nonrenal OTRs only (8 of 34 [23.5%] vs 44 of 112 [39.3%], respectively), although the latter difference was not significant (P = .09). Independent predictors of

  5. N-ω-chloroacetyl-L-ornithine has in-vitro activity against cancer cell lines and in-vivo activity against ascitic and solid tumors.

    Science.gov (United States)

    Vargas-Ramírez, Alba L; Medina-Enríquez, Miriam M; Cordero-Rodríguez, Neira I; Ruiz-Cuello, Tatiana; Aguilar-Faisal, Leopoldo; Trujillo-Ferrara, José G; Alcántara-Farfán, Verónica; Rodríguez-Páez, Lorena

    2016-07-01

    N-ω-chloroacetyl-L-ornithine (NCAO) is an ornithine decarboxylase (ODC) inhibitor that is known to exert cytotoxic and antiproliferative effects on three neoplastic human cancer cell lines (HeLa, MCF-7, and HepG2). Here, we show that NCAO has antiproliferative activity in 13 cancer cell lines, of diverse tissue origin from human and mice, and in a mouse cancer model in vivo. All cell lines were sensitive to NCAO after 72 h of treatment (the EC50 ranged from 1 to 50.6 µmol/l). The Ca Ski cell line was the most sensitive (EC50=1.18±0.07 µmol/l) and MDA-MB-231 was the least sensitive (EC50=50.6±0.3 µmol/l). This ODC inhibitor showed selectivity for cancer cells, exerting almost no cytotoxic effect on the normal Vero cell line (EC50>1000 µmol/l). NCAO induced apoptosis and inhibited tumor cell migration in vitro. Furthermore, in vivo, this compound (at 50 and 100 mg/kg, daily intraperitoneal injection for 7 days) exerted potent antitumor activity against both solid and ascitic tumors in a mouse model using the myeloma (Ag8) cell line. At these same two doses, the toxicological evaluation showed that NCAO has no obvious systemic toxicity. The current results suggest that the antitumor activity is exerted by apoptosis related not only to a local but also a systemic cytotoxic effect exerted by NCAO on tumor cells. The applications for NCAO as an antitumor agent may be extensive; however, further studies are needed to ascertain the antitumor activity on other types of tumor in vivo and to determine the precise molecular mechanism of its activity.

  6. Lysis of fresh human solid tumors by autologous lymphocytes activated in vitro with lectins

    International Nuclear Information System (INIS)

    Mazumder, A.; Grimm, E.A.; Zhang, H.Z.; Rosenberg, S.A.

    1982-01-01

    Human peripheral blood lymphocytes (PBL), obtained from patients with a variety of cancers, were incubated in vitro with phytohemagglutinin, concanavalin A, and crude or lectin-free T-cell growth factors. The lectin-activated PBL of nine patients were capable of lysing fresh autologous tumor during a 4-hr 51Cr release assay. Multiple metastases from the same patient were equivalently lysed by these activated autologous PBL. No lysis of fresh PBL or lectin-induced lymphoblast cell targets was seen, although tumor, PBL, and lymphoblast cells were shown to be equally lysable using allosensitized cells. The activated cells could be expanded without loss of cytotoxicity in crude or lectin-free T-cell growth factors. The generation of cells lytic to fresh autologous tumor was dependent on the presence of adherent cells, although the lytic cell itself was not adherent. Proliferation was not involved in the induction of lytic cells since equal lysis was induced in irradiated and nonirradiated lymphocytes. Lectin was not required in the lytic assay, and the addition of alpha-methyl-D-mannoside to concanavalin A-activated lymphoid cells did not increase the lysis of fresh tumor cells. Activation by lectin for 3 days appears to be an efficient and convenient method for generating human cells lytic to fresh autologous tumor. These lytic cells may be of value for studies of the cell-mediated lysis of human tumor and possibly for tumor immunotherapy as well

  7. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening

    OpenAIRE

    Katki, Hormuzd A.; Cheung, Li C.; Fetterman, Barbara; Castle, Philip E.; Sundaram, Rajeshwari

    2015-01-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interv...

  8. Radiation-Related New Primary Solid Cancers in the Childhood Cancer Survivor Study: Comparative Radiation Dose Response and Modification of Treatment Effects

    International Nuclear Information System (INIS)

    Inskip, Peter D.; Sigurdson, Alice J.; Veiga, Lene; Bhatti, Parveen; Ronckers, Cécile; Rajaraman, Preetha; Boukheris, Houda; Stovall, Marilyn; Smith, Susan; Hammond, Sue; Henderson, Tara O.

    2016-01-01

    Objectives: The majority of childhood cancer patients now achieve long-term survival, but the treatments that cured their malignancy often put them at risk of adverse health outcomes years later. New cancers are among the most serious of these late effects. The aims of this review are to compare and contrast radiation dose–response relationships for new solid cancers in a large cohort of childhood cancer survivors and to discuss interactions among treatment and host factors. Methods: This review is based on previously published site-specific analyses for subsequent primary cancers of the brain, breast, thyroid gland, bone and soft tissue, salivary glands, and skin among 12,268 5-year childhood cancer survivors in the Childhood Cancer Survivor Study. Analyses included tumor site–specific, individual radiation dose reconstruction based on radiation therapy records. Radiation-related second cancer risks were estimated using conditional logistic or Poisson regression models for excess relative risk (ERR). Results: Linear dose–response relationships over a wide range of radiation dose (0-50 Gy) were seen for all cancer sites except the thyroid gland. The steepest slopes occurred for sarcoma, meningioma, and nonmelanoma skin cancer (ERR/Gy > 1.00), with glioma and cancers of the breast and salivary glands forming a second group (ERR/Gy = 0.27-0.36). The relative risk for thyroid cancer increased up to 15-20 Gy and then decreased with increasing dose. The risk of thyroid cancer also was positively associated with chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses of radiation to the thyroid. The excess risk of radiation-related breast cancer was sharply reduced among women who received 5 Gy or more to the ovaries. Conclusions: The results suggest that the effect of high-dose irradiation is consistent with a linear dose–response for most organs, but they also reveal important organ-specific and host

  9. Radiation-Related New Primary Solid Cancers in the Childhood Cancer Survivor Study: Comparative Radiation Dose Response and Modification of Treatment Effects

    Energy Technology Data Exchange (ETDEWEB)

    Inskip, Peter D., E-mail: inskippeter@gmail.com [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Sigurdson, Alice J.; Veiga, Lene [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Bhatti, Parveen [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Ronckers, Cécile [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Department of Pediatric Oncology, Emma Children' s Hospital/Academic Medical Center, Amsterdam (Netherlands); Rajaraman, Preetha [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Boukheris, Houda [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); The University of Oran School of Medicine (Algeria); Stovall, Marilyn; Smith, Susan [Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas (United States); Hammond, Sue [Department of Laboratory Medicine and Pathology, Children' s Hospital and Ohio State University College of Medicine, Columbus, Ohio (United States); Henderson, Tara O. [University of Chicago Department of Pediatrics, Section of Hematology, Oncology and Stem Cell Transplantation, Chicago, Illinois (United States); and others

    2016-03-15

    Objectives: The majority of childhood cancer patients now achieve long-term survival, but the treatments that cured their malignancy often put them at risk of adverse health outcomes years later. New cancers are among the most serious of these late effects. The aims of this review are to compare and contrast radiation dose–response relationships for new solid cancers in a large cohort of childhood cancer survivors and to discuss interactions among treatment and host factors. Methods: This review is based on previously published site-specific analyses for subsequent primary cancers of the brain, breast, thyroid gland, bone and soft tissue, salivary glands, and skin among 12,268 5-year childhood cancer survivors in the Childhood Cancer Survivor Study. Analyses included tumor site–specific, individual radiation dose reconstruction based on radiation therapy records. Radiation-related second cancer risks were estimated using conditional logistic or Poisson regression models for excess relative risk (ERR). Results: Linear dose–response relationships over a wide range of radiation dose (0-50 Gy) were seen for all cancer sites except the thyroid gland. The steepest slopes occurred for sarcoma, meningioma, and nonmelanoma skin cancer (ERR/Gy > 1.00), with glioma and cancers of the breast and salivary glands forming a second group (ERR/Gy = 0.27-0.36). The relative risk for thyroid cancer increased up to 15-20 Gy and then decreased with increasing dose. The risk of thyroid cancer also was positively associated with chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses of radiation to the thyroid. The excess risk of radiation-related breast cancer was sharply reduced among women who received 5 Gy or more to the ovaries. Conclusions: The results suggest that the effect of high-dose irradiation is consistent with a linear dose–response for most organs, but they also reveal important organ-specific and host

  10. c-Myc-Dependent Cell Competition in Human Cancer Cells.

    Science.gov (United States)

    Patel, Manish S; Shah, Heta S; Shrivastava, Neeta

    2017-07-01

    Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. 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.

  12. PIXE analysis of cancer-afflicted human bladder

    Energy Technology Data Exchange (ETDEWEB)

    Raju, G.J. Naga; Sarita, P.; Kumar, M. Ravi [Department of Physics, Institute of Technology, GITAM University, Visakhapatnam (India); Reddy, S. Bhuloka [Swami Jnanananda Laboratories for Nuclear Research, Andhra University, Visakhapatnam (India)

    2013-07-01

    Full text: The proton induced x-ray emission (PIXE) technique was used for analysis of trace elements in small quantities of biological samples. Both the biological samples of normal and cancer-afflicted human bladder tissues were studied. The present experiment was performed using a 3 MV pelletron accelerator at the Institute of Physics in Bhubaneswar, India. A proton beam of 3 MeV energy was used to excite the samples. NIST SRM 1577b Bovine Liver Tissue was used as external standards for the determination of trace element concentration in the biological tissue samples. The elements CI, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, and Se were identified and their concentrations were estimated. The concentrations of Ti and Zn are lower (p < 0.005) and that of Cr, Mn, Fe, Ni, and Cu are significantly higher (p < 0.001) in cancerous tissues than that in normal tissues. The deficiency or excess of different trace elements observed in the cancer tissues relative to the normal tissues of bladder are correlated to the pathology of cancer. (author)

  13. Breast Cancer Mortality In Brazil: Correlation With Human Development Index

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    Mara Rejane Barroso Barcelos

    2017-01-01

    Full Text Available Background: Mortality from breast cancer decreased in high-income countries, while countries with middle and low incomes as Brazil still has upward trend. However, large geographical variations among the federal units are observed in the country. The aim of the study was to evaluate the trend of specific mortality from breast cancer in women over 20 years old years among different states of Brazil from 1996 to 2012.  Methods and Findings: Ecological study, using linear regression model for temporal analysis of specific mortality coefficient from malignant neoplasm of breast. We also checked the degree of its correlation with the HDI for the states of Brazil during the stated period. There was an increase in the specific mortality rate for malignant neoplasm of the breast in order of 33%, with range from 23.2 to 30.8 / 100,000 inhabitants. The states with the highest human development HDI in 2010, showed the largest specific mortality rates of breast cancer. Conclusion: Taking the trends of mortality from cancer an important role, this study confirms the need for improvements in mammography coverage, following radiological lesions suspected and access to appropriate therapy.

  14. Zinc in human prostate gland. Normal, hyperplastic and cancerous

    International Nuclear Information System (INIS)

    Zaichick, V.Ye.; Sviridova, T.V.; Zaichick, S.V.

    1997-01-01

    Zinc concentration in a prostate gland is much higher than that in other human tissues. Data about zinc changes for different prostate diseases are limited and greatly contradictory. Zinc content was determined for biopsy and resected materials of transrectal puncture tissues from benign prostate hyperplasia (BPH) and prostate cancer. There were 109 patients (50 BPH and 59 cancer) available for the present study. Control group consisted of 37 intact glands of men died an unexpected death (accident, murder, acute cardiac insufficiency, etc.). All materials studied were divided into two parts. One of them was morphologically examined, while another one was subjected to zinc analysis by INAA. Zinc contents (M ± SE) of normal, benign hyperplastic and cancerous prostate glands were found to be 1018 ± 124, 1142 ± 77, and 146 ± 10 μg/g dry tissue, respectively. It was shown that zinc assessments in the materials of transrectal puncture biopsy of indurated prostate sites can be used as an additional test for differential diagnostics of BPH and cancer. Accuracy, sensitivity and specificity of the test are 98 ± 2%. (author)

  15. Effect of primarily cultured human lung cancer-associated fibroblasts on radiosensitivity of lung cancer cells

    International Nuclear Information System (INIS)

    Ji Xiaoqin; Ji Jiang; Chen Yongbing; Shan Fang; Lu Xueguan

    2014-01-01

    Objective: To investigate the effect of human lung cancer-associated fibroblasts (CAF) on the radiosensitivity of lung cancer cells when CAF is placed in direct contact co-culture with lung cancer cells. Methods: Human lung CAF was obtained from fresh human lung adenocarcinoma tissue specimens by primary culture and subculture and was then identified by immunofluorescence staining. The CAF was placed in direct contact co-culture with lung cancer A 549 and H 1299 cells, and the effects of CAF on the radiosensitivity of A 549 and H 1299 cells were evaluated by colony-forming assay. Results: The human lung CAF obtained by adherent culture could stably grow and proliferate, and it had specific expression of α-smooth muscle actin, vimentin, and fibroblast activation protein,but without expression of cytokeratin-18. The plating efficiency (PE, %) of A 549 cells at 0 Gy irradiation was (20.0 ± 3.9)% when cultured alone versus (32.3 ± 5.5)% when co-cultured with CAF (t=3.16, P<0.05), and the PE of H 1299 cells at 0 Gy irradiation was (20.6 ± 3.1)% when cultured alone versus (35.2 ± 2.3)% when co-cultured with CAF (t=6.55, P<0.05). The cell survival rate at 2 Gy irradiation (SF 2 ) of A 549 cells was 0.727 ±0.061 when cultured alone versus 0.782 ± 0.089 when co-cultured with CAF (t=0.88, P>0.05), and the SF 2 of H 1299 cells was 0.692 ±0.065 when cultured alone versus 0.782 ± 0.037 when co-cultured with CAF (t=2.08, P>0.05). The protection enhancement ratios of human lung CAF for A 549 cells and H 1299 cells were 1.29 and 1.25, respectively. Conclusions: Human lung CAF reduces the radiosensitivity of lung cancer cells when placed in direct contact co-culture with them, and the radioprotective effect may be attributed to CAF promoting the proliferation of lung cancer cells. (authors)

  16. Differential expression of carbohydrate antigen 19-9 in human colorectal cancer: A comparison with colon and rectal cancers

    Science.gov (United States)

    ZHANG, SHUAI; CHEN, YIJUN; ZHU, ZHANMENG; DING, YUNLONG; REN, SHUANGYI; ZUO, YUNFEI

    2013-01-01

    Colorectal cancer is one of the leading causes of cancer-related mortality, being the third most commonly diagnosed cancer among men and the second among women. Accumulating evidence regarding carbohydrate antigen (CA) demonstrated that tumor-associated antigens are clinically useful for the diagnosis, staging and monitoring of human gastrointestinal cancers, particularly colorectal cancer. There has been an extensive investigation for sensitive and specific markers of this disease. Currently, the gastrointestinal cancer-associated carbohydrate antigen 19-9 (CA19-9) is the most widely applied tumor marker in cancer diagnosis. Despite a similar etiology and cancer incidence rates, there are anatomical and clinical differences between colon and rectal cancer, as well as differences regarding tumor progression and adjuvant treatments. To investigate whether CA19-9 is differentially expressed between colon and rectal cancer, we conducted a differential analysis of serum CA19-9 levels among 227 cases of colorectal cancer, analyzing gender, age, Dukes’ stage and distant metastasis for human colon and rectal cancer as a single entity, separately and as matched pairs. We demonstrated that the serum CA19-9 levels in colorectal cancer were upregulated in advanced stages with distant metastasis. By contrast, the serum CA19-9 levels in colon cancer displayed a differential and upregulated behavior in advanced stages with distant metastasis. By analyzing as matched pairs, the upregulated serum CA19-9 levels in rectal cancer during the early stages without distant metastasis further supported our hypothesis that the expression of CA19-9 displays a site-specific differential behavior. The integrative analysis suggested a significant difference between human colon and rectal cancer, justifying individualized therapy for these two types of cancer. PMID:24649295

  17. Inhibition of phospholipaseD2 increases hypoxia-induced human colon cancer cell apoptosis through inactivating of the PI3K/AKT signaling pathway.

    Science.gov (United States)

    Liu, Maoxi; Fu, Zhongxue; Wu, Xingye; Du, Kunli; Zhang, Shouru; Zeng, Li

    2016-05-01

    Hypoxia is a common feature of solid tumor, and is a direct stress that triggers apoptosis in many human cell types. As one of solid cancer, hypoxia exists in the whole course of colon cancer occurrence and progression. Our previous studies shown that hypoxia induce high expression of phospholipase D2 (PLD2) and survivin in colon cancer cells. However, the correlation between PLD2 and survivin in hypoxic colon cancer cells remains unknown. In this study, we observed significantly elevated PLD2 and survivin expression levels in colon cancer tissues and cells. This is a positive correlation between of them, and co-expression of PLD2 and survivin has a positive correlation with the clinicpatholic features including tumor size, TNM stage, and lymph node metastasis. We also found that hypoxia induced the activity of PLD increased significant mainly caused by PLD2 in colon cancer cells. However, inhibition the activity of PLD2 induced by hypoxia promotes the apoptosis of human colon cancer cells, as well as decreased the expression of apoptosis markers including survivin and bcl2. Moreover, the pharmacological inhibition of PI3K/AKT supported the hypothesis that promotes the apoptosis of hypoxic colon cancer cells by PLD2 activity inhibition may through inactivation of the PI3K/AKT signaling pathway. Furthermore, interference the PLD2 gene expression leaded to the apoptosis of hypoxic colon cancer cells increased and also decreased the expression level of survivin and bcl2 may through inactivation of PI3K/AKT signaling pathway. These results indicated that PLD2 play antiapoptotic role in colon cancer under hypoxic conditions, inhibition of the activity, or interference of PLD2 gene expression will benefit for the treatment of colon cancer patients.

  18. Expression of neurotensin and NT1 receptor in human breast cancer: a potential role in tumor progression.

    Science.gov (United States)

    Souazé, Frédérique; Dupouy, Sandra; Viardot-Foucault, Véronique; Bruyneel, Erik; Attoub, Samir; Gespach, Christian; Gompel, Anne; Forgez, Patricia

    2006-06-15

    Emerging evidence supports neurotensin as a trophic and antiapoptotic factor, mediating its control via the high-affinity neurotensin receptor (NT1 receptor) in several human solid tumors. In a series of 51 patients with invasive ductal breast cancers, 34% of all tumors were positive for neurotensin and 91% positive for NT1 receptor. We found a coexpression of neurotensin and NT1 receptor in a large proportion (30%) of ductal breast tumors, suggesting a contribution of the neurotensinergic signaling cascade within breast cancer progression. Functionally expressed NT1 receptor, in the highly malignant MDA-MB-231 human breast cancer cell line, coordinated a series of transforming functions, including cellular migration, invasion, induction of the matrix metalloproteinase (MMP)-9 transcripts, and MMP-9 gelatinase activity. Disruption of NT1 receptor signaling by silencing RNA or use of a specific NT1 receptor antagonist, SR48692, caused the reversion of these transforming functions and tumor growth of MDA-MB-231 cells xenografted in nude mice. Our findings support the contribution of neurotensin in human breast cancer progression and point out the utility to develop therapeutic molecules targeting neurotensin or NT1 receptor signaling cascade. These strategies would increase the range of therapeutic approaches and be beneficial for specific patients.

  19. [Solid state isotope hydrogen exchange for deuterium and tritium in human gene-engineered insulin].

    Science.gov (United States)

    Zolotarev, Yu A; Dadayan, A K; Kozik, V S; Gasanov, E V; Nazimov, I V; Ziganshin, R Kh; Vaskovsky, B V; Murashov, A N; Ksenofontov, A L; Haribin, O N; Nikolaev, E N; Myasoedov, N F

    2014-01-01

    The reaction of high temperature solid state catalytic isotope exchange in peptides and proteins under the action of catalyst-activated spillover hydrogen was studied. The reaction of human gene-engineered insulin with deuterium and tritium was conducted at 120-140° C to produce insulin samples containing 2-6 hydrogen isotope atoms. To determine the distribution of the isotope label over tritium-labeled insulin's amino acid residues, oxidation of the S-S bonds of insulin by performic acid was performed and polypeptide chains isolated; then their acid hydrolysis, amino acid analysis and liquid scintillation counts of tritium in the amino acids were conducted. The isotope label was shown to be incorporated in all amino acids of the protein, with the peptide fragment FVNQHLCGSHLVE of the insulin β-chain showing the largest incorporation. About 45% of the total protein isotope label was incorporated in His5 and His10 of this fragment. For the analysis of isotope label distribution in labeled insulin's peptide fragments, the recovery of the S-S bonds by mercaptoethanol, the enzymatic hydrolysis by glutamyl endopeptidase from Bacillus intermedius and HPLC division of the resulting peptides were carried out. Attribution of the peptide fragments formed due to hydrolysis at the Glu-X bond in the β-chain was accomplished by mass spectrometry. Mass spectrometry analysis data of the deuterium-labeled insulin samples' isotopomeric composition showed that the studied solid state isotope exchange reaction equally involved all the protein molecules. Biological studying of tritium-labeled insulin showed its physiological activity to be completely retained.

  20. Using oxidized liquid and solid human waste as nutrients for Chlorella vulgaris and cyanobacterium Oscillatoria deflexa

    Science.gov (United States)

    Trifonov, Sergey V.; Kalacheva, Galina; Tirranen, Lyalya; Gribovskaya, Iliada

    At stationary terrestrial and space stations with closed and partially closed substance exchange not only plants, but also algae can regenerate atmosphere. Their biomass can be used for feeding Daphnia and Moina species, which, in their turn, serve as food for fish. In addition, it is possible to use algae for production of biological fuel. We suggested two methods of human waste mineralization: dry (evaporation with subsequent incineration in a muffle furnace) and wet (oxidation in a reactor using hydrogen peroxide). The research task was to prepare nutrient media for green alga Chlorella vulgaris and cyanobacterium Oscillatoria deflexa using liquid human waste mineralized by dry method, and to prepare media for chlorella on the basis of 1) liquid and 2) liquid and solid human waste mineralized by wet method. The algae were grown in batch culture in a climate chamber with the following parameters: illumination 7 klx, temperature 27-30 (°) C, culture density 1-2 g/l of dry weight. The control for chlorella was Tamiya medium, pH-5, and for oscillstoria — Zarrouk medium, pH-10. Maximum permissible concentrations of NaCl, Cl, urea (NH _{2}) _{2}CO, and native urine were established for algae. Missing ingredients (such as salts and acids) for experimental nutrient media were determined: their addition made it possible to obtain the biomass production not less than that in the control. The estimation was given of the mineral and biochemical composition of algae grown on experimental media. Microbiological test revealed absence of foreign microbial flora in experimental cultures.

  1. Apoptosis induced by GanoPoly in human gastric cancer cell line ...

    African Journals Online (AJOL)

    use

    2011-12-12

    Dec 12, 2011 ... ... cancer's active therapy. Key words: Apoptosis, polysaccharide, human gastric cancer cells. ... The active components of polysaccharides are all glucans, which have a ... for the treatment of alleviated fatigue, night sweating,.

  2. Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer

    Science.gov (United States)

    2018-05-23

    Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Human Papillomavirus Infection; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    BACKGROUND AND PURPOSE: Colorectal cancer (CRC) remains one of the most common cancer forms developing in industrialized countries, and its incidence appears to be rising. Studies of human population groups provide insufficient information about carcinogenesis, pathogenesis, and treatment of CRC...

  4. 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....

  5. Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948-2008.

    Directory of Open Access Journals (Sweden)

    Mikhail Sokolnikov

    Full Text Available Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948-2008. The cohort of Mayak Production Association (PA workers in Russia offers a unique opportunity to study the effects of prolonged low dose rate external gamma exposures and exposure to plutonium in a working age population. We examined radiation effects on the risk of mortality from solid cancers excluding sites of primary plutonium deposition (lung, liver, and bone surface among 25,757 workers who were first employed in 1948-1982. During the period 1948-2008, there were 1,825 deaths from cancers other than lung, liver and bone. Using colon dose as a representative external dose, a linear dose response model described the data well. The excess relative risk per Gray for external gamma exposure was 0.16 (95% CI: 0.07 - 0.26 when unadjusted for plutonium exposure and 0.12 (95% CI 0.03 - 0.21 when adjusted for plutonium dose and monitoring status. There was no significant effect modification by sex or attained age. Plutonium exposure was not significantly associated with the group of cancers analyzed after adjusting for monitoring status. Site-specific risks were uncertainly estimated but positive for 13 of the 15 sites evaluated with a statistically significant estimate only for esophageal cancer. Comparison with estimates based on the acute exposures in atomic bomb survivors suggests that the excess relative risk per Gray for prolonged external exposure in Mayak workers may be lower than that for acute exposure but, given the uncertainties, the possibility of equal effects cannot be dismissed.

  6. Solid Lymph Nodes as an Imaging Biomarker for Risk Stratification in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma.

    Science.gov (United States)

    Rath, T J; Narayanan, S; Hughes, M A; Ferris, R L; Chiosea, S I; Branstetter, B F

    2017-07-01

    Human papillomavirus-related oropharyngeal squamous cell carcinoma is associated with cystic lymph nodes on CT and has a favorable prognosis. A subset of patients with aggressive disease experience treatment failure. Our aim was to determine whether the extent of cystic lymph node burden on staging CT can serve as an imaging biomarker to predict treatment failure in human papillomavirus-related oropharyngeal squamous cell carcinoma. We identified patients with human papilloma virus-related oropharyngeal squamous cell carcinoma and staging neck CTs. Demographic and clinical variables were recorded. We retrospectively classified the metastatic lymph node burden on CT as cystic or solid and assessed radiologic extracapsular spread. Biopsy, subsequent imaging, or clinical follow-up was the reference standard for treatment failure. The primary end point was disease-free survival. Cox proportional hazard regression analyses of clinical, demographic, and anatomic variables for treatment failure were performed. One hundred eighty-three patients were included with a mean follow-up of 38 months. In univariate analysis, the following variables had a statistically significant association with treatment failure: solid-versus-cystic lymph nodes, clinical T-stage, clinical N-stage, and radiologic evidence of extracapsular spread. The multivariate Cox proportional hazard model resulted in a model that included solid-versus-cystic lymph nodes, T-stage, and radiologic evidence of extracapsular spread as independent predictors of treatment failure. Patients with cystic nodal metastasis at staging had significantly better disease-free survival than patients with solid lymph nodes. In human papilloma virus-related oropharyngeal squamous cell carcinoma, patients with solid lymph node metastases are at higher risk for treatment failure with worse disease-free survival. Solid lymph nodes may serve as an imaging biomarker to tailor individual treatment regimens. © 2017 by American Journal

  7. Nano-sized cosmetic formulations or solid nanoparticles in sunscreens: a risk to human health?

    Science.gov (United States)

    Nohynek, Gerhard J; Dufour, Eric K

    2012-07-01

    Personal care products (PCP) often contain micron- or nano-sized formulation components, such as nanoemulsions or microscopic vesicles. A large number of studies suggest that such vesicles do not penetrate human skin beyond the superficial layers of the stratum corneum. Nano-sized PCP formulations may enhance or reduce skin absorption of ingredients, albeit at a limited scale. Modern sunscreens contain insoluble titanium dioxide (TiO₂) or zinc oxide (ZnO) nanoparticles (NP), which are efficient filters of UV light. A large number of studies suggest that insoluble NP do not penetrate into or through human skin. A number of in vivo toxicity tests, including in vivo intravenous studies, showed that TiO₂ and ZnO NP are non-toxic and have an excellent skin tolerance. Cytotoxicity, genotoxicity, photo-genotoxicity, general toxicity and carcinogenicity studies on TiO₂ and ZnO NP found no difference in the safety profile of micro- or nano-sized materials, all of which were found to be non-toxic. Although some published in vitro studies on insoluble nano- or micron-sized particles suggested cell uptake, oxidative cell damage or genotoxicity, these data are consistent with those from micron-sized particles and should be interpreted with caution. Data on insoluble NP, such as surgical implant-derived wear debris particles or intravenously administered magnetic resonance contrast agents suggest that toxicity of small particles is generally related to their chemistry rather than their particle size. Overall, the weight of scientific evidence suggests that insoluble NP used in sunscreens pose no or negligible risk to human health, but offer large health benefits, such as the protection of human skin against UV-induced skin ageing and cancer.

  8. Direct solid-phase microextraction combined with gas and liquid chromatography for the determination of lidocaine in human urine

    NARCIS (Netherlands)

    Koster, E.H M; Hofman, N.S K; de Jong, G.J.

    Solid-phase microextraction (SPME) has been combined with gas chromatography (GC) and liquid chromatography (LC) for the determination of lidocaine in human urine. A polydimethylsiloxane (PDMS) coated fibre was directly immersed into buffered urine. Extraction conditions such as time, pH, ionic

  9. Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors.

    Science.gov (United States)

    Gandhi, Leena; Bahleda, Rastislav; Tolaney, Sara M; Kwak, Eunice L; Cleary, James M; Pandya, Shuchi S; Hollebecque, Antoine; Abbas, Richat; Ananthakrishnan, Revathi; Berkenblit, Anna; Krygowski, Mizue; Liang, Yali; Turnbull, Kathleen W; Shapiro, Geoffrey I; Soria, Jean-Charles

    2014-01-10

    Human epidermal growth factor (HER) -mediated signaling is critical in many cancers, including subsets of breast and lung cancer. HER family members signal via the phosphatidylinositide 3-kinase (PI3K) -AKT/protein kinase B-mammalian target of rapamycin (mTOR) cascade; mTOR activation is critical for the expression of multiple contributors to tumor growth and invasion. On the basis of preclinical data suggesting synergy of HER2 inhibition and mTOR inhibition in breast and lung cancer models, we conducted a phase I combination study of neratinib, a small-molecule irreversible pan-HER tyrosine kinase inhibitor, and temsirolimus, an mTOR inhibitor, in patients with advanced solid tumors. This study enrolled patients to dosing combinations of neratinib and temsirolimus. The primary objective was to estimate the toxicity contour of the combination and establish recommended phase II doses. Sixty patients were treated on 12 of 16 possible dosing combinations. Diarrhea was the most common drug-related (93%) and dose-limiting toxicity (DLT), constituting four of 10 DLTs. Dose-limiting grade 3 metabolic abnormalities were also observed. Other frequent drug-related toxicities included nausea, stomatitis (both 53%), and anemia (48%). Two maximum-tolerated dose combinations were identified: 200 mg of neratinib/25 mg of temsirolimus and 160 mg of neratinib/50 mg of temsirolimus. Responses were noted in patients with HER2-amplified breast cancer resistant to trastuzumab, HER2-mutant non-small-cell lung cancer, and tumor types without identified mutations in the HER-PI3K-mTOR pathway. The combination of neratinib and temsirolimus was tolerable and demonstrated antitumor activity in multiple tumor types, warranting further evaluation.

  10. 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.

  11. 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.

  12. 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

  13. Large-Scale Analysis of Network Bistability for Human Cancers

    Science.gov (United States)

    Shiraishi, Tetsuya; Matsuyama, Shinako; Kitano, Hiroaki

    2010-01-01

    Protein–protein interaction and gene regulatory networks are likely to be locked in a state corresponding to a disease by the behavior of one or more bistable circuits exhibiting switch-like behavior. Sets of genes could be over-expressed or repressed when anomalies due to disease appear, and the circuits responsible for this over- or under-expression might persist for as long as the disease state continues. This paper shows how a large-scale analysis of network bistability for various human cancers can identify genes that can potentially serve as drug targets or diagnosis biomarkers. PMID:20628618

  14. Biological relevance of human papillomaviruses in vulvar cancer.

    Science.gov (United States)

    Halec, Gordana; Alemany, Laia; Quiros, Beatriz; Clavero, Omar; Höfler, Daniela; Alejo, Maria; Quint, Wim; Pawlita, Michael; Bosch, Francesc X; de Sanjose, Silvia

    2017-04-01

    The carcinogenic role of high-risk human papillomavirus (HR-HPV) types in the increasing subset of vulvar intraepithelial neoplasia and vulvar cancer in young women has been established. However, the actual number of vulvar cancer cases attributed to HPV is still imprecisely defined. In an attempt to provide a more precise definition of HPV-driven vulvar cancer, we performed HPV-type-specific E6*I mRNA analyses available for 20 HR-/possible HR (pHR)-HPV types, on tissue samples from 447 cases of vulvar cancer. HPV DNA genotyping was performed using SPF10-LiPA 25 assay due to its high sensitivity in formalin-fixed paraffin-embedded tissues. Data on p16 INK4a expression was available for comparative analysis via kappa statistics. The use of highly sensitive assays covering the detection of HPV mRNA in a broad spectrum of mucosal HPV types resulted in the detection of viral transcripts in 87% of HPV DNA+ vulvar cancers. Overall concordance between HPV mRNA+ and p16 INK4a upregulation (strong, diffuse immunostaining in >25% of tumor cells) was 92% (K=0.625, 95% confidence interval (CI)=0.531-0.719). Among these cases, 83% were concordant pairs of HPV mRNA+ and p16 INK4a + and 9% were concordant pairs of HPV mRNA- and p16 INK4a -. Our data confirm the biological role of HR-/pHR-HPV types in the great majority of HPV DNA+ vulvar cancers, resulting in an HPV-attributable fraction of at least 21% worldwide. Most HPV DNA+ vulvar cancers were associated with HPV16 (85%), but a causative role for other, less frequently occurring mucosal HPV types (HPV26, 66, 67, 68, 70 and 73) was also confirmed at the mRNA level for the first time. These findings should be taken into consideration for future screening options as HPV-associated vulvar preneoplastic lesions have increased in incidence in younger women and require different treatment than vulvar lesions that develop from rare autoimmune-related mechanisms in older women.

  15. Risk of cancer in the vicinity of municipal solid waste incinerators: importance of using a flexible modelling strategy

    Directory of Open Access Journals (Sweden)

    Goria Sarah

    2009-05-01

    Full Text Available Abstract Background We conducted an ecological study in four French administrative departments and highlighted an excess risk in cancer morbidity for residents around municipal solid waste incinerators. The aim of this paper is to show how important are advanced tools and statistical techniques to better assess weak associations between the risk of cancer and past environmental exposures. Methods The steps to evaluate the association between the risk of cancer and the exposure to incinerators, from the assessment of exposure to the definition of the confounding variables and the statistical analysis carried out are detailed and discussed. Dispersion modelling was used to assess exposure to sixteen incinerators. A geographical information system was developed to define an index of exposure at the IRIS level that is the geographical unit we considered. Population density, rural/urban status, socio-economic deprivation, exposure to air pollution from traffic and from other industries were considered as potential confounding factors and defined at the IRIS level. Generalized additive models and Bayesian hierarchical models were used to estimate the association between the risk of cancer and the index of exposure to incinerators accounting for the confounding factors. Results Modelling to assess the exposure to municipal solid waste incinerators allowed accounting for factors known to influence the exposure (meteorological data, point source characteristics, topography. The statistical models defined allowed modelling extra-Poisson variability and also non-linear relationships between the risk of cancer and the exposure to incinerators and the confounders. Conclusion In most epidemiological studies distance is still used as a proxy for exposure. This can lead to significant exposure misclassification. Additionally, in geographical correlation studies the non-linear relationships are usually not accounted for in the statistical analysis. In studies of

  16. Clofibric acid, a peroxisome proliferator-activated receptor alpha ligand, inhibits growth of human ovarian cancer.

    Science.gov (United States)

    Yokoyama, Yoshihito; Xin, Bing; Shigeto, Tatsuhiko; Umemoto, Mika; Kasai-Sakamoto, Akiko; Futagami, Masayuki; Tsuchida, Shigeki; Al-Mulla, Fahd; Mizunuma, Hideki

    2007-04-01

    Recent reports have shown that peroxisome proliferator-activated receptor (PPAR)alpha ligands reduce growth of some types of malignant tumors and prevent carcinogenesis. In this study, we investigated the inhibitory effect of clofibric acid (CA), a ligand for PPARalpha on growth of ovarian malignancy, in in vivo and in vitro experiments using OVCAR-3 and DISS cells derived from human ovarian cancer and aimed to elucidate the molecular mechanism of its antitumor effect. CA treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted s.c. and significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared with control. CA also dose-dependently inhibited cell proliferation of cultured cell lines. CA treatment increased the expression of carbonyl reductase (CR), which promotes the conversion of prostaglandin E(2) (PGE(2)) to PGF(2alpha), in implanted OVCAR-3 tumors as well as cultured cells. CA treatment decreased PGE(2) level as well as vascular endothelial growth factor (VEGF) amount in both of OVCAR-3-tumor and DISS-derived ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR-3 tumors treated by CA. Transfection of CR expression vector into mouse ovarian cancer cells showed significant reduction of PGE(2) level as well as VEGF expression. These results indicate that CA produces potent antitumor effects against ovarian cancer in conjunction with a reduction of angiogenesis and induction of apoptosis. We conclude that CA could be an effective agent in ovarian cancer and should be tested alone and in combination with other anticancer drugs.

  17. Risk of solid cancer in the offspring of female workers of the Mayak nuclear facility in the Southern Urals, Russian Federation

    International Nuclear Information System (INIS)

    Tsareva, Y.; Sokolnikov, M.; Okatenko, P.; Deltour, I.; Schonfeld, S.J.; Schuez, J.; Vostrotin, V.V.

    2016-01-01

    Studies of cancer risk following in utero exposure to ionizing radiation are limited in number, particularly for adult-onset cancers, and the evidence is unclear. In the present study, the risk of solid cancer incidence following in utero radiation exposure is examined among 8466 offspring of female nuclear workers at one of the largest nuclear facilities (Mayak Production Association) in the Russian Federation. Poisson regression methods were used to estimate excess relative risks (ERRs) per Gray (Gy). Mother's uterine gamma dose served as a surrogate for fetal gamma dose. During 277,002 person-years of follow-up (1948-2009), there were 177 first primary solid cancers excluding non-melanoma skin cancers. Estimated in utero gamma and plutonium doses exceeded zero for 41 and 23 % of offspring, respectively. Of the 177 solid cancers, 66 occurred among individuals with some in utero exposure to gamma radiation and 53 among those with estimated plutonium exposures. There was no indication of a statistically significantly increased risk of solid cancer incidence from in utero gamma exposure (linear ERR/Gy -1.0; upper 95 % confidence limit 0.5). This result was unchanged after accounting for subsequent occupational exposure. Plutonium doses were estimated but were too low to obtain meaningful risk estimates. Thus, in this cohort in utero radiation exposure was not associated with solid cancer risk. This is consistent with an earlier report of mortality in the cohort, but is based on twice as many cases and less susceptible to biases inherent in mortality analyses. Given the relatively young age of the cohort with respect to cancer, continued follow-up should be done as the number of cancer cases increases. (orig.)

  18. Risk of solid cancer in the offspring of female workers of the Mayak nuclear facility in the Southern Urals, Russian Federation

    Energy Technology Data Exchange (ETDEWEB)

    Tsareva, Y.; Sokolnikov, M.; Okatenko, P. [Southern Urals Biophysics Institute (SUBI), Epidemiology Laboratory, Ozyorsk (Russian Federation); Deltour, I.; Schonfeld, S.J.; Schuez, J. [International Agency for Research on Cancer (IARC), Section of Environment and Radiation, Lyon Cedex 08 (France); Vostrotin, V.V. [Southern Urals Biophysics Institute (SUBI), Laboratory of Radiation Safety, Ozyorsk (Russian Federation)

    2016-08-15

    Studies of cancer risk following in utero exposure to ionizing radiation are limited in number, particularly for adult-onset cancers, and the evidence is unclear. In the present study, the risk of solid cancer incidence following in utero radiation exposure is examined among 8466 offspring of female nuclear workers at one of the largest nuclear facilities (Mayak Production Association) in the Russian Federation. Poisson regression methods were used to estimate excess relative risks (ERRs) per Gray (Gy). Mother's uterine gamma dose served as a surrogate for fetal gamma dose. During 277,002 person-years of follow-up (1948-2009), there were 177 first primary solid cancers excluding non-melanoma skin cancers. Estimated in utero gamma and plutonium doses exceeded zero for 41 and 23 % of offspring, respectively. Of the 177 solid cancers, 66 occurred among individuals with some in utero exposure to gamma radiation and 53 among those with estimated plutonium exposures. There was no indication of a statistically significantly increased risk of solid cancer incidence from in utero gamma exposure (linear ERR/Gy -1.0; upper 95 % confidence limit 0.5). This result was unchanged after accounting for subsequent occupational exposure. Plutonium doses were estimated but were too low to obtain meaningful risk estimates. Thus, in this cohort in utero radiation exposure was not associated with solid cancer risk. This is consistent with an earlier report of mortality in the cohort, but is based on twice as many cases and less susceptible to biases inherent in mortality analyses. Given the relatively young age of the cohort with respect to cancer, continued follow-up should be done as the number of cancer cases increases. (orig.)

  19. Saudi anti-human cancer plants database (SACPD): A collection of plants with anti-human cancer activities.

    Science.gov (United States)

    Al-Zahrani, Ateeq Ahmed

    2018-01-30

    Several anticancer drugs have been developed from natural products such as plants. Successful experiments in inhibiting the growth of human cancer cell lines using Saudi plants were published over the last three decades. Up to date, there is no Saudi anticancer plants database as a comprehensive source for the interesting data generated from these experiments. Therefore, there was a need for creating a database to collect, organize, search and retrieve such data. As a result, the current paper describes the generation of the Saudi anti-human cancer plants database (SACPD). The database contains most of the reported information about the naturally growing Saudi anticancer plants. SACPD comprises the scientific and local names of 91 plant species that grow naturally in Saudi Arabia. These species belong to 38 different taxonomic families. In Addition, 18 species that represent16 family of medicinal plants and are intensively sold in the local markets in Saudi Arabia were added to the database. The website provides interesting details, including plant part containing the anticancer bioactive compounds, plants locations and cancer/cell type against which they exhibit their anticancer activity. Our survey revealed that breast, liver and leukemia were the most studied cancer cell lines in Saudi Arabia with percentages of 27%, 19% and 15%, respectively. The current SACPD represents a nucleus around which more development efforts can expand to accommodate all future submissions about new Saudi plant species with anticancer activities. SACPD will provide an excellent starting point for researchers and pharmaceutical companies who are interested in developing new anticancer drugs. SACPD is available online at https://teeqrani1.wixsite.com/sapd.

  20. Human gastric emptying and colonic filling of solids characterized by a new method

    Energy Technology Data Exchange (ETDEWEB)

    Camilleri, M.; Colemont, L.J.; Phillips, S.F.; Brown, M.L.; Thomforde, G.M.; Chapman, N.; Zinsmeister, A.R. (Mayo Clinic and Foundation, Rochester, MN (USA))

    1989-08-01

    Our first aim was to compare {sup 111}In-labeled Amberlite IR-12OP resin pellets and {sup 131}I-labeled fiber in the assessment of gastric and small bowel transit and colonic filling in healthy humans. Both radiolabels were highly stable for 3 h in an in vitro stomach model and remained predominantly bound to solid phase of stools collected over 5 days (90.5 +/- 2.1 (SE)% for {sup 131}I and 87.4 +/- 1.4% for {sup 111}In). The lag phase of gastric emptying was shorter for {sup 111}In-pellets (30 +/- 11 min compared with 58 +/- 12 min for {sup 131}I-fiber, P less than 0.05). However, the slope of the postlag phase of gastric emptying and the half time of small bowel transit were not significantly different for {sup 111}In-pellets and {sup 131}I-fiber. Filling of the colon was characterized by bolus movements of the radiolabel (10-80% range, 26% mean) followed by plateaus (periods of no movement of isotope into colon lasting 15-120 min, range; 51 min, mean). Half of the bolus movements occurred within 1 h of the intake of a second meal. Thus {sup 111}In-labeled Amberlite pellets provide an excellent marker for the study of gastric and small bowel transit and colonic filling in humans. The ileum acts as a reservoir and transfers boluses of variable sizes into the colon, often soon after the intake of a subsequent meal.

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

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi

    2016-12-01

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

  2. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    Science.gov (United States)

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

    2015-01-01

    SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy. PMID:25557080

  3. Yeast-expressed human membrane protein aquaporin-1 yields excellent resolution of solid-state MAS NMR spectra

    International Nuclear Information System (INIS)

    Emami, Sanaz; Fan Ying; Munro, Rachel; Ladizhansky, Vladimir; Brown, Leonid S.

    2013-01-01

    One of the biggest challenges in solid-state NMR studies of membrane proteins is to obtain a homogeneous natively folded sample giving high spectral resolution sufficient for structural studies. Eukaryotic membrane proteins are especially difficult and expensive targets in this respect. Methylotrophic yeast Pichia pastoris is a reliable producer of eukaryotic membrane proteins for crystallography and a promising economical source of isotopically labeled proteins for NMR. We show that eukaryotic membrane protein human aquaporin 1 can be doubly ( 13 C/ 15 N) isotopically labeled in this system and functionally reconstituted into phospholipids, giving excellent resolution of solid-state magic angle spinning NMR spectra.

  4. Human Papilloma Virus in Head and Neck Squamous Cell Cancer

    Science.gov (United States)

    Asvadi Kermani, I; Seifi, SH; Dolatkhah, R; Sakhinia, E; Dastgiri, S; Ebrahimi, A; Lotfy, A; Esmaeili, HA; G, Mohammadi; M, Naderpour; SH, Hajalipour; Haggi A, Asghari; M, Nadri

    2012-01-01

    Background Epidemiologic and molecular evidences have established a strong link between high risk types of Human Papilloma Virus and a subgroup of Head and Neck Squamous Cell Carcinomas (HNSCC). We evaluated the frequency of HPV positivity in HNSCC and its relationship to demographic and some risk factor variables in an open case- control study. Methods Fourteen recently diagnosed patients with squamous cell cancer of oropharynx, hypopharynx and larynx aged 18-50 years were examined from 2008-2010 in Tabriz, Iran. HPV DNA was extracted from paraffin-embedded blocks of each patient's sample for PCR evaluation. Saliva samples of 94 control cancer-free subjects were collected for DNA analysis. Multivariable logistic regression method was used to calculate odds ratio for case-control comparisons. Results High risk HPV was detected in 6(42.8%) patients, and 6(5.3%) control subjects which was statistically significant (p<0.0001). HPV-18 was the most frequent type both in the cases and controls. HPV-16 DNA was detected in two patients of the case group, but it was not detected in any of the controls. The relation between demographic and risk factor variables was not statistically significant. Conclusion HPV infection has a significant impact on HNSCC. Despite HPV-16 stronger impact, HPV-18 is more likely to cause malignant degeneration in such cancers amongst some communities. It is vital to introduce and conduct immunization schedules in health care systems to protect communities to some extent. PMID:25780535

  5. Defining Driver DNA Methylation Changes in Human Cancer

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    Gerd P. Pfeifer

    2018-04-01

    Full Text Available Human malignant tumors are characterized by pervasive changes in the patterns of DNA methylation. These changes include a globally hypomethylated tumor cell genome and the focal hypermethylation of numerous 5′-cytosine-phosphate-guanine-3′ (CpG islands, many of them associated with gene promoters. It has been challenging to link specific DNA methylation changes with tumorigenesis in a cause-and-effect relationship. Some evidence suggests that cancer-associated DNA hypomethylation may increase genomic instability. Promoter hypermethylation events can lead to silencing of genes functioning in pathways reflecting hallmarks of cancer, including DNA repair, cell cycle regulation, promotion of apoptosis or control of key tumor-relevant signaling networks. A convincing argument for a tumor-driving role of DNA methylation can be made when the same genes are also frequently mutated in cancer. Many of the most commonly hypermethylated genes encode developmental transcription factors, the methylation of which may lead to permanent gene silencing. Inactivation of such genes will deprive the cells in which the tumor may initiate from the option of undergoing or maintaining lineage differentiation and will lock them into a perpetuated stem cell-like state thus providing an additional window for cell transformation.

  6. Current status of immunologic studies in human lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gross, R.L.

    1978-06-01

    Several aspects of the immunology of human malignancy are reviewed, with particular emphasis on relevant findings in lung cancer. The existence of tumor-specific cell-mediated immune responses in patients with cancer has been demonstrated in numerous tumor types. Of more relevance in clinical situations is the association of generalized immunologic depression with malignancy. In the vast majority of cases, progressive declines in both tumor-specific and nonspecific immunologic parameters are observed with advancing disease. The approach to the immunologic evaluation of cancer patients and the potential usefulness of this approach to the diagnosis, prognosis, management, and assessment of therapeutic response are discussed. Evidence aimed at elucidating the mechanism of immunosuppression in malignancy, such as serum-blocking factors, immunoregulatory alpha globulins, and suppressor cells, is presented. Finally, emphasis is placed on the various forms of immunotherapy, including both specific active methods such as tumor cell or tumor antigen vaccines and nonspecific active immunotherapy involving agents like Bacillus Calmette-Guerin and levamisole. Early results from clinical immunotherapeutic trials are discussed.

  7. Targeting telomerase and DNA repair in human cancers

    International Nuclear Information System (INIS)

    Prakash Hande, M.

    2014-01-01

    Telomerase reactivation is essential for telomere maintenance in human cancer cells ensuring indefinite proliferation. Targeting telomere homeostasis has become one of the promising strategies in the therapeutic management of tumours. One major potential drawback, however, is the time lag between telomerase inhibition and critically shortened telomeres triggering cell death, allowing cancer cells to acquire drug resistance. Numerous studies over the last decade have highlighted the role of DNA repair proteins such as Poly (ADP-Ribose) Polymerase-1 (PARP-1), and DNA-dependent protein kinase (DNA-PKcs) in the maintenance of telomere homoeostasis. Dysfunctional telomeres, resulting from the loss of telomeric DNA repeats or the loss of function of telomere-associated proteins trigger DNA damage responses similar to that observed for double strand breaks. We have been working on unravelling such synthetic lethality in cancer cells and this talk would be on one such recently concluded study that demonstrates that inhibition of DNA repair pathways, i.e., NHEJ pathway and that of telomerase could be an alternative strategy to enhance anti-tumour effects and circumvent the possibility of drug resistance. (author)

  8. Prolactin-inducible proteins in human breast cancer cells

    International Nuclear Information System (INIS)

    Shiu, R.P.; Iwasiow, B.M.

    1985-01-01

    The mechanism of action of prolactin in target cells and the role of prolactin in human breast cancer are poorly understood phenomena. The present study examines the effect of human prolactin (hPRL) on the synthesis of unique proteins by a human breast cancer cell line, T-47D, in serum-free medium containing bovine serum albumin. [ 35 S]Methionine-labeled proteins were analysed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis and fluorography. Treatment of cells with hPRL (1-1000 ng/ml) and hydrocortisone (1 microgram/ml) for 36 h or longer resulted in the synthesis and secretion of three proteins having molecular weights of 11,000, 14,000, and 16,000. Neither hPRL nor hydrocortisone alone induced these proteins. Of several other peptide hormones tested, only human growth hormone, a hormone structurally and functionally similar to hPRL, could replace hPRL in causing protein induction. These three proteins were, therefore, referred to as prolactin-inducible proteins (PIP). Each of the three PIPs was purified to homogeneity by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and specific antibodies were generated to them in rabbits. By immunoprecipitation and immunoblotting (Western blot) of proteins secreted by T-47D cells, it was demonstrated that the three PIPs were immunologically identical to one another. In addition, the 16-kDa and 14-kDa proteins (PIP-16 and PIP-14), and not the 11-kDa protein (PIP-11), incorporated [ 3 H]glycosamine. Furthermore, 2-deoxyglucose (2 mM) and tunicamycin (0.5 micrograms/ml), two compounds known to inhibit glycosylation, blocked the production of PIP-16 and PIP-14, with a concomitant increase in the accumulation of PIP-11

  9. Predictors of Venous Thromboembolism in Patients with Advanced Common Solid Cancers

    International Nuclear Information System (INIS)

    Hall, I. E.; Andersen, M. S.; Gross, C. P.; Krumholz, H. M.; Gross, C. P.; Krumholz, H. M.

    2009-01-01

    There is uncertainty about risk heterogeneity for venous thromboembolism (VTE) in older patients with advanced cancer and whether patients can be stratified according to VTE risk. We performed a retrospective cohort study of the linked Medicare-Surveillance, Epidemiology, and End Results cancer registry in older patients with advanced cancer of lung, breast, colon, prostate, or pancreas diagnosed between 1995-1999. We used survival analysis with demographics, co morbidities, and tumor characteristics/treatment as independent variables. Outcome was VTE diagnosed at least one month after cancer diagnosis. VTE rate was highest in the first year (3.4%). Compared to prostate cancer (1.4 VTEs/100 person-years), there was marked variability in VTE risk (hazard ratio (HR) for male-colon cancer 3.73 (95% CI 2.1-6.62), female-colon cancer HR 6.6 (3.83-11.38), up to female-pancreas cancer HR 21.57 (12.21-38.09). Stage IV cancer and chemotherapy resulted in higher risk (HRs 1.75 (1.44-2.12) and 1.31 (1.0-1.57), resp.). Stratifying the cohort by cancer type and stage using recursive partitioning analysis yielded five groups of VTE rates (non localized prostate cancer 1.4 VTEs/100 person-years, to non localized pancreatic cancer 17.4 VTEs/100 patient-years). In a high-risk population with advanced cancer, substantial variability in VTE risk exists, with notable differences according to cancer type and stage.

  10. Predictors of Venous Thromboembolism in Patients with Advanced Common Solid Cancers

    Directory of Open Access Journals (Sweden)

    Isaac E. Hall

    2009-01-01

    Full Text Available There is uncertainty about risk heterogeneity for venous thromboembolism (VTE in older patients with advanced cancer and whether patients can be stratified according to VTE risk. We performed a retrospective cohort study of the linked Medicare-Surveillance, Epidemiology, and End Results cancer registry in older patients with advanced cancer of lung, breast, colon, prostate, or pancreas diagnosed between 1995–1999. We used survival analysis with demographics, comorbidities, and tumor characteristics/treatment as independent variables. Outcome was VTE diagnosed at least one month after cancer diagnosis. VTE rate was highest in the first year (3.4%. Compared to prostate cancer (1.4 VTEs/100 person-years, there was marked variability in VTE risk (hazard ratio (HR for male-colon cancer 3.73 (95% CI 2.1–6.62, female-colon cancer HR 6.6 (3.83–11.38, up to female-pancreas cancer HR 21.57 (12.21–38.09. Stage IV cancer and chemotherapy resulted in higher risk (HRs 1.75 (1.44–2.12 and 1.31 (1.0–1.57, resp.. Stratifying the cohort by cancer type and stage using recursive partitioning analysis yielded five groups of VTE rates (nonlocalized prostate cancer 1.4 VTEs/100 person-years, to nonlocalized pancreatic cancer 17.4 VTEs/100 patient-years. In a high-risk population with advanced cancer, substantial variability in VTE risk exists, with notable differences according to cancer type and stage.

  11. A taxonomy of epithelial human cancer and their metastases

    Directory of Open Access Journals (Sweden)

    De Moor Bart

    2009-12-01

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

  12. Radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma: Dosimetric comparison and risk assessment of solid secondary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Sun Hyun; Park, Hee Chul; Lim, Do Hoon [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Dong Wook [Dept. of Radiation Oncology, Kyung Hee University Hospital at Gangdong, Seoul (Korea, Republic of); Kim, Mi Sook [Dept. of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Shin, Myung Hee [Dept. of Social and Preventive Medicine, Sungkyunkwan University School of Medicine, Suwon (Korea, Republic of)

    2017-03-15

    We compared the dosimetric parameters and the risk of solid secondary cancer from scattered doses among anterior-posterior/posterior-anterior parallel-opposed fields (AP/PA), anterior, posterior, right, and left lateral fields (4{sub f}ield), 3-dimensional conformal radiotherapy (3D-CRT) using noncoplanar beams, and intensity-modulated radiotherapy composed of 7 coplanar beams (IMRT{sub c}o) and 7 coplanar and noncoplanar beams (IMRT{sub n}on). We retrospectively generated 5 planning techniques for 5 patients with gastric MALToma. Homogeneity index (HI), conformity index (CI), and mean doses of the kidney and liver were calculated from the dose-volume histograms. Applied the Biological Effects of Ionizing Radiation VII report to scattered doses, the lifetime attributable risk (LAR) was calculated to estimate the risk of solid secondary cancer. The best value of CI was obtained with IMRT, although the HI varied among patients. The mean kidney dose was the highest with AP/PA, followed by 4{sub f}ield, 3D-CRT, IMRT{sub c}o, and IMRT{sub n}on. On the other hand, the mean liver dose was the highest with 4{sub f}ield and the lowest with AP/PA. Compared with 4{sub f}ield, the LAR for 3D-CRT decreased except the lungs, and the LAR for IMRT{sub c}o and IMRT{sub n}on increased except the lungs. However, the absolute differences were much lower than <1%. Tailored RT techniques seem to be beneficial because it could achieve adjacent organ sparing with very small and clinically irrelevant increase of secondary solid cancer risk compared to the conventional techniques.

  13. 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.

  14. [High oncogenic risk human papillomavirus and urinary bladder cancer].

    Science.gov (United States)

    Loran, O B; Sinyakova, L A; Gundorova, L V; Kosov, V A; Kosova, I V; Pogodina, I E; Kolbasov, D N

    2017-07-01

    To determine the role of human papillomavirus (HPV) of high oncogenic risk in the development of urinary bladder cancer. 100 patients (72 men and 28 women) aged 38 to 90 years (mean age 65+/-10 years) diagnosed with bladder cancer were examined and underwent treatment. Clinical assessment was complemented by enzyme-linked immunosorbent assays for the presence of antiviral antibodies to herpes simplex virus (HSV) type 1 and type 2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), urethra scraping for detecting high oncogenic risk HPV. Tumor tissue was sampled for PCR virus detection. Semi-quantitative analysis was used to evaluate the components of lymphocyte-plasmocyte and leukocyte infiltrates and cytopathic changes in tumor tissue. There were positive correlations between cytopathic cell changes (koylocytosis and intranuclear inclusions, as manifestations of HPV) and the level of antiviral antibodies, the presence of viruses in the tumor, as well as with the components of the lymphoid-plasmocyte infiltrate. Negative correlations were found between the presence of papillomatosis and the above changes. Human papillomavirus is believed to be a trigger for the initiation of a tumor in young patients with a latent infection (CMV and EBV, HSV, HPV). Cytopathic changes (kylocytosis and intranuclear inclusions) were associated with the activity and morphological features of herpes-viral infections. Their degree varied depending on the stage of the process, but not on the anaplasia degree. Papillomatosis is associated with a more favorable course of the tumor process.

  15. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Potential Therapeutic Roles of Tanshinone IIA in Human Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sheng-Chun Chiu

    2014-09-01

    Full Text Available Tanshinone IIA (Tan-IIA, one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae, has been found to exhibit anticancer activity in various cancer cells. We have demonstrated that Tan-IIA induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. Here we explored the anticancer effect of Tan-IIA in human bladder cancer cell lines. Our results showed that Tan-IIA caused bladder cancer cell death in a time- and dose-dependent manner. Tan-IIA induced apoptosis through the mitochondria-dependent pathway in these bladder cancer cells. Tan-IIA also suppressed the migration of bladder cancer cells as revealed by the wound healing and transwell assays. Finally, combination therapy of Tan-IIA with a lower dose of cisplatin successfully killed bladder cancer cells, suggesting that Tan-IIA can serve as a potential anti-cancer agent in bladder cancer.

  17. Differential diagnosis of pancreatic cancer from other solid tumours arising from the periampullary area on MDCT

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Suk Ki [Bundang Jesaeng General Hospital, Departments of Radiology, Daejin Medical Center, Seognam-si, Gyeonggi-do (Korea, Republic of); Kim, Jung Hoon; Joo, Ijin; Jeon, Ju Hyun; Han, Joon Koo; Choi, Byung Ihn [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, Chongno-gu, Seoul (Korea, Republic of); Shin, Kyung Sook [Chungnam National University School of Medicine, Department of Radiology, 266 Munhwa-ro, Jung-gu, Daejeon (Korea, Republic of)

    2015-10-15

    To investigate CT features and differential diagnosis of pancreatic adenocarcinoma compared to other solid tumours arising in the periampullary area. One hundred and ninety-five patients with pathologically proven, solid periampullary tumours, including pancreatic adenocarcinoma (n = 98), neuroendocrine tumours (n = 52), gastrointestinal stromal tumours (n = 31), and solid pseudopapillary neoplasms (n = 14), underwent preoperative CT. Two radiologists reviewed CT features and rated the possibility of pancreatic adenocarcinoma. Statistically common findings for pancreatic adenocarcinoma included: patient age >50 years; ill-defined margin; completely solid mass; homogeneous enhancement; hypoenhancement on arterial and venous phases; atrophy; and duct dilatation. Statistically common findings for GIST included: heterogeneous enhancement; hyperenhancement on arterial and venous phases; rim enhancement; and prominent feeding arteries. The hyperenhancement on arterial and venous phases is statistically common in NET, and heterogeneous enhancement, hypoenhancement on the arterial and venous phases are statistically common in SPN. Diagnostic performance of CT for differentiating pancreatic adenocarcinomas from other solid periampullary tumours was 0.962 and 0.977 with excellent interobserver agreement (κ = 0.824). CT is useful not only for differentiating pancreatic adenocarcinoma form other solid tumours but also for differentiating between other solid tumours, including NET, SPN, and GIST, arising in the periampullary area. (orig.)

  18. Ribosomopathy-like properties of murine and human cancers.

    Directory of Open Access Journals (Sweden)

    Sucheta Kulkarni

    Full Text Available Ribosomopathies comprise a heterogeneous group of hematologic and developmental disorders, often characterized by bone marrow failure, skeletal and other developmental abnormalities and cancer predisposition. They are associated with mutations and/or haplo-insufficiencies of ribosomal proteins (RPs and inefficient ribosomal RNA (rRNA processing. The resulting ribosomal stress induces the canonical p19ARF/Mdm2/p53 tumor suppressor pathway leading to proliferative arrest and/or apoptosis. It has been proposed that this pathway is then inactivated during subsequent neoplastic evolution. We show here that two murine models of hepatoblastoma (HB and hepatocellular carcinoma (HCC unexpectedly possess features that mimic the ribosomopathies. These include loss of the normal stoichiometry of RP transcripts and proteins and the accumulation of unprocessed rRNA precursors. Silencing of p19ARF, cytoplasmic sequestration of p53, binding to and inactivation of Mdm2 by free RPs, and up-regulation of the pro-survival protein Bcl-2 may further cooperate to drive tumor growth and survival. Consistent with this notion, re-instatement of constitutive p19ARF expression in the HB model completely suppressed tumorigenesis. In >2000 cases of human HCC, colorectal, breast, and prostate cancer, RP transcript deregulation was a frequent finding. In HCC and breast cancer, the severity of this dysregulation was associated with inferior survival. In HCC, the presence of RP gene mutations, some of which were identical to those previously reported in ribosomopathies, were similarly negatively correlated with long-term survival. Taken together, our results indicate that many if not all cancers possess ribosomopathy-like features that may affect their biological behaviors.

  19. Determination of Scopolamine in Human Saliva Using Solid Phase Extraction and LC/MS/MS

    Science.gov (United States)

    Wang, Zuwei; Vaksman, Zalman; Boyd, Jason; Putcha, Lakshmi

    2007-01-01

    Purpose: Scopolamine is the preferred treatment for motion sickness during space flight because of its quick onset of action, short half-life and favorable side-effect profile. The dose administered depends on the mode of administration and usually ranges between 0.1 and 0.8 mg. Such small doses make it difficult to detect concentrations of scopolamine in biological fluids by using conventional HPLC methods. To measure scopolamine in saliva and thereby to evaluate the pharmacokinetics of scopolamine, we developed an LC/MS/MS method using off-line solid phase extraction. Method: Samples (0.5mL) were loaded onto Waters Oasis HLB co-polymer cartridges (10 mg, 1 mL) and eluted with 0.5 mL methanol without evaporation and reconstitution. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 4 minutes. The mobile phase for separation was 90:10 (v/v) methanol: ammonium acetate (2 mM) in water, pH 5.0 +/- 0.1. Concentrations of scopolamine were determined using a Micromass Quattro Micro(TM) mass spectrometer with electrospray ionization (ESI). ESI mass spectra were acquired in positive ion mode with multiple reaction monitoring for the determination of scopolamine m/z = 304.2 yields 138.1 and internal standard (IS) hyoscyamine m/z = 290.2 yields 124.1. Results: The method is rapid, reproducible, specific and has the following parameters: scopolamine and the IS are eluted at 1.7 and 3.2 min respectively. The linear range is 50-5000 pg/mL for scopolamine in saliva with correlation coefficients > 0.99 with a CV < 0.5 %. The intra-day and inter-day CVs are < 15 % for quality control samples with concentrations of 75, 300, 750 and 3000 pg/mL of scopolamine in human saliva. Conclusion: Solid phase extraction allows more rapid sample preparation and greater precision than liquid extraction. Furthermore, we increased the sensitivity and specificity by adjusting the LC mobile phase and using an MS

  20. Qualitative and quantitative expression status of the human chromosome 20 genes in cancer tissues and the representative cell lines.

    Science.gov (United States)

    Wang, Quanhui; Wen, Bo; Yan, Guangrong; Wei, Junying; Xie, Liqi; Xu, Shaohang; Jiang, Dahai; Wang, Tingyou; Lin, Liang; Zi, Jin; Zhang, Ju; Zhou, Ruo; Zhao, Haiyi; Ren, Zhe; Qu, Nengrong; Lou, Xiaomin; Sun, Haidan; Du, Chaoqin; Chen, Chuangbin; Zhang, Shenyan; Tan, Fengji; Xian, Youqi; Gao, Zhibo; He, Minghui; Chen, Longyun; Zhao, Xiaohang; Xu, Ping; Zhu, Yunping; Yin, Xingfeng; Shen, Huali; Zhang, Yang; Jiang, Jing; Zhang, Chengpu; Li, Liwei; Chang, Cheng; Ma, Jie; Yan, Guoquan; Yao, Jun; Lu, Haojie; Ying, Wantao; Zhong, Fan; He, Qing-Yu; Liu, Siqi

    2013-01-04

    Under the guidance of the Chromosome-centric Human Proteome Project (C-HPP), (1, 2) we conducted a systematic survey of the expression status of genes located at human chromosome 20 (Chr.20) in three cancer tissues, gastric, colon, and liver carcinoma, and their representative cell lines. We have globally profiled proteomes in these samples with combined technology of LC-MS/MS and acquired the corresponding mRNA information upon RNA-seq and RNAchip. In total, 323 unique proteins were identified, covering 60% of the coding genes (323/547) in Chr.20. With regards to qualitative information of proteomics, we overall evaluated the correlation of the identified Chr.20 proteins with target genes of transcription factors or of microRNA, conserved genes and cancer-related genes. As for quantitative information, the expression abundances of Chr.20 genes were found to be almost consistent in both tissues and cell lines of mRNA in all individual chromosome regions, whereas those of Chr.20 proteins in cells are different from tissues, especially in the region of 20q13.33. Furthermore, the abundances of Chr.20 proteins were hierarchically evaluated according to tissue- or cancer-related distribution. The analysis revealed several cancer-related proteins in Chr.20 are tissue- or cell-type dependent. With integration of all the acquired data, for the first time we established a solid database of the Chr.20 proteome.

  1. Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization.

    Science.gov (United States)

    Pauletti, G; Godolphin, W; Press, M F; Slamon, D J

    1996-07-04

    Amplification and overexpression of the HER-2/neu gene occurs in 25-30% of human breast cancers. This genetic alteration is associated with a poor clinical prognosis in women with either node negative or node positive breast cancers. The initial studies testing this association were somewhat controversial and this controversy was due in large part to significant heterogeneity in both the methods and/or reagents used in testing archival material for the presence of the alteration. These methods included a number of solid matrix blotting techniques for DNA, RNA and protein as well as immunohistochemistry. Fluorescence in situ hybridization (FISH) represents the newest methodologic approach for testing for this genetic alteration. In this study, FISH is compared to Southern, Northern and Western blot analyses as well as immunohistochemistry in a large cohort of archival human breast cancer specimens. FISH was found to be superior to all other methodologies tested in assessing formalin fixed, paraffin embedded material for HER-2/neu amplification. The results from this study also confirm that overexpression of HER-2/neu rarely occurs in the absence of gene amplification in breast cancer (approximately 3% of cases). This method of analysis is rapid, reproducible and extremely reliable in detecting presence of HER-2/neu gene amplification and should have clinical utility.

  2. Cervical cancer and the human immunodeficiency virus: a review ...

    African Journals Online (AJOL)

    Globally cervical cancer is one of the commonest cancers in women. It comprises approximately 12% of all cancers and is the commonest cancer in women in developing countries. The most recent compilation of global data indicates that an estimated 490 000 new cases of cervical cancer occur annually worldwide and ...

  3. Effects of liquid versus solid diet on colonic transit in humans. Evaluation by standard colonic transit scintigraphy

    International Nuclear Information System (INIS)

    Kaufman, P.N.; Richter, J.E.; Chilton, H.M.; Kerr, R.M.; Cowan, R.C.; Gelfand, D.W.; Ott, D.J.

    1990-01-01

    The effects of liquid versus solid diet on human colonic transit were investigated, and transit following cecal instillation of tracer was compared with transit following instillation in the proximal jejunum. In a randomized cross-over, single-blind fashion, 6 normal volunteers ingesting either normal solid foods or a liquid diet were studied using colonic transit scintigraphy. 111In-DTPA was instilled either into the cecum via a long intestinal tube or into the proximal jejunum via a feeding tube. Compared with the liquid diet, the solid diet slowed transit in the cecum and ascending colon (p less than 0.025) and delayed progression of the geometric center (p less than 0.05) during the first 4 h of the study. Transit from 18 to 48 h was similar on the 2 diets. On the solid diet, transit was similar whether 111In-DTPA was instilled into the proximal jejunum or into the cecum. Transit from the terminal ileum to the cecum was assessed in an additional 5 volunteers following jejunal instillation of 99mTc-DTPA. Cecal filling was rapid (T1/2 = 0.49 h) and complete in all subjects before the onset of cecal emptying. These results suggest that colonic transit is slower on a solid than a liquid diet and that jejunal instillation of radiopharmaceuticals should be suitable for colonic transit studies in most subjects

  4. CBT-501 Study for Select Advanced or Relapsed/Recurrent Solid Tumors

    Science.gov (United States)

    2018-02-07

    Solid Tumor; Advanced Cancer; ColoRectal Cancer; Endometrial Cancer; Gastric Cancer; Hepatocellular Cancer; Nonsmall Cell Lung Cancer; Mesothelioma; Ovarian Cancer; Renal Cancer; Nasopharyngeal Cancer; Esophageal Cancer; Gastroesophageal Junction Adenocarcinoma

  5. Novel anti-c-Mpl monoclonal antibodies identified multiple differentially glycosylated human c-Mpl proteins in megakaryocytic cells but not in human solid tumors.

    Science.gov (United States)

    Zhan, Jinghui; Felder, Barbara; Ellison, Aaron R; Winters, Aaron; Salimi-Moosavi, Hossein; Scully, Sheila; Turk, James R; Wei, Ping

    2013-06-01

    Thrombopoietin and its cognate receptor, c-Mpl, are the primary molecular regulators of megakaryocytopoiesis and platelet production. To date the pattern of c-Mpl expression in human solid tumors and the distribution and biochemical properties of c-Mpl proteins in hematopoietic tissues are largely unknown. We have recently developed highly specific mouse monoclonal antibodies (MAb) against human c-Mpl. In this study we used these antibodies to demonstrate the presence of full-length and truncated human c-Mpl proteins in various megakaryocytic cell types, and their absence in over 100 solid tumor cell lines and in the 12 most common primary human tumor types. Quantitative assays showed a cell context-dependent distribution of full-length and truncated c-Mpl proteins. All forms of human c-Mpl protein were found to be modified with extensive N-linked glycosylation but different degrees of sialylation and O-linked glycosylation. Of note, different variants of full-length c-Mpl protein exhibiting differential glycosylation were expressed in erythromegakaryocytic leukemic cell lines and in platelets from healthy human donors. This work provides a comprehensive analysis of human c-Mpl mRNA and protein expression on normal and malignant hematopoietic and non-hematopoietic cells and demonstrates the multiple applications of several novel anti-c-Mpl antibodies.

  6. Modulation of TIP60 by Human Papilloma Virus in Breast Cancer

    Science.gov (United States)

    2013-04-01

    1 AG________ Award Number: W81XWH-11-1-0687 Title Modulation of TIP60 by Human Papilloma Virus in Breast Cancer... Human Papilloma Virus in Breast Cancer 5b. GRANT NUMBER 1 H 11 1 06 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond 5d. PROJECT...virus (EBV), Hepatitis B Virus (HBV), Hepatitis C virus (HCV), Human Papilloma virus (HPV), Human T-cell lymphotropic virus (HTLV-1) and Kaposi’s

  7. Excess relative risk for solid cancer mortality during prolonged exposure to high-background natural radiation in Yangjiang area of China

    International Nuclear Information System (INIS)

    Sun Quanfu; Tao Zufan; Yuan Yongling; Zou Jianming; Cha Yongru; Jian Yuannu; Wei Luxin; Akiba, S.

    2002-01-01

    Objective: To estimate the excess relative risk for solid cancer associated with chronically exposure to high-background natural radiation in Yangjiang area of China. Methods: Based on hamlet-specific environmental doses and sex-and age-specific occupancy factors, the authors calculated cumulative doses for each cohort member. Assuming a linear dose response relationship and using cancer mortality data for the period 1979-1995 and Poisson model, the authors estimated the excess relative risk (ERR) for solid cancer. Results: The ERR per Sv of all solid cancer is estimated to be -0.11 (95% CI, -0.67, 0.69 to 95%). The corresponding figures for cancers of liver, nasopharynx, lungs and stomach are -0.99 (-1.60, 0.10), 0.10 (-1.21, 3.28), -0.68 (-1.58, 1.66) and -0.27 (-1.37, 2.69) respectively. Conclusion: The association between ERR of solid cancer and dose can not be found

  8. Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells

    International Nuclear Information System (INIS)

    Perkel, V.S.; Mohan, S.; Herring, S.J.; Baylink, D.J.; Linkhart, T.A.

    1990-01-01

    Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis. In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation ([3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens

  9. Solid Matter

    CERN Document Server

    Angelo, Joseph A

    2011-01-01

    Supported by a generous quantity of full-color illustrations and interesting sidebars, Solid Matter introduces the basic characteristics and properties of solid matter. It briefly describes the cosmic connection of the elements, leading readers through several key events in human pre-history that resulted in more advanced uses of matter in the solid state. Chapters include:. -Solid Matter: An Initial Perspective. -Physical Behavior of Matter. -The Gravity of Matter. -Fundamentals of Materials Science. -Rocks and Minerals. -Metals. -Building Materials. -Carbon Earth's Most Versatile Element. -S

  10. A simple solid-phase radioimmunoassay for the measurement of IgG secreted in vitro by human lymphocytes

    International Nuclear Information System (INIS)

    Romagnani, S.; Prete, G.F. del; Giudizi, G.M.; Almerigogna, F.; Ricci, M.

    1979-01-01

    A radioimmunoassay is described for measuring IgG, based on the ability of immunoglobulins of this class to inhibit the binding of radioiodinated staphylococcal protein A to IgG linked to a solid phase. The solid phase is represented by ox erythrocytes coated with anti-ox erthrocyte rabbit IgG, a reagent used for detecting cells equipped with receptors for the Fc fragment of IgG. By this assay the IgG secreted in vitro by human peripheral blood lymphocytes stimulated with PWM and those present in samples of very diluted human sera were measured. It was found that the assay is a very rapid, simple and and reproducible procedure for the detection of IgG immunoglobulin at the nanogram level. (Auth.)

  11. Anti-cancer effects of bioactive compounds from rose hip fruit in human breast cancer cell lines

    OpenAIRE

    Zhong, Lijie

    2017-01-01

    Rose hips have long been used in human diets as a food ingredient and supplement. Their multiple medical properties, which have been attributed to their abundant carotenoid composition, have attracted widespread scientific attention. This thesis examined the carotenoid composition in rose hips from five rose species. The anti-cancer effect of different carotenoid fractions from rose hips was investigated in human breast cancer cell lines, using the natural variation in carotenoid content in h...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Immunotherapy has increased overall survival of metastatic cancer patients, and cancer antigens are promising vaccine targets. To fulfill the promise, appropriate tailoring of the vaccine formulations to mount in vivo cytotoxic T cell (CTL) responses toward co-delivered cancer antigens is essential...... and the porcine immunome is closer related to the human counterpart, we here introduce pigs as a supplementary large animal model for human cancer vaccine development. IDO and RhoC, both important in human cancer development and progression, were used as vaccine targets and 12 pigs were immunized with overlapping......C-derived peptides across all groups with no adjuvant being superior. These findings support the further use of pigs as a large animal model for vaccine development against human cancer....

  13. Microbiota dysbiosis in select human cancers: Evidence of association and causality.

    Science.gov (United States)

    Chen, Jie; Domingue, Jada C; Sears, Cynthia L

    2017-08-01

    The human microbiota is a complex ecosystem of diverse microorganisms consisting of bacteria, viruses, and fungi residing predominantly in epidermal and mucosal habitats across the body, such as skin, oral cavity, lung, intestine and vagina. These symbiotic communities in health, or dysbiotic communities in disease, display tremendous interaction with the local environment and systemic responses, playing a critical role in the host's nutrition, immunity, metabolism and diseases including cancers. While the profiling of normal microbiota in healthy populations is useful and necessary, more recent studies have focused on the microbiota associated with disease, particularly cancers. In this paper, we review current evidence on the role of the human microbiota in four cancer types (colorectal cancer, head and neck cancer, pancreatic cancer, and lung cancer) proposed as affected by both the oral and gut microbiota, and provide a perspective on current gaps in the knowledge of the microbiota and cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 99MTC Alpha-Fetoprotein: A Novel, Specific Agent for the Detection of Human Breast Cancer

    National Research Council Canada - National Science Library

    Line, Bruce

    1998-01-01

    .... We have demonstrated that technetium-99m radiolabeled human alpha-fetoprotein (99mTc AFP) localizes in human breast cancer cells in-vivo, most likely concentrating in breast cancer cells due to a specific receptor not found in normal adult breast tissue...

  15. 99MTC Alpha-Fetoprotein: A Novel, Specific Agent for the Detection of Human Breast Cancer

    National Research Council Canada - National Science Library

    Line, Bruce

    1999-01-01

    .... We have demonstrated that technetium-99m radiolabeled human alpha-fetoprotein (99mTc AFP) localizes in human breast cancer cells in-vivo, most likely concentrating in breast cancer cells due to a specific receptor not found in normal adult breast tissue...

  16. Rhein induces apoptosis of HCT-116 human colon cancer cells via ...

    African Journals Online (AJOL)

    Rhein, a major compound in rhubarb, has been found to have anti-tumor properties in many human cancer cells. However, the details about rhein suppressing the growth of human colon cancer cells remained elusive. In this paper, we explored the potential of rhein as a chemotherapeutic agent on HCT- 116 cells and ...

  17. Apoptosis induced by GanoPoly in human gastric cancer cell line ...

    African Journals Online (AJOL)

    In order to investigate polysaccharide effect on the cultured human gastric cancer cells (SGC7901), DNA ladder, flow cytometry and western blot were used to examine the morpholog, proliferation and apoptosis of human gastric cancer SGC-7901 cells when they were affected by polysaccharide. Results show that ...

  18. Risk of solid cancer in low dose-rate radiation epidemiological studies and the dose-rate effectiveness factor.

    Science.gov (United States)

    Shore, Roy; Walsh, Linda; Azizova, Tamara; Rühm, Werner

    2017-10-01

    Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF). We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR Gy -1 ) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF. The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta-analyses that included only cohorts in which the mean dose was LDR data provide direct evidence regarding risk from exposures at low dose rates as an important complement to the LSS risk estimates used

  19. Glucose Metabolism of Human Prostate Cancer Mouse Xenografts

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2005-04-01

    Full Text Available We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG accumulation in androgen-sensitive (CWR-22 and androgen-independent (PC-3 human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm3 = 14.913 e0.108 × days, R2 = .96, n = 5. The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm3 = 0.3511 × days2 + 49.418 × day −753.33, R2 = .96, n = 3. The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05. The 3-week maximal standardized uptake value (SUVmax was 0.99 ± 0.43 (mean ± SD for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUVmax was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUVmax was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18% and the 5-week (by 9.6% micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer.

  20. An integrated disease/pharmacokinetic/pharmacodynamic model suggests improved interleukin-21 regimens validated prospectively for mouse solid cancers.

    Directory of Open Access Journals (Sweden)

    Moran Elishmereni

    2011-09-01

    Full Text Available Interleukin (IL-21 is an attractive antitumor agent with potent immunomodulatory functions. Yet thus far, the cytokine has yielded only partial responses in solid cancer patients, and conditions for beneficial IL-21 immunotherapy remain elusive. The current work aims to identify clinically-relevant IL-21 regimens with enhanced efficacy, based on mathematical modeling of long-term antitumor responses. For this purpose, pharmacokinetic (PK and pharmacodynamic (PD data were acquired from a preclinical study applying systemic IL-21 therapy in murine solid cancers. We developed an integrated disease/PK/PD model for the IL-21 anticancer response, and calibrated it using selected "training" data. The accuracy of the model was verified retrospectively under diverse IL-21 treatment settings, by comparing its predictions to independent "validation" data in melanoma and renal cell carcinoma-challenged mice (R(2>0.90. Simulations of the verified model surfaced important therapeutic insights: (1 Fractionating the standard daily regimen (50 µg/dose into a twice daily schedule (25 µg/dose is advantageous, yielding a significantly lower tumor mass (45% decrease; (2 A low-dose (12 µg/day regimen exerts a response similar to that obtained under the 50 µg/day treatment, suggestive of an equally efficacious dose with potentially reduced toxicity. Subsequent experiments in melanoma-bearing mice corroborated both of these predictions with high precision (R(2>0.89, thus validating the model also prospectively in vivo. Thus, the confirmed PK/PD model rationalizes IL-21 therapy, and pinpoints improved clinically-feasible treatment schedules. Our analysis demonstrates the value of employing mathematical modeling and in silico-guided design of solid tumor immunotherapy in the clinic.

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

    Science.gov (United States)

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

    1993-04-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    of human-derived antibody fragments able to modulate laminin-regulated biological functions would allow the development of new strategies to improve treatment of cancer patients. In this report, we explore the use of phage display technology to isolate human anti-laminin antibody fragments. A library...... to mouse, rat and human laminin. and show strong immunohistochemical reactivity with basement membranes in human and murine tissue sections. Their properties make them ideal candidates for in vivo applications....

  3. Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

    Science.gov (United States)

    2016-09-01

    analysis of tumor necrosis factor - alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype...AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor - Associated...Cancer and Impairs Tumor -Associated Angiogenesis 5b. GRANT NUMBER W81XWH-15-1-0296 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  4. Is Human Papillomavirus Associated with Prostate Cancer Survival?

    Directory of Open Access Journals (Sweden)

    Mariarosa Pascale

    2013-01-01

    Full Text Available The role of human papillomavirus (HPV in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa, whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67% patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS (median 4.59 years compared to HPV-negative (median 8.24 years, P=0.0381. In multivariate analysis age (P<0.001, Gleason score (P<0.001, nuclear grading (P=0.002, and HPV status (P=0.034 were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.

  5. STAT3 Target Genes Relevant to Human Cancers

    International Nuclear Information System (INIS)

    Carpenter, Richard L.; Lo, Hui-Wen

    2014-01-01

    Since its discovery, the STAT3 transcription factor has been extensively studied for its function as a transcriptional regulator and its role as a mediator of development, normal physiology, and pathology of many diseases, including cancers. These efforts have uncovered an array of genes that can be positively and negatively regulated by STAT3, alone and in cooperation with other transcription factors. Through regulating gene expression, STAT3 has been demonstrated to play a pivotal role in many cellular processes including oncogenesis, tumor growth and progression, and stemness. Interestingly, recent studies suggest that STAT3 may behave as a tumor suppressor by activating expression of genes known to inhibit tumorigenesis. Additional evidence suggested that STAT3 may elicit opposing effects depending on cellular context and tumor types. These mixed results signify the need for a deeper understanding of STAT3, including its upstream regulators, parallel transcription co-regulators, and downstream target genes. To help facilitate fulfilling this unmet need, this review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers

  6. Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma.

    Science.gov (United States)

    Palmini, Gaia; Zonefrati, Roberto; Mavilia, Carmelo; Aldinucci, Alessandra; Luzi, Ettore; Marini, Francesca; Franchi, Alessandro; Capanna, Rodolfo; Tanini, Annalisa; Brandi, Maria Luisa

    2016-10-14

    The current improvements in therapy against osteosarcoma (OS) have prolonged the lives of cancer patients, but the survival rate of five years remains poor when metastasis has occurred. The Cancer Stem Cell (CSC) theory holds that there is a subset of tumor cells within the tumor that have stem-like characteristics, including the capacity to maintain the tumor and to resist multidrug chemotherapy. Therefore, a better understanding of OS biology and pathogenesis is needed in order to advance the development of targeted therapies to eradicate this particular subset and to reduce morbidity and mortality among patients. Isolating CSCs, establishing cell cultures of CSCs, and studying their biology are important steps to improving our understanding of OS biology and pathogenesis. The establishment of human-derived OS-CSCs from biopsies of OS has been made possible using several methods, including the capacity to create 3-dimensional stem cell cultures under nonadherent conditions. Under these conditions, CSCs are able to create spherical floating colonies formed by daughter stem cells; these colonies are termed "cellular spheres". Here, we describe a method to establish CSC cultures from primary cell cultures of conventional OS obtained from OS biopsies. We clearly describe the several passages required to isolate and characterize CSCs.

  7. Trends in human papillomavirus-related oropharyngeal cancer in Israel.

    Science.gov (United States)

    Amit, Moran; Ilana, Kaplan; Avraham, Sharon Pelles; Binenbaum, Yoav; Bachar, Gideon; Billan, Salem; Zaarura, Suliman; Czerninski, Rakefet; Bar-Tov, Matan; Maly, Alexander; Akrish, Sharon; Gil, Ziv

    2016-04-01

    The role of human papillomavirus (HPV) infection in oropharyngeal cancer (SCC) is well established. The annual incidence of oropharyngeal SCC in Israel is considerably lower than that in the United States. The purpose of this study was to assess the rate of HPV-related oropharyngeal SCC in Israel. The cohort included patients with oropharyngeal SCC who were treated during 1999 to 2011 in Israel. HPV typing was carried out using reverse hybridization and immunohistochemistry. Of the 74 patients analyzed, 25 (33.7%) had detectable HPV DNA. Patients in the HPV-positive group tended to be younger, with a higher rate of nodal metastases, and no history of smoking (p Israel as approximately 3-fold lower than in Western countries. Low exposure to HPV-16, a lower rate of transformation, to cancer or protective genetic factors may contribute to the lower rate of oropharyngeal SCC in Israel. © 2015 Wiley Periodicals, Inc. Head Neck 38: E274-E278, 2016. © 2015 Wiley Periodicals, Inc.

  8. [Human papilloma virus and its association with oral cancer].

    Science.gov (United States)

    Bologna-Molina, Ronell E; Castañeda-Castaneira, Raúl E; Molina-Frechero, Nelly; Pérez-Rodríguez, Eréndira

    2006-01-01

    Oral cancer it a pathology of multifactorial etiology, where some factors such as age, sex, race, genetic predisposition, nutrition, and the use of tobacco and alcohol have a bearing on. In the last years, some authors showed the implication of the human papilloma virus (HPV) in the development of precarcinogenic lesions and of oral squamous cell carcinoma. The infection by HPV has been associated to hyperplastic epithelial lesions, papilloma and warty carcinoma in skin and in different types of mucosa, including the anus-genital, cervical, urethral, tracheobronchial, nasal, laryngeal and oral mucosa tracts. The viral high-risk geno-types (oncogenic) such as 16, 18, 31, 33 and 35 are frequently associated to leukoplakia and squamous carcinoma. An association of HPV with oral squamous carcinoma in patients that consume tobacco and alcohol has been fundamentally established. It is important to study and to frequently review the role that viral infections and cancer have, and maybe in the future, it would be possible to create a vaccine that diminishes the frequency of oncological problems.

  9. A Monoclonal Antibody against Wnt-1 Induces Apoptosis in Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Biao He

    2004-01-01

    Full Text Available Aberrant activation of the Wingless-type (Wnt/β-catenin signaling pathway is associated with a variety of human cancers. Little is known regarding the role that Wnt ligands play in human carcinogenesis. To test whether a Wnt-1 signal is a survival factor in human cancer cells and thus may serve as a potential cancer therapeutic target, we investigated the effect of inhibition of Wnt-1 signaling in a variety of human cancer cell lines, including non small cell lung cancer, breast cancer, mesothelioma, and sarcoma. Both monoclonal antibody and RNA interference (RNAi were used to inhibit Wnt-1 signaling. We found that incubation of a monoclonal anti-Wnt-1 antibody induced apoptosis and caused downstream protein changes in cancer cells overexpressing Wnt-1. In contrast, apoptosis was not detected in cells lacking or having minimal Wnt-1 expression after the antibody incubation. RNAi targeting of Wnt-1 in cancer cells overexpressing Wnt-1 demonstrated similar downstream protein changes and induction of apoptosis. The antibody also suppressed tumor growth in vivo. Our results indicate that both monoclonal anti-Wnt-1 antibody and Wnt-1 siRNA inhibit Wnt-1 signaling and can induce apoptosis in human cancer cells. These findings hold promise as a novel therapeutic strategy for cancer.

  10. Characterization of human mesothelin transcripts in ovarian and pancreatic cancer

    International Nuclear Information System (INIS)

    Muminova, Zhanat E; Strong, Theresa V; Shaw, Denise R

    2004-01-01

    Mesothelin is an attractive target for cancer immunotherapy due to its restricted expression in normal tissues and high level expression in several tumor types including ovarian and pancreatic adenocarcinomas. Three mesothelin transcript variants have been reported, but their relative expression in normal tissues and tumors has been poorly characterized. The goal of the present study was to clarify which mesothelin transcript variants are commonly expressed in human tumors. Human genomic and EST nucleotide sequences in the public databases were used to evaluate sequences reported for the three mesothelin transcript variants in silico. Subsequently, RNA samples from normal ovary, ovarian and pancreatic carcinoma cell lines, and primary ovarian tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing to directly identify expressed transcripts. In silico comparisons of genomic DNA sequences with available EST sequences supported expression of mesothelin transcript variants 1 and 3, but there were no sequence matches for transcript variant 2. Newly-derived nucleotide sequences of RT-PCR products from tissues and cell lines corresponded to mesothelin transcript variant 1. Mesothelin transcript variant 2 was not detected. Transcript variant 3 was observed as a small percentage of total mesothelin amplification products from all studied cell lines and tissues. Fractionation of nuclear and cytoplasmic RNA indicated that variant 3 was present primarily in the nuclear fraction. Thus, mesothelin transcript variant 3 may represent incompletely processed hnRNA. Mesothelin transcript variant 1 represents the predominant mature mRNA species expressed by both normal and tumor cells. This conclusion should be important for future development of cancer immunotherapies, diagnostic tests, and gene microarray studies targeting mesothelin

  11. Clinicopathological aspects and prevalence of human papillomavirus in anal cancer

    Directory of Open Access Journals (Sweden)

    Marina Tayla Mesquita Aguiar

    2014-04-01

    Full Text Available Anal cancer is relatively rare; however, its incidence has increased in recent years. Several risk factors are associated with the development of anal cancer, including age older than 50 years, low-fiber diet, chronic anal fistulas, smoking, multiple partners, anal intercourse practice, Human Immunodeficiency Virus infection and immunosuppression. However, the presence of human papillomavirus represents the main risk factor for the development of anal cancer. The aim of this study was to evaluate the clinicopathological aspects of a series of patients with anal carcinomas diagnosed in Hospital Araújo Jorge, Goiânia-Goiás, as well as the prevalence of human papillomavirus genome in these tumors. Clinical, pathological and socio-demographic data were collected from the respective medical files and paraffin blocks containing anal carcinomas specimens were used for DNA extraction and detection of human papillomavirus, by means of polymerase chain reaction, using short PCR fragment primers. Forty-three cases were selected and had the data analyzed, while 38 cases were tested for human papillomavirus genome detection. Among the evaluated patients, 62.8% were women; 53.4% of tumors were squamous cell carcinoma and 46.5% of the patients were aged between 60 and 75 years. Risk factors, such as smoking (39.5% and alcoholism (20.9% were recorded in the studied group. Lymph node metastases were detected in 30.2% of cases and 7.0% had distant metastasis. The detection of human papillomavirus DNA was positive in 76% of cases assessed and this was significantly associated with squamous cell carcinomas. Aggressive behavior and advanced stage of anal cancer described in this study highlight the need for preventive measures that contemplate these tumors, including vaccination against human papillomavirus. Resumo: O câncer anal é relativamente raro, entretanto, sua incidência aumentou nos últimos anos. Vários fatores de risco são associados ao

  12. Characteristics of human amniotic fluid mesenchymal stem cells and their tropism to human ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Liru Li

    Full Text Available The mesenchymal stem cells (MSCs derived from amniotic fluid (AF have become an attractive stem cells source for cell-based therapy because they can be harvested at low cost and avoid ethical disputes. In human research, stem cells derived from AF gradually became a hot research direction for disease treatment, specifically for their plasticity, their reduced immunogenicity and their tumor tropism regardless of the tumor size, location and source. Our work aimed to obtain and characterize human amniotic fluid mesenchymal stem cells (AFMSCs and detect their ovarian cancer tropsim in nude mice model. Ten milliliters of twenty independent amniotic fluid samples were collected from 16-20 week pregnant women who underwent amniocentesis for fetal genetic determination in routine prenatal diagnosis in the first affiliated hospital of Harbin medical university. We successfully isolated the AFMSCs from thirteen of twenty amniotic fluid samples. AFMSCs presented a fibroblastic-like morphology during the culture. Flow cytometry analyses showed that the cells were positive for specific stem cell markers CD73,CD90, CD105, CD166 and HLA-ABC (MHC class I, but negative for CD 45,CD40, CD34, CD14 and HLA-DR (MHC class II. RT-PCR results showed that the AFMSCs expressed stem cell marker OCT4. AFMSCs could differentiate into bone cells, fat cells and chondrocytes under certain conditions. AFMSCs had the high motility to migrate to ovarian cancer site but didn't have the tumorigenicity. This study enhances the possibility of AFMSCs as drug carrier in human cell-based therapy. Meanwhile, the research emphasis in the future can also put in targeting therapy of ovarian cancer.

  13. Biologic activities of recombinant human-beta-defensin-4 toward cultured human cancer cells.

    Science.gov (United States)

    Gerashchenko, O L; Zhuravel, E V; Skachkova, O V; Khranovska, N N; Filonenko, V V; Pogrebnoy, P V; Soldatkina, M A

    2013-06-01

    The aim of the study was in vitro analysis of biological activity of recombinant human beta-defensin-4 (rec-hBD-4). hBD-4 cDNA was cloned into pGEX-2T vector, and recombinant plasmid was transformed into E. coli BL21(DE3) cells. To purify soluble fusion GST-hBD-4 protein, affinity chromatography was applied. Rec-hBD-4 was cleaved from the fusion protein with thrombin, and purified by reverse phase chromatography on Sep-Pack C18. Effects of rec-hBD-4 on proliferation, viability, cell cycle distribution, substrate-independent growth, and mobility of cultured human cancer cells of A431, A549, and TPC-1 lines were analyzed by direct cell counting technique, MTT assay, flow cytofluorometry, colony forming assay in semi-soft medium, and wound healing assay. Rec-hBD-4 was expressed in bacterial cells as GST-hBD-4 fusion protein, and purified by routine 3-step procedure (affine chromatography on glutathione-agarose, cleavage of fusion protein by thrombin, and reverse phase chromatography). Analysis of in vitro activity of rec-hBD-4 toward three human cancer cell lines has demonstrated that the defensin is capable to affect cell behaviour in concentration-dependent manner. In 1-100 nM concentrations rec-hBD-4 significantly stimulates cancer cell proliferation and viability, and promotes cell cycle progression through G2/M checkpoint, greatly enhances colony-forming activity and mobility of the cells. Treatment of the cells with 500 nM of rec-hBD-4 resulted in opposite effects: significant suppression of cell proliferation and viability, blockage of cell cycle in G1/S checkpoint, significant inhibition of cell migration and colony forming activity. Recombinant human beta-defensin-4 is biologically active peptide capable to cause oppositely directed effects toward biologic features of cancer cells in vitro dependent on its concentration.

  14. Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

    International Nuclear Information System (INIS)

    Wang, Jing; Yang, Qifeng; Haffty, Bruce G.; Li, Xiaoyan; Moran, Meena S.

    2013-01-01

    Highlights: ► Fulvestrant radiosensitizes MCF-7 cells. ► Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ► Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy ± fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 ± 0.013 vs. 0.622 ± 0.029 @2 Gy, 0.599 ± 0.045 vs. 0.475 ± 0.054 @4 Gy, and 0.472 ± 0.021 vs. 0.380 ± 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT

  15. Emergence of fractal geometry on the surface of human cervical epithelial cells during progression towards cancer

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  16. Epigenetic modulation of cancer-germline antigen gene expression in tumorigenic human mesenchymal stem cells: implications for cancer therapy

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Burns, Jorge S; Nielsen, Ole

    2009-01-01

    Cancer-germline antigens are promising targets for cancer immunotherapy, but whether such therapies will also eliminate the primary tumor stem cell population remains undetermined. We previously showed that long-term cultures of telomerized adult human bone marrow mesenchymal stem cells can...... spontaneously evolve into tumor-initiating, mesenchymal stem cells (hMSC-TERT20), which have characteristics of clinical sarcoma cells. In this study, we used the hMSC-TERT20 tumor stem cell model to investigate the potential of cancer-germline antigens to serve as tumor stem cell targets. We found...... of cancer-germline antigens in hMSC-TERT20 cells, while their expression levels in primary human mesenchymal stem cells remained unaffected. The expression pattern of cancer-germline antigens in tumorigenic mesenchymal stem cells and sarcomas, plus their susceptibility to enhancement by epigenetic...

  17. Hypoxic conditions induce a cancer-like phenotype in human breast epithelial cells

    DEFF Research Database (Denmark)

    Vaapil, Marica; Helczynska, Karolina; Villadsen, René

    2012-01-01

    Solid tumors are less oxygenated than their tissue of origin. Low intra-tumor oxygen levels are associated with worse outcome, increased metastatic potential and immature phenotype in breast cancer. We have reported that tumor hypoxia correlates to low differentiation status in breast cancer. Less...... is known about effects of hypoxia on non-malignant cells. Here we address whether hypoxia influences the differentiation stage of non-malignant breast epithelial cells and potentially have bearing on early stages of tumorigenesis....

  18. Docetaxel-loaded solid lipid nanoparticles as a basis for a targeted and dose-sparing personalized breast cancer treatment strategy

    Directory of Open Access Journals (Sweden)

    Danilova NV

    2015-03-01

    Full Text Available Natalia V Danilova,1,2 Zhomart R Kalzhanov,3 Nina A Nefedova,2 Pavel G Mal’kov,2 Ioannis P Kosmas,1,4 Marina Y Eliseeva,1,5 Ospan A Mynbaev1,5,6 1International Translational Medicine and Biomodeling Research Team, MIPT Center for Human Physiology, Laboratory of Cellular and Molecular Technologies, Moscow Institute of Physics and Technology, State University, 2Department of Physiology and Basic Pathology, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia; 3Department of Human Metabolism, Academic Unit of Reproductive and Developmental Medicine, Sheffield University, Sheffield, UK; 4Department of Obstetrics and Gynecology, Ioannina State General Hospital G Chatzikosta, Ioannina, Greece; 5Department of Obstetrics, Gynecology and Reproductive Medicine, Peoples’ Friendship University of Russia, 6Laboratory of Immunology, Moscow State University of Medicine and Dentistry named after AI Evdokimov, Moscow, Russia The long-term survival rate of patients with breast cancer was improved by the application of systemic adjuvant chemotherapy,1 although the primary breast cancer treatment strategy consists of mastectomy with lymphadenectomy and radiotherapy followed by breast reconstruction.2–5 Unfortunately, most adjuvant chemotherapeutic agents trigger major side effects.1,6 Therefore, we have read with great interest an article in the International Journal of Nanomedicine on the design of docetaxel-loaded solid lipid nanoparticles (DSNs aimed at reducing the systemic toxicity of standardized docetaxel treatment.7 Read the original article 

  19. Approaches to drug resistance in solid tumors : with emphasis on lung cancer

    NARCIS (Netherlands)

    Bakker, Marleen

    2005-01-01

    De novo or acquired resistance of tumor cells to anticancer agents remains a major problem for the therapeutic efficacy of chemotherapeutic drugs. Most solid tumors are intrinsically insensitive or acquire resistance after initial response to chemotherapy. Different mechanisms seem to play a role in

  20. Fluorescence spectroscopy for throat cancer detection using human saliva

    Science.gov (United States)

    Kumar, Pavan; Singh, Ashutosh; Zaffar, Mohammad; Pradhan, Asima

    2018-02-01

    Throat precancer detection using fluorescence from human saliva is reported here. It may be noted that accessing the throat for investigation is cumbersome and use of saliva as a diagnostic medium may ease the process. The study has been conducted on three groups of patients: oral squamous cell carcinoma (OSCC), dysplasia, and normal (control). An in-house developed compact set-up has been used for fluorescence measurements. The compact system consist of a 375 nm laser diode, collimating lens, long pass filter, fibers, and cuvette holder. Major and minor bands of flavin adenine dinucleotide (FAD) and porphyrin are observed in the spectra. A receiver operating characteristic (ROC) analysis has been used to evaluate the diagnostic performance. Area under the spectra has been chosen for discrimination among the groups and is able to differentiate OSCC to normal, dysplasia to normal, and OSCC to dysplasia with sensitivities 100% (48/48), 92% (32/35), 77% (37/48), and specificities 96% (50/52), 96% (50/52), 89% (31/35) with the accuracy of 98%, 94% and 82% respectively. Sensitivity and specificity, when differentiating OSCC to normal and dysplasia to normal, are significantly large, which indicates that human saliva may be an excellent diagnostic medium for early detection of throat cancer.

  1. Development of solid phase radioimmunoassay using antibody coupled magnetizable particles for measurement of progesterone in human serum

    International Nuclear Information System (INIS)

    Mehany, N.L.

    2007-01-01

    The aim of the present study was to prepare solid phase radioimmunoassay (RIA) reagents. Development as well as optimization and validation of RIA system using solid phase magnetic particles for the measurement of progesterone in human serum are described. The production of polyclonal antibodies was carried out by immunizing five white New-Zealand rabbits subcutaneously. Low density magnetizable cellulose iron oxide particles have been used to couple covalently to the IgG fraction of polyclonal anti-progesterone using carbonyl diimidazole activation method and applied as a solid phase separating agent for RIA of serum progesterone. 125 I-progesterone tracer was prepared using chloramine-T and iodogen oxidation methods and purified using high performance liquid chromatography. The progesterone standards were prepared using highly purified progesterone powder with hormone free serum as standard matrix. Optimization and validation of the assay were carried out. The results obtained provide a low cost, simple, sensitive, specific and accurate RIA system of progesterone based on magnetizable solid phase separation. This may be extremely helpful in diagnosis and proper management of ovulation during childbearing years

  2. Development Of Solid Phase Radioimmunoassay Using Antibody Coupled Cellulose Particles For Measurement Of Prolactin In Human Serum

    International Nuclear Information System (INIS)

    Abdel-Ghany, I.Y.

    2013-01-01

    The objective of the present study was to prepare solid phase radioimmunoassay (RIA) reagents. Development as well as optimization and validation of RIA system using solid phase cellulose particles for the measurement of prolactin (PRL) in human serum were described. The production of polyclonal antibodies was carried out by immunizing three Balb/C mice intraperitoneal through primary injection and two booster doses. The activation of cellulose particles using 1,1-carbonyl diimidazole (CDI) and coupling of these solid phase particles with IgG fraction of mouse anti-PRL were carried out. Preparation of 125 I-PRL tracer was prepared using lactoperoxidase method then purified by gel filtration using sephadex G-100. The PRL standards were prepared using a highly purified PRL antigen with assay buffer as standard matrix. Optimization and validation of the assay were carried out. The results obtained provide a low cost, simple, sensitive, specific and accurate RIA system of prolactin based on solid phase separation. These cellulose particles retain their characteristics during storage for 6 months at 4 degree C. In conclusion, this assay could be used as a useful diagnostic tool for pituitary dysfunctions and possible reproductive disability

  3. Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival.

    Science.gov (United States)

    Pai, Vaibhav P; Marshall, Aaron M; Hernandez, Laura L; Buckley, Arthur R; Horseman, Nelson D

    2009-01-01

    The breast microenvironment can either retard or accelerate the events associated with progression of latent cancers. However, the actions of local physiological mediators in the context of breast cancers are poorly understood. Serotonin (5-HT) is a critical local regulator of epithelial homeostasis in the breast and other organs. Herein, we report complex alterations in the intrinsic mammary gland serotonin system of human breast cancers. Serotonin biosynthetic capacity was analyzed in human breast tumor tissue microarrays using immunohistochemistry for tryptophan hydroxylase 1 (TPH1). Serotonin receptors (5-HT1-7) were analyzed in human breast tumors using the Oncomine database. Serotonin receptor expression, signal transduction, and 5-HT effects on breast cancer cell phenotype were compared in non-transformed and transformed human breast cells. In the context of the normal mammary gland, 5-HT acts as a physiological regulator of lactation and involution, in part by favoring growth arrest and cell death. This tightly regulated 5-HT system is subverted in multiple ways in human breast cancers. Specifically, TPH1 expression undergoes a non-linear change during progression, with increased expression during malignant progression. Correspondingly, the tightly regulated pattern of 5-HT receptors becomes dysregulated in human breast cancer cells, resulting in both ectopic expression of some isoforms and suppression of others. The receptor expression change is accompanied by altered downstream signaling of 5-HT receptors in human breast cancer cells, resulting in resistance to 5-HT-induced apoptosis, and stimulated proliferation. Our data constitutes the first report of direct involvement of 5-HT in human breast cancer. Increased 5-HT biosynthetic capacity accompanied by multiple changes in 5-HT receptor expression and signaling favor malignant progression of human breast cancer cells (for example, stimulated proliferation, inappropriate cell survival). This occurs

  4. Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells

    International Nuclear Information System (INIS)

    Villa, Nancy Y.; Bartee, Eric; Mohamed, Mohamed R.; Rahman, Masmudur M.; Barrett, John W.; McFadden, Grant

    2010-01-01

    Myxoma (MYXV) and vaccinia (VACV) viruses have recently emerged as potential oncolytic agents that can infect and kill different human cancer cells. Although both are structurally similar, it is unknown whether the pathway(s) used by these poxviruses to enter and cause oncolysis in cancer cells are mechanistically similar. Here, we compared the entry of MYXV and VACV-WR into various human cancer cells and observed significant differences: 1 - low-pH treatment accelerates fusion-mediated entry of VACV but not MYXV, 2 - the tyrosine kinase inhibitor genistein inhibits entry of VACV, but not MYXV, 3 - knockdown of PAK1 revealed that it is required for a late stage event downstream of MYXV entry into cancer cells, whereas PAK1 is required for VACV entry into the same target cells. These results suggest that VACV and MYXV exploit different mechanisms to enter into human cancer cells, thus providing some rationale for their divergent cancer cell tropisms.

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

    Science.gov (United States)

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

    2016-01-19

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

  6. Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCE(TM).

    Science.gov (United States)

    Jang, Won-Hee; Jung, Kyoung-Mi; Yang, Hye-Ri; Lee, Miri; Jung, Haeng-Sun; Lee, Su-Hyon; Park, Miyoung; Lim, Kyung-Min

    2015-07-01

    The eye irritation potential of drug candidates or pharmaceutical ingredients should be evaluated if there is a possibility of ocular exposure. Traditionally, the ocular irritation has been evaluated by the rabbit Draize test. However, rabbit eyes are more sensitive to irritants than human eyes, therefore substantial level of false positives are unavoidable. To resolve this species difference, several three-dimensional human corneal epithelial (HCE) models have been developed as alternative eye irritation test methods. Recently, we introduced a new HCE model, MCTT HCE(TM) which is reconstructed with non-transformed human corneal cells from limbal tissues. Here, we examined if MCTT HCE(TM) can be employed to evaluate eye irritation potential of solid substances. Through optimization of washing method and exposure time, treatment time was established as 10 min and washing procedure was set up as 4 times of washing with 10 mL of PBS and shaking in 30 mL of PBS in a beaker. With the established eye irritation test protocol, 11 solid substances (5 non-irritants, 6 irritants) were evaluated which demonstrated an excellent predictive capacity (100% accuracy, 100% specificity and 100% sensitivity). We also compared the performance of our test method with rabbit Draize test results and in vitro cytotoxicity test with 2D human corneal epithelial cell lines.

  7. Gut microbiota modulate T cell trafficking into human colorectal cancer.

    Science.gov (United States)

    Cremonesi, Eleonora; Governa, Valeria; Garzon, Jesus Francisco Glaus; Mele, Valentina; Amicarella, Francesca; Muraro, Manuele Giuseppe; Trella, Emanuele; Galati-Fournier, Virginie; Oertli, Daniel; Däster, Silvio Raffael; Droeser, Raoul A; Weixler, Benjamin; Bolli, Martin; Rosso, Raffaele; Nitsche, Ulrich; Khanna, Nina; Egli, Adrian; Keck, Simone; Slotta-Huspenina, Julia; Terracciano, Luigi M; Zajac, Paul; Spagnoli, Giulio Cesare; Eppenberger-Castori, Serenella; Janssen, Klaus-Peter; Borsig, Lubor; Iezzi, Giandomenica

    2018-02-06

    Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing. CRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival. Gut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. An update on the safety and efficacy of regorafenib in the treatment of solid cancers.

    Science.gov (United States)

    Chan, Stephen L; Ma, Brigette By

    2014-11-01

    Regorafenib is a multi-targeted kinase inhibitor that has been approved recently for the treatment of certain gastrointestinal (GI) cancers. This review examines the scientific evidence on the efficacy and safety of this agent in Phase I to III studies. A literature review was performed based on published studies from PubMed and abstracts from international conferences. Regorafenib has expanded the treatment options of patients with treatment-refractory gastrointestinal stromal tumor (GIST) and metastatic colorectal cancer (CRC). Ongoing studies are now investigating the activity of regorafenib as earlier line of therapy in CRC as monotherapy or in combination with chemotherapy. In the next 5 years, the activity of regorafenib will be further defined in other cancers such as renal cell cancer (RCC), hepato-biliary and upper GI cancers. In terms of safety, clinical trials suggest that the incidence and severity of toxicities may be higher in certain populations such as those with RCC or GIST. However, most of the common toxicities of regorafenib could be managed with dose modification without resorting to permanent drug discontinuation. Education of both patients and clinicians is thus important in minimizing treatment-related toxicities and improving drug compliance.

  9. Identification of differentially expressed microRNAs in human male breast cancer

    Directory of Open Access Journals (Sweden)

    Schipper Elisa

    2010-03-01

    Full Text Available Abstract Background The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases. Methods The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods. Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer. Results Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer. Conclusions Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.

  10. Oncogenic impact of human papilloma virus in head and neck cancer.

    LENUS (Irish Health Repository)

    Heffernan, C B

    2012-02-01

    There is considerable debate within the literature about the significance of human papilloma virus in head and neck squamous cell carcinoma, and its potential influence on the prevention, diagnosis, grading, treatment and prognosis of these cancers. Cigarette smoking and alcohol consumption have traditionally been cited as the main risk factors for head and neck cancers. However, human papilloma virus, normally associated with cervical and other genital carcinomas, has emerged as a possible key aetiological factor in head and neck squamous cell carcinoma, especially oropharyngeal cancers. These cancers pose a significant financial burden on health resources and are increasing in incidence. The recent introduction of vaccines targeted against human papilloma virus types 16 and 18, to prevent cervical cancer, has highlighted the need for ongoing research into the importance of human papilloma virus in head and neck squamous cell carcinoma.

  11. Preventing gastric sieving by blending a solid/water meal enhances satiation in healthy humans.

    Science.gov (United States)

    Marciani, Luca; Hall, Nicholas; Pritchard, Susan E; Cox, Eleanor F; Totman, John J; Lad, Mita; Hoad, Caroline L; Foster, Tim J; Gowland, Penny A; Spiller, Robin C

    2012-07-01

    Separation of solids and liquids within the stomach allows faster gastric emptying of liquids compared with solids, a phenomenon known as sieving. We tested the hypothesis that blending a solid and water meal would abolish sieving, preventing the early rapid decrease in gastric volume and thereby enhancing satiety. We carried out 2 separate studies. Study 1 was a 2-way, crossover, satiety study of 22 healthy volunteers who consumed roasted chicken and vegetables with a glass of water (1008 kJ) or the same blended to a soup. They completed satiety visual analogue scales at intervals for 3 h. Study 2 was a 2-way, crossover, mechanistic study of 18 volunteers who consumed the same meals and underwent an MRI to assess gastric emptying, gallbladder contraction, and small bowel water content (SBWC) at intervals for 3 h. In Study 1, the soup meal was associated with reduced hunger (P = 0.02). In Study 2, the volume of the gastric contents after the soup meal decreased more slowly than after the solid/liquid meal (P = 0.0003). The soup meal caused greater gallbladder contraction (P < 0.04). SBWC showed a biphasic response with an initial "gastric" phase during which SBWC was greater when the solid/liquid meal was consumed (P < 0.001) and a later "small bowel" phase when SBWC was greater when the soup meal was consumed (P < 0.01). Blending the solid/liquid meal to a soup delayed gastric emptying and increased the hormonal response to feeding, which may contribute to enhanced postprandial satiety.

  12. Glucocorticoid receptor beta increases migration of human bladder cancer cells.

    Science.gov (United States)

    McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D

    2016-05-10

    Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

  13. Laparoscopic optical coherence tomographic imaging of human ovarian cancer

    Science.gov (United States)

    Hariri, Lida P.; Bonnema, Garret T.; Schmidt, Kathy; Korde, Vrushali; Winkler, Amy M.; Hatch, Kenneth; Brewer, Molly; Barton, Jennifer K.

    2009-02-01

    Ovarian cancer is the fourth leading cause of cancer-related death among women. If diagnosed at early stages, 5-year survival rate is 94%, but drops to 68% for regional disease and 29% for distant metastasis; only 19% of cases are diagnosed at early, localized stages. Optical coherence tomography is a recently emerging non-destructive imaging technology, achieving high axial resolutions (10-20 µm) at imaging depths up to 2 mm. Previously, we studied OCT in normal and diseased human ovary ex vivo. Changes in collagen were suggested with several images that correlated with changes in collagen seen in malignancy. Areas of necrosis and blood vessels were also visualized using OCT, indicative of an underlying tissue abnormality. We recently developed a custom side-firing laparoscopic OCT (LOCT) probe fabricated for in vivo imaging. The LOCT probe, consisting of a 38 mm diameter handpiece terminated in a 280 mm long, 4.6 mm diameter tip for insertion into the laparoscopic trocar, is capable of obtaining up to 9.5 mm image lengths at 10 µm axial resolution. In this pilot study, we utilize the LOCT probe to image one or both ovaries of 17 patients undergoing laparotomy or transabdominal endoscopy and oophorectomy to determine if OCT is capable of differentiating normal and neoplastic ovary. We have laparoscopically imaged the ovaries of seventeen patients with no known complications. Initial data evaluation reveals qualitative distinguishability between the features of undiseased post-menopausal ovary and the cystic, non-homogenous appearance of neoplastic ovary such as serous cystadenoma and endometroid adenocarcinoma.

  14. Effects of hypoxia on human cancer cell line chemosensitivity

    Science.gov (United States)

    2013-01-01

    Background Environment inside even a small tumor is characterized by total (anoxia) or partial oxygen deprivation, (hypoxia). It has been shown that radiotherapy and some conventional chemotherapies may be less effective in hypoxia, and therefore it is important to investigate how different drugs act in different microenvironments. In this study we perform a large screening of the effects of 19 clinically used or experimental chemotherapeutic drugs on five different cell lines in conditions of normoxia, hypoxia and anoxia. Methods A panel of 19 commercially available drugs: 5-fluorouracil, acriflavine, bortezomib, cisplatin, digitoxin, digoxin, docetaxel, doxorubicin, etoposide, gemcitabine, irinotecan, melphalan, mitomycin c, rapamycin, sorafenib, thalidomide, tirapazamine, topotecan and vincristine were tested for cytotoxic activity on the cancer cell lines A2780 (ovarian), ACHN (renal), MCF-7 (breast), H69 (SCLC) and U-937 (lymphoma). Parallel aliquots of the cells were grown at different oxygen pressures and after 72 hours of drug exposure viability was measured with the fluorometric microculture cytotoxicity assay (FMCA). Results Sorafenib, irinotecan and docetaxel were in general more effective in an oxygenated environment, while cisplatin, mitomycin c and tirapazamine were more effective in a low oxygen environment. Surprisingly, hypoxia in H69 and MCF-7 cells mostly rendered higher drug sensitivity. In contrast ACHN appeared more sensitive to hypoxia, giving slower proliferating cells, and consequently, was more resistant to most drugs. Conclusions A panel of standard cytotoxic agents was tested against five different human cancer cell lines cultivated at normoxic, hypoxic and anoxic conditions. Results show that impaired chemosensitivity is not universal, in contrast different cell lines behave different and some drugs appear even less effective in normoxia than hypoxia. PMID:23829203

  15. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Xiufeng; Zhang, Ting; Wang, Jie; Li, Meng; Zhang, Xiaolei; Tu, Jing [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Sun, Shiqin [College of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319 (China); Chen, Xiangmei, E-mail: xm_chen6176@bjmu.edu.cn [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Lu, Fengmin [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China)

    2014-04-25

    Highlights: • The expression of Fbx4 was significantly lower in HCC tissues. • Novel splicing variants of Fbx4 were identified. • These novel variants are much more abundant in human cancer tissues and cells. • The novel Fbx4 isoforms could promote cell proliferation and migration in vitro. • These isoforms showed less capability for cyclin D1 binding and degradation. - Abstract: Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4α and the C-terminal truncated Fbx4β have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4γ (missing 168–245nt of exon1), Fbx4δ (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4β, Fbx4γ and Fbx4δ could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4α that mainly exists in cytoplasm, Fbx4β, Fbx4γ, and Fbx4δ locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant

  16. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer

    International Nuclear Information System (INIS)

    Chu, Xiufeng; Zhang, Ting; Wang, Jie; Li, Meng; Zhang, Xiaolei; Tu, Jing; Sun, Shiqin; Chen, Xiangmei; Lu, Fengmin

    2014-01-01

    Highlights: • The expression of Fbx4 was significantly lower in HCC tissues. • Novel splicing variants of Fbx4 were identified. • These novel variants are much more abundant in human cancer tissues and cells. • The novel Fbx4 isoforms could promote cell proliferation and migration in vitro. • These isoforms showed less capability for cyclin D1 binding and degradation. - Abstract: Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4α and the C-terminal truncated Fbx4β have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4γ (missing 168–245nt of exon1), Fbx4δ (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4β, Fbx4γ and Fbx4δ could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4α that mainly exists in cytoplasm, Fbx4β, Fbx4γ, and Fbx4δ locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant

  17. Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2002-04-01

    To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ({sup 18}F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes.

  18. Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

    International Nuclear Information System (INIS)

    Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul

    2002-01-01

    To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ( 18 F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes

  19. Tangeretin sensitises human lung cancer cells to TRAIL- induced ...

    African Journals Online (AJOL)

    Keywords: Apoptosis, Death receptors, Lung cancer, Tangeretin, Reactive oxygen ... strategies that specifically target molecules .... concentrations were determined using a Bio-Rad ..... suppresses invasion of colon and pancreatic cancer.

  20. Molecular Analyses Reveal Inflammatory Mediators in the Solid Component and Cyst Fluid of Human Adamantinomatous Craniopharyngioma.

    Science.gov (United States)

    Donson, Andrew M; Apps, John; Griesinger, Andrea M; Amani, Vladimir; Witt, Davis A; Anderson, Richard C E; Niazi, Toba N; Grant, Gerald; Souweidane, Mark; Johnston, James M; Jackson, Eric M; Kleinschmidt-DeMasters, Bette K; Handler, Michael H; Tan, Aik-Choon; Gore, Lia; Virasami, Alex; Gonzalez-Meljem, Jose Mario; Jacques, Thomas S; Martinez-Barbera, Juan Pedro; Foreman, Nicholas K; Hankinson, Todd C

    2017-09-01

    Pediatric adamantinomatous craniopharyngioma (ACP) is a highly solid and cystic tumor, often causing substantial damage to critical neuroendocrine structures such as the hypothalamus, pituitary gland, and optic apparatus. Paracrine signaling mechanisms driving tumor behavior have been hypothesized, with IL-6R overexpression identified as a potential therapeutic target. To identify potential novel therapies, we characterized inflammatory and immunomodulatory factors in ACP cyst fluid and solid tumor components. Cytometric bead analysis revealed a highly pro-inflammatory cytokine pattern in fluid from ACP compared to fluids from another cystic pediatric brain tumor, pilocytic astrocytoma. Cytokines and chemokines with particularly elevated concentrations in ACPs were IL-6, CXCL1 (GRO), CXCL8 (IL-8) and the immunosuppressive cytokine IL-10. These data were concordant with solid tumor compartment transcriptomic data from a larger cohort of ACPs, other pediatric brain tumors and normal brain. The majority of receptors for these cytokines and chemokines were also over-expressed in ACPs. In addition to IL-10, the established immunosuppressive factor IDO-1 was overexpressed by ACPs at the mRNA and protein levels. These data indicate that ACP cyst fluids and solid tumor components are characterized by an inflammatory cytokine and chemokine expression pattern. Further study regarding selective cytokine blockade may inform novel therapeutic interventions. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  1. Solid waste

    International Nuclear Information System (INIS)

    1995-01-01

    The article drawn up within the framework of 'the assessment of the state of the environment in Lebanon' provides an overview of solid waste management, and assesses future wastes volume and waste disposal issues.In particular it addresses the following concerns: - Long term projections of solid waste arisings (i.e. domestic, industrial, such commercial wastes, vehicle types, construction waste, waste oils, hazardous toxic wastes and finally hospital and clinical wastes) are described. - Appropriate disposal routes, and strategies for reducing volumes for final disposal - Balance between municipal and industrial solid waste generation and disposal/treatment and - environmental impacts (aesthetics, human health, natural environment )of existing dumps, and the potential impact of government plans for construction of solid waste facilities). Possible policies for institutional reform within the waste management sector are proposed. Tables provides estimations of generation rates and distribution of wastes in different regions of Lebanon. Laws related to solid waste management are summarized

  2. Performance comparison of digital microRNA profiling technologies applied on human breast cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Erik Knutsen

    Full Text Available MicroRNA profiling represents an important first-step in deducting individual RNA-based regulatory function in a cell, tissue, or at a specific developmental stage. Currently there are several different platforms to choose from in order to make the initial miRNA profiles. In this study we investigate recently developed digital microRNA high-throughput technologies. Four different platforms were compared including next generation SOLiD ligation sequencing and Illumina HiSeq sequencing, hybridization-based NanoString nCounter, and miRCURY locked nucleic acid RT-qPCR. For all four technologies, full microRNA profiles were generated from human cell lines that represent noninvasive and invasive tumorigenic breast cancer. This study reports the correlation between platforms, as well as a more extensive analysis of the accuracy and sensitivity of data generated when using different platforms and important consideration when verifying results by the use of additional technologies. We found all the platforms to be highly capable for microRNA analysis. Furthermore, the two NGS platforms and RT-qPCR all have equally high sensitivity, and the fold change accuracy is independent of individual miRNA concentration for NGS and RT-qPCR. Based on these findings we propose new guidelines and considerations when performing microRNA profiling.

  3. Human breast cancer histoid: an in vitro 3-dimensional co-culture model that mimics breast cancer tissue.

    Science.gov (United States)

    Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R; Ingram, Marylou; Imam, S Ashraf

    2011-12-01

    Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue.

  4. Trace elements determinations in cancerous and non-cancerous human tissues using instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Choi, Insup.

    1989-01-01

    Recent improvements in analyzing techniques when coupled to the growing knowledge of trace element biochemistry provide a powerful tool to investigate the relationship between trace elements and cancer. It is hoped that selective delivery or restriction of specific minerals may aid in cancer prevention or treatment. Tissues were collected at the time of surgery of various cancer patients including colon cancer and breast cancer. Three kinds of tissues were taken from a patient; cancerous, noncancerous, and transitional tissue obtained from a region located between the cancer and healthy tissues. A total of 57 tissues were obtained from 19 cancer patients. Seven of them were colon cancer patients, and 5 of them were breast cancer patients. Nine elements were determined using instrumental activation analysis. Cancerous colon tissue had significantly higher concentrations of selenium and iron than healthy tissues. Cancerous breast tissue had significantly higher concentrations of selenium, iron, manganese, and rubidium than healthy tissues. Iron can be enriched in cancer tissue because cancer tissue retains more blood vessels. Selenium is enriched in cancer tissue, possibly in an effort of the body to inhibit the growth of tumors. The manganese enrichment can be explained in the same manner as selenium considering its suspected anticarcinogenicity. It is not certain why rubidium was enriched in cancer tissue. It could be that this is the result of alteration of cell membrane permeability, change in extracellular matrix, or increased metabolism in cancer tissue

  5. Human papilloma virus infection in head and neck cancer.

    Science.gov (United States)

    Tribius, Silke; Hoffmann, Markus

    2013-03-01

    The causal link between cervical cancer and human papilloma virus (HPV) is well known. It is now becoming clear that some types of squamous-cell carcinoma of the head and neck, particularly oropharyngeal carcinoma (OPC), are also linked to HPV infection. The development of vaccines against certain HPV genotypes has changed the management strategy for HPV-associated diseases of the uterine cervix. An analogous approach is now being considered for the prevention of HPV-associated diseases of the head and neck. We review pertinent articles retrieved by a selective search of the literature for phase II and III trials providing evidence about a possible effect of HPV status on the survival rates of patients with OPC. Seven trials fulfilled our search criteria: four phase III trials with retrospective HPV analysis and three phase II trials with retrospective and prospective HPV analysis. Patients with HPV-positive OPC survive significantly longer than those with HPV-negative OPC. Tobacco smoking has been identified as a negative prognostic factor in patients with either HPV-negative or HPV-positive disease. The established treatment strategy for OPC in patients with and without the traditional risk factors (tobacco and alcohol consumption) is now being reconsidered in the light of what we have learned about the role of HPV infection. Ongoing and projected clinical trials with risk-factor stratification may soon lead to changes in treatment. Further study is needed to answer the question whether HPV infection in the head and neck region is carcinogenic.

  6. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...... staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined...

  7. Glycerol restores the p53 function in human lingual cancer cells bearing mutant p53

    International Nuclear Information System (INIS)

    Ota, Ichiro; Yane, Katsunari; Yuki, Kazue; Kanata, Hirokazu; Hosoi, Hiroshi; Miyahara, Hiroshi

    2001-01-01

    Mutations in p53, tumor suppressor gene, have recently been shown to have an impact on the clinical course of several human tumors, including head and neck cancers. The genetic status of the p53 gene has been focused on as the most important candidate among various cancer-related genes for prognosis-predictive assays of cancer therapy. We examined the restoration of radiation- or cisplatin (CDDP)-induced p53-dependent apoptosis in human lingual cancer cells. The results suggest that glycerol is effective in inducing a conformational change of p53 and restoring normal function of mutant p53, leading to enhanced radiosensitivity or chemosensitivity through the induction of apoptosis. We have also represented the same results in vivo as in vitro. Thus, this novel tool for enhancement of radiosensitivity or chemosensitivity in cancer cells bearing m p53 may be applicable for p53-targeted cancer therapy. (author)

  8. Some aspects of cancer biomarkers and their clinical application in solid tumors – revisited

    Directory of Open Access Journals (Sweden)

    Isaac D

    2017-07-01

    Full Text Available Cancer biomarkers can be used for a variety of purposes related to screening, prediction, stratification, detection, diagnosis, prognosis, treatment design, and monitoring of a therapeutic response. One of the most important characteristics of a given biomarker includes ease of collection allowing for a non-invasive approach and frequent sampling. Such samples may be obtained from serum or plasma, sputum, bronchoalveolar lavage, saliva, nipple discharge, pleural, or peritoneal effusions. Validation of different biomarkers is considered a mandatory method for useful evaluation. In this review, we highlight the clinical applicability of some cancer biomarkers, as well as future approaches for their development and collection, which may help guide clinicians and researchers. The role of liquid biopsies will also be summarized. Further studies using liquid biopsies are needed to elucidate the significance of various sources of biomarkers suitable for clinical application.

  9. Radiation exposure due to local fallout from Soviet atmospheric nuclear weapons testing in Kazakhstan: solid cancer mortality in the Semipalatinsk historical cohort, 1960-1999.

    Science.gov (United States)

    Bauer, Susanne; Gusev, Boris I; Pivina, Ludmila M; Apsalikov, Kazbek N; Grosche, Bernd

    2005-10-01

    Little information is available on the health effects of exposures to fallout from Soviet nuclear weapons testing and on the combined external and internal environmental exposures that have resulted from these tests. This paper reports the first analysis of the Semipalatinsk historical cohort exposed in the vicinity of the Semipalatinsk nuclear test site, Kazakhstan. The cohort study, which includes 19,545 inhabitants of exposed and comparison villages of the Semipalatinsk region, was set up in the 1960s and comprises 582,750 person-years of follow-up between 1960 and 1999. Cumulative effective radiation dose estimates in this cohort range from 20 mSv to approximately 4 Sv. Rates of mortality and cancer mortality in the exposed group substantially exceeded those of the comparison group. Dose-response analyses within the exposed group confirmed a significant trend with dose for all solid cancers (P sites, a significant trend with dose was observed for lung cancer (P = 0.0001), stomach cancer (P = 0.0050), and female breast cancer (P = 0.0040) as well as for esophagus cancer in women (P = 0.0030). The excess relative risk per sievert for all solid cancers combined was 1.77 (1.35; 2.27) based on the total cohort data, yet a selection bias regarding the comparison group could not be entirely ruled out. The excess relative risk per sievert based on the cohort's exposed group was 0.81 (0.46; 1.33) for all solid cancers combined and thus still exceeds current risk estimates from the Life Span Study. Future epidemiological assessments based on this cohort will benefit from extension of follow-up and ongoing validation of dosimetric data.

  10. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jin Boo [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States); Lee, Seong-Ho, E-mail: slee2000@umd.edu [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. Black-Right-Pointing-Pointer PCA enhanced transcriptional downregulation of cyclin D1 gene. Black-Right-Pointing-Pointer PCA suppressed HDAC2 expression and activity. Black-Right-Pointing-Pointer These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

  11. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    International Nuclear Information System (INIS)

    Jeong, Jin Boo; Lee, Seong-Ho

    2013-01-01

    Highlights: ► Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. ► PCA enhanced transcriptional downregulation of cyclin D1 gene. ► PCA suppressed HDAC2 expression and activity. ► These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

  12. Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer

    International Nuclear Information System (INIS)

    Lee, Kiwon; Liu, Yin; Mo, Jun Qin; Zhang, Jinsong; Dong, Zhongyun; Lu, Shan

    2008-01-01

    Our previous study revealed that Vav3 oncogene is overexpressed in human prostate cancer, activates androgen receptor, and stimulates growth in prostate cancer cells. The current study is to determine a potential role of Vav3 oncogene in human breast cancer and impact on estrogen receptor a (ERα)-mediated signaling axis. Immunohistochemistry analysis was performed in 43 breast cancer specimens and western blot analysis was used for human breast cancer cell lines to determine the expression level of Vav3 protein. The impact of Vav3 on breast cancer cell growth was determined by siRNA knockdown of Vav3 expression. The role of Vav3 in ERα activation was examined in luciferase reporter assays. Deletion mutation analysis of Vav3 protein was performed to localize the functional domain involved in ERα activation. Finally, the interaction of Vav3 and ERα was assessed by GST pull-down analysis. We found that Vav3 was overexpressed in 81% of human breast cancer specimens, particularly in poorly differentiated lesions. Vav3 activated ERα partially via PI3K-Akt signaling and stimulated growth of breast cancer cells. Vav3 also potentiated EGF activity for cell growth and ERα activation in breast cancer cells. More interestingly, we found that Vav3 complexed with ERα. Consistent with its function for AR, the DH domain of Vav3 was essential for ERα activation. Vav3 oncogene is overexpressed in human breast cancer. Vav3 complexes with ERα and enhances ERα activity. These findings suggest that Vav3 overexpression may aberrantly enhance ERα-mediated signaling axis and play a role in breast cancer development and/or progression

  13. Interaction enthalpies of solid human serum albumin with water-dioxane mixtures: comparison with water and organic solvent vapor sorption

    International Nuclear Information System (INIS)

    Sirotkin, Vladimir A.; Faizullin, Djihanguir A.

    2004-01-01

    Enthalpy changes (ΔH tot ) on the immersion of dehydrated human serum albumin (HSA) into water-dioxane mixtures have been measured using a Setaram BT-2.15 calorimeter at 298 K. Thermodynamic activity of water was varied from 0 to 1. Calorimetric results are discussed together with the FTIR-spectroscopic data on water and organic solvent vapor adsorption/desorption isotherms on solid HSA. Dioxane sorption exhibits a pronounced hysteresis. Calorimetric and dioxane desorption dependencies consist of two parts. No dioxane sorption was observed in low water activity region (a w tot values are close to zero. At water activity about 0.5 the sharp exothermic drop of the interaction enthalpy values was observed. This exothermic drop is accompanied by the sharp increase in the amount of sorbed dioxane and additional water sorption (compared with that for pure water). Dioxane adsorption branch resembles a smooth curve. In this case, solid HSA binds more than 300 mol dioxane/mol HSA at low water activities. By using a water activity-based comparison we distinguished between dioxane-assisted and dioxane-competitive effect on water sorption. The obtained results demonstrate that the hydration 'history' of solid protein is an important factor that controls as the state of protein macromolecule as well as the sorption of low-molecular organic molecules

  14. The human papillomavirus vaccine: A powerful tool for the primary prevention of cervical cancer.

    OpenAIRE

    Nubia Muñoz; Julio César Reina; Gloria Inés Sánchez

    2009-01-01

    Prophylactic human papillomavirus (HPV) vaccine is the most promissory public health tool for primary prevention of cervical cancer. Immunization of females before the acquisition of HPV infection has the greatest impact in preventing pre-neoplasic lesions and cervical cancer. Current HPV vaccines do not eliminate cervical cancer risk, therefore, screening should continue covering vaccinated as well as women that do not get the vaccine. The strategies that include combination of high-coverage...

  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. Somatic mutations of the histone H3K27 demethylase, UTX, in human cancer

    Science.gov (United States)

    van Haaften, Gijs; Dalgliesh, Gillian L; Davies, Helen; Chen, Lina; Bignell, Graham; Greenman, Chris; Edkins, Sarah; Hardy, Claire; O’Meara, Sarah; Teague, Jon; Butler, Adam; Hinton, Jonathan; Latimer, Calli; Andrews, Jenny; Barthorpe, Syd; Beare, Dave; Buck, Gemma; Campbell, Peter J; Cole, Jennifer; Dunmore, Rebecca; Forbes, Simon; Jia, Mingming; Jones, David; Kok, Chai Yin; Leroy, Catherine; Lin, Meng-Lay; McBride, David J; Maddison, Mark; Maquire, Simon; McLay, Kirsten; Menzies, Andrew; Mironenko, Tatiana; Lee, Mulderrig; Mudie, Laura; Pleasance, Erin; Shepherd, Rebecca; Smith, Raffaella; Stebbings, Lucy; Stephens, Philip; Tang, Gurpreet; Tarpey, Patrick S; Turner, Rachel; Turrell, Kelly; Varian, Jennifer; West, Sofie; Widaa, Sara; Wray, Paul; Collins, V Peter; Ichimura, Koichi; Law, Simon; Wong, John; Yuen, Siu Tsan; Leung, Suet Yi; Tonon, Giovanni; DePinho, Ronald A; Tai, Yu-Tzu; Anderson, Kenneth C; Kahnoski, Richard J.; Massie, Aaron; Khoo, Sok Kean; Teh, Bin Tean; Stratton, Michael R; Futreal, P Andrew

    2010-01-01

    Somatically acquired epigenetic changes are present in many cancers. Epigenetic regulation is maintained via post-translational modifications of core histones. Here, we describe inactivating somatic mutations in the histone lysine demethylase, UTX, pointing to histone H3 lysine methylation deregulation in multiple tumour types. UTX reintroduction into cancer cells with inactivating UTX mutations resulted in slowing of proliferation and marked transcriptional changes. These data identify UTX as a new human cancer gene. PMID:19330029

  17. Effect of New Water-Soluble Dendritic Phthalocyanines on Human Colorectal and Liver Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Ebru YABAŞ

    2017-08-01

    Full Text Available Human hepatocellular carcinoma (HepG2 cells and colorectal adenocarcinoma (DLD-1 cells were treated with the synthesized water soluble phthalocyanine derivatives to understand the effect of the compounds both on colorectal and liver cancer cells. The compounds inhibited cell proliferation and displayed cytotoxic effect on these cancer cell lines however; the effect of the compounds on healthy control fibroblast cell line was comparatively lower. The compounds can be employed for cancer treatment as anticancer agents.

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

    OpenAIRE

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

    2016-01-01

    Background The incidence and mortality of kidney cancer have steadily increased by 2%- 3% per decade worldwide, and an increased risk of kidney cancer has been observed in many Asian countries. The information on the incidence and mortality of a disease and its distribution is essential for better planning for prevention and further studies. Objectives This study aimed to assess the incidence and mortality of kidney cancer and their correlation with the human development index (HDI) in Asia. ...

  19. Controversies surrounding Human Papilloma Virus infection, head & neck vs oral cancer, implications for prophylaxis and treatment

    OpenAIRE

    Campisi, G.; Giovannelli, L.

    2009-01-01

    Head & Neck Cancer (HNC) represents the sixth most common malignancy worldwide and it is historically linked to well-known behavioural risk factors, i.e., tobacco smoking and/or the alcohol consumption. Recently, substantial evidence has been mounting that Human Papillomavirus (HPV) infection is playing an increasing important role in oral cancer. Because of the attention and clamor surrounding oral HPV infection and related cancers, as well as the use of HPV prophylactic vaccines, in this in...

  20. Human papilloma virus: a new risk factor in a subset of head and neck cancers.

    Science.gov (United States)

    Bisht, Manisha; Bist, Sampan Singh

    2011-01-01

    Head and neck cancer is the sixth most common malignancy worldwide. Tobacco smoking and alcohol consumption are two well known behavioral risk factors associated with head and neck cancer. Recently, evidence is mounting that infection with human papilloma virus, most commonly human papilloma virus-16 is responsible for a subset of head and neck squamous cell carcinoma especially tumors of tonsillar origin. The molecular pathway used by human papilloma virus to trigger malignant transformation of tissue is different from that of other well known risk factors, i.e. smoking and alcohol, associated with squamous cell carcinoma. Apparently, these subsets of patients with human papilloma virus positive tumor are more likely to have a better prognosis than human papilloma virus negative tumor. Considering this fact, the human papilloma virus infection should be determined in all oropharyngeal cancers since it can have a major impact on the decision making process of the treatment.

  1. Human Monoclonal antibodies - A dual advantaged weapon to tackle cancer and viruses

    Directory of Open Access Journals (Sweden)

    Kurosawa G

    2014-11-01

    Full Text Available Human monoclonal antibodies (mAbs are powerful tools as pharmaceutical agents to tackle cancer and infectious diseases. Antibodies (Abs are present in blood at the concentration of 10 mg/ml and play a vital role in humoral immunity. Many therapeutic Abs have been reported since early 1980s. Human mAb technology was not available at that time and only the hybridoma technology for making mouse mAbs had been well established. In order to avoid various potential problems associated with use of mouse proteins, two different technologies to make human/mouse chimeric Ab as well as humanized Ab were developed crossing the various hurdles for almost twenty years and mAb based drugs such as rituximab, anti-CD20 Ab, and trastuzumab, anti-HER2 Ab, have been approved by the US Food and Drug Administration (FDA for treatment of non-Hodgkin's lymphoma and breast cancer in 1997 and 1998, respectively. These drugs are well recognized and accepted by clinicians for treatment of patients. The clinical outcome of the treatment with mAb has strongly encouraged the researchers to develop much more refined mAbs. In addition to chimeric Ab and humanized Ab, now human mAbs can be produced by two technologies. The first is transgenic mice that produce human Abs and the second is human Ab libraries using phage-display system. Until now, several hundreds of mAbs against several tens of antigens (Ags have been developed and subjected to clinical examinations. While many Abs have been approved as therapeutic agents against hematological malignancies, the successful mAbs against solid tumors are still limited. However, many researchers have suggested that developing potential mAbs agents should be possible and incurable cancers may become curable within another decade. Though it is hard to say explicitly that this prediction is correct, a passion for this development should be worth supporting to lead to a successful outcome which will lead to patient benefits. Our institute

  2. ¹H NMR-based metabolic profiling of human rectal cancer tissue

    Science.gov (United States)

    2013-01-01

    Background Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Methods Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer. Results Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would

  3. Clinical solid waste management practices and its impact on human health and environment - A review

    International Nuclear Information System (INIS)

    Hossain, Md. Sohrab; Santhanam, Amutha; Nik Norulaini, N.A.; Omar, A.K. Mohd

    2011-01-01

    Research highlights: → Appropriate waste management technology for safe handling and disposal of clinical solid waste. → Infectious risk assessment on unsafe handling of clinical solid waste. → Recycling-reuse program of clinical solid waste materials. → Effective sterilization technology to reduce exposure of infectious risk. - Abstract: The management of clinical solid waste (CSW) continues to be a major challenge, particularly, in most healthcare facilities of the developing world. Poor conduct and inappropriate disposal methods exercised during handling and disposal of CSW is increasing significant health hazards and environmental pollution due to the infectious nature of the waste. This article summarises a literature review into existing CSW management practices in the healthcare centers. The information gathered in this paper has been derived from the desk study of open literature survey. Numerous researches have been conducted on the management of CSW. Although, significant steps have been taken on matters related to safe handling and disposal of the clinical waste, but improper management practice is evident from the point of initial collection to the final disposal. In most cases, the main reasons of the mismanagement of CSW are the lack of appropriate legislation, lack of specialized clinical staffs, lack of awareness and effective control. Furthermore, most of the healthcare centers of the developing world have faced financial difficulties and therefore looking for cost effective disposal methods of clinical waste. This paper emphasizes to continue the recycle-reuse program of CSW materials after sterilization by using supercritical fluid carbon dioxide (SF-CO2) sterilization technology at the point of initial collection. Emphasis is on the priority to inactivate the infectious micro-organisms in CSW. In that case, waste would not pose any threat to healthcare workers. The recycling-reuse program would be carried out successfully with the non

  4. CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer.

    NARCIS (Netherlands)

    Guo, Z.; Linn, J.F.; Wu, G.; Anzick, S.L.; Eisenberger, C.F.; Halachmi, S.; Cohen, Y.; Fomenkov, A.; Hoque, M.O.; Okami, K.; Steiner, G.; Engles, J.M.; Osada, M.; Moon, C.; Ratovitski, E.; Trent, J.M.; Meltzer, P.S.; Westra, W.H.; Kiemeney, L.A.L.M.; Schoenberg, M.P.; Sidransky, D.; Trink, B.

    2004-01-01

    Genomic amplification at 20q11-13 is a common event in human cancers. We isolated a germline translocation breakpoint at 20q11 from a bladder cancer patient. We identified CDC91L1, the gene encoding CDC91L1 (also called phosphatidylinositol glycan class U (PIG-U), a transamidase complex unit in the

  5. Physical status of multiple human papillomavirus genotypes in flow-sorted cervical cancer cells

    NARCIS (Netherlands)

    Vermeulen, Christine F. W.; Jordanova, Ekaterina S.; Szuhai, Karoly; Kolkman-Uljee, Sandra; Vrede, M. Albert; Peters, Alexander A. W.; Schtturing, Ed; Fleuren, Gert Jan

    Multiple human papilloma virus (HPV) infections have been detected in cervical cancer. To investigate the significance of multiple HPV infections, we studied their prevalence in cancer samples from a low-risk (Dutch) and a high-risk (Surinamese) population and the correlation of HPV infection with

  6. In vitro cytotoxicity of Indonesian stingless bee products against human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Paula M. Kustiawan

    2014-07-01

    Conclusions: Propolis from T. incisa and Trigona fusco-balteata contain an in vitro cytotoxic activity against human cancer cell lines. Further study is required, including the isolation and characterization of the active antiproliferative agent(s.

  7. A Role for the NF-kb/Rel Transcription Factors in Human Breast Cancer

    National Research Council Canada - National Science Library

    Baldwin, Albert

    1998-01-01

    Human breast cancer is characterized by the inappropriate expression of growth factors, kinases and possibly certain transcription factors Our project has focused on the regulation of the NF-kB family...

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

    International Nuclear Information System (INIS)

    Riaz, Muhammad; Elstrodt, Fons; Hollestelle, Antoinette; Dehghan, Abbas; Klijn, Jan GM; Schutte, Mieke

    2009-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Claudio Pulito

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

  11. Frequency Distribution of Second Solid Cancer Locations in Relation to the Irradiated Volume Among 115 Patients Treated for Childhood Cancer

    International Nuclear Information System (INIS)

    Diallo, Ibrahima; Haddy, Nadia; Adjadj, Elisabeth; Samand, Akhtar; Quiniou, Eric; Chavaudra, Jean; Alziar, Iannis; Perret, Nathalie; Guerin, Sylvie; Lefkopoulos, Dimitri; Vathaire, Florent de

    2009-01-01

    Purpose: To provide better estimates of the frequency distribution of second malignant neoplasm (SMN) sites in relation to previous irradiated volumes, and better estimates of the doses delivered to these sites during radiotherapy (RT) of the first malignant neoplasm (FMN). Methods and Materials: The study focused on 115 patients who developed a solid SMN among a cohort of 4581 individuals. The homemade software package Dos E G was used to estimate the radiation doses delivered to SMN sites during RT of the FMN. Three-dimensional geometry was used to evaluate the distances between the irradiated volume, for RT delivered to each FMN, and the site of the subsequent SMN. Results: The spatial distribution of SMN relative to the irradiated volumes in our cohort was as follows: 12% in the central area of the irradiated volume, which corresponds to the planning target volume (PTV), 66% in the beam-bordering region (i.e., the area surrounding the PTV), and 22% in regions located more than 5 cm from the irradiated volume. At the SMN site, all dose levels ranging from almost zero to >75 Gy were represented. A peak SMN frequency of approximately 31% was identified in volumes that received <2.5 Gy. Conclusion: A greater volume of tissues receives low or intermediate doses in regions bordering the irradiated volume with modern multiple-beam RT arrangements. These results should be considered for risk-benefit evaluations of RT.

  12. Cytotoxic activity of kenaf (Hibiscus cannabinus L.) seed extract and oil against human cancer cell lines

    Science.gov (United States)

    Wong, Yu Hua; Tan, Wai Yan; Tan, Chin Ping; Long, Kamariah; Nyam, Kar Lin

    2014-01-01

    Objective To examine the cytotoxic properties of both the kenaf (Hibiscus cannabinus L.) seed extract and kenaf seed oil on human cervical cancer, human breast cancer, human colon cancer and human lung cancer cell lines. Methods The in vitro cytotoxic activity of the kenaf (Hibiscus cannabinus L.) seed extract and kenaf seed oil on human cancer cell lines was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and sulforhodamine B assays. Cell morphological changes were observed by using an inverted light microscope. Results The kenaf seed extract (KSE) exhibited a lower IC50 than kenaf seed oil (KSO) in all of the cancer cell lines. Morphological alterations in the cell lines after KSE and KSO treatment were observed. KSE and KSO possessed effective cytotoxic activities against all the cell lines been selected. Conclusions KSE and KSO could be potential sources of natural anti-cancer agents. Further investigations on using kenaf seeds for anti-proliferative properties are warranted. PMID:25183141

  13. History of human papillomavirus, warts and cancer: what do we know today?

    Science.gov (United States)

    Onon, Toli S

    2011-10-01

    Human papillomavirus has been a cause of infection in humans for thousands of years. The history of papillomaviruses, knowledge of their causative role in benign and malignant disease, and their structural characteristics have led to the development of vaccines to prevent cervical and anogenital cancers. Many questions remain unanswered before HPV vaccines can be optimised; however, the concept of virtual eradication of cervical cancer is not impossible, and remains a realistic aspiration. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. The Human L1 Element Causes DNA Double-Strand Breaks in Breast Cancer

    Science.gov (United States)

    2006-08-01

    cancer is complex. However, defects in DNA repair genes in the double-strand break repair pathway are cancer predisposing. My lab has characterized...a new potentially important source of double-strand breaks (DSBs) in human cells and are interested in characterizing which DNA repair genes act on...this particular source of DNA damage. Selfish DNA accounts for 45% of the human genome. We have recently demonstrated that one particular selfish

  15. Molecular Modulation of Inhibitors of Apoptosis as a Novel Approach for Radiosensitization of Human Prostate Cancer

    Science.gov (United States)

    2008-11-01

    in multiple myeloma cells is associated with a cleavage of Mcl-1 and Bim and a decrease in the Mcl-1/Bim...improved tumor control by radiotherapy in vivo [66], advocating a distinct role for XIAP in radiation resistant phenotype of human cancers, and...about the role of endogenous Smac in cells treated with Smac- mimetic IAP-inhibitors and irradiation. In multiple human cancer models,

  16. Role of Notch Signaling in Human Breast Cancer Pathogenesis

    Science.gov (United States)

    2006-11-01

    transform HMLE cells. Similarly, overexpression of ErbB2, a receptor tyrosine kinase upstream of Ras normally found overexpressed in many breast cancers ...Assess Notch-Ras cooperation in breast cancers in vivo: Since the major observation in this project has been the cooperation of Notch and Ras in HMLE ...metastasis. The in vitro cooperation between Notch and Ras in HMLE cells is mimicked in naturally arising breast cancers in vivo. Further dissection of the

  17. Ceramide species are elevated in human breast cancer and are associated with less aggressiveness

    Science.gov (United States)

    Moro, Kazuki; Kawaguchi, Tsutomu; Tsuchida, Junko; Gabriel, Emmanuel; Qi, Qianya; Yan, Li; Wakai, Toshifumi; Takabe, Kazuaki; Nagahashi, Masayuki

    2018-01-01

    Sphingolipids have emerged as key regulatory molecules in cancer cell survival and death. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients are yet to be revealed. The aim of this study was to investigate the ceramide levels and its biosynthesis pathways in human breast cancer patients. Breast cancer, peri-tumor and normal breast tissue samples were collected from surgical specimens from a series of 44 patients with breast cancer. The amount of sphingolipid metabolites in the tissue were determined by mass spectrometry. The Cancer Genome Atlas was used to analyze gene expression related to the sphingolipid metabolism. Ceramide levels were higher in breast cancer tissue compared to both normal and peri-tumor breast tissue. Substrates and enzymes that generate ceramide were significantly increased in all three ceramide biosynthesis pathways in cancer. Further, higher levels of ceramide in breast cancer were associated with less aggressive cancer biology presented by Ki-67 index and nuclear grade of the cancer. Interestingly, patients with higher gene expressions of enzymes in the three major ceramide synthesis pathways showed significantly worse prognosis. This is the first study to reveal the clinical relevance of ceramide metabolism in breast cancer patients. We demonstrated that ceramide levels in breast cancer tissue were significantly higher than those in normal tissue, with activation of the three ceramide biosynthesis pathways. We also identified that ceramide levels have a significant association with aggressive phenotype and its enzymes have prognostic impact on breast cancer patients. PMID:29731990

  18. E3B1/ABI-1 Isoforms Are Down-Regulated in Cancers of Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Rafia A. Baba

    2012-01-01

    Full Text Available The expression of E3B1/ABI-1 protein and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors. In this study, we examined the expression pattern of E3B1/ABI-1 protein in histologically confirmed cases of esophageal (squamous cell carcinoma and adenocarcinoma, gastro-esophageal junction, colorectal cancers and corresponding normal tissues freshly resected from a cohort of 135 patients, by Western Blotting and Immunofluorescence Staining. The protein is present in its phosphorylated form in cells and tissues. Depending on the extent of phosphorylation it is either present in hyper-phosphorylated (M. Wt. 72 kDa form or in hypo-phosphorylated form (M. Wt. 68 kDa and 65 kDa. A thorough analysis revealed that expression of E3B1/ABI-1 protein is significantly decreased in esophageal, gastro-esophageal junction and colorectal carcinomas irrespective of age, gender, dietary and smoking habits of the patients. The decrease in expression of E3B1/ABI-1 was consistently observed for all the three isoforms. However, the decrease in the expression of isoforms varied with different forms of cancers. Down-regulation of E3B1/ABI-1 expression in human carcinomas may play a critical role in tumor progression and in determining disease prognosis.

  19. Anti-Inflammatory Agent Indomethacin Reduces Invasion and Alters Metabolism in a Human Breast Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Ellen Ackerstaff

    2007-03-01

    Full Text Available Hostile physiological environments such as hypoxia and acidic extracellular pH, which exist in solid tumors, may promote invasion and metastasis through inflammatory responses and formation of eicosanoids. Here, we have investigated the effects of the antiinflammatory agent indomethacin on the invasion and metabolism of the human breast cancer cell line MDAMB-435 in Dulbecco's Modified Eagles (DME-based or Roswell Park Memorial Institute (RPMI-based cell medium, using a magnetic resonance-compatible invasion assay. Indomethacin treatment significantly reduced the invasion of MDA-MB-435 cells independent of the culture and perfusion conditions examined. Significant changes were detected in levels of intracellular choline phospholipid metabolites and in triglyceride (TG concentrations of these cells, depending on indomethacin treatment and basal cell medium used. Additionally, genetic profiling of breast cancer cells, grown and treated with low-dose indomethacin in cell culture using an RPMI-based medium, revealed the upregulation of several genes implicating cyclooxygenaseindependent targets of indomethacin. These data confirm the ability of an anti-inflammatory agent to reduce breast cancer invasion and demonstrate, depending on cell culture and perfusion conditions, that the indomethacin-induced decrease in invasion is associated with changes in choline phospholipid metabolism, TG metabolism, and gene expression.

  20. An Embryonic Growth Pathway is Reactivated in Human Prostate Cancer

    National Research Council Canada - National Science Library

    Bushman, Wade

    2005-01-01

    .... This research postulates that prostate cancer cells commandeer this normal epithelial-mesenchymal signaling pathway to recruit stromal cells to support abnormal tumor growth and tests the hypothesis...

  1. An Embryonic Growth Pathway is Reactivated in Human Prostate Cancer

    National Research Council Canada - National Science Library

    Bushman, Wade

    2003-01-01

    .... This research postulates that prostate cancer cells commandeer this normal epithelial-mesenchymal signaling pathway to recruit stromal cells to support abnormal tumor growth and tests the hypothesis...

  2. Autofluorescence Imaging and Spectroscopy of Human Lung Cancer

    Directory of Open Access Journals (Sweden)

    Mengyan Wang

    2016-12-01

    Full Text Available Lung cancer is one of the most common cancers, with high mortality rate worldwide. Autofluorescence imaging and spectroscopy is a non-invasive, label-free, real-time technique for cancer detection. In this study, lung tissue sections excised from patients were detected by laser scan confocal microscopy and spectroscopy. The autofluorescence images demonstrated the cellular morphology and tissue structure, as well as the pathology of stained images. Based on the spectra study, it was found that the majority of the patients showed discriminating fluorescence in tumor tissues from normal tissues. Therefore, autofluorescence imaging and spectroscopy may be a potential method for aiding the diagnosis of lung cancer.

  3. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...

  4. /sup 99m/Tc-labeled solid-phase meal: a quantitative clinical measurement of human gastric emptying

    International Nuclear Information System (INIS)

    Martin, J.L.; Beck, W.J.; McDonald, A.P.; Carlson, G.M.; Mathias, J.R.

    1983-01-01

    A solid-phase meal labeled with /sup 99m/Tc-sulfur colloid provides an improved clinical test for the quantitative evaluation of human gastric emptying. We studied 12 healthy male controls and five male patients with known gastric stasis secondary to a vagotomy and drainage procedure. All subjects were fasted for 8 hours before the study, and each consumed an unbuttered biscuit and a poached egg white containing 1 mCi of /sup 99m/Tc-sulfur colloid. For 2 hours, 60-second counts were measured every 10 minutes by a Pho Gamma III scintillation camera. The t 1 / 2 for control subjects was 60 minutes, at which time patients with gastric stasis had retained 98% of the test meal. At 120 minutes, control subjects and patients with gastric stasis had 4.7% and 89%, respectively, of the meal remaining in the stomach. The solid-phase test meal labeled with /sup 99m/Tc-sulfur colloid is easy to perform and can be used clinically to quantitatively measure gastric emptying in humans. This test can discriminate between control subjects and patients with known gastric stasis

  5. /sup 99m/Tc-labeled solid-phase meal: a quantitative clinical measurement of human gastric emptying

    Energy Technology Data Exchange (ETDEWEB)

    Martin, J.L.; Beck, W.J.; McDonald, A.P.; Carlson, G.M.; Mathias, J.R.

    1983-08-01

    A solid-phase meal labeled with /sup 99m/Tc-sulfur colloid provides an improved clinical test for the quantitative evaluation of human gastric emptying. We studied 12 healthy male controls and five male patients with known gastric stasis secondary to a vagotomy and drainage procedure. All subjects were fasted for 8 hours before the study, and each consumed an unbuttered biscuit and a poached egg white containing 1 mCi of /sup 99m/Tc-sulfur colloid. For 2 hours, 60-second counts were measured every 10 minutes by a Pho Gamma III scintillation camera. The t/sup 1///sup 2/ for control subjects was 60 minutes, at which time patients with gastric stasis had retained 98% of the test meal. At 120 minutes, control subjects and patients with gastric stasis had 4.7% and 89%, respectively, of the meal remaining in the stomach. The solid-phase test meal labeled with /sup 99m/Tc-sulfur colloid is easy to perform and can be used clinically to quantitatively measure gastric emptying in humans. This test can discriminate between control subjects and patients with known gastric stasis.

  6. The landscape of isoform switches in human cancers

    DEFF Research Database (Denmark)

    Vitting-Seerup, Kristoffer; Sandelin, Albin Gustav

    2017-01-01

    highly predictive of patient survival independent of cancer types. Our data constitute an important resource for cancer researchers, available through interactive web tools. Moreover, our methods, available as an R package, enable systematic analysis of isoform switches from other RNA-seq datasets...

  7. Melatonin and breast cancer: Evidences from preclinical and human studies.

    Science.gov (United States)

    Kubatka, Peter; Zubor, Pavol; Busselberg, Dietrich; Kwon, Taeg Kyu; Adamek, Mariusz; Petrovic, Daniel; Opatrilova, Radka; Gazdikova, Katarina; Caprnda, Martin; Rodrigo, Luis; Danko, Jan; Kruzliak, Peter

    2018-02-01

    The breast cancer affects women with high mortality and morbidity worldwide. The risk is highest in the most developed world but also is markedly rising in the developing countries. It is well documented that melatonin has a significant anti-tumor activities demonstrated on various cancer types in a plethora of preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen-dependent cell signaling, resulting in a reduction of estrogen-stimulated cells, moreover, it's obvious neuro-immunomodulatory effect in organism was described. Several prospective studies have demonstrated the inverse correlation between melatonin metabolites and the risk of breast cancer. This correlation was confirmed by observational studies that found lower melatonin levels in breast cancer patients. Moreover, clinical studies have showed that circadian disruption of melatonin synthesis, specifically night shift work, is linked to increased breast cancer risk. In this regard, proper light/dark exposure with more selective use of light at night along with oral supplementation of melatonin may have benefits for high-risk women. The results of current preclinical studies, the mechanism of action, and clinical efficacy of melatonin in breast cancer are reviewed in this paper. Melatonin alone or in combined administration seems to be appropriate drug for the treatment of early stages of breast cancer with documented low toxicity over a wide range of doses. These and other issues are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Cervical Cancer and Human Papilloma Virus Knowledge and ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    This study was aimed at determining the knowledge of cervical cancer and HPV as well as the ... is a global public health issue as it is the second ... younger population with the highest rate in the age range of 20 to 30 years which include many college-aged students5,9. ... If the current mortality trend of cervical cancer.

  9. Comparative proteome analysis of human epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Gagné Jean-Philippe

    2007-09-01

    Full Text Available Abstract Background Epithelial ovarian cancer is a devastating disease associated with low survival prognosis mainly because of the lack of early detection markers and the asymptomatic nature of the cancer until late stage. Using two complementary proteomics approaches, a differential protein expression profile was carried out between low and highly transformed epithelial ovarian cancer cell lines which realistically mimic the phenotypic changes observed during evolution of a tumour metastasis. This investigation was aimed at a better understanding of the molecular mechanisms underlying differentiation, proliferation and neoplastic progression of ovarian cancer. Results The quantitative profiling of epithelial ovarian cancer model cell lines TOV-81D and TOV-112D generated using iTRAQ analysis and two-dimensional electrophoresis coupled to liquid chromatography tandem mass spectrometry revealed some proteins with altered expression levels. Several of these proteins have been the object of interest in cancer research but others were unrecognized as differentially expressed in a context of ovarian cancer. Among these, series of proteins involved in transcriptional activity, cellular metabolism, cell adhesion or motility and cytoskeleton organization were identified, suggesting their possible role in the emergence of oncogenic pathways leading to aggressive cellular behavior. Conclusion The differential protein expression profile generated by the two proteomics approaches combined to complementary characterizations studies will open the way to more exhaustive and systematic representation of the disease and will provide valuable information that may be helpful to uncover the molecular mechanisms related to epithelial ovarian cancer.

  10. Application of monoclonal antibodies for diagnosis and treatment of human digestive cancer

    International Nuclear Information System (INIS)

    Otsuji, Eigo

    2007-01-01

    Radioimmunoscintigraphic applications of monoclonal antibodies (Mabs) for noninvasive detection and visualization of target tumors have grown immensely, and it suggests that Mabs can reach specifically to the targeted tumors in the human body. Radionuclides, cytotoxic drugs and anti-cancer drugs can be coupled to these specific MAbs to detect the extent of disease and/or to treat the tumors. Many of such immunoconjugates were studied for targeting therapy for cancer in animal experiments and some of them have applied to human. In this paper, we described the existing status of application of Mabs for diagnosis and immunotargeting therapy of digestive cancers. (author)

  11. Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract.

    Science.gov (United States)

    Fallah, S; Karimi, A; Panahi, G; Gerayesh Nejad, S; Fadaei, R; Seifi, M

    2016-03-31

    The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

  12. Parallel gastric emptying of nonhydrolyzable fat and water after a solid-liquid meal in humans

    International Nuclear Information System (INIS)

    Cortot, A.; Phillips, S.F.; Malagelada, J.R.

    1982-01-01

    Our aim was to examine the control of gastric emptying of the oil phase of a mixed solid and liquid meal. Previous studies had shown that liquid dietary fats normally leave the stomach at a slower rate than does water. We wished to determine whether the slower emptying of fats was due to the physical characteristics of food (lower density and greater viscosity than water), to retardation by duodenal feedback mechanisms, or whether both factors contributed. Thus, we quantified the emptying rates of water and sucrose polyester (a nonabsorbable analog of dietary fat) ingested by healthy volunteers as a mixed solid and liquid meal. Gastric emptying was quantified by an intubation-perfusion method incorporating an occlusive jejunal balloon to facilitate recovery. Four phase-specific, nonabsorbable markers were used. [14C[Sucrose octaoleate and polyethylene glycol were incorporated in the meal and traced the lipid and water phases, respectively; [3H]glycerol triether and phenolsulfonphthalein were used as duodenal recovery markers. Sucrose polyester (substituting for dietary fat) was emptied very rapidly, and at about the same rate as was water, in contrast to natural fat, which empties very slowly. Emptying of water was rapid and comparable to that observed after mixed meals containing natural fat. These results imply that gastric emptying of the oil phase is controlled by receptors sensitive to the hydrolytic products of fat digestion and that the slow emptying of dietary fat is not simply due to its lower density

  13. Lung Cancer and Human Papilloma Viruses (HPVs: Examining the Molecular Evidence

    Directory of Open Access Journals (Sweden)

    Priya R. Prabhu

    2012-01-01

    Full Text Available Human papilloma virus (HPV, known to be an etiological agent for genital cancers, has been suggested also to be a possible contributory agent for lung cancer. Alternatively, lung cancer, formerly considered to be solely a smoker's disease, may now be more appropriately categorised into never smoker's and smoker's lung cancer. Through this paper we attempt to bring forth the current knowledge regarding mechanisms of HPV gaining access into the lung tissue, various strategies involved in HPV-associated tumorigenesis in lung tissue.

  14. Human papilloma virus: An etiological and prognostic factor for oral cancer?

    Science.gov (United States)

    Lafaurie, Gloria I; Perdomo, Sandra J; Buenahora, María R; Amaya, Sandra; Díaz-Báez, David

    2018-05-01

    The increasing prevalence of human papilloma virus (HPV)-positive oral tumors can be considered an epidemic. Although the incidence of HPV cervical cancer is decreasing, the incidence of oral cavity and oropharyngeal cancers associated with HPV is increasing. The presence of certain HPV genotypes could be a predictor of future oral cancer lesions, although lesions associated with HPV could be less aggressive and exhibit a higher survival rate. In the present study, we review the most important biologic, clinic, epidemiologic, and prognostic factors associated with HPV infection and oral cancer. © 2018 John Wiley & Sons Australia, Ltd.

  15. Wise Investment? Modeling Industry Profitability and Risk of Targeted Chemotherapy for Incurable Solid Cancers.

    Science.gov (United States)

    Conter, Henry J; Chu, Quincy S C

    2012-03-01

    Pharmaceutical development involves substantial financial risk. This risk, rising development costs, and the promotion of continued research and development have been cited as major drivers in the progressive increase in drug prices. Currently, cost-effective analyses are being used to determine the value of treatment. However, cost-effective analyses practically function as a threshold for value and do not directly address the rationale for drug prices. We set out to create a functional model for industry price decisions and clarify the minimum acceptable profitability of new drugs. Assuming that industry should only invest in profitable ventures, we employed a linear cost-volume-profit breakeven analysis to equate initial capital investment and risk and post-drug-approval profits, where drug development represents the bulk of investment. A Markov decision analysis model was also used to define the relationships between investment events risk. A systematic literature search was performed to determine event probabilities, clinical trial costs, and total expenses as inputs into the model. Disease-specific inputs, current market size across regions, and lengths of treatment for cancer types were also included. With development of single novel chemotherapies costing from $802 to $1,042 million (2002 US dollars), pharmaceutical profits should range from $4.3 to $5.2 billion, with an expected rate of return on investment of 11% annually. However, diversification across cancer types for chemotherapy can reduce the minimum required profit to less than $3 billion. For optimal diversification, industry should study four tumor types per drug; however, nonprofit organizations could tolerate eight parallel development tracks to minimize the risk of development failure. Assuming that pharmaceutical companies hold exclusive rights for drug sales for only 5 years after market approval, the minimum required profit per drug per month per patient ranges from $294 for end-stage lung

  16. Wise Investment? Modeling Industry Profitability and Risk of Targeted Chemotherapy for Incurable Solid Cancers

    Science.gov (United States)

    Conter, Henry J.; Chu, Quincy S.C.

    2012-01-01

    Purpose: Pharmaceutical development involves substantial financial risk. This risk, rising development costs, and the promotion of continued research and development have been cited as major drivers in the progressive increase in drug prices. Currently, cost-effective analyses are being used to determine the value of treatment. However, cost-effective analyses practically function as a threshold for value and do not directly address the rationale for drug prices. We set out to create a functional model for industry price decisions and clarify the minimum acceptable profitability of new drugs. Methods: Assuming that industry should only invest in profitable ventures, we employed a linear cost-volume-profit breakeven analysis to equate initial capital investment and risk and post–drug-approval profits, where drug development represents the bulk of investment. A Markov decision analysis model was also used to define the relationships between investment events risk. A systematic literature search was performed to determine event probabilities, clinical trial costs, and total expenses as inputs into the model. Disease-specific inputs, current market size across regions, and lengths of treatment for cancer types were also included. Results: With development of single novel chemotherapies costing from $802 to $1,042 million (2002 US dollars), pharmaceutical profits should range from $4.3 to $5.2 billion, with an expected rate of return on investment of 11% annually. However, diversification across cancer types for chemotherapy can reduce the minimum required profit to less than $3 billion. For optimal diversification, industry should study four tumor types per drug; however, nonprofit organizations could tolerate eight parallel development tracks to minimize the risk of development failure. Assuming that pharmaceutical companies hold exclusive rights for drug sales for only 5 years after market approval, the minimum required profit per drug per month per patient ranges

  17. Cancer Care and Control as a Human Right: Recognizing Global Oncology as an Academic Field.

    Science.gov (United States)

    Eniu, Alexandru E; Martei, Yehoda M; Trimble, Edward L; Shulman, Lawrence N

    2017-01-01

    The global burden of cancer incidence and mortality is on the rise. There are major differences in cancer fatality rates due to profound disparities in the burden and resource allocation for cancer care and control in developed compared with developing countries. The right to cancer care and control should be a human right accessible to all patients with cancer, regardless of geographic or economic region, to avoid unnecessary deaths and suffering from cancer. National cancer planning should include an integrated approach that incorporates a continuum of education, prevention, cancer diagnostics, treatment, survivorship, and palliative care. Global oncology as an academic field should offer the knowledge and skills needed to efficiently assess situations and work on solutions, in close partnership. We need medical oncologists, surgical oncologists, pediatric oncologists, gynecologic oncologists, radiologists, and pathologists trained to think about well-tailored resource-stratified solutions to cancer care in the developing world. Moreover, the multidisciplinary fundamental team approach needed to treat most neoplastic diseases requires coordinated investment in several areas. Current innovative approaches have relied on partnerships between academic institutions in developed countries and local governments and ministries of health in developing countries to provide the expertise needed to implement effective cancer control programs. Global oncology is a viable and necessary field that needs to be emphasized because of its critical role in proposing not only solutions in developing countries, but also solutions that can be applied to similar challenges of access to cancer care and control faced by underserved populations in developed countries.

  18. Syndecan-1 suppresses epithelial-mesenchymal transition and migration in human oral cancer cells.

    Science.gov (United States)

    Wang, Xiaofeng; He, Jinting; Zhao, Xiaoming; Qi, Tianyang; Zhang, Tianfu; Kong, Chenfei

    2018-04-01

    Epithelial-mesenchymal transition (EMT) is one of the major processes that contribute to the occurrence of cancer metastasis. EMT has been associated with the development of oral cancer. Syndecan‑1 (SDC1) is a key cell‑surface adhesion molecule and its expression level inversely correlates with tumor differentiation and prognosis. In the present study, we aimed to determine the role of SDC1 in oral cancer progression and investigate the molecular mechanisms through which SDC1 regulates the EMT and invasiveness of oral cancer cells. We demonstrated that basal SDC1 expression levels were lower in four oral cancer cell lines (KB, Tca8113, ACC2 and CAL‑27), than in normal human periodontal ligament fibroblasts. Ectopic overexpression of SDC1 resulted in morphological transformation, decreased expression of EMT‑associated markers, as well as decreased migration, invasiveness and proliferation of oral cancer cells. In contrast, downregulation of the expression of SDC1 caused the opposite results. Furthermore, the knockdown of endogenous SDC1 activated the extracellular signal‑regulated kinase (ERK) cascade, upregulated the expression of Snail and inhibited the expression of E‑cadherin. In conclusion, our findings revealed that SDC1 suppressed EMT via the modulation of the ERK signaling pathway that, in turn, negatively affected the invasiveness of human oral cancer cells. Our results provided useful evidence about the potential use of SDC1 as a molecular target for therapeutic interventions in human oral cancer.

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

    Science.gov (United States)

    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 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. PMID:24843386

  20. Dihydrochalcone Compounds Isolated from Crabapple Leaves Showed Anticancer Effects on Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Qin

    2015-11-01

    Full Text Available Seven dihydrochalcone compounds were isolated from the leaves of Malus crabapples, cv. “Radiant”, and their chemical structures were elucidated by UV, IR, ESI-MS, 1H-NMR and 13C-NMR analyses. These compounds, which include trilobatin (A1, phloretin (A2, 3-hydroxyphloretin (A3, phloretin rutinoside (A4, phlorizin (A5, 6′′-O-coumaroyl-4′-O-glucopyranosylphloretin (A6, and 3′′′-methoxy-6′′-O-feruloy-4′-O-glucopyranosyl-phloretin (A7, all belong to the phloretin class and its derivatives. Compounds A6 and A7 are two new rare dihydrochalcone compounds. The results of a MTT cancer cell growth inhibition assay demonstrated that phloretin and these derivatives showed significant positive anticancer activities against several human cancer cell lines, including the A549 human lung cancer cell line, Bel 7402 liver cancer cell line, HepG2 human ileocecal cancer cell line, and HT-29 human colon cancer cell line. A7 had significant effects on all cancer cell lines, suggesting potential applications for phloretin and its derivatives. Adding a methoxyl group to phloretin dramatically increases phloretin’s anticancer activity.

  1. 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. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer.

    Science.gov (United States)

    Staquicini, Fernanda I; Qian, Ming D; Salameh, Ahmad; Dobroff, Andrey S; Edwards, Julianna K; Cimino, Daniel F; Moeller, Benjamin J; Kelly, Patrick; Nunez, Maria I; Tang, Ximing; Liu, Diane D; Lee, J Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R M; Lobb, Roy R; Edelman, Martin J; Sidman, Richard L; Wistuba, Ignacio I; Arap, Wadih; Pasqualini, Renata

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. Finally, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Variations with time and age in the relative risks of solid cancer incidence after radiation exposure

    International Nuclear Information System (INIS)

    Little, M.P.; Muirhead, C.R.; de Vathaire, F.; Charles, M.W.

    1997-01-01

    The Japanese atomic bomb survivor cancer incidence dataset and data on five groups exposed to radiation for medical reasons in childhood are analysed and evidence found for a reduction in the radiation-induced relative risk of cancers other than leukaemia with increasing time since exposure and age at exposure. The rate of the reductions in relative risk with time since exposure are not significantly different for those exposed in childhood and for those exposed in adulthood, if adjustment is made for the effects on the relative risk of age at exposure. For those irradiated in childhood, there is a statistically significant annual reduction of 5.8% (95% Cl 2.8, 8.9) in excess relative risk, and there are no strong indications of inter-cohort heterogeniety in the speed of reduction of relative risk. After adjustment for the effects of age at exposure, there is a significant annual reduction of 3.6% (95% Cl 1.6, 5.6) in excess relative risk in all age-at-exposure groups. There are significant reductions of 5.2% (95% Cl 3.7, 6.8) in excess relative risk per year of age at exposure. There are statistically significant (P = 0.04) interactions between the exponential adjustments to the excess relative risk for age at exposure and time since exposure in the Japanese data, but no indications (P = 0.38) of such interactions when powers of time since exposure and attained age are used to adjust the excess relative risk, so that the fit of the model with power adjustments is to be preferred to that of the model with exponential adjustments. (author)

  4. Diet and Cancer Prevention: Chewing on the Human Complexities | Division of Cancer Prevention

    Science.gov (United States)

    Speaker Johanna W. Lampe, PhD, RD Research Professor University of Washington Full Member and Associate Division Director Cancer Prevention Program Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle, WA |

  5. Feasible way of Human Solid and Liquid Wastes' Inclusion Into Intersystem Mass Exchange of Biological-Technical Life Support Systems

    Science.gov (United States)

    Ushakova, Sofya; Tikhomirov, Alexander A.; Tikhomirova, Natalia; Kudenko, Yurii; Griboskaya, Illiada; Gros, Jean-Bernard; Lasseur, Christophe

    The basic objective arising at use of mineralized human solid and liquid wastes serving as the source of mineral elements for plants cultivation in biological-technical life support systems appears to be NaCl presence in them. The given work is aimed at feasibility study of mineralized human metabolites' utilization for nutrient solutions' preparation for their further employment at a long-term cultivation of uneven-aged wheat and Salicornia europaea L. cenosis in a conveyer regime. Human solid and liquid wastes were mineralized by the "wet incineration" method developed by Yu. Kudenko. On their base the solutions were prepared which were used for cultivation of 5-aged wheat conveyer with the time step-interval of 14 days. Wheat was cultivated by hydroponics method on expanded clay aggregate. For partial demineralization of nutrient solution every two weeks after regular wheat harvesting 12 L of solution was withdrawn from the wheat irrigation tank and used for Salicornia europaea cultivation by the water culture method in a conveyer regime. The Salicornia europaea conveyer was represented by 2 ages with the time step-interval of 14 days. Resulting from repeating withdrawal of the solution used for wheat cultivation, sodium concentration in the wheat irrigation solution did not exceed 400 mg/l, and mineral elements contained in the taken solution were used for Salicornia europaea cultivation. The experiment lasted 7 months. Total wheat biomass productivity averaged 30.1 g*m-2*day-1 at harvest index equal to 36.8The work was carried out under support of SB RAS grant 132 and INTAS 05-1000008-8010

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

    Directory of Open Access Journals (Sweden)

    Fabien J Cousin

    Full Text Available 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.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.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.

  7. Milk Fermented by Propionibacterium freudenreichii Induces Apoptosis of HGT-1 Human Gastric Cancer Cells

    Science.gov (United States)

    Cousin, Fabien J.; Jouan-Lanhouet, Sandrine; Dimanche-Boitrel, Marie-Thérèse; Corcos, Laurent; Jan, Gwénaël

    2012-01-01

    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. PMID:22442660

  8. Rel/Nuclear factor-kappa B apoptosis pathways in human cervical cancer cells

    Science.gov (United States)

    Shehata, Marlene F

    2005-01-01

    Cervical cancer is considered a common yet preventable cause of death in women. It has been estimated that about 420 women out of the 1400 women diagnosed with cervical cancer will die during 5 years from diagnosis. This review addresses the pathogenesis of cervical cancer in humans with a special emphasis on the human papilloma virus as a predominant cause of cervical cancer in humans. The current understanding of apoptosis and regulators of apoptosis as well as their implication in carcinogenesis will follow. A special focus will be given to the role of Rel/NF-κB family of genes in the growth and chemotherapeutic treatment of the malignant HeLa cervical cells emphasizing on Xrel3, a cRel homologue. PMID:15857509

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

    Directory of Open Access Journals (Sweden)

    Hector Guillen-Ahlers

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

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

    International Nuclear Information System (INIS)

    Li, Fang-qiu; Han, Yan-ling; Liu, Qun; Wu, Bo; Huang, Wen-bin; Zeng, Su-yun

    2009-01-01

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

  11. 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

  12. 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.

  13. Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer

    International Nuclear Information System (INIS)

    Kitkumthorn, Nakarin; Mutirangura, Apiwat; Yanatatsanajit, Pattamawadee; Kiatpongsan, Sorapop; Phokaew, Chureerat; Triratanachat, Surang; Trivijitsilp, Prasert; Termrungruanglert, Wichai; Tresukosol, Damrong; Niruthisard, Somchai

    2006-01-01

    The aim of this study was to evaluate epigenetic status of cyclin A1 in human papillomavirus-associated cervical cancer. Y. Tokumaru et al., Cancer Res 64, 5982-7 (Sep 1, 2004)demonstrated in head and neck squamous-cell cancer an inverse correlation between cyclin A1 promoter hypermethylation and TP53 mutation. Human papillomavirus-associated cervical cancer, however, is deprived of TP53 function by a different mechanism. Therefore, it was of interest to investigate the epigenetic alterations during multistep cervical cancer development. In this study, we performed duplex methylation-specific PCR and reverse transcriptase PCR on several cervical cancer cell lines and microdissected cervical cancers. Furthermore, the incidence of cyclin A1 methylation was studied in 43 samples of white blood cells, 25 normal cervices, and 24, 5 and 30 human papillomavirus-associated premalignant, microinvasive and invasive cervical lesions, respectively. We demonstrated cyclin A1 methylation to be commonly found in cervical cancer, both in vitro and in vivo, with its physiological role being to decrease gene expression. More important, this study demonstrated that not only is cyclin A1 promoter hypermethylation strikingly common in cervical cancer, but is also specific to the invasive phenotype in comparison with other histopathological stages during multistep carcinogenesis. None of the normal cells and low-grade squamous intraepithelial lesions exhibited methylation. In contrast, 36.6%, 60% and 93.3% of high-grade squamous intraepithelial lesions, microinvasive and invasive cancers, respectively, showed methylation. This methylation study indicated that cyclin A1 is a potential tumor marker for early diagnosis of invasive cervical cancer

  14. Studies on Purification and Coatation of Polyclonal Antibody for Prolactin Solid Phase Radioimmunoassay in Human Serum

    International Nuclear Information System (INIS)

    El-Bayoumy, A.S.A.; Sallam, Kh.M.; Shafik, H.M.

    2012-01-01

    The objective of the present study was oriented to produce purified polyclonal antibody to prepare a prolactin solid phase coated tubes radioimmunoassay system. In the present study, production of polyclonal antibodies was carried out through immunization of three healthy white male mature New Zealand rabbits with a highly purified sheep prolactin antigen. The obtained anti-sera was purified using an anion exchange reactive group, diethylamino ethyle (DEAE) covalently linked to Sepharose. The purified polyclonal antibody was used for coating polystyrene tubes. The preparation of 125 I-prolactin tracer was carried out using chloramine-T method. The preparation of standards was performed using assay buffer to cover the range from 2 to 200 ng/ml. The optimization and validation tests of the assay were performed to evaluate the validity of the prepared system. In conclusion, this low cost assay would be used in diagnosis of pituitary dysfunction and diagnosis of infertility in males and females

  15. Studies on Purification and Coatation of Polyclonal Antibody for Prolactin Solid Phase Radioimmunoassay in Human Serum

    International Nuclear Information System (INIS)

    El-Bayoumy, A.S.A.; Sallam, Kh.M.; Shafik, H.M.

    2014-01-01

    The objective of the present study was oriented to produce purified polyclonal antibody to prepare a prolactin solid phase coated tubes radioimmunoassay system. In the present study, production of polyclonal antibodies was carried out through immunization of three healthy white male mature New Zealand rabbits with a highly purified sheep prolactin antigen. The obtained anti-sera was purified using an anion exchange reactive group, diethylamino ethyle (DEAE) covalently linked to Sepharose. The purified polyclonal antibody was used for coating polystyrene tubes. The preparation of 125 I-prolactin tracer was carried out using chloramine-T method. The preparation of standards was performed using assay buffer to cover the range from 2 to 200 ng/ml. The optimization and validation tests of the assay were performed to evaluate the validity of the prepared system. In conclusion, this low cost assay would be used in diagnosis of pituitary dysfunction and diagnosis of infertility in males and females.

  16. Young Asian Americans' knowledge and perceptions of cervical cancer and the human papillomavirus.

    Science.gov (United States)

    Gor, Beverly J; Chilton, Janice A; Camingue, Pamela T; Hajek, Richard A

    2011-02-01

    Cervical cancer is a major health disparity among Asian Americans, with cervical cancer rates of Vietnamese women being significantly higher than for the general US female population and low screening rates reported for Asian American females. Focus groups and interviews were conducted with young Vietnamese, Filipino, and Korean adults (ages 18-29) to collect information on knowledge, perceptions and sources of information regarding cervical cancer, Pap tests and the human papillomavirus. 16 Korean, 18 Vietnamese, and 18 Filipino (50% female) adults participated in the study. Many participants had never heard of HPV, cervical cancer and Pap testing. Cervical cancer screening rates were low for Korean and Vietnamese females and were influenced by moral beliefs and lack of awareness. Culturally relevant education materials that consider specific Asian ethnicity and language are needed to increase awareness of cervical cancer, Pap testing, and HPV among Asian American young adults.

  17. Cervical Cancer Incidence in Young U.S. Females After Human Papillomavirus Vaccine Introduction.

    Science.gov (United States)

    Guo, Fangjian; Cofie, Leslie E; Berenson, Abbey B

    2018-05-30

    Since 2006, human papillomavirus vaccine has been recommended for young females in the U.S. This study aimed to compare cervical cancer incidence among young women before and after the human papillomavirus vaccine was introduced. This cross-sectional study used data from the National Program for Cancer Registries and Surveillance, Epidemiology, and End Results Incidence-U.S. Cancer Statistics 2001-2014 database for U.S. females aged 15-34 years. This study compared the 4-year average annual incidence of invasive cervical cancer in the 4 years before human papillomavirus vaccine was introduced (2003-2006) and the 4 most recent years in the vaccine era (2011-2014). Joinpoint regression models of cervical incidence from 2001 to 2014 were fitted to identify the discrete joints (year) that represent statistically significant changes in the direction of the trend after the introduction of human papillomavirus vaccination in 2006. Data were collected in 2001-2014, released, and analyzed in 2017. The 4-year average annual incidence rates for cervical cancer in 2011-2014 were 29% lower than that in 2003-2006 (6.0 vs 8.4 per 1,000,000 people, rate ratio=0.71, 95% CI=0.64, 0.80) among females aged 15-24 years, and 13.0% lower among females aged 25-34 years. Joinpoint analyses of cervical cancer incidence among females aged 15-24 years revealed a significant joint at 2009 for both squamous cell carcinoma and non-squamous cell carcinoma. Among females aged 25-34 years, there was no significant decrease in cervical cancer incidence after 2006. A significant decrease in the incidence of cervical cancer among young females after the introduction of human papillomavirus vaccine may indicate early effects of human papillomavirus vaccination. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  18. INHIBITION OF SPONTANEOUS APOPTOSIS IN HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    邵志敏; 江明; 吴炅; 余黎民; 韩企夏; 张延璆; 沈镇宙

    1996-01-01

    Breast tumorigenesis proceeds through an accumulation of specific genetic alteration. Breast malignant transformation is dependent on not only the rate of cell production but also on apoptcsis,a genetically prograined process of autonomous ceil death. We investigated whether breast tumorigenesis involved an altered susceptibility to apoptosis and proliferation by examining normal breast epithelium and breast cancer sampies. We found there is a great inhibition of spontaneous apoptosis in breast cancer ceils compared with normal breast epithelium. The inhibition of apoptosis in breast cancer may contribute to neoplastic transformation.

  19. Choline Phospholipid Metabolites of Human Vascular Endothelial Cells Altered by Cyclooxygenase Inhibition, Growth Factor Depletion, and Paracrine Factors Secreted by Cancer Cells

    Directory of Open Access Journals (Sweden)

    Noriko Mori

    2003-04-01

    Full Text Available Magnetic resonance studies have previously shown that solid tumors and cancer cells in culture typically exhibit high phosphocholine and total choline. Treatment of cancer cells with the anti-inflammatory agent, indomethacin (INDO, reverted the phenotype of choline phospholipid metabolites in cancer cells towards a less malignant phenotype. Since endothelial cells form a key component of tumor vasculature, in this study, we used MR spectroscopy to characterize the phenotype of choline phospholipid metabolites in human umbilical vein endothelial cells (HUVECs. We determined the effect of growth factors, the anti-inflammatory agent INDO, and conditioned media obtained from a malignant cell line, on choline phospholipid metabolites. Growth factor depletion or treatment with INDO induced similar changes in the choline phospholipid metabolites of HUVECs. Treatment with conditioned medium obtained from MDA-MB-231 cancer cells induced changes similar to the presence of growth factor supplements. These results suggest that cancer cells secrete growth factors and/or other molecules that influence the choline phospholipid metabolism of HUVECs. The ability of INDO to alter choline phospholipid metabolism in the presence of growth factor supplements suggests that the inflammatory response pathways of HUVECs may play a role in cancer cell-HUVEC interaction and in the response of HUVECs to growth factors.

  20. Incidence and mortality of solid cancer among emergency workers of the Chernobyl accident: assessment of radiation risks for the follow-up period of 1992-2009

    Energy Technology Data Exchange (ETDEWEB)

    Kashcheev, V.V.; Chekin, S.Yu.; Maksioutov, M.A.; Tumanov, K.A.; Kochergina, E.V.; Kashcheeva, P.V.; Shchukina, N.V.; Ivanov, V.K. [Russian Ministry of Health, Federal State Institution, Medical Radiological Research Center, Obninsk, Kaluga Region (Russian Federation)

    2015-03-15

    This paper presents the results of a retrospective cohort study of cancer incidence and mortality among emergency workers of the Chernobyl accident, for the follow-up period 1992-2009. The cohort selected for analysis consists of 67,568 emergency workers who worked in the Chernobyl exclusion zone in 1986-1987. External radiation whole-body absorbed dose varied from 0.0001 gray (Gy) to 1.24 Gy, with a median of 0.102 Gy. Over the follow-up period 1992-2009, a total of 4,002 solid cancers of different sites were identified as the result of annual compulsory health examination, and a total of 2,442 deaths from all solid cancers in the study cohort were reported. Poisson regression was applied for the analysis of cancer incidence and mortality. The analysis of the standardized incidence ratio (SIR) has shown a statistically significant increase in cancer incidence in the cohort as compared with baseline cancer incidence among males of Russia. The average excess over the entire follow-up period is 18 % [SIR = 1.18, 95 % confidence interval (CI) 1.15; 1.22]. In contrast, however, no increase in the mortality from all cancers among the emergency workers as compared to the baseline mortality in Russian men was found. Values of excess relative risk of cancer incidence and mortality per 1 Gy (ERR Gy{sup -1}) are 0.47 (95 % CI 0.03; 0.96, p value = 0.034) and 0.58 (95 % CI 0.002; 1.25, p value = 0.049), respectively. These values are statistically significant. (orig.)

  1. Elevated expression and potential roles of human Sp5, a member of Sp transcription factor family, in human cancers

    International Nuclear Information System (INIS)

    Chen Yongxin; Guo Yingqiu; Ge Xijin; Itoh, Hirotaka; Watanabe, Akira; Fujiwara, Takeshi; Kodama, Tatsuhiko; Aburatani, Hiroyuki

    2006-01-01

    In this report, we describe the expression and function of human Sp5, a member of the Sp family of zinc finger transcription factors. Like other family members, the Sp5 protein contains a Cys2His2 zinc finger DNA binding domain at the C-terminus. Our experiments employing Gal4-Sp5 fusion proteins reveal multiple transcriptional domains, including a N-terminal activity domain, an intrinsic repressive element, and a C-terminal synergistic domain. Elevated expression of Sp5 was noted in several human tumors including hepatocellular carcinoma, gastric cancer, and colon cancer. To study the effects of the Sp5 protein on growth properties of human cancer cells and facilitate the identification of its downstream genes, we combined an inducible gene expression system with microarray analysis to screen for its transcriptional targets. Transfer of Sp5 into MCF-7 cells that expressed no detectable endogenous Sp5 protein elicited significant growth promotion activity. Several of the constitutively deregulated genes have been associated with tumorigenesis (CDC25C, CEACAM6, TMPRSS2, XBP1, MYBL1, ABHD2, and CXCL12) and Wnt/β-Catenin signaling pathways (BAMBI, SIX1, IGFBP5, AES, and p21 WAF1 ). This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against human cancers

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Jannatul Fardows

    2016-09-01

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

  4. Cloning of Novel Oncogenes Involved in Human Breast Cancer

    National Research Council Canada - National Science Library

    Der, Channing J

    2000-01-01

    ... markers for early detection. The rationale for using the invasive tumor tissue is that these cancer cells are likely to harbor more genetic defects that noninvasive tumor cells and consequently, our chances of detection are increased...

  5. Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer : A Nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition Study

    NARCIS (Netherlands)

    Kreimer, Aimee R.; Brennan, Paul; Kuhs, Krystle A. Lang; Waterboer, Tim; Clifford, Gary; Franceschi, Silvia; Michel, Angelika; Willhauck-Fleckenstein, Martina; Riboli, Elio; Castellsague, Xavier; Hildesheim, Allan; Fortner, Renee Turzanski; Kaaks, Rudolf; Palli, Domenico; Ljuslinder, Ingrid; Panico, Salvatore; Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Peeters, Petra H.; Cross, Amanda J.; Bueno-de-Mesquita, H. Bas; Vineis, Paolo; Larranaga, Nerea; Pala, Valeria; Sanchez, Maria-Jose; Navarro, Carmen; Barricarte, Aurelio; Tumino, Rosario; Khaw, Kay-Tee; Wareham, Nicholas; Boeing, Heiner; Steffen, Annika; Travis, Ruth C.; Ramon Quiros, J.; Weiderpass, Elisabete; Pawlita, Michael; Johansson, Mattias

    2015-01-01

    Purpose Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

    Adams, Allie K.; Wise-Draper, Trisha M.; Wells, Susanne I.

    2014-01-01

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

  9. Experimental studies on interactions of radiation and cancer chemotherapeutic drugs in normal tissues and a solid tumour

    International Nuclear Information System (INIS)

    Maase, H. van der

    1986-01-01

    The interactions of radiation and seven cancer chemotherapeutic drugs have been investigated in four normal tissues and in a solid C 3 H mouse mammary carcinoma in vivo. The investigated drugs were adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorouracil (5-FU), methotrexate (MTX), mitomycin C (MM-C) and cis-diamminedichloroplatinum(II) (cis-DDP). The drugs enhanced the radiation response in most cases. However, signs of radioprotection was observed for CTX in skin and for MTX in haemopoietic tissue. The interval and the sequence of the two treatment modalities were of utmost importance for the normal tissue reactions. In general, the most serious interactions occurred when drugs were administered simultaneously with or a few hours before radiation. The radiation-modifying effect of the drugs deviated from this pattern in the haemopoietic tissue as the radiation response was most enhanced on drug administration 1-3 days after radiation. Enhancement of the radiation response was generally less pronounced in the tumour model than in the normal tissues. The combined drug-radiation effect was apparently less time-dependent in the tumour than in the normal tissues. (Auth.)

  10. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening.

    Science.gov (United States)

    Katki, Hormuzd A; Cheung, Li C; Fetterman, Barbara; Castle, Philip E; Sundaram, Rajeshwari

    2015-10-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interval-censored data by developing a novel joint model for time to clearance of HPV and time to precancer/cancer using shared random-effects, where the estimated mean duration of each woman's HPV infection is a covariate in the submodel for time to precancer/cancer. The model was fit to data on 9,553 HPV-positive/Pap-negative women undergoing cervical cancer screening at Kaiser Permanente Northern California, data that were pivotal to the development of US screening guidelines. We compare the implications for screening intervals of this joint model to those from population-average marginal models of precancer/cancer risk. In particular, after 2 years the marginal population-average precancer/cancer risk was 5%, suggesting a 2-year interval to control population-average risk at 5%. In contrast, the joint model reveals that almost all women exceeding 5% individual risk in 2 years also exceeded 5% in 1 year, suggesting that a 1-year interval is better to control individual risk at 5%. The example suggests that sophisticated risk models capable of predicting individual risk may have different implications than population-average risk models that are currently used for informing medical guideline development.

  11. FLAX OIL FROM TRANSGENIC LINUM USITATISSIMUM SELECTIVELY INHIBITS IN VITRO PROLIFERATION OF HUMAN CANCER CELL LINES.

    Science.gov (United States)

    Gebarowski, Tomasz; Gebczak, Katarzyna; Wiatrak, Benita; Kulma, Anna; Pelc, Katarzyna; Czuj, Tadeusz; Szopa, Jan; Gasiorowski, Kazimierz

    2017-03-01

    Emulsions made of oils from transgenic flaxseeds significantly decreased in vitro proliferation of six tested human cancer cell lines in 48-h cultures, as assessed with the standard sulforhodamine assay. However, the emulsions also increased proliferation rate of normal human dermal fibroblasts and, to a lower extend, of keratinocytes. Both inhibition of in vitro proliferation of human cancer cell lines and stimulation of proliferation of normal dermal fibroblasts and keratinocytes were especially strong with the emulsion type B and with emulsion type M. Oils from seeds of transgenic flax type B and M should be considered as valuable adjunct to standard cytostatic therapy of human cancers and also could be applied to improve the treatment of skin lesions in wound healing.

  12. Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

    Science.gov (United States)

    Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

    2010-01-01

    The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

  13. Routine ultramicro-measurement of human growth hormone in plasma by solid-phase radioimmunoassay and its clinical application

    International Nuclear Information System (INIS)

    Ogawa, Norio; Takahara, Jiro; Ofuji, Tadashi

    1975-01-01

    The development and application of the method for the ultramicromeasurement of human growth hormone (HGH) in plasma based on the solid-phase radioimmunoassay (RIA) by using antibody-coated disposable microtiter trays was reported. There was no statistical significance between the basal HGH level obtained from this method and that from the double-antibody RIA in normal subjects. On the other hand, the mean basal plasma HGH level after an overnight fasting in 21 hypopituitary patients was 484 pg/ml (+-282; 1 SD) by this method, and this was significantly lower (P<0.001) than 1376 pg/ml (+-498; 1 SD) by the double-antibody RIA. These data show that determination of basal plasma HGH levels by this method is of much value in the diagnosis of hypopituitarism. (JPN)

  14. Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children.

    Science.gov (United States)

    Sawada, Akihisa; Inoue, Masami; Kondo, Osamu; Yamada-Nakata, Kayo; Ishihara, Takashi; Kuwae, Yuko; Nishikawa, Masanori; Ammori, Yasuhiro; Tsuboi, Akihiro; Oji, Yusuke; Koyama-Sato, Maho; Oka, Yoshihiro; Yasui, Masahiro; Sugiyama, Haruo; Kawa, Keisei

    2016-02-01

    Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies. The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02. Vaccination using the WT1 peptide (CYTWNQMNL), which was modified for higher affinity to this HLA-type molecule with the adjuvant Montanide ISA51, was performed weekly 12 times. Twenty-six patients were enrolled and 13 (50.0%) completed the vaccination 12 times. Evidence for the induction of WT1-specific cytotoxic T-lymphocyte (CTL) responses without severe systemic side effects was obtained. Two out of 12 patients with bulky disease exhibited a transient clinical effect (one mixed response and one stable disease), three out of six patients with minimal residual disease achieved transient molecular remission, and five out of eight patients without a detectable level of the molecular marker, but with a high risk of relapse, had the best outcome of long-term continuous complete remission. WT1 vaccination is a safe immunotherapy and induced WT1-specific CTL responses in children; however, as a single agent, vaccination only provided patients in remission, but with a high risk of relapse, with "long-term benefits" in the context of its use for relapse prevention. WT1 peptide-based treatments in combination with other modalities, such as anti-tumor drugs or immunomodulating agents, need to be planned. © 2015 Wiley Periodicals, Inc.

  15. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.

    Science.gov (United States)

    Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

    2015-12-01

    Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Knowledge about Human Papillomavirus and Cervical Cancer: Predictors of HPV Vaccination among Dental Students

    Science.gov (United States)

    Rajiah, Kingston; Maharajan, Mari Kannan; Fang Num, Kelly Sze; How Koh, Raymond Chee

    2017-06-25

    Background: The objective of this study is to determine the influence of dental students’ knowledge and attitude regarding human papillomavirus infection of cervical cancer on willingness to pay for vaccination. Basic research design: A convenience sampling method was used. The minimal sample size of 136 was calculated using the Raosoft calculator with a 5 % margin of error and 95% confidence level. Participants: The study population were all final year dental students from the School of Dentistry. Methods: A self-administered questionnaire was used to measure knowledge levels and attitudes regarding human papillomavirus vaccination. Contingent valuation was conducted for willingness to pay for vaccination. Main outcome measures: The Center for Disease Control and Prevention has stated that human papillomavirus are associated with oropharynx cancer and the American Dental Association insist on expanding public awareness of the oncogenic potential of some HPV infections. Thus, as future dental practitioners, dental students should be aware of human papillomavirus and their links with cancer and the benefits of vaccination. Results: Knowledge on HPV and cervical cancer did not impact on attitudes towards vaccines. However, significant correlation existed between knowledge and willingness to pay for vaccination. Conclusions: Dental students’ knowledge on HPV and cervical cancer has no influence on their attitude towards HPV vaccines. However, their willingness to pay for HPV vaccination is influenced by their knowledge of cervical cancer and HPV vaccination. Creative Commons Attribution License

  17. Semi-synthetic salinomycin analogs exert cytotoxic activity against human colorectal cancer stem cells.

    Science.gov (United States)

    Klose, Johannes; Kattner, Sarah; Borgström, Björn; Volz, Claudia; Schmidt, Thomas; Schneider, Martin; Oredsson, Stina; Strand, Daniel; Ulrich, Alexis

    2018-01-01

    Salinomycin, a polyether antibiotic, is a well-known inhibitor of human cancer stem cells. Chemical modification of the allylic C20 hydroxyl of salinomycin has enabled access to synthetic analogs that display increased cytotoxic activity compared to the native structure. The aim of this study was to investigate the activity of a cohort of C20-O-acyl analogs of salinomycin on human colorectal cancer cell lines in vitro. Two human colorectal cancer cell lines (SW480 and SW620) were exposed to three C20-O-acylated analogs and salinomycin. The impact of salinomycin and its analogs on tumor cell number, migration, cell death, and cancer stem cell specifity was analyzed. Exposure of human colorectal cancer cells to the C20-O-acylated analogs of salinomycin resulted in reduced tumor cell number and impaired tumor cell migration at lower concentrations than salinomycin. When used at higher (micromolar) concentrations, these effects were accompanied by induction of apoptotic cell death. Salinomycin analogs further expose improved activity against cancer stem cells compared to salinomycin. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Prokineticin 1 protein expression is a useful new prognostic factor for human sporadic colorectal cancer.

    Science.gov (United States)

    Nakazawa, Toshiyuki; Goi, Takanori; Hirono, Yasuo; Yamaguchi, Akio

    2015-05-01

    Hematogenous metastasis, regarded as closely related to angiogenic growth factors, is associated with colorectal cancer prognosis. The angiogenic growth factor prokineticin 1 (PROK1) has been cloned from endocrine cells. However, its protein expression in human malignant tumors has not been studied. The current study established the anti-PROK1 monoclonal antibody (mAb) and examined the relationship between the expression of PROK1 protein and human colorectal cancer. The expression of PROK1 protein was assessed in 620 resected sporadic colorectal cancer tissue samples by immunohistochemical staining with in-house-developed human PROK1 mAb to investigate the relationship of PROK1 expression to clinicopathologic factors, recurrence, and survival rate and to evaluate its prognostic significance. The expression of PROK1 protein was detected in 36 % (223/620) of human primary colorectal cancer lesions but no in the healthy mucosa adjacent to the colorectal cancer lesions. According to the clinicopathologic examinations, the frequency of positive PROK1 expression was significantly higher in cases with serosal invasion, lymphatic invasion, venous invasion, lymph node metastasis, liver metastasis, hematogenous metastasis, and higher stage disease. The recurrence rate and prognosis for patients with PROK1 expression-positive lesions were significantly worse. In the Cox proportional hazard model, PROK1 expression was an independent prognostic factor. The expression of PROK1 protein was identified for the first time as a new prognostic factor in colorectal cancer.

  19. Recurrent chimeric RNAs enriched in human prostate cancer identified by deep sequencing

    Science.gov (United States)

    Kannan, Kalpana; Wang, Liguo; Wang, Jianghua; Ittmann, Michael M.; Li, Wei; Yen, Laising

    2011-01-01

    Transcription-induced chimeric RNAs, possessing sequences from different genes, are expected to increase the proteomic diversity through chimeric proteins or altered regulation. Despite their importance, few studies have focused on chimeric RNAs especially regarding their presence/roles in human cancers. By deep sequencing the transcriptome of 20 human prostate cancer and 10 matched benign prostate tissues, we obtained 1.3 billion sequence reads, which led to the identification of 2,369 chimeric RNA candidates. Chimeric RNAs occurred in significantly higher frequency in cancer than in matched benign samples. Experimental investigation of a selected 46 set led to the confirmation of 32 chimeric RNAs, of which 27 were highly recurrent and previously undescribed in prostate cancer. Importantly, a subset of these chimeras was present in prostate cancer cell lines, but not detectable in primary human prostate epithelium cells, implying their associations with cancer. These chimeras contain discernable 5′ and 3′ splice sites at the RNA junction, indicating that their formation is mediated by splicing. Their presence is also largely independent of the expression of parental genes, suggesting that other factors are involved in their production and regulation. One chimera, TMEM79-SMG5, is highly differentially expressed in human cancer samples and therefore a potential biomarker. The prevalence of chimeric RNAs may allow the limited number of human genes to encode a substantially larger number of RNAs and proteins, forming an additional layer of cellular complexity. Together, our results suggest that chimeric RNAs are widespread, and increased chimeric RNA events could represent a unique class of molecular alteration in cancer. PMID:21571633

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

    Directory of Open Access Journals (Sweden)

    Horng-Jyh Tsai

    2015-04-01

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

  1. Light Up the Word update 2001-2002 : solid state lighting for human development

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, K.; Irvine-Halliday, D. [Calgary Univ., AB (Canada). Dept. of Electrical and Computer Engineering, Light Up the World Foundation; Craine, S. [Curtin Univ. of Technology (Australia)]|[Calgary Univ., AB (Canada). Dept. of Electrical and Computer Engineering, Light Up the World Foundation; Stone, R. [Fernbank Electronic Systems Ltd., Stittsville, ON (Canada)

    2002-07-01

    Light Up the World Foundation (LUTW) is a humanitarian organization founded in 1997 to bring safe, healthy, reliable, environmentally sound and affordable home lighting to developing countries. LUTW is a world leader in using solid state lighting (SSL) technologies to improve the quality of life for underprivileged people living in villages with little realistic prospect for affordable electrification. SSL technology uses white light-emitting diodes (LEDs) to provide lighting at low power consumption, often from batteries that get recharged by solar panels or other renewable energy sources. LUTW is active in more than 12 countries and has set the standards to raising the quality of SSL as a community development tool around the world. This report described how LUTW developed its market for SSL and the basic component for forging a relationship between industrial and social entrepreneurship. The international efforts to reduce greenhouse gas (GHG) emissions under climate change mitigation mechanisms such as carbon reduction emission credits, allows LUTW to obtain additional revenues to help sustain its projects. This is because the amount of fossil fuel and GHG reductions from SSL systems can be readily quantified. 4 refs., 1 tab., 1 fig.

  2. Immune responses of mice and human breast cancer patients following immunization with synthetic sialyl-Tn conjugated to KLH plus detox adjuvant.

    Science.gov (United States)

    Longenecker, B M; Reddish, M; Koganty, R; MacLean, G D

    1993-08-12

    We generated a synthetic epitope, NANA alpha(2-6) GalNAc alpha-O-Crotyl (STn-crotyl), designed to "mimic" the natural O-linked epitope expressed on human carcinoma cells, NANA alpha(2-6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm, and a "vaccine" containing STn-KLH plus DETOX adjuvant was formulated. The immunogenicity of the vaccine was evaluated preclinically in CAF1 mice and subsequently in patients with metastatic breast cancer. The specificity and titers of IgG antibodies were evaluated by kinetic ELISA on synthetic STn-HSA and on ovine submaxillary mucin (OSM) solid phases. Ovine submaxillary mucin is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 micrograms of STn-KLH produced IgG titers ranging from 1:10(4) to 1:10(5) when tested on solid phase OSM. Anti-OSM IgG, both polyclonal and monoclonal antibodies, generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens. These monoclonal antibodies also bound to STn determinants on human tumor cell surfaces. Breast cancer patients immunized with 100 micrograms of the same vaccine produced median peak IgG titers 1:1280 measured on STn-HSA and 1:160 on OSM. Hapten inhibition experiments with the human sera demonstrated the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not against several other related synthetic haptens. We found little evidence that the artificial linker arm (crotyl linker) contributed substantially to either the titer or affinity of the antibodies generated in either mice or human breast cancer patients. This suggests that the antibodies recognized the cancer-associated disaccharide NANA alpha(2-->6)-GalNAc. Small but not large doses of STn-KLH immunogen induced anti-STn DTH

  3. Clinical Implication of Elevated Human Cervical Cancer Oncogene-1 Expression in Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

    2012-01-01

    The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantit...

  4. The Role of XMRV, a Novel Xenotropic Murine Retrovirus, in Human Prostate Cancers

    Science.gov (United States)

    2011-05-01

    ultimately determine the true prevalence of these viruses in humans and then to determine whether there is a link to any pathology. BODY...characterization of the novel XMRV virus , documenting its tissue tropism and interferon-sensitivity. We also documented the prevalence of the virus in human ...correlation of XMRV with prostate cancer prognosis. The recog- nition that human papilloma viruses most often initiate cervical carcinomas has focused

  5. B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells

    International Nuclear Information System (INIS)

    Wu, Qiang; Kong, Xiang-jun; Xu, Xiao-chun; Lobie, Peter E; Zhu, Tao; Wu, Zheng-sheng; Liu, Xue; Yan, Hong; He, Yin-huan; Ye, Shan; Cheng, Xing-wang; Zhu, Gui-lu; Wu, Wen-yong; Wang, Xiao-nan

    2014-01-01

    B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer

  6. Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation.

    Directory of Open Access Journals (Sweden)

    Yasuko eKikuchi

    2013-12-01

    Full Text Available Cancer arises through accumulation of epigenetic and genetic alteration. Aberrant promoter methylation is a common epigenetic mechanism of gene silencing in cancer cells. We here performed genome-wide analysis of DNA methylation of promoter regions by Infinium HumanMethylation27 BeadChip, using 14 clinical papillary thyroid cancer samples and 10 normal thyroid samples. Among the 14 papillary cancer cases, 11 showed frequent aberrant methylation, but the other three cases showed no aberrant methylation at all. Distribution of the hypermethylation among cancer samples was non-random, which implied existence of a subset of preferentially methylated papillary thyroid cancer. Among 25 frequently methylated genes, methylation status of six genes (HIST1H3J, POU4F2, SHOX2, PHKG2, TLX3, HOXA7 was validated quantitatively by pyrosequencing. Epigenetic silencing of these genes in methylated papillary thyroid cancer cell lines was confirmed by gene re-expression following treatment with 5-aza-2'-deoxycytidine and trichostatin A, and detected by real-time RT-PCR. Methylation of these six genes was validated by analysis of additional 20 papillary thyroid cancer and 10 normal samples. Among the 34 cancer samples in total, 26 cancer samples with preferential methylation were significantly associated with mutation of BRAF/RAS oncogene (P=0.04, Fisher’s exact test. Thus we identified new genes with frequent epigenetic hypermethylation in papillary thyroid cancer, two subsets of either preferentially methylated or hardly methylated papillary thyroid cancer, with a concomitant occurrence of oncogene mutation and gene methylation. These hypermethylated genes may constitute potential biomarkers for papillary thyroid cancer.

  7. Making a virtue of necessity: the pleiotropic role of human endogenous retroviruses in cancer.

    Science.gov (United States)

    Kassiotis, George; Stoye, Jonathan P

    2017-10-19

    Like all other mammals, humans harbour an astonishing number of endogenous retroviruses (ERVs), as well as other retroelements, embedded in their genome. These remnants of ancestral germline infection with distinct exogenous retroviruses display various degrees of open reading frame integrity and replication capability. Modern day exogenous retroviruses, as well as the infectious predecessors of ERVs, are demonstrably oncogenic. Further, replication-competent ERVs continue to cause cancers in many other species of mammal. Moreover, human cancers are characterized by transcriptional activation of human endogenous retroviruses (HERVs). These observations conspire to incriminate HERVs as causative agents of human cancer. However, exhaustive investigation of cancer genomes suggests that HERVs have entirely lost the ability for re-infection and thus the potential for insertional mutagenic activity. Although there may be non-insertional mechanisms by which HERVs contribute to cancer development, recent evidence also uncovers potent anti-tumour activities exerted by HERV replication intermediates or protein products. On balance, it appears that HERVs, despite their oncogenic past, now represent potential targets for immune-mediated anti-tumour mechanisms.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Authors.

  8. Effect of cyclophilin A on gene expression in human pancreatic cancer cells.

    Science.gov (United States)

    Li, Min; Wang, Hao; Li, Fei; Fisher, William E; Chen, Changyi; Yao, Qizhi

    2005-11-01

    We previously found that cyclophilin A (CypA) is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147. In this study, we further investigated the effect of CypA on gene expression of several key molecules that are involved in pancreatic cancer cell proliferation. Human pancreatic cancer cell lines (Panc-1, MIA PaCa-2, and BxPC-3) and human pancreatic ductal epithelial (HPDE) cells were used. The messenger RNA (mRNA) levels of CypA, CypB, CD147, neuropilins (NRPs), vascular endothelial growth factor (VEGF), and VEGF receptors upon the treatment of exogenous recombinant human CypA were determined by real-time reverse-transcription polymerase chain reaction. Exogenous human recombinant CypA reduced the mRNA levels of NRP-1 and VEGF, but not endogenous CypA, CypB, and CD147, in Panc-1, MIA PaCa-2, and BxPC-3 cells. In contrast, HPDE cells showed a decrease of endogenous CypA and CD147 mRNA, but not detectable changes of CypB, NRPs, and VEGF mRNA levels upon exogenous CypA treatment. These data show that exogenous CypA downregulates NRP-1 and VEGF expression in pancreatic cancer cells. This effect is different in normal HPDE cells. Thus, soluble CypA may affect cell growth of pancreatic cancer.

  9. Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination

    Directory of Open Access Journals (Sweden)

    Takao Itoi

    2017-04-01

    Full Text Available This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC from malignant diseases, such as biliary tract cancer (BTC, intraductal papillary mucinous carcinoma (IPMC, and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41 of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140. Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel–Dwass test. Four multiple logistic regression models (MLR were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC of 0.970 (95% confidential interval (CI, 0.946–0.994, p < 0.0001. Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650–1.01, p = 0.0020 with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, pancreatic cancer-associated antigen (DUPAN2 and s-pancreas-1 antigen (SPAN1. Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

  10. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

    International Nuclear Information System (INIS)

    Raufman, Jean-Pierre; Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng

    2011-01-01

    Highlights: ► Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. ► Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. ► Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers – this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre-treatment with anti-MMP1 antibody. This study contributes to understanding

  11. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

  12. Cancer-associated fibroblasts are positively correlated with metastatic potential of human gastric cancers

    Directory of Open Access Journals (Sweden)

    Zhang Hao

    2010-06-01

    Full Text Available Abstract Background The prognosis of gastric cancer patients is difficult to predict because of defects in establishing the surgical-pathological features. Cancer-associated fibroblasts (CAFs have been found to play prominent role in promoting tumor growth, invasion and metastasis. Thus raises the hypothesis that the extent of CAFs prevalence may help to establish the prognosis of gastric cancer patients. Methods Immunochemistry and realtime-PCR experiments were carried out to compare the expression of proteins which are specific markers of CAFs or secreted by CAFs in the tumor and normal tissue specimens. The extent of CAFs' prevalence was graded according to immunochemical staining, and correlation was further analyzed between CAFs' prevalence and other tumor characteristics which may influence the prognosis of gastric cancer patients. Results Nearly 80 percent of normal gastric tissues were negative or weak positive for CAFs staining, while more than 60 percent of gastric cancer tissues were moderate or strong positive for CAFs staining. Realtime-PCR results also showed significant elevated expression of FAP, SDF-1 and TGF-β1 in gastric cancer tissues compared to normal gastric tissues. Further analysis showed that CAFs' prevalence was correlated with tumor size, depth of the tumor, lymph node metastasis, liver metastasis or peritoneum metastasis. Conclusions Reactive cancer associated fibroblasts (CAFs were frequently accumulated in gastric cancer tissues, and the prevalence of CAFs was correlated with tumor size, depth of the tumor and tumor metastasis, thus give some supports for establishing the prognosis of the gastric cancer patients.

  13. The role of human papillomavirus in head and neck cancer

    DEFF Research Database (Denmark)

    Lajer, Christel Braemer; Buchwald, Christian von

    2010-01-01

    Over the last 20 years, there has been increasing awareness of a subset of squamous cell carcinomas of the head and neck (HNSCC), i.e. HPV-positive HNSCC. These cancers seem to differ somewhat from HPV-negative HNSCC. Patients with HPV-positive HNSCC tend to be younger and have a lower intake...... of tobacco and alcohol. Distinct molecular profiles separate them from HPV-negative cancers and show similarities with HPV-positive cervical SCC. There is evidence that HPV-positive HNSCC is a sexually transmitted disease. Patients with HPV-positive HNSCC are often diagnosed at a late stage with large cystic......-negative HNSCC, and this seems to be related to the immune system. Whether the new vaccines for HPV will protect not only against cervical cancer but also against HPV-positive HNSCC remains unknown....

  14. AR-Signaling in Human Malignancies: Prostate Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Michael T. Schweizer

    2017-01-01

    Full Text Available In the 1940s Charles Huggins reported remarkable palliative benefits following surgical castration in men with advanced prostate cancer, and since then the androgen receptor (AR has remained the main therapeutic target in this disease. Over the past couple of decades, our understanding of AR-signaling biology has dramatically improved, and it has become apparent that the AR can modulate a number of other well-described oncogenic signaling pathways. Not surprisingly, mounting preclinical and epidemiologic data now supports a role for AR-signaling in promoting the growth and progression of several cancers other than prostate, and early phase clinical trials have documented preliminary signs of efficacy when AR-signaling inhibitors are used in several of these malignancies. In this article, we provide an overview of the evidence supporting the use of AR-directed therapies in prostate as well as other cancers, with an emphasis on the rationale for targeting AR-signaling across tumor types.

  15. Epigenome-based personalized medicine in human cancer.

    Science.gov (United States)

    Yan, Wenji; Herman, James G; Guo, Mingzhou

    2016-01-01

    Cancer genome sequencing has created an opportunity for precision medicine. Thus far, genetic alterations can only be used to guide treatment for small subsets of certain cancer types with these key alterations. Similar to mutations, epigenetic events are equally suitable for personalized medicine. DNA methylation alterations have been used to identify tumor-specific drug responsive markers. Methylation of MGMT sensitizes gliomas to alkylating agents is an example of epigenetic personalized medicine. Recent studies have revealed that 5-azacytidine and decitabine show activity in myelodysplasia, lung and other cancers. There are currently at least 20 kinds of histone deacetylase inhibitors in clinical testing. Inhibitors targeting other epigenetic regulators are being clinically tested, such as EZH2 inhibitor EPZ-6438.

  16. Human monoclonal antibody 99mTc-88BV59: detection of colorectal cancer, recurrent or metastatic disease and immunogenicity assessment

    International Nuclear Information System (INIS)

    Krause, B.J.; Baum, R.P.; Staib-Sebler, E.; Lorenz, M.; Niesen, A.; Hoer, G.

    1997-01-01

    This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of 99m Tc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). None of the patients showed a HAHA response as assessed by a solid-phase ELISA assay. The antibody scan detected about 25% more lesions than CT. In the detection of extrahepatic disease, the sensitivity of the antibody scan proved to be 68%, whereas the sensitivity of CT was 41%. (orig.). With 3 figs., 1 tab

  17. Human monoclonal antibody 99mTc-88BV59: detection of colorectal cancer, recurrent or metastatic disease and immunogenicity assessment.

    Science.gov (United States)

    Krause, B J; Baum, R P; Staib-Sebler, E; Lorenz, M; Niesen, A; Hör, G

    1997-01-01

    This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of 99mTc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). N