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Sample records for cancer killing effect

  1. Killing effect of different doses of preoperative iodine 131 therapy on thyroid cancer cells and its effect on salivary gland function

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Zheng; Tao Pu; Yi Luo; Xing-An Zhang; Zu-Mao Li

    2015-01-01

    Objective:To study the killing effect of different doses of preoperative iodine 131 therapy on thyroid cancer cells and its effect on salivary gland function.Methods:Patients diagnosed with thyroid cancer in our hospital from May 2013 to June 2014 were enrolled for study, given preoperative iodine 131 therapy and randomly divided into control group, low dose group, middle dose group and high dose group. Then cell apoptotic rate, cell cycle, cancer promoting gene and cancer suppressor gene expression in thyroid carcinoma tissue as well as salivary gland function were detected.Results: (1) cancer cell killing effect: compared with control group, cell apoptotic rates and number of cells in G0/G1 phase of low dose group, middle dose group and high dose group increased, number of cells in S and G2/M phase decreased, BRAF, Livin, MCM7 and CDK2 expression decreased, CCNG2 and PTEN expression increased; cell killing effect of middle dose group and high dose group were better than that of low dose group, and cell killing effect of middle dose group and high dose group had no differences; (2) salivary gland function: compared with control group, UI and SR in bilateral parotid and bilateral submandibular glands of low dose group, middle dose group and high dose group decreased; salivary gland damage effect of low dose group and middle dose group were weaker than that of high dose group, and salivary gland damage effect of low dose group and middle dose group had no differences.Conclusion:Middle dose of iodine 131 can take the killing effect on cancer cells and the protective effect on salivary glands into account; it’s an ideal dosage for preoperative iodine 131 internal radiation therapy of thyroid cancer patients.

  2. Surface chemistry influences cancer killing effect of TiO2 nanoparticles.

    Science.gov (United States)

    Thevenot, Paul; Cho, Jai; Wavhal, Dattatray; Timmons, Richard B; Tang, Liping

    2008-09-01

    Photocatalyzed titanium dioxide (TiO2) nanoparticles have been shown to eradicate cancer cells. However, the required in situ introduction of ultraviolet light limits the use of such a therapy in humans. In the present study the nonphotocatalytic anticancer effect of surface-functionalized TiO2 was examined. Nanoparticles bearing -OH, -NH(2), or -COOH surface groups were tested for their effect on in vitro survival of several cancer and control cell lines. The cells tested included B16F10 melanoma, Lewis lung carcinoma, JHU prostate cancer cells, and 3T3 fibroblasts. Cell viability was observed to depend on particle concentrations, cell types, and surface chemistry. Specifically, -NH(2) and -OH groups showed significantly higher toxicity than -COOH. Microscopic and spectrophotometric studies revealed nanoparticle-mediated cell membrane disruption leading to cell death. The results suggest that functionalized TiO2, and presumably other nanoparticles, can be surface-engineered for targeted cancer therapy.

  3. Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing

    Science.gov (United States)

    Wang, Xin; Liu, Kai; Yang, Guangbao; Cheng, Liang; He, Lu; Liu, Yumeng; Li, Yonggang; Guo, Liang; Liu, Zhuang

    2014-07-01

    Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via

  4. Killing effect of adenoviral mediated cytosine deaminase gene on human pancreatic cancer cell line PaTu 8988

    Institute of Scientific and Technical Information of China (English)

    PAN Xue; LI Zhao-shen; XU Guo-ming; CUI Long; ZHANG Su-zhen; GONG Yan-fang; TU Zhen-xing

    2001-01-01

    Objective: To evaluate the in vitro killing effects of cytosine deaminase gene mediated by adenovirus vector on human pancreatic carcinoma. Methods: Cytosine Deaminase (CD) gene was cloned into pAdTrack-CMV-CD, pAdTrack-CMV-CD and pAdEasy-1 were recombined in bacteria, and the products containing green fluorescent protein (GFP)were propagated in 293 cells and purified by cesium chloride gradient centrifugation. Human pancreatic carcinoma cell line 8988 were infected with this virus, then 5-FC was added; XTT assay was used to estimate the relative numbers of viable cells. Results: The positive clones were confirmed by using endonuclease digestion, and the titer of the virus containing CD gene was 2 × 1011 pfu/ml. It was found that 5-FC possessed significant cytotoxic activities for CD gene transfected 8988cell line, but had little effects on non-transfected pancreatic carcinoma cells. Conclusion: CD gene mediated by adenovirus has a high infectivity and is efficient for killing cultured pancreatic carcinoma cells, indicating suicide gene may be effective for pancreatic cancer in furure.

  5. GP73-regulated oncolytic adenoviruses possess potent killing effect on human liver cancer stem-like cells

    Science.gov (United States)

    Zhang, Rong; Ma, Buyun; Liu, Tao; Yang, Yu; Xie, Wenjie; Liu, Xianglei; Huang, Fang; Liu, Tao; Zhou, Xiumei; Liu, Xinyuan; Wang, Yigang

    2016-01-01

    Cancer stem cells (CSCs), also known as tumor-initiating cells, are highly metastatic, chemo-resistant and tumorigenic, and are critical for cancer development, maintenance and recurrence. Oncolytic adenovirus could targetedly kill CSCs and has been acted as a promising anticancer agent. Currently, a novel GP73-regulated oncolytic adenovirus GD55 was constructed to specifically treat liver cancer and exhibited obvious cytotoxicity effect. However, there remains to be confirmed that whether GD55 could effectively eliminate liver CSCs. We first utilized the suspension culture to enrich the liver CSCs-like cells, which acquires the properties of liver CSCs in self-renewal, differentiation, quiescence, chemo-resistance and tumorigenicity. The results indicated that GD55 elicited more significant cytotoxicity and stronger oncolytic effect in liver CSC-like cells compared to common oncolytic virus ZD55. Additionally, GD55 possessed the greater efficacy in suppressing the growth of implanted tumors derived from liver CSC-like cells than ZD55. Furthermore, GD55 induced remarkable apoptosis of liver CSC-like cells in vitro and in vivo, and inhibited the propogation of cells and angiogenesis in xenograft tumor tissues. Thus, GD55 may virtually represent an attractive therapeutic agent for targeting liver CSCs to achieve better clinical outcomes for HCC patients. PMID:27121064

  6. Targeting the Checkpoint to Kill Cancer Cells

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    Jan Benada

    2015-08-01

    Full Text Available Cancer treatments such as radiotherapy and most of the chemotherapies act by damaging DNA of cancer cells. Upon DNA damage, cells stop proliferation at cell cycle checkpoints, which provides them time for DNA repair. Inhibiting the checkpoint allows entry to mitosis despite the presence of DNA damage and can lead to cell death. Importantly, as cancer cells exhibit increased levels of endogenous DNA damage due to an excessive replication stress, inhibiting the checkpoint kinases alone could act as a directed anti-cancer therapy. Here, we review the current status of inhibitors targeted towards the checkpoint effectors and discuss mechanisms of their actions in killing of cancer cells.

  7. Novel innate cancer killing activity in humans

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    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.

  8. Dendritic cells loaded with pancreatic Cancer Stem Cells (CSCs lysates induce antitumor immune killing effect in vitro.

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    Tao Yin

    Full Text Available According to the cancer stem cells (CSCs theory, malignant tumors may be heterogeneous in which a small population of CSCs drive the progression of cancer. Because of their intrinsic abilities, CSCs may survive a variety of treatments and then lead to therapeutic resistance and cancer recurrence. Pancreatic CSCs have been reported to be responsible for the malignant behaviors of pancreatic cancer, including suppression of immune protection. Thus, development of immune strategies to eradicate pancreatic CSCs may be of great value for the treatment of pancreatic cancer. In this study, we enriched pancreatic CSCs by culturing Panc-1 cells under sphere-forming conditions. Panc-1 CSCs expressed low levels of HLA-ABC and CD86, as measured by flow cytometry analysis. We further found that the Panc-1 CSCs modulate immunity by inhibiting lymphocyte proliferation which is promoted by phytohemagglutinin (PHA and anti-CD3 monoclonal antibodies. The monocyte derived dendritic cells (DCs were charged with total lysates generated from Panc-1 CSCs obtained from tumor sphere culturing. After co-culturing with lymphocytes at different ratios, the Panc-1 CSCs lysates modified DC effectively promoted lymphocyte proliferation. The activating efficiency reached 72.4% and 74.7% at the ratios of 1∶10 and 1∶20 with lymphocytes. The activated lymphocytes secreted high levels of INF-γ and IL-2, which are strong antitumor cytokines. Moreover, Panc-1 CSCs lysates modified DC induced significant cytotoxic effects of lymphocytes on Panc-1 CSCs and parental Panc-1 cells, respectively, as shown by lactate dehydrogenase (LDH assay. Our study demonstrates that the development of CSCs-based vaccine is a promising strategy for treating pancreatic cancer.

  9. Low Temperature Plasma Kills SCaBER Cancer Cells

    Science.gov (United States)

    Barekzi, Nazir; van Way, Lucas; Laroussi, Mounir

    2013-09-01

    Squamous cell carcinoma of the bladder is a rare type of bladder cancer that forms as a result of chronic irritation of the epithelial lining of the bladder. The cell line used in this study is SCaBER (ATCC® HTB-3™) derived from squamous cell carcinoma of the human urinary bladder. Current treatments of bladder cancer include surgery, radiation and chemotherapy. However, the cost of these treatments, the potential toxicity of the chemotherapeutic agents and the systemic side-effects warrant an alternative to current cancer treatment. This paper represents preliminary studies to determine the effects of biologically tolerant plasma (BTP) on a cell line of human bladder cancer cells. Previous work by our group using the plasma pencil revealed the efficacy of BTP on leukemia cells suspended in solution. Based on these earlier findings we hypothesized that the plasma exposure would elicit a similar programmed cell death in the SCaBER cells. Trypan blue exclusion and MTT assays revealed the cell killing after exposure to BTP. Our study indicates that low temperature plasma generated by ionizing helium gas and the reactive species may be a suitable and safe alternative for cancer therapy.

  10. Preparation of arsenic trioxide-loaded albuminutes immuno-nanospheres and its specific killing effect on bladder cancer cell in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jie; ZENG Fu-qing; LI Chong; TONG Qiang-song; GAO Xiang; XIE Shu-sheng; YU Li-zhang

    2005-01-01

    Background Recently, arsenic trioxide (As2O3) was considered as a novel anti-tumor agent. However, it showed severe toxicity effect on normal tissue at the same time. To improve its therapeutic efficacy and decrease its toxicity,we prepared arsenic trioxide-loaded albuminutes immuno-nanospheres [As2O3-(HAS-NS)-BDI-1] targeted with nonoclonal antibody (McAb) BDI-1 and tested its specific killing effect against bladder cancer cell. Methods As2O3-HAS-NS was prepared by chemical cross-linking method. Monoclonal antibody BDI-1 was purified with ammonium sulphate saltingout and chromatography. Albuminutes microspheres were conjugated with McAb by SPDP cross-linking method.Concentration of As in As2O3- (HAS-NS)-BDI-1 and As2O3-HAS-NS was measured by atomic fluometry method. As2O3- (HAS-NS)-BDI-1 and its activity were detected by SDS-PAGE reduction electrophoresis, indirect immunofluorescence test, light microscope and scanning electron microscope observation. Acridine orange staining and tritiated thymidine (3H-TdR) incorporation tests were used to indicate specific killing activity of As2O3-(HAS-NS)-BDI-1 in vitro. Results In As2O3- (HAS-NS)-BDI-1 groups, we saw two protein bands in SDS-PAGE reduction electrophoresis.Albuminutes immuno-nanospheres were rounded with clear green fluorescence by immunofluorescence test. Under microscope, we observed that BIU-87 cells were covered with the As2O3- (HAS-NS)-BDI-1 and that As2O3- (HAS-NS)-BDI-1 moved with the BIU-87 cells. The albuminutes immuno-nanospheres were tightly junctioned with the BIU-87 cells.Specific killing activity of As2O3-(HAS-NS)-BDI-1 on bladder tumor cells was observed by acridine orange staining and 3H-TdR incorporation assays. Conclusions As2O3- (HAS-NS)-BDI-1 might bind specifically against BIU-87 cells, thus leading to high activity of killing bladder tumor cells.

  11. How Taxol/paclitaxel kills cancer cells

    OpenAIRE

    Weaver, Beth A

    2014-01-01

    Taxol (generic name paclitaxel) is a microtubule-stabilizing drug that is approved by the Food and Drug Administration for the treatment of ovarian, breast, and lung cancer, as well as Kaposi's sarcoma. It is used off-label to treat gastroesophageal, endometrial, cervical, prostate, and head and neck cancers, in addition to sarcoma, lymphoma, and leukemia. Paclitaxel has long been recognized to induce mitotic arrest, which leads to cell death in a subset of the arrested population. However, r...

  12. How Taxol/paclitaxel kills cancer cells.

    Science.gov (United States)

    Weaver, Beth A

    2014-09-15

    Taxol (generic name paclitaxel) is a microtubule-stabilizing drug that is approved by the Food and Drug Administration for the treatment of ovarian, breast, and lung cancer, as well as Kaposi's sarcoma. It is used off-label to treat gastroesophageal, endometrial, cervical, prostate, and head and neck cancers, in addition to sarcoma, lymphoma, and leukemia. Paclitaxel has long been recognized to induce mitotic arrest, which leads to cell death in a subset of the arrested population. However, recent evidence demonstrates that intratumoral concentrations of paclitaxel are too low to cause mitotic arrest and result in multipolar divisions instead. It is hoped that this insight can now be used to develop a biomarker to identify the ∼50% of patients that will benefit from paclitaxel therapy. Here I discuss the history of paclitaxel and our recently evolved understanding of its mechanism of action.

  13. Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer.

    Science.gov (United States)

    Roh, Jong-Lyel; Kim, Eun Hye; Park, Jin Young; Kim, Ji Won; Kwon, Minsu; Lee, Byung-Heon

    2014-10-15

    Adaptation to cellular stress is not a vital function of normal cells but is required of cancer cells, and as such might be a sensible target in cancer therapy. Piperlongumine is a naturally occurring small molecule selectively toxic to cancer cells. This study assesses the cytotoxicity of piperlongumine and its combination with cisplatin in head-and-neck cancer (HNC) cells in vitro and in vivo. The effect of piperlongumine, alone and in combination with cisplatin, was assessed in human HNC cells and normal cells by measuring growth, death, cell cycle progression, reactive oxygen species (ROS) production, and protein expression, and in tumor xenograft mouse models. Piperlongumine killed HNC cells regardless of p53 mutational status but spared normal cells. It increased ROS accumulation in HNC cells, an effect that can be blocked by the antioxidant N-acetyl-L-cysteine. Piperlongumine induced selective cell death in HNC cells by targeting the stress response to ROS, leading to the induction of death pathways involving JNK and PARP. Piperlongumine increased cisplatin-induced cytotoxicity in HNC cells in a synergistic manner in vitro and in vivo. Piperlongumine might be a promising small molecule with which to selectively kill HNC cells and increase cisplatin antitumor activity by targeting the oxidative stress response. PMID:25193861

  14. Role of nitric oxide in Salmonella typhimurium-mediated cancer cell killing

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    Contag Christopher H

    2010-04-01

    Full Text Available Abstract Background Bacterial targeting of tumours is an important anti-cancer strategy. We previously showed that strain SL7838 of Salmonella typhimurium targets and kills cancer cells. Whether NO generation by the bacteria has a role in SL7838 lethality to cancer cells is explored. This bacterium has the mechanism for generating NO, but also for decomposing it. Methods Mechanism underlying Salmonella typhimurium tumour therapy was investigated through in vitro and in vivo studies. NO measurements were conducted either by chemical assays (in vitro or using Biosensors (in vivo. Cancer cells cytotoxic assay were done by using MTS. Bacterial cell survival and tumour burden were determined using molecular imaging techniques. Results SL7838 generated nitric oxide (NO in anaerobic cell suspensions, inside infected cancer cells in vitro and in implanted 4T1 tumours in live mice, the last, as measured using microsensors. Thus, under these conditions, the NO generating pathway is more active than the decomposition pathway. The latter was eliminated, in strain SL7842, by the deletion of hmp- and norV genes, making SL7842 more proficient at generating NO than SL7838. SL7842 killed cancer cells more effectively than SL7838 in vitro, and this was dependent on nitrate availability. This strain was also ca. 100% more effective in treating implanted 4T1 mouse tumours than SL7838. Conclusions NO generation capability is important in the killing of cancer cells by Salmonella strains.

  15. Role of nitric oxide in Salmonella typhimurium-mediated cancer cell killing

    International Nuclear Information System (INIS)

    Bacterial targeting of tumours is an important anti-cancer strategy. We previously showed that strain SL7838 of Salmonella typhimurium targets and kills cancer cells. Whether NO generation by the bacteria has a role in SL7838 lethality to cancer cells is explored. This bacterium has the mechanism for generating NO, but also for decomposing it. Mechanism underlying Salmonella typhimurium tumour therapy was investigated through in vitro and in vivo studies. NO measurements were conducted either by chemical assays (in vitro) or using Biosensors (in vivo). Cancer cells cytotoxic assay were done by using MTS. Bacterial cell survival and tumour burden were determined using molecular imaging techniques. SL7838 generated nitric oxide (NO) in anaerobic cell suspensions, inside infected cancer cells in vitro and in implanted 4T1 tumours in live mice, the last, as measured using microsensors. Thus, under these conditions, the NO generating pathway is more active than the decomposition pathway. The latter was eliminated, in strain SL7842, by the deletion of hmp- and norV genes, making SL7842 more proficient at generating NO than SL7838. SL7842 killed cancer cells more effectively than SL7838 in vitro, and this was dependent on nitrate availability. This strain was also ca. 100% more effective in treating implanted 4T1 mouse tumours than SL7838. NO generation capability is important in the killing of cancer cells by Salmonella strains

  16. Ag nanoparticles sensitize IR-induced killing of cancer cells

    Institute of Scientific and Technical Information of China (English)

    Ruizhi Xu; Jun Ma; Xinchen Sun; Zhongping Chen; Xiaoli Jiang; Zhirui Guo; Lan Huang; Yang Li; Meng Wang; Changling Wang; Jiwei Liu; Xu Fan; Jiayu Gu; Xi Chen; Yu Zhang; Ning Gu

    2009-01-01

    @@ Dear Editor, Nanosized particulate systems combining better can-cer diagnosis with therapeutic effect are being designed based on the merging of nanotechnology with cellular and molecular techniques.

  17. Antibacterial activity of silver-killed bacteria: the "zombies" effect

    Science.gov (United States)

    Wakshlak, Racheli Ben-Knaz; Pedahzur, Rami; Avnir, David

    2015-04-01

    We report a previously unrecognized mechanism for the prolonged action of biocidal agents, which we denote as the zombies effect: biocidally-killed bacteria are capable of killing living bacteria. The concept is demonstrated by first killing Pseudomonas aeruginosa PAO1 with silver nitrate and then challenging, with the dead bacteria, a viable culture of the same bacterium: Efficient antibacterial activity of the killed bacteria is observed. A mechanism is suggested in terms of the action of the dead bacteria as a reservoir of silver, which, due to Le-Chatelier's principle, is re-targeted to the living bacteria. Langmuirian behavior, as well as deviations from it, support the proposed mechanism.

  18. Killing effect of TNF-related apoptosis inducing ligand regulated by tetracycline on gastric cancer cell line NCI-N87

    Institute of Scientific and Technical Information of China (English)

    Xiao-Chao Wei; Xin-Juan Wang; Kai-Chen; Lei Zhang; Yu Liang; Xin-Li Lin

    2001-01-01

    AIM To clone the cDNA fragment of human TRAIL (TNFrelated apoptosis inducing ligand) into a tetracyclineregulated gene expression system, the RevTet-On system, transduce expression vectors into a gastric carcinoma cell line-NCl-N87 and examine the effects of controlled expression of TRAIL in vitro on the gastric carcinoma cells. METHODS The full-length cDNA of TRAIL was inserted into a vector under the control of the tetracyclineresponsive element (TRE) to obtain the plasmid pRevTRETRAIL, which was transfected into a packaging cell line PT67. In addition, vector pRev-Tet- On and pRevTRE were also transfected into PT67 separately. After hygromycin and G418 selection, the viral titer was determined. The medium containing retroviral vectors was collected and used to transduce a gastric carcinoma cell line NCI-N87.The resulting cell line NCI-N87-Tet-On-TRE-TRAIL and a control cell line, NCI-N87-Tet-On-TRE, were established.TRAIL expression in the cell line was induced by incubating cells with doxycycline (Dox), which is a tetracycline analogue. The killing effect on gastric carcinoma cells was analyzed after induction. RESULTS The recombinant plasmid pRev-TRE-TRAIL was constructed. After hygromycin or G418 selection, the producer cell lines PT67-TRE, PT67-TRE-TRAIL and PT67TetOn were obtained, with titers of about 108CFU@ L-1 By transducing NCI-N87 cells with retroviral vectors from these cell lines, stable cell lines NCI-N87-Tet-On-TRETRAIL (NN3T) and control cell line NCI-N87-Tet-On-TRE (NN2T) were established. The growth curves of the selected cell lines were the same with the wild type NCIN87. When Dox was added, cell death was obvious in the test groups (29% -77%), whereas no difference was observed in control and wild type cell lines. With the addition of a medium from the test group, human leukemia cell line Jurkat was activated till death (83%), indicating the secretion of active TRAIL proteins from the test cells to the medium. CONCLUSION With the use of the

  19. Oncolytic adenoviruses kill breast cancer initiating CD44+CD24-/low cells.

    Science.gov (United States)

    Eriksson, Minna; Guse, Kilian; Bauerschmitz, Gerd; Virkkunen, Pekka; Tarkkanen, Maija; Tanner, Minna; Hakkarainen, Tanja; Kanerva, Anna; Desmond, Renee A; Pesonen, Sari; Hemminki, Akseli

    2007-12-01

    Cancer stem cells have been indicated in the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. In breast cancer, they may reside in the CD44(+)CD24(-/low) population. The use of oncolytic adenoviruses presents an attractive anti-tumor approach for eradication of these cells because their entry occurs through infection and they are, therefore, not susceptible to those mechanisms that commonly render stem cells resistant to many drugs. We isolated CD44(+)CD24(-/low) cells from patient pleural effusions and confirmed stem cell-like features including oct4 and sox2 expression and Hoechst 33342 exclusion. CD44(+)CD24(-/low) cells, including the Hoechst excluding subpopulation, could be effectively killed by oncolytic adenoviruses Ad5/3-Delta24 and Ad5.pk7-Delta24. In mice, CD44(+)CD24(-/low) cells formed orthotopic breast tumors but virus infection prevented tumor formation. Ad5/3-Delta24 and Ad5.pk7-Delta24 were effective against advanced orthotopic CD44(+)CD24(-/low)-derived tumors. In summary, Ad5/3-Delta24 and Ad5.pk7-Delta24 can kill CD44(+)CD24(-/low), and also committed breast cancer cells, making them promising agents for treatment of breast cancer. PMID:17848962

  20. Snail-Killing Effects of Streptomyces 218 Powder

    OpenAIRE

    V.O. Aina; A.A.J. Adewumi; C.O. Yao; M.Z. Shi; Hu, D. Y.; W.H. Chai

    2012-01-01

    This study is aimed at finding out the snail-killing effects of Streptomyces 218 powder on Oncomelania hupensis snails which are the vectors or intermediate host of Schiltosoma Japonicum (intestinal schistosomiasis) in china the tests were carried out in the laboratory and on the field. The snail-killing effects of Streptomyces218 powder, isolated from snail habitat at Anchang Village of Anxiang country in China was tested using the immersion and spraying methods. The tests on the Oncomelania...

  1. Sulindac enhances the killing of cancer cells exposed to oxidative stress.

    Directory of Open Access Journals (Sweden)

    Maria Marchetti

    Full Text Available BACKGROUND: Sulindac is an FDA-approved non-steroidal anti-inflammatory drug (NSAID that affects prostaglandin production by inhibiting cyclooxygenases (COX 1 and 2. Sulindac has also been of interest for more than decade as a chemopreventive for adenomatous colorectal polyps and colon cancer. PRINCIPAL FINDINGS: Pretreatment of human colon and lung cancer cells with sulindac enhances killing by an oxidizing agent such as tert-butyl hydroperoxide (TBHP or hydrogen peroxide. This effect does not involve cyclooxygenase (COX inhibition. However, under the conditions used, there is a significant increase in reactive oxygen species (ROS within the cancer cells and a loss of mitochondrial membrane potential, suggesting that cell death is due to apoptosis, which was confirmed by Tunel assay. In contrast, this enhanced killing was not observed with normal lung or colon cells. SIGNIFICANCE: These results indicate that normal and cancer cells handle oxidative stress in different ways and sulindac can enhance this difference. The combination of sulindac and an oxidizing agent could have therapeutic value.

  2. Selective cancer-killing ability of metal-based nanoparticles: implications for cancer therapy.

    Science.gov (United States)

    Akhtar, Mohd Javed; Alhadlaq, Hisham A; Kumar, Sudhir; Alrokayan, Salman A; Ahamed, Maqusood

    2015-11-01

    There has been little focus on the promising ability of metal-based nanoparticles (NPs) to kill cancer cells while sparing normal cells. Many in vitro and in vivo reports suggest that certain metal-based NPs are able to induce apoptosis and autophagy in cancer cells at specific concentrations that are not significantly toxic to non-cancerous cells. Those NPs are thought to exploit the oxidative stress conditions that prevail in cancer cells, which are largely exhausted of antioxidant ability. This review considers the induction of reactive oxygen species (ROS) by metal-based NPs as a mechanism for the specific killing of cancer cells. The article concomitantly provides a comprehensive description of the important pathways and molecules leading to programmed cell death (PCD), which occurs mainly via apoptosis, autophagy, and necroptosis. The PCD pathways are followed as ROS-burdened cancer cells succumb to ROS-generating metal-based NPs. Exploration of nanotechnology interventions in anticancer therapy demands further research into the mechanism of intracellular induction of ROS by metal-based NPs. Furthermore, the induction of ROS by NPs should be strictly controlled if ROS-based therapy is to become a paradigm in cancer therapy.

  3. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively?

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    Ravindran, Jayaraj; Prasad, Sahdeo; Aggarwal, Bharat B

    2009-09-01

    Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail. PMID:19590964

  4. Silver nanocrystals sensitize magnetic-nanoparticle-mediated thermo-induced killing of cancer cells

    Institute of Scientific and Technical Information of China (English)

    Lianke Liu; Fang Ni; Jianchao Zhang; Xiaoli Jiang; Xiang Lu; Zhirui Guo; Ruizhi Xu

    2011-01-01

    Magnetic nanoparticles (MNPs) can heat up tumor tissues and induce killing of cancer cells under external AC magnetic field. However, magnetic nanoparticles hyperthermia (MNPH) requires high concentration of MNPs that are injected into the tumor in order to obtain clinically needed thermal dose because of the complicated heat transfer in v/vo and the limited heat quality of MNPs. To cut down the dose of MNPs and enhance the effect of this Nanotherapy, we prepared silver nanoparticles (AgNPs) with different sizes and investigated the effects of these AgNPs on cancer cells in MNPH treatment. It was found that AgNPs could enhance thermo-sensitivity of glioma cells and this effect was size dependent. AgNPs could induce cell cycles arrested in G2/M phase and enhanced the apoptosis rate of cancer cells after hyperthermia. In glioma bearing rats model, MNPH combined with AgNPs could enhance Bax expression in cancer cells. Our results suggested that AgNPs could be a potential thermo-sensitizer and could be further developed for the design of Ag nanostructurebased thermal seeds for MNPH therapy.

  5. Synergistically killing activity of aspirin and histone deacetylase inhibitor valproic acid (VPA) on hepatocellular cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaofei; Zhu, Yanshuang [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); He, Huabin [Department of Orthopedics, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Lou, Lianqing; Ye, Weiwei; Chen, Yongxin [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Wang, Jinghe, E-mail: Xiaofeili2000@163.com [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China)

    2013-06-28

    Highlights: •Novel combination therapy using aspirin and valproic acid (VPA). •Combination of aspirin and VPA elicits synergistic cytotoxic effects. •Combination of aspirin and VPA significantly reduces the drug dosage required alone. •Combination of aspirin and VPA significantly inhibit tumor growth. •Lower dose of aspirin in combination therapy will minimize side effects of aspirin. -- Abstract: Aspirin and valproic acid (VPA) have been extensively studied for inducing various malignancies growth inhibition respectively, despite their severe side effects. Here, we developed a novel combination by aspirin and VPA on hepatocellular cancer cells (HCCs). The viability of HCC lines were analyzed by MTT assay, apoptotic analysis of HepG2 and SMMC-7721 cell was performed. Real time-PCR and Western blotting were performed to determine the expression of apoptosis related genes and proteins such as Survivin, Bcl-2/Bax, Cyclin D1 and p15. Moreover, orthotopic xenograft tumors were challenged in nude mice to establish murine model, and then therapeutic effect was analyzed after drug combination therapy. The viability of HCC lines’ significantly decreased after drug combination treatment, and cancer cell apoptosis in combination group increasingly induced compared with single drug use. Therapeutic effect was significantly enhanced by combination therapy in tumor volume and tumor weight decrease. From the data shown here, aspirin and VPA combination have a synergistic killing effect on hepatocellular cancers cells proliferation and apoptosis.

  6. A novel transferrin receptor-targeted hybrid peptide disintegrates cancer cell membrane to induce rapid killing of cancer cells

    Directory of Open Access Journals (Sweden)

    Kawamoto Megumi

    2011-08-01

    D cancer cells just in 10 min, to effectively kill these cells and induce approximately 80% apoptotic cell death but not in normal cells. The intravenous administration of TfR-lytic peptide in the athymic mice model significantly inhibited tumor progression. Conclusions TfR-lytic peptide might provide a potent and selective anticancer therapy for patients.

  7. Pseudomonas Exotoxin A: optimized by evolution for effective killing

    Directory of Open Access Journals (Sweden)

    Marta eMichalska

    2015-09-01

    Full Text Available Pseudomonas Exotoxin A (PE is the most toxic virulence factor of the pathogenic bacterium Pseudomonas aeruginosa. This review describes current knowledge about the intoxication pathways of PE. Moreover, PE represents a remarkable example for pathoadaptive evolution, how bacterial molecules have been structurally and functionally optimized under evolutionary pressure to effectively impair and kill their host cells.

  8. Selective killing of cancer cells by nanoparticle-assisted ultrasound

    OpenAIRE

    Kosheleva, Olga K.; Lai, Tsung-Ching; Chen, Nelson G.; Hsiao, Michael; Chen, Chung-Hsuan

    2016-01-01

    Background Intense ultrasound, such as that used for tumor ablation, does not differentiate between cancerous and normal cells. A method combining ultrasound and biocompatible gold or magnetic nanoparticles (NPs) was developed under in vitro conditions using human breast and lung epithelial cells, which causes ultrasound to preferentially destroy cancerous cells. Results Co-cultures of BEAS-2B normal lung cells and A549 cancerous lung cells labeled with green and red fluorescent proteins, res...

  9. Doxorubicin loaded 17β-estradiol based SWNT dispersions for target specific killing of cancer cells.

    Science.gov (United States)

    Ghosh, Moumita; Das, Prasanta Kumar

    2016-06-01

    The present work reports the synthesis of a 17β-estradiol based amphiphiles comprising of polyethylene glycol (PEG) moiety linked through succinic acid that non-covalently dispersed (76%) the single walled carbon nanotubes (SWNTs) in water. The superior exfoliation of carbon nanotubes was characterized by microscopic and spectroscopic studies. Significant stability of these SWNT dispersions was observed in the presence of protein in cell culture media and the nanohybrids were highly biocompatible toward mammalian cells. Anticancer drug doxorubicin loaded on these nanohybrids was selectively delivered within estrogen receptor rich cancer cells, MCF7 (breast cancer cell) and A549 (lung cancer cell). Microscopic studies showed the localization of doxorubicin within the cancer cell nucleus whereas no such localization was observed in ER negative cells. Both these ER positive cancer cells were killed by ∼3 fold higher efficiency than that of ER negative MDA-MB-231 (advanced breast cancer cell) and HeLa cells that are deprived of estrogen receptors. Thus, judiciously designed estradiol based nanohybrids proved to be excellent tool for SWNT dispersion and also for selectively killing of ER positive cancer cells. To the best of our knowledge, for the first time non-covalently modified SWNTs by estradiol based amphiphilic dispersing agent have been used for selective killing of ER positive cancer cells by doxorubicin loaded on dispersed SWNTs. It holds immense promise to be exploited as a cancer therapeutic agent. PMID:26970825

  10. Killing cancer cells by targeted drug-carrying phage nanomedicines

    Directory of Open Access Journals (Sweden)

    Yacoby Iftach

    2008-04-01

    Full Text Available Abstract Background Systemic administration of chemotherapeutic agents, in addition to its anti-tumor benefits, results in indiscriminate drug distribution and severe toxicity. This shortcoming may be overcome by targeted drug-carrying platforms that ferry the drug to the tumor site while limiting exposure to non-target tissues and organs. Results We present a new form of targeted anti-cancer therapy in the form of targeted drug-carrying phage nanoparticles. Our approach is based on genetically-modified and chemically manipulated filamentous bacteriophages. The genetic manipulation endows the phages with the ability to display a host-specificity-conferring ligand. The phages are loaded with a large payload of a cytotoxic drug by chemical conjugation. In the presented examples we used anti ErbB2 and anti ERGR antibodies as targeting moieties, the drug hygromycin conjugated to the phages by a covalent amide bond, or the drug doxorubicin conjugated to genetically-engineered cathepsin-B sites on the phage coat. We show that targeting of phage nanomedicines via specific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release, resulting in growth inhibition of the target cells in vitro with a potentiation factor of >1000 over the corresponding free drugs. Conclusion The results of the proof-of concept study presented here reveal important features regarding the potential of filamentous phages to serve as drug-delivery platform, on the affect of drug solubility or hydrophobicity on the target specificity of the platform and on the effect of drug release mechanism on the potency of the platform. These results define targeted drug-carrying filamentous phage nanoparticles as a unique type of antibody-drug conjugates.

  11. Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer

    OpenAIRE

    Roh, Jong-Lyel; Kim, Eun Hye; Park, Jin Young; Kim, Ji Won; Kwon, Minsu; Lee, Byung-Heon

    2014-01-01

    Adaptation to cellular stress is not a vital function of normal cells but is required of cancer cells, and as such might be a sensible target in cancer therapy. Piperlongumine is a naturally occurring small molecule selectively toxic to cancer cells. This study assesses the cytotoxicity of piperlongumine and its combination with cisplatin in head-and-neck cancer (HNC) cells in vitro and in vivo. The effect of piperlongumine, alone and in combination with cisplatin, was assessed in human HNC c...

  12. Snail-Killing Effects of Streptomyces 218 Powder

    Directory of Open Access Journals (Sweden)

    V.O. Aina

    2012-12-01

    Full Text Available This study is aimed at finding out the snail-killing effects of Streptomyces 218 powder on Oncomelania hupensis snails which are the vectors or intermediate host of Schiltosoma Japonicum (intestinal schistosomiasis in china the tests were carried out in the laboratory and on the field. The snail-killing effects of Streptomyces218 powder, isolated from snail habitat at Anchang Village of Anxiang country in China was tested using the immersion and spraying methods. The tests on the Oncomelania hupensis snails which are intermediate host of Streptomyces japonicum infection were carried out in the laboratory and in the field. The mean corrected snail mortalities of the immersion technique in the laboratory were 81.70 and 98.63% in 10 ppm of 218 solutions after 24 and 48 h, respectively. The mean corrected snail mortalities of the spraying tests in the laboratory were 82.90 and 87.90% at 3 and 5 days, respectively with 10 g/m2 218 powders. The snail-killing ability of 218 powders on the field determines by immersion and spraying methods were comparable to that of the chemical molluscicide-Niclosamide. The corrected snail mortality at 150 ppm of 218 powder (g/m2 and at 2 ppm of Niclosamide by immersion was 100% at the second time test after 24, 48 and 72 h. In the field spraying test, the mean corrected snail mortality at 100 ppm of 218 powders were 61.96 and 70.00% after 3 and 7 days of spraying respectively. At 2 ppm niclosamide, this was found to be 65.58 and 63.81%, respectively. The effective ingredients for the snail-killing are found to be located in the spore chains. Streptomyces 218 powder, although at higher concentrations, seems to be a promising mollusciciding biological agent. If developed further, this could compliment existing mollusciciding agents.

  13. A novel bispecific antibody, S-Fab, induces potent cancer cell killing.

    Science.gov (United States)

    Li, Li; He, Ping; Zhou, Changhua; Jing, Li; Dong, Bin; Chen, Siqi; Zhang, Ning; Liu, Yawei; Miao, Ji; Wang, Zhong; Li, Qing

    2015-01-01

    Bispecific antibodies that engage immune cells to kill cancer cells have been actively studied in cancer immunotherapy. In this study, we present a novel bispecific format, S-Fab, fabricated by linking a single-domain anti-carcinoembryonic antigen VHH to a conventional anti-CD3 Fab. In contrast to most bispecific antibodies, the S-Fab bispecific antibody can be efficiently expressed and purified from bacteria. The purified S-Fab is stable in serum and is able to recruit T cells to drive potent cancer cell killing. In xenograft models, the S-Fab antibody suppresses tumor growth in the presence of human immune cells. Our study suggested that the bispecific S-Fab format can be applied to a wide range of immunotherapies.

  14. 双特异性单抗对胃肠癌的体内杀伤作用%In vivo killing effect of bispecific single-chain antibody on gastric and colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    刘洪一; 李荣; 刘巨超; 李力; 梁文涛; 钟苑; 徐迎新

    2012-01-01

    Objective To investigate the killing effect of CIK cells mediated by bispecific single - chain antibody, anti - CD3 and anti - CEA, on gastric and colon cancer cells in vivo. Methods Gastric and colon cancer models in nude mice were established after BGC823 cells from human poorly differentiated gastric adenocarcinoma and SW1116 cells from human moderately differentiated colon adenocarcinoma were planted into nude mice. The mice were divided into 3 groups, which were injected with normal saline, CIK cells and CIK cells plus bispecific antibody, respectively, once every 3 days for 6 times. Then the tumors were removed and weighed, and the inhibition rate in each group was calculated. Results Both the CIK cells and CIK cells plus bispecific single - chain antibody could inhibit tumor growth. Inhibition rates of gastric cancer were 29. 90% and 44. 33% respectively. Inhibition rates of colon cancer were 14. 93% and 38. 81% respectively. Compared with CIK cell group, the size and weight of the tumor were significantly smaller in CIK cells plus bispecific singlechain antibody group. Conclusion CIK cells alone can inhibit tumor cell growth and combination of CIK cells and the bispecific single - chain antibody, anti - CD3 and anti - CEA, is more effective in inhibiting tumor growth.%目的 探讨抗CD3抗CEA双特异性单链抗体介导CIK细胞在体内杀伤胃肠癌的作用.方法 分别将人胃低分化腺癌BGC823细胞和人结肠中分化腺癌SW1116细胞种植裸鼠后,建立裸鼠胃癌及肠癌模型,分为3组分别经尾静脉注入生理盐水、CIK细胞及CIK细胞+双特异性单抗,每3天治疗1次,共6次,取出肿瘤组织称重,并计算出各组的抑瘤率.结果 在体内,CIK组和CIK+双抗组均可抑制肿瘤生长,对胃癌的抑瘤率分别为29.90%和44.33%.对结肠癌的抑瘤率分别为14.93%和38.81%.CIK+双抗组:胃癌及结肠癌的瘤体积、瘤重明显小于CIK组.结论 CIK细胞本身可以抑制肿瘤

  15. A Drosera-bioinspired hydrogel for catching and killing cancer cells

    OpenAIRE

    Shihui Li; Niancao Chen; Gaddes, Erin R.; Xiaolong Zhang; Cheng Dong; Yong Wang

    2015-01-01

    A variety of bioinspired materials have been successfully synthesized to mimic the sophisticated structures or functions of biological systems. However, it is still challenging to develop materials with multiple functions that can be performed synergistically or sequentially. The purpose of this work was to demonstrate a novel bioinspired hydrogel that can interact with cancer cells, functionally similar to Drosera in catching and killing prey. This hydrogel had two layers with the top one fu...

  16. A Drosera-bioinspired hydrogel for catching and killing cancer cells.

    Science.gov (United States)

    Li, Shihui; Chen, Niancao; Gaddes, Erin R; Zhang, Xiaolong; Dong, Cheng; Wang, Yong

    2015-01-01

    A variety of bioinspired materials have been successfully synthesized to mimic the sophisticated structures or functions of biological systems. However, it is still challenging to develop materials with multiple functions that can be performed synergistically or sequentially. The purpose of this work was to demonstrate a novel bioinspired hydrogel that can interact with cancer cells, functionally similar to Drosera in catching and killing prey. This hydrogel had two layers with the top one functionalized with oligonucleotide aptamers and the bottom one functionalized with double-stranded DNA. The results show that the top hydrogel layer was able to catch target cells with high efficiency and specificity, and that the bottom hydrogel layer could sequester doxorubicin (Dox) for sustained drug release. Importantly, the released Dox could kill 90% of the cells after 1-h residence of the cells on the hydrogel. After the cell release, this bifunctional hydrogel could be regenerated for continuous cell catching and killing. Therefore, the data presented in this study has successfully demonstrated the potential of developing a material system with the functions of attracting, catching and killing diseased cells (e.g., circulating tumor cells) or even invading microorganisms (e.g., bacteria). PMID:26396063

  17. Synergistic killing of lung cancer cells by cisplatin and radiation via autophagy and apoptosis.

    Science.gov (United States)

    Liu, Min; Ma, Shumei; Liu, Mingbo; Hou, Yufei; Liang, Bing; Su, Xu; Liu, Xiaodong

    2014-06-01

    Cisplatin is a commonly used drug for chemotherapy, however, whether it may be used synergistically with radiotherapy remains unclear. The present study investigated the underlying mechanisms of synergistic killing by radiosensitization and cisplatin, with a focus on the growth inhibition, apoptosis and autophagy of non-small cell human lung cancer cells in vitro and in a tumor xenograft in vivo. A549 cells were used for the in vitro experiments and divided into the following four treatment groups: Sham-irradiated; conventional radiotherapy (CRT) of five doses of 2 Gy every day; hyperfractionated radiotherapy of five doses of 2 Gy (1 Gy twice a day at 4 h intervals) every day; and CRT plus cisplatin. A xenograft tumor-bearing C57BL/6 model was established for the in vivo experiments and the above-mentioned treatments were administered. MTT and colony formation assays were used to detect cell viability and western blotting was performed to detect the levels of protein expression. Monodansylcadaverine staining and the immunofluorescence technique were used to analyze the autophagy rate, while flow cytometry and immunohistochemistry were performed to detect the expression levels of the genes associated with apoptosis and autophagy, including microtubule-associated protein 1 light chain 3 (MAPLC3)-II, phosphoinositide 3-kinase (PI3K) III, Beclin1, phosphorylated protein kinase B (p-AKT), damage-regulated autophagy modulator (DRAM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, caspase-3 and p21. The MTT assay demonstrated that cisplatin exhibits a dose-dependent cytotoxicity in A549 cells and synergizes with radiation to promote the cell-killing effect of radiation. In the xenograft mouse model of Lewis cells, cisplatin plus ionizing radiation (IR) (five doses of 2 Gy) yielded the most significant tumor suppression. The autophagic vacuoles, the ratio of MAPLC3-II to MAPLC3-I (LC3-II/LC3-I) and the levels of Beclin1 were found to increase in all treatment

  18. An Aqueous Extract of Marine Microalgae Exhibits Antimetastatic Activity through Preferential Killing of Suspended Cancer Cells and Anticolony Forming Activity

    Science.gov (United States)

    Somasekharan, Syam Prakash; El-Naggar, Amal; Sorensen, Poul H.

    2016-01-01

    Research on marine natural products as potential anticancer agents is still limited. In the present study, an aqueous extract of a Canadian marine microalgal preparation was assessed for anticancer activities using various assays and cell lines of human cancers, including lung, prostate, stomach, breast, and pancreatic cancers, as well as an osteosarcoma. In vitro, the microalgal extract exhibited marked anticolony forming activity. In addition, it was more toxic, as indicated by increased apoptosis, to nonadherent cells (grown in suspension) than to adherent cells. In vivo, an antimetastatic effect of the extract was observed in NOD-SCID mice carrying subrenal capsule xenografts of PC3 prostate cancer cells. The results of the present study suggest that the antimetastatic effect of the aqueous microalgal extract is based on inhibition of colony forming ability of cancer cells and the preferential killing of suspended cancer cells. Further research aimed at identification of the molecular basis of the anticancer activities of the microalgal extract appears to be warranted.

  19. 纳秒级陡脉冲电场对荷瘤小鼠乳腺癌的杀伤作用研究%In vivo killing effects of nanosecond pulsed electric fields on mouse breast cancer

    Institute of Scientific and Technical Information of China (English)

    刘轶; 薛志孝; 王超; 张海霞; 吕东灏

    2015-01-01

    Objective To explore the in vivo killing effects of nanosecond pulsed electric fields on mouse breast cancer in tumor bearing BALB/c mice. Methods Twenty four BALB/c mice models with subcutaneous EMT-6 breast cancer were prepared and divided into experimental group and control group (n=12). In experimental group, the mice were treated by the pulsed electric fields with peak voltage of 700 V/cm, rise times of 57 ns, durations of 70μs and duty ratio of 50%on the tumor tissue with two parallel electrodes under anaesthesia. One hundred pulses were given and the energy was just 9.75 J with effective action period of 7 ms. Tumor volume, animal weight and histopathologic changes after 1, 3, 5 and 7 d were observed after irreversible electroporation. Results The tumor volume in experimental group increased more slowly than that in control group, especially at the 1-3 d after treatment with a standstill. Histopathological examination results showed that the tumor tissue had obvious coagulation necrosis and tissue edema after electrical stimulation treatment, and mass vacuole like structure appeared in tumor tissue from the third day after treatment and vascular injury occurred at the early stage. Conclusions In the given field conditions, steep pulsed electric field has inhibitory effect on tumor growth. In order to achieve more ideal tumor therapy effect, further studies on steep pulse dose are needed.%目的:以BALB/c荷瘤小鼠为对象,探讨纳秒级陡脉冲电场对在体小鼠乳腺癌的杀伤效应。方法取24只皮下接种小鼠乳腺癌细胞EMT-6的BALB/c荷瘤鼠,分为实验组和对照组,每组12只。在麻醉状态下,采用场强为700 V/cm、脉宽为70μs、上升时间为57 ns、占空比为50%的陡脉冲电场,利用自制的电极针插入实验组小鼠肿瘤两端进行电刺激处理,脉冲个数为100个,能量为9.75 J,有效作用时间仅为7 ms。对照组不进行电刺激,其他处理相同。隔天测量动物

  20. The effect of road kills on amphibian populations

    OpenAIRE

    Hels, Tove; Buchwald,, Erik

    2001-01-01

    The diurnal movement patterns of Triturus vulgaris, T. cristatus, Pelobates fuscus, Bufo bufo, Rana temporaria, and R. arvalis were investigated during five breeding seasons (1994-1998). Two main questions were addressed: 1) What is the probability of an individual amphibian getting killed when crossing the road? and 2) What fraction of the amphibian populations gets killed by traffic? The rate of movement of 203 adult amphibians was recorded. Information on traffic loads was provided, and mo...

  1. Carbon-ion beam irradiation kills X-ray-resistant p53-null cancer cells by inducing mitotic catastrophe.

    Directory of Open Access Journals (Sweden)

    Napapat Amornwichet

    Full Text Available BACKGROUND AND PURPOSE: To understand the mechanisms involved in the strong killing effect of carbon-ion beam irradiation on cancer cells with TP53 tumor suppressor gene deficiencies. MATERIALS AND METHODS: DNA damage responses after carbon-ion beam or X-ray irradiation in isogenic HCT116 colorectal cancer cell lines with and without TP53 (p53+/+ and p53-/-, respectively were analyzed as follows: cell survival by clonogenic assay, cell death modes by morphologic observation of DAPI-stained nuclei, DNA double-strand breaks (DSBs by immunostaining of phosphorylated H2AX (γH2AX, and cell cycle by flow cytometry and immunostaining of Ser10-phosphorylated histone H3. RESULTS: The p53-/- cells were more resistant than the p53+/+ cells to X-ray irradiation, while the sensitivities of the p53+/+ and p53-/- cells to carbon-ion beam irradiation were comparable. X-ray and carbon-ion beam irradiations predominantly induced apoptosis of the p53+/+ cells but not the p53-/- cells. In the p53-/- cells, carbon-ion beam irradiation, but not X-ray irradiation, markedly induced mitotic catastrophe that was associated with premature mitotic entry with harboring long-retained DSBs at 24 h post-irradiation. CONCLUSIONS: Efficient induction of mitotic catastrophe in apoptosis-resistant p53-deficient cells implies a strong cancer cell-killing effect of carbon-ion beam irradiation that is independent of the p53 status, suggesting its biological advantage over X-ray treatment.

  2. 白细胞介素-2增强淋巴细胞对乳腺癌细胞的杀伤作用%Killing effect of interlukin-2 on breast cancer cells by promoting expansion of lymphocytes in vitro

    Institute of Scientific and Technical Information of China (English)

    熊一全; 黄韬; 赵向旺; 田元; 张景辉

    2015-01-01

    Objective To discuss the inhibitory effect of lymphocytes and interlukin-2 (IL-2)on hormone receptor positive (ER +) breast cancer cells MCF-7,and to investigate the mechanism by which IL-2 promotes the killing effects of lymphocytes.Methods Lymphocytes and IL-2 with different concentrations were co-cultured with MCF-7 cells respectively.Cell counting kit-8 (CCK-8) was used to analyze the the viability of cancer cells.Results In MCF-7 cells treated with 1 000 U IL-2,the effect of IL-2 promoting expansion of lymphocytes was 30.94%,and the killing effect of IL-2 on MCF-7 cells by lymphocytes was 91.24%.The killing effect of lymphocytes on MCF-7 cells was not enhanced by increasing the concentration of IL-2.Conclusion IL-2 prompted the tumor inhibitory effect on ER + breast cancer cells MCF-7%目的 观察淋巴细胞以及白细胞介素-2(IL-2)联合淋巴细胞对于激素受体阳性(ER+)的乳癌细胞株MCF-7的杀伤作用,探讨IL-2增强淋巴细胞的抑癌效应.方法 分别用不同浓度的淋巴细胞以及IL-2加淋巴细胞与乳腺癌细胞株MCF-7共培养,细胞计数试剂盒(CCK-8)法对比分析淋巴细胞对MCF-7细胞的杀伤效应的差异.结果 每孔1 000 U IL-2促进淋巴细胞增殖效应为30.94%;促进淋巴细胞杀伤MCF-7效应为91.24%,增加IL-2的浓度并未增加淋巴细胞杀伤MCF-7能力.结论 IL-2能促进淋巴细胞对MCF-7的杀伤作用.

  3. A partner monoclonal antibody to Moab 730 kills 100% of DU145 and PC3 androgen-independent cancer cells

    Indian Academy of Sciences (India)

    Hemant Kumar Vyas; Rahul Pal; Nirmal K Lohiya; G P Talwar

    2009-12-01

    A number of therapeutic options are available for patients with prostate carcinoma till the time that the tumour is hormone dependent. However, no fully effective therapy is available for the treatment of androgen-independent prostate carcinomas. Antibodies directed at epitopes unique to or overexpressed on the cancer cells could be of therapeutic utility. A monoclonal antibody (Moab) 2C4 has been generated, which binds with cells of two androgenindependent prostate cancers, DU145 and PC3, and does not bind to peripheral blood leukocytes (PBLs) of healthy donors. This antibody, along with the previously developed Moab 730, kills 100% of both DU145 and PC3 cells in the presence of complement and does not have a deleterious effect on PBLs of healthy males. The anti-tumour action of the two antibodies prevents the establishment of DU145 cell tumour in nude mice in vivo. Moab 2C4 in combination with 730 has potential for use as therapy for androgen-independent cancers.

  4. Effects of Vegetation Structure on the Location of Lion Kill Sites in African Thicket.

    Directory of Open Access Journals (Sweden)

    Andrew B Davies

    Full Text Available Predator-prey relationships are integral to ecosystem stability and functioning. These relationships are, however, difficult to maintain in protected areas where large predators are increasingly being reintroduced and confined. Where predators make kills has a profound influence on their role in ecosystems, but the relative importance of environmental variables in determining kill sites, and how these might vary across ecosystems is poorly known. We investigated kill sites for lions in South Africa's thicket biome, testing the importance of vegetation structure for kill site locations compared to other environmental variables. Kill sites were located over four years using GPS telemetry and compared to non-kill sites that had been occupied by lions, as well as to random sites within lion ranges. Measurements of 3D vegetation structure obtained from Light Detection and Ranging (LiDAR were used to calculate the visible area (viewshed around each site and, along with wind and moonlight data, used to compare kill sites between lion sexes, prey species and prey sexes. Viewshed area was the most important predictor of kill sites (sites in dense vegetation were twice as likely to be kill sites compared to open areas, followed by wind speed and, less so, moonlight. Kill sites for different prey species varied with vegetation structure, and male prey were killed when wind speeds were higher compared to female prey of the same species. Our results demonstrate that vegetation structure is an important component of predator-prey interactions, with varying effects across ecosystems. Such differences require consideration in terms of the ecological roles performed by predators, and in predator and prey conservation.

  5. Effects of Vegetation Structure on the Location of Lion Kill Sites in African Thicket

    Science.gov (United States)

    Davies, Andrew B.; Tambling, Craig J.; Kerley, Graham I. H.; Asner, Gregory P.

    2016-01-01

    Predator-prey relationships are integral to ecosystem stability and functioning. These relationships are, however, difficult to maintain in protected areas where large predators are increasingly being reintroduced and confined. Where predators make kills has a profound influence on their role in ecosystems, but the relative importance of environmental variables in determining kill sites, and how these might vary across ecosystems is poorly known. We investigated kill sites for lions in South Africa’s thicket biome, testing the importance of vegetation structure for kill site locations compared to other environmental variables. Kill sites were located over four years using GPS telemetry and compared to non-kill sites that had been occupied by lions, as well as to random sites within lion ranges. Measurements of 3D vegetation structure obtained from Light Detection and Ranging (LiDAR) were used to calculate the visible area (viewshed) around each site and, along with wind and moonlight data, used to compare kill sites between lion sexes, prey species and prey sexes. Viewshed area was the most important predictor of kill sites (sites in dense vegetation were twice as likely to be kill sites compared to open areas), followed by wind speed and, less so, moonlight. Kill sites for different prey species varied with vegetation structure, and male prey were killed when wind speeds were higher compared to female prey of the same species. Our results demonstrate that vegetation structure is an important component of predator-prey interactions, with varying effects across ecosystems. Such differences require consideration in terms of the ecological roles performed by predators, and in predator and prey conservation. PMID:26910832

  6. Oxidative stress contributes to the tamoxifen-induced killing of breast cancer cells: implications for tamoxifen therapy and resistance

    OpenAIRE

    Bekele, Raie T.; Ganesh Venkatraman; Rong-Zong Liu; Xiaoyun Tang; Si Mi; Benesch, Matthew G. K.; Mackey, John R; Roseline Godbout; Curtis, Jonathan M.; McMullen, Todd P. W.; Brindley, David N.

    2016-01-01

    Tamoxifen is the accepted therapy for patients with estrogen receptor-α (ERα)-positive breast cancer. However, clinical resistance to tamoxifen, as demonstrated by recurrence or progression on therapy, is frequent and precedes death from metastases. To improve breast cancer treatment it is vital to understand the mechanisms that result in tamoxifen resistance. This study shows that concentrations of tamoxifen and its metabolites, which accumulate in tumors of patients, killed both ERα-positiv...

  7. Combining carbon ion irradiation and non-homologous end-joining repair inhibitor NU7026 efficiently kills cancer cells

    International Nuclear Information System (INIS)

    Our previous data demonstrated that targeting non-homologous end-joining repair (NHEJR) yields a higher radiosensitivity than targeting homologous recombination repair (HRR) to heavy ions using DNA repair gene knockouts (KO) in mouse embryonic fibroblast (MEF). In this study, we determined if combining the use of an NHEJR inhibitor with carbon (C) ion irradiation was more efficient in killing human cancer cells compared with only targeting a HRR inhibitor. The TP53-null human non-small cell lung cancer cell line H1299 was used for testing the radiosensitizing effect of NHEJR-related DNA-dependent protein kinase (DNA-PK) inhibitor NU7026, HRR-related Rad51 inhibitor B02, or both to C ion irradiation using colony forming assays. The mechanism underlying the inhibitor radiosensitization was determined by flow cytometry after H2AX phosphorylation staining. HRR-related Rad54-KO, NHEJR-related Lig4-KO, and wild-type TP53-KO MEF were also included to confirm the suppressing effect specificity of these inhibitors. NU7026 showed significant sensitizing effect to C ion irradiation in a concentration-dependent manner. In contrast, B02 showed a slight sensitizing effect to C ion irradiation. The addition of NU7026 significantly increased H2AX phosphorylation after C ion and x-ray irradiations in H1299 cells, but not B02. NU7026 had no effect on radiosensitivity to Lig4-KO MEF and B02 had no effect on radiosensitivity to Rad54-KO MEF in both irradiations. These results suggest that inhibitors targeting the NHEJR pathway could significantly enhance radiosensitivity of human cancer cells to C ion irradiation, rather than targeting the HRR pathway. The online version of this article (doi:10.1186/s13014-015-0536-z) contains supplementary material, which is available to authorized users

  8. Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy

    Directory of Open Access Journals (Sweden)

    Jeyamohan P

    2013-07-01

    Full Text Available Prashanti Jeyamohan, Takashi Hasumura, Yutaka Nagaoka, Yasuhiko Yoshida, Toru Maekawa, D Sakthi Kumar Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Japan Abstract: The photothermal effect of single-walled carbon nanotubes (SWCNTs in combination with the anticancer drug doxorubicin (DOX for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX binds at physiological pH (pH 7.4 and is released only at a lower pH, ie, lysosomal pH (pH 4.0, which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light–heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy. Keywords: cancer, nanotherapy, SWCNTs, targeted drug delivery

  9. Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?

    OpenAIRE

    Ravindran, Jayaraj; Prasad, Sahdeo; Aggarwal, Bharat B.

    2009-01-01

    Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one ...

  10. Effect of Ciprofloxacin on Killing of Actinobacillus actinomycetemcomitans by Polymorphonuclear Leukocytes

    OpenAIRE

    Cacchillo, David A.; Walters, John D.

    2002-01-01

    Actinobacillus actinomycetemcomitans, a pathogen associated with aggressive periodontitis, resists phagocytic killing by polymorphonuclear leukocytes (PMNs). It is susceptible to ciprofloxacin, which PMNs actively accumulate. This study tested the hypothesis that ciprofloxacin-loaded PMNs are more effective at killing A. actinomycetemcomitans than control PMNs. Isolated human PMNs were loaded by brief incubation with 0.5 μg of ciprofloxacin/ml. Opsonized bacteria (ATCC 43718) were incubated a...

  11. The Effect of Bacteriophage Preparations on Intracellular Killing of Bacteria by Phagocytes

    Directory of Open Access Journals (Sweden)

    Ewa Jończyk-Matysiak

    2015-01-01

    Full Text Available Intracellular killing of bacteria is one of the fundamental mechanisms against invading pathogens. Impaired intracellular killing of bacteria by phagocytes may be the reason of chronic infections and may be caused by antibiotics or substances that can be produced by some bacteria. Therefore, it was of great practical importance to examine whether phage preparations may influence the process of phagocyte intracellular killing of bacteria. It may be important especially in the case of patients qualified for experimental phage therapy (approximately half of the patients with chronic bacterial infections have their immunity impaired. Our analysis included 51 patients with chronic Gram-negative and Gram-positive bacterial infections treated with phage preparations at the Phage Therapy Unit in Wroclaw. The aim of the study was to investigate the effect of experimental phage therapy on intracellular killing of bacteria by patients’ peripheral blood monocytes and polymorphonuclear neutrophils. We observed that phage therapy does not reduce patients’ phagocytes’ ability to kill bacteria, and it does not affect the activity of phagocytes in patients with initially reduced ability to kill bacteria intracellularly. Our results suggest that experimental phage therapy has no significant adverse effects on the bactericidal properties of phagocytes, which confirms the safety of the therapy.

  12. Selective killing of cancer cells by iron oxide nanoparticles mediated through reactive oxygen species via p53 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ahamed, Maqusood, E-mail: maqusood@gmail.com; Alhadlaq, Hisham A.; Khan, M. A. Majeed [King Saud University, King Abdullah Institute for Nanotechnology (Saudi Arabia); Akhtar, Mohd. Javed [University of Lucknow, Department of Zoology (India)

    2013-01-15

    Iron oxide (Fe{sub 3}O{sub 4}) nanoparticles (NPs) are increasingly recognized for their utility in biomedical applications. However, little is known about the anticancer activity of Fe{sub 3}O{sub 4} NPs. This study was designed to investigate whether Fe{sub 3}O{sub 4} NPs induced toxicity in a cell-specific manner and determine the possible mechanisms of toxicity caused by Fe{sub 3}O{sub 4} NPs in cancer cells. Fe{sub 3}O{sub 4} NPs used in this study were synthesized by green method using {alpha}-d-glucose as a reducing agent. Prepared Fe{sub 3}O{sub 4} NPs were spherical in shape with a smooth surface, were fairly distributed, and had an average diameter of 23 nm. Cytotoxicity of Fe{sub 3}O{sub 4} NPs was examined against two types of cancer cells (human hepatocellular carcinoma HepG2 and human lung adenocarcinoma A549) and two normal cells (human lung fibroblast IMR-90 and rat hepatocytes). Fe{sub 3}O{sub 4} NPs exerted distinct effects on cell viability via killing of cancer cells while posing no toxicity on normal cells. Fe{sub 3}O{sub 4} NPs were found to induce depletion of glutathione and induction of reactive oxygen species (ROS) in both types of cancer cells (HepG2 and A549). Further, co-exposure of ascorbic acid significantly attenuated the Fe{sub 3}O{sub 4} NPs-induced oxidative stress. The mRNA levels of tumor suppressor gene p53 and apoptotic genes (caspase-3 and caspase-9) were up-regulated in both types of cancer cells due to Fe{sub 3}O{sub 4} NPs exposure. Protein level of p53, along with the higher activity of caspase-3 and caspase-9 enzymes, was also up-regulated by Fe{sub 3}O{sub 4} NPs. Taken together, our data demonstrated that Fe{sub 3}O{sub 4} NPs selectively induced apoptosis in cancer cells (HepG2 and A549) through up-regulation of p53 that might be mediated by ROS through which most of the anticancer drugs trigger apoptosis. The present study warrants further investigation on anticancer activity of Fe{sub 3}O{sub 4} NPs in relevant

  13. Effect of Shark Liver Oil on Peritoneal Murine Macrophages in Responses to Killed-Candida albicans

    Directory of Open Access Journals (Sweden)

    Monire Hajimoradi

    2009-09-01

    Full Text Available Objective(sShark Liver Oil (SLO is an immunomodulator. Macrophages play a key role in host defense against pathogens like fungi. Candida albicans have mechanisms to escape immune system. We determined the effect of killed-Candida on the in vitro viability of macrophages and the effect of SLO on augmentation of this potency.Materials and MethodsPeritoneal macrophages were separated and cultured (3×105/well. At first, the effect of killed-Candida (200 cells/well on macrophage viability was evaluated, using MTT test. Then, MTT was performed on macrophages stimulated with killed-Candida in the presence of SLO. ResultsKilled-Candida suppressed the ability of MTT reduction and hence macrophages viability (P=0.026, but addition of SLO (100 mg/ml significantly enhanced cell viability (P=0.00. So, SLO could neutralize the inhibitory effect of Candida.ConclusionSimultaneous with cytotoxic effect of killed-Candida cells on macrophages viability, SLO augment macrophages viability. So, it can be applied in candidiasis as a complement.

  14. Design, synthesis, and in vitro and in vivo biological studies of a 3'-deoxythymidine conjugate that potentially kills cancer cells selectively.

    Directory of Open Access Journals (Sweden)

    Qiong Wei

    Full Text Available Thymidine kinases (TKs have been considered one of the potential targets for anticancer therapeutic because of their elevated expressions in cancer cells. However, nucleobase analogs targeting TKs have shown poor selective cytotoxicity in cancer cells despite effective antiviral activity. 3'-Deoxythymidine phenylquinoxaline conjugate (dT-QX was designed as a novel nucleobase analog to target TKs in cancer cells and block cell replication via conjugated DNA intercalating quinoxaline moiety. In vitro cell screening showed that dT-QX selectively kills a variety of cancer cells including liver carcinoma, breast adenocarcinoma and brain glioma cells; whereas it had a low cytotoxicity in normal cells such as normal human liver cells. The anticancer activity of dT-QX was attributed to its selective inhibition of DNA synthesis resulting in extensive mitochondrial superoxide stress in cancer cells. We demonstrate that covalent linkage with 3'-deoxythymidine uniquely directed cytotoxic phenylquinoxaline moiety more toward cancer cells than normal cells. Preliminary mouse study with subcutaneous liver tumor model showed that dT-QX effectively inhibited the growth of tumors. dT-QX is the first molecule of its kind with highly amendable constituents that exhibits this selective cytotoxicity in cancer cells.

  15. Selective Killing Effects of Cold Atmospheric Pressure Plasma with NO Induced Dysfunction of Epidermal Growth Factor Receptor in Oral Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Jung-Hwan Lee

    Full Text Available The aim of this study is to investigate the effects of cold atmospheric pressure plasma (CAP-induced radicals on the epidermal growth factor receptor (EGFR, which is overexpressed by oral squamous cell carcinoma, to determine the underlying mechanism of selective killing. CAP-induced highly reactive radicals were observed in both plasma plume and cell culture media. The selective killing effect was observed in oral squamous cell carcinoma compared with normal human gingival fibroblast. Degradation and dysfunction of EGFRs were observed only in the EGFR-overexpressing oral squamous cell carcinoma and not in the normal cell. Nitric oxide scavenger pretreatment in cell culture media before CAP treatment rescued above degradation and dysfunction of the EGFR as well as the killing effect in oral squamous cell carcinoma. CAP may be a promising cancer treatment method by inducing EGFR dysfunction in EGFR-overexpressing oral squamous cell carcinoma via nitric oxide radicals.

  16. Selective Killing Effects of Cold Atmospheric Pressure Plasma with NO Induced Dysfunction of Epidermal Growth Factor Receptor in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Lee, Jung-Hwan; Om, Ji-Yeon; Kim, Yong-Hee; Kim, Kwang-Mahn; Choi, Eun-Ha; Kim, Kyoung-Nam

    2016-01-01

    The aim of this study is to investigate the effects of cold atmospheric pressure plasma (CAP)-induced radicals on the epidermal growth factor receptor (EGFR), which is overexpressed by oral squamous cell carcinoma, to determine the underlying mechanism of selective killing. CAP-induced highly reactive radicals were observed in both plasma plume and cell culture media. The selective killing effect was observed in oral squamous cell carcinoma compared with normal human gingival fibroblast. Degradation and dysfunction of EGFRs were observed only in the EGFR-overexpressing oral squamous cell carcinoma and not in the normal cell. Nitric oxide scavenger pretreatment in cell culture media before CAP treatment rescued above degradation and dysfunction of the EGFR as well as the killing effect in oral squamous cell carcinoma. CAP may be a promising cancer treatment method by inducing EGFR dysfunction in EGFR-overexpressing oral squamous cell carcinoma via nitric oxide radicals.

  17. ROS accumulation by PEITC selectively kills ovarian cancer cells via UPR-mediated apoptosis

    Directory of Open Access Journals (Sweden)

    Yoon-hee eHong

    2015-07-01

    Full Text Available Unfolded protein response (UPR is crucial for both survival and death of mammalian cells, which is regulated by reactive oxygen species (ROS and nutrient depletion. In this study, we demonstrated the effect of ROS-accumulation, induced by β-phenethyl isothiocyanate (PEITC, on UPR mediated apoptosis in ovarian cancer cells. We used ovarian cancer cell lines, PA-1 and SKOV-3, with different p53 status (wild- and null- type, respectively. PEITC caused increased ROS-accumulation and inhibited proliferation selectively in ovarian cancer cells, and glutathione (GSH depletion in SKOV-3. However, PEITC did not cause any effect in normal ovarian epithelial cells and peripheral blood mononuclear cells. After 48 h of PEITC treatment (5 µM, apoptotic cell death was shown to increase significantly in the ovarian cancer cells and not in the normal cells. The key regulator of UPR-mediated apoptosis, CHOP/GADD153 and ER resident chaperone BiP/GRP78 were parallely up-regulated with activation of two major sensors of the UPR (PERK and ATF-6 in PA-1; PERK, and IRE1α in SKOV-3 in response to ROS accumulation induced by PEITC (5 µM. ROS scavenger, N-acetyl-cysteine (NAC, attenuated the effect of PEITC on UPR signatures (P-PERK, IRE1α, CHOP/GADD153, and BiP/GRP78, suggesting the involvement of ROS in UPR-mediated apoptosis. Altogether, PEITC induces UPR-mediated apoptosis in ovarian cancer cells via accumulation of ROS in a cancer-specific manner.

  18. EFFECTS OF CARBOXYMETHLY DEXTRAN MAGNETIC NANOPARTICLES CARRIER SYSTEM ASSOCIATED WITH EXTERNAL MAGNETIC FIELDS ON KILLING TUMOR CELLS AND GENE TRANSFECTION

    Institute of Scientific and Technical Information of China (English)

    CAO Zheng-guo; ZHOU Si-wei; LIU Ji-hong

    2005-01-01

    Objective: To investigate the preparation of the carboxymethly dextran iron oxide magnetic nanoparticles (CDMN) and the effects of CDMN carrier system associated with external magnetic fields on killing tumor cells and gene transfection in vitro. Methods: Epirubicin-CDMN (EPI-CDMN) and green fluorescent protein (GFP) plasmid-CDMN (GFP-CDMN) were prepared by the oxidation-reduction procedure and their characters were detected, respectively. The effects of EPI-CDMN associated with external pulsed electromagnetic fields (PEMFs) (10 mT) on killing human bladder cancer BIU-87 cells were studied by MTT assay and Annexin-V/PI double-labeled flow cytometry technique, respectively. And the transfection efficiency of GFP when CDMN were used as gene carrier associated with the external magnetic fields was evaluated under fluorescence microscope in vitro. Results: The diameter of EPI-CDMN and GFP-CDMN were about 8~10 nm and 5~9 nm, respectively, and saturation magnetization were 0.22 emu/g and 0.26 emu/g, respectively. EPI-CDMN associated with PEMFs could significantly inhibit the proliferation of BIU-87 cells and induce cells apoptosis, the growth inhibitory rate and apoptosis rate were (21.82(3.18)% and (16.79(3.37)%, respectively. The transfection efficiency of GFP-CDMN combined with PEMFs was significant higher than that of GFP-CDMN without PEMFs [(45.70(4.32)% vs (35.85(2.16)%, P<0.05]. Conclusion: It seemed that EPI-CDMN associated with external magnetic fields could significantly killed human bladder cancer BIU-87 cells and CDMN could effectively transfer GFP gene into tumors cells with the help of external magnetic fields which provided experimental basis for the magnetic targeting therapy of tumor.

  19. Optimization of total body irradiation: the match between (maximal) leukemic cell kill and (minimal) late effects

    NARCIS (Netherlands)

    Harteveld, M.L. van

    2007-01-01

    Optimization of total body irradiation: the match between (maximal) leukemic cell kill and (minimal) late effects: In this thesis, cataract formation and renal dysfunction as late effects of high-dose total body irradiation (TBI) as part of the conditioning before hematological stem cell transplanta

  20. Effect of Legionella pneumophila sonicate on killing of Listeria monocytogenes by human polymorphonuclear neutrophils and monocytes

    DEFF Research Database (Denmark)

    Rechnitzer, C; Bangsborg, Jette Marie; Shand, G H

    1993-01-01

    polymorphonuclear neutrophils and monocytes. Preincubation of neutrophils with L. pneumophila sonicate did not affect phagocytosis of L. monocytogenes, whereas Listeria killing was significantly inhibited at sonicate concentrations of 1 and 2 mg/ml. The phenol phase of a phenol-water extraction, containing most...... of the lipopolysaccharide (LPS), had no inhibitory effect on the listericidal activity of neutrophils. Killing of Listeria by monocytes was inhibited in a similar manner. The inhibitory activity was mainly recovered in the sonicate fraction above 100 kDa, suggesting that components organized in larger molecular complexes...... are most likely to represent the inhibitory factors. The inhibitory activity of L. pneumophila sonic extract appears to be related to inhibition of killing mechanisms since uptake of Listeria was not affected by the sonicate. Our observations indicate that as Legionella infection progresses, bacterial...

  1. The Killing Effect on EJ Bladder Cancer Cells by Combination of Radiation-responsive Promoter Conjoined CD Gene and Ionizing Radiation of 125 I%辐射敏感性启动子调控CD基因表达联合125I照射对膀肤癌EJ细胞的杀伤作用

    Institute of Scientific and Technical Information of China (English)

    李玲; 张春丽; 李囡; 康磊; 卢霞; 张丽; 闫平; 王荣福

    2011-01-01

    以脂质体介导的辐射敏感性基因联合胞嘧啶脱氨酶(cytosine deantinase,CD)基因转染膀胱癌EJ细胞,研究放射性核素125 I照射后5-氟胞嘧啶(5-fluorocytosine,5-FC)对转染膀胧癌EJ细胞的杀伤作用.人工合成辐射敏感性启动子E8,将启动子克隆至质粒pCD2的CD基因上游,构建以E8为启动子、CD基因为目的基因的新质粒,并采用DNA测序法测定E8和CD基因的序列;脂质体Lipofectamine2000介导pE8-CD转染膀胧癌EJ细胞,用[3]I照射(吸收剂量为2舜)后,蛋白质免疫印迹分析(Western blot)测定CD蛋白表达;在转染EJ细胞中分别加人不同剂量125 I勺和5-FC,四哇盐比色法(MTT法)测定各组细胞存活率,并以未经125 I勺照射组、未加5-FC组和5-氟尿啼吮(5-FU)组(阳性对照组)进行对照.DNA测序显示构建的pE8-CD质粒含E8启动子及CD基因序列;Westem blot可检测到CD基因表达;125 I加5-FC组细胞存活率明显低于未经125 I照射组及未加5-FC组,与5-FU组相近.这表明放射性核素与基因治疗联合对肿瘤细胞具有协同杀伤作用.%To investigate the killing effect on EJ human bladder cancer cells by combination of radiation-responsive gene promoter conjoined CD/S-FC system and ionizing radiation with radionuclide 125 I, plasmid vector containing synthetic gene promoter E8 responsive to ionizing radiation(IR)and CD gene in downstream was constructed, analyzed by DNA sequencing, and transiently transfected into EJ bladder cancer cells by liposome-mediated method. Expression of downstream CD gene was detected via ionizing radiation of radionuclide 1311 at 2Gy by Western Blot. The killing effect induced by different doses of 125I and 5-FC in plasmid-transfected EJ cells was investigated by MTT colorimetric assay. DNA sequencing demonstrated that the plasmid vector contained E8 promoter and CD gene sequences , Western Blot detected the protein CD, and MTT colorimetric assay showed that the death rate of plasmid

  2. Killing effect of CIKs on pancreatic cancer cells enhanced by DCs loaded with K-ras mutant peptide%K-ras突变多肽负载的DC细胞增强CIK细胞对胰腺癌细胞的杀伤作用

    Institute of Scientific and Technical Information of China (English)

    窦春鹏; 李奎武; 谭广

    2015-01-01

    Objective:To observe the killing effect of the cytokine induced killer cells (CIKs) atfer co-culture with dendritic cells (DCs) harboring K-ras (12-Val) mutant peptide on pancreatic cancer PANC-1 cells. Methods:DCs and CIKs were induced and enriched from peripheral blood of healthy donors, respectively. DCs were loaded with the K-ras mutant epitope peptide (K-ras-DCs), and CIKs were co-cultured with un-loaded DCs or K-ras-DCs to obtain the DC-CIKs and K-ras-DC-CIKs, respectively. hTe proliferative activities between CIKs and K-ras-DC-CIKs were compared, the difference in immunophenotype between DCs and K-ras-DCs as well as between CIKs and K-ras-DC-CIKs were analyzed, the IFN-γand IL-12 levels in the culture supernatants from CIKs, DC-CIKs and K-ras-DC-CIKs were measured, and the killing abilities of CIKs, DC-CIKs and K-ras-DC-CIKs on PANC-1 cells in vitro were determined. Results:The proliferative ability of K-ras-DC-CIKs was significantly greater than that of the untreated CIKs (P Conclusion:K-ras mutant peptide can promote DCs maturation, and DCs harboring K-ras mutant peptide can increase the proliferation of CIKs and killing effect on pancreatic cancer cells.%目的:观察经K-ras(12-Val)突变多肽负载的树突状细胞(DC)与细胞因子诱导的杀伤细胞(CIK)共培养以后对胰腺癌PANC-1细胞的杀伤作用。  方法:取健康人外周血体外诱导分别扩增出DC和CIK;用K-ras突变体抗原表位肽负载DC(K-ras-DC),将单纯DC或K-ras-DC与CIK共培养,获得DC-CIK或K-ras-DC-CIK。比较CIK与K-ras-DC-CIK的增殖活性;分别分析DC与K-ras-DC以及CIK与K-ras-DC-CIK的免疫表型差异;检测CIK、DC-CIK、K-ras-DC-CIK上清液中IFN-γ、IL-12的水平;检测K-ras-DC-CIK、DC-CIK、CIK对PANC-1细胞的体外杀伤力。  结果:K-ras-DC-CIK的增殖能力明显强于单纯CIK(P  结论:K-ras突变多肽负载后能促进DC的成熟,负载K-ras突变多肽后的DC能增加CIK

  3. 三种热效应激光汽化兼热杀癌的理论计算与应用方法讨论%The theoretical calculations of vaporizing and heat-killing therapy of cancer with the three thermal-effect lasers and discussion on the applied methods

    Institute of Scientific and Technical Information of China (English)

    田晓明; 冯永振

    2001-01-01

    本文根据激光汽化兼热杀癌肿瘤的理论模型〔1,2〕,对三种常见热效应激光进行了理论计算和结果对比,讨论了在较大汽化域情况下尽可能减少照射治疗时间的应用方法和措施,为激光治疗较大肿瘤提供具体理论参考数据。%Based on the theoretical models of vaporizing and heat-killing therapy of cancer with laser,the theoretical calculations of three common thermal-effect lasers have been made,and the results are shown and compared in this paper.We discuss on the applied methods to get the irradiating time as short as possible under more large vaporizing area.These theoretical calculated data will be valuable for reference.

  4. Selective killing of cancer cells by small molecules targeting heat shock stress response.

    Science.gov (United States)

    Zhang, Daniel; Zhang, Bin

    2016-09-30

    HSF1 heat shock response has emerged as a valuable non-oncogenetic intervention point in targeted cancer therapy. Current reporter based high throughput screening has led to the discovery of several compounds or chemotypes that are effective in the growth inhibition of multiple cancer cell lines and relevant animal tumor models. However, some intrinsic limitations of reporter based assays can potentially lead to biased results. Using a previously validated high content image based assay, we performed a phenotypic screen targeting HSF1 heat shock pathway with a chemically diversified library of over 100,000 compounds. Several novel functional inhibitors of HSF1 pathway were identified with different chemotypes. Western blot analysis confirmed that selective compounds inhibit phosphorylation of HSF1, followed by reduced expression of HSP proteins. Moreover, HeLa cells stably transfected with HSF1 shRNA were more resistant to the compound treatment under lethal temperature than cells containing HSF1, validating HSF1 dependent mechanism of action. These compounds demonstrate nanomolar potency toward multiple cancer cell lines with relatively low cytotoxicity to normal cells. Further SAR and target identification study will pave the way for the potential development of next generation anticancer drugs. PMID:27553278

  5. Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

    International Nuclear Information System (INIS)

    In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. - Highlights: ► Plant cyclopeptide RA-V kills human breast cancer cells. ► RA-V triggered mitochondrial apoptotic pathway in human breast cancer cells. ► RA-V inhibited phosphorylation of AKT and PDK1 in breast cancer MCF-7 cells. ► Its mechanism is related to the blockage of the interaction between PDK1 and AKT

  6. Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Xian-Ying; Chen, Wei [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Fan, Jun-Ting [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Song, Ran; Wang, Lu [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Gu, Yan-Hong [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zeng, Guang-Zhi [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Shen, Yan; Wu, Xue-Feng [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Tan, Ning-Hua, E-mail: nhtan@mail.kib.ac.cn [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Sun, Yang, E-mail: yangsun@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China)

    2013-02-15

    In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. - Highlights: ► Plant cyclopeptide RA-V kills human breast cancer cells. ► RA-V triggered mitochondrial apoptotic pathway in human breast cancer cells. ► RA-V inhibited phosphorylation of AKT and PDK1 in breast cancer MCF-7 cells. ► Its mechanism is related to the blockage of the interaction between PDK1 and AKT.

  7. Cocoa Extract Indicated Has Activity on Selectively Killing Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ariza Budi Tunjung Sari

    2015-09-01

    Full Text Available Effect of the cocoa crude extract on mortality of breast cancer cell lines i.e. MCF-7, T47D and normal cell (Vero, was observed. Crude cocoa extract prepared from a freshly dried cocoa bean that was containing 14% catechin and 0.6% caffeine. Catechin and caffeine content were modulated to 2-folds (28% catechin or 1.2% caffeine and 3-folds (42% catechin or 1.8% caffeine by adding pure compounds. Extracts were dissolved in dimethylsulfoxide (DMSO at concentrations ranging from 200 to 1600 μg/ml. The positive control was doxorubicin (0.5-16 μg/ml in DMSO. Cell lines (MCF-7, T47D, and Vero were incubated in test sample for 24h at 37°, prior to 3-(4,4-dimetylthiazole-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. The absorbance of each well was measured at 550 nm, and lethal concentration (LC50 was calculated. The cocoa extract induced mortality of breast cancer cell lines but not in Vero cells. The effect on MCF-7 was greater than on T47D, given the LC50 was 1236 μg/ml (MCF-7 and 1893 μg/ml (T47D. Cytotoxic potential of cocoa extract was much lower than doxorubicin whose LC50 was 0,777 μg/ml (MCF-7 and 0,082 μg/ml (T47D. Increasing catechin content to 2-folds did not significantly affect LC50 value, but 3-folds catechin content reduced LC50 to 1021 μg/ml. Meanwhile increasing caffeine content to 2-folds significantly reduced LC50 to 750 μg/ml, however, 3-fold content resulted in slightly higher LC50 at 780 μg/ml. This indicates that cocoa extract have anti-cancer potential, and purification may improve this property.

  8. Differential protective effects of antioxidants against cell killing and mutagenesis of Salmonella typhimurium by gamma radiation

    International Nuclear Information System (INIS)

    A commercial mixture of phenolic antioxidants containing BHA (butylated hydroxyanisole), BHT (butylated hydroxytoluene) and PG (propyl gallate), commonly used in the food industry, was found to protect Salmonella typhimurium against killing and induction of his+ mutations by gamma radiation. The protective effect was apparent only when irradiation was performed in the presence of oxygen and no protection could be detected in its absence. When each of the components of the antioxidant mixture was tested separately, only PG displayed a protective effects. The amount of protection provided by the mixture of antioxidants was close to the protection afforded by hypoxia. Also, protection against cell killing was very similar in magnitude to protection against induction of mutations. The protective effect could be detected only when antioxidants were added to the cells before irradiation. No protection was afforded upon addition immediately after irradiation. (author)

  9. Enhanced killing of breast cancer cells by a d-amino acid analog of the winter flounder-derived pleurocidin NRC-03.

    Science.gov (United States)

    Hilchie, Ashley L; Haney, Evan F; Pinto, Devanand M; Hancock, Robert E W; Hoskin, David W

    2015-12-01

    Cationic antimicrobial peptides (CAPs) defend against pathogens and, in some cases, exhibit potent anticancer activities. We previously reported that the pleurocidin NRC-03 causes lysis of breast cancer and multiple myeloma cells. NRC-03 also reduces the EC50 of other cytotoxic compounds and prevents tumor growth in vivo. However, the therapeutic utility of NRC-03 may be limited by its susceptibility to degradation by proteases. The goal of this study was to characterize the anticancer activities of a d-amino acid analog of NRC-03 ([D]-NRC-03) that was predicted to be resistant to proteolytic degradation. Unlike NRC-03, [D]-NRC-03 was not degraded by human serum or trypsin and, in comparison to NRC-03, showed increased killing of breast cancer cells, including multidrug-resistant cells; however, [D]-NRC-03 was somewhat more cytotoxic than NRC-03 for several types of normal cells. Importantly, [D]-NRC-03 was more effective than NRC-03 in vivo since 4-fold less peptide was required for an equivalent inhibitory effect on the growth of breast cancer cell xenografts in immune-deficient mice. These findings demonstrate that a d-amino acid analog of NRC-03 overcomes a major limitation to the therapeutic use of NRC-03, namely peptide stability. Further modification of [D]-NRC-03 is required to improve its selectivity for cancer cells.

  10. Construction of recombinant adenovirus carrying HSV-TK controlled by hMAM enhancer and promoter and its targeted killing effect on human breast cancer cells%hMAM-EP调控HSV-TK腺病毒载体的构建及其对乳腺癌细胞的靶向杀伤

    Institute of Scientific and Technical Information of China (English)

    于建刚; 吴金香; 庞春秀; 林德馨

    2012-01-01

    breast cancer. Methods: Two recombinant plasmid vectors, hMAM-EP-EGFP and hMAM-EP-TK, were constructed, which respectively carried reporter gene EGFP and suicide gene HSV-TK at the downstream of hMAM-EP. Recombinant adenovirus vectors Ad-EP-EGFP and Ad-EP-TK were obtained after the target genes from the recombinant plasmids were transferred into adenovirus skeleton cosmid pAxcwit2; recombinant adenovirus vectors Ad-EP-EGFP and Ad-EP-TK were then transfected into breast cancer T-47D cells, ZR-75-30 cells and nasopharyngeal cancer 5-8F cells. The expression of EGFP was observed under a fluorescence microscope. Recombinant adenovirus AdEP-TK-infected T-47D cells were cultured with 1 , 10, 20 and 50μg/ml prodrug GCV to observe specific cell-killing effect on breast cancer cells. Results: The recombinant plasmid vectors Ad-EP-EGFP and Ad-EP-TK controlled by hMAM-EP were successfully constructed. EGFP could be observed in human breast cancer T-47D cells infected with Ad-EP-EGFP recombinant adenovirus, and could not be detected in ZR-75-30 and 5-8F cells. Compared with un-infected and Ad-EP-EGFP-infected groups, the survival rate of T-47D cells in Ad-EP-EGFP-infection combined with GCV (50 jig/ml) group was significantly decreased ( [35. 69 ±0. O7]% vs [91. 74 ±0.02]% , [87.69 ±0. 11 ] % , P<0.05). With an increase in mass concentration of GCV, the survival rate decreased. Cell survival rates were (94. 34 ± 0. 04)% , (86. 26 ±0.02)%, (66.51 ±0.09)% and (35.69 ±0.07)% when T47D cells were infected with hMAM-EP-TK in a MOI of 100 and cultured with 1, 10, 20, and 50 |xg/ml GCV. HSV-TK suicide gene controlled by hMAM-EP is specifically expressed in breast cancer T-47D cells, and T-47D cells can be killed by Ad-EP-TK combined with GCV.

  11. Photocatalytic killing effect of TiO2 nanoparticles on Ls-174-t human colon carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Ai-Ping Zhang; Yan-Ping Sun

    2004-01-01

    AIM: To investigate the photocatalytic killing effect of photoexcited TiO2 nanoparticles on human colon carcinoma cell line (Ls-174-t) and to study the mechanism underlying the action of photoexcited TiO2 nanoparticles on malignant cells.METHODS: Ls-174-t human colon carcinoma cells were cultured in RPMI 1640 medium supplemented with 199 mL/L calf serum in a humidified incubator with an atmosphere of 50 mL/L CO2 at 37 ℃. Viable cells in the samples were measured by using the MlT method. A GGZ-300 W high pressure Hg lamp with a maximum ultraviolet-A (UVA, 320-400 nm) irradiation peak at 365 nm was used as light source in the photocatalytic killing test.RESULTS: The photocatalytic killing of Ls-174-t cells was carried out in vitro with TiO2 nanoparticles. The killing effect was weak by using UVA irradiation without TiO2 nanoparticles.In our studies, the photocatalytic killing effect was correlated with the concentration of TiO2 and illumination time. Once TiO2 was added, Ls-174-t cells were killed at a much higher rate. In the presence of 1 000 μg/mL TiO2, 44% of cells were killed after 10 min of UVA irradiation, and 88% of cells were killed after 30 min of UVA irradiation.CONCLUSION: When the concentration of TiO2 is below 200 μg/mL, the photocatalytic killing effect on human colon carcinoma cells is almost the same as that of UVA irradiation alone. When the concentration of TiO2 is above 200 μg/mL,the remarkable killing effect of photoexcited TiO2 nanoparticles can be found.

  12. Engineered metal nanoparticles in the sub-nanomolar levels kill cancer cells

    Directory of Open Access Journals (Sweden)

    Vodyanoy V

    2016-04-01

    Full Text Available Vitaly Vodyanoy,1 Yasmine Daniels,2 Oleg Pustovyy,1 William A MacCrehan,2 Shin Muramoto,2 Gheorghe Stan21Department of Anatomy, Physiology and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL, 2Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MA, USA Background: Small metal nanoparticles obtained from animal blood were observed to be toxic to cultured cancer cells, whereas noncancerous cells were much less affected. In this work, engineered zinc and copper metal nanoparticles were produced from bulk metal rods by an underwater high-voltage discharge method. The metal nanoparticles were characterized by atomic force microscopy and X-ray photoelectron spectroscopy. The metal nanoparticles, with estimated diameters of 1 nm–2 nm, were determined to be more than 85% nonoxidized. A cell viability assay and high-resolution light microscopy showed that exposure of RG2, cultured rat brain glioma cancer cells, to the zinc and copper nanoparticles resulted in cell morphological changes, including decreased cell adherence, shrinking/rounding, nuclear condensation, and budding from cell bodies. The metal-induced cell injuries were similar to the effects of staurosporine, an active apoptotic reagent. The viability experiments conducted for zinc and copper yielded values of dissociation constants of 0.22±0.08 nmol/L (standard error [SE] and 0.12±0.02 nmol/L (SE, respectively. The noncancerous astrocytes were not affected at the same conditions. Because metal nanoparticles were lethal to the cancer cells at sub-nanomolar concentrations, they are potentially important as nanomedicine.Purpose: Lethal concentrations of synthetic metal nanoparticles reported in the literature are a few orders of magnitude higher than the natural, blood-isolated metal nanoparticles; therefore, in this work, engineered metal nanoparticles were examined to mimic the properties of endogenous metal

  13. Synergistic killing effect of chloroquine and androgen deprivation in LNCaP cells

    International Nuclear Information System (INIS)

    Highlights: ► Chloroquine synergistically killed LNCaP cells during androgen deprivation treatment. ► Chloroquine inhibited the function of autolysosomes and decreases the cytosolic ATP. ► Chloroquine induced nuclear and DNA fragmentation in androgen deprived LNCaP. ► Chloroquine may be an useful adjuvant in hormone ablation therapy in PCa patients. -- Abstract: Modulation of autophagy is a new paradigm in cancer therapeutics. Recently a novel function of chloroquine (CLQ) in inhibiting degradation of autophagic vesicles has been revealed, which raises the question whether CLQ can be used as an adjuvant in targeting autophagic pro-survival mechanism in prostate cancer (PCa). We previously showed that autophagy played a protective role during hormone ablation therapy, in part, by consuming lipid droplets in PCa cells. In addition, blocking autophagy by genetic and pharmacological means in the presence of androgen deprivation caused cell death in PCa cells. To further investigate the importance of autophagy in PCa survival and dissect the role of CLQ in PCa death, we treated hormone responsive LNCaP cells with CLQ in combination with androgen deprivation. We observed that CLQ synergistically killed LNCaP cells during androgen deprivation in a dose- and time-dependent manner. We further confirmed that CLQ inhibited the maturation of autophagic vesicles and decreased the cytosolic ATP. Moreover, CLQ induced nuclear condensation and DNA fragmentation, a hallmark of apoptosis, in androgen deprived LNCaP cells. Taken together, our finding suggests that CLQ may be an useful adjuvant in hormone ablation therapy to improve the therapeutic efficacy.

  14. Troxerutin, a natural flavonoid binds to DNA minor groove and enhances cancer cell killing in response to radiation.

    Science.gov (United States)

    Panat, Niranjan A; Singh, Beena G; Maurya, Dharmendra K; Sandur, Santosh K; Ghaskadbi, Saroj S

    2016-05-01

    Troxerutin, a flavonoid best known for its radioprotective and antioxidant properties is of considerable interest of study due to its broad pharmacological activities. The present study on troxerutin highlights its abilities to bind DNA and enhance cancer cell killing in response to radiation. Troxerutin showed strong binding with calf thymus DNA in vitro. Troxerutin-DNA interaction was confirmed by CD spectropolarimetry. The mode of binding of troxerutin to DNA was assessed by competing troxerutin with EtBr or DAPI, known DNA intercalator and a minor groove binder, respectively. DAPI fluorescence was drastically reduced with linear increase in troxerutin concentration suggesting possible binding of troxerutin to DNA minor groove. Further, computational studies of docking of troxerutin molecule on mammalian DNA also indicated possible troxerutin-DNA interaction at minor groove of DNA. Troxerutin was found to mainly localize in the nucleus of prostate cancer cells. It induced cytotoxicity in radioresistant (DU145) and sensitive (PC3) prostate cancer cells. When troxerutin pre-treated DU145 and PC3 cells were exposed to γ-radiation, cytotoxicity as estimated by MTT assay, was found to be further enhanced. In addition, the % subG1 population detected by propidium iodide staining also showed similar response when combined with radiation. A similar trend was observed in terms of ROS generation and DNA damage in DU145 cells when troxerutin and radiation were combined. DNA binding at minor groove by troxerutin may have contributed to strand breaks leading to increased radiation induced cell death.

  15. Autophagy inhibition plays the synergetic killing roles with radiation in the multi-drug resistant SKVCR ovarian cancer cells

    International Nuclear Information System (INIS)

    Autophagy has attracted attentions as a novel mechanism for tumor development. In this study Human ovarian carcinoma cell line SKOV3 and multidrug-resistant phenotype SKVCR cells were used and the roles of autophagy in radiation-induced cell death were analyzed. Cell viability was examined by colony formation and cell counting kit-8 (CCK-8) assay, 3MA and ZVAD were used to block autophagy and apoptosis, respectively. Quantitative real-time PCR was used to detect mRNA level and Western blot was used to detect protein expression, monodansylcadaverine (MDC) staining and flow cytometery were used for autophagy, apoptosis and cell cycle dynamics, respectively. (1) The radiosensitivity exhibited differently in SKOV3 and SKVCR cells (SKOV3: D0=3.37, SKVCR: D0= 4.18); compared with SKOV3 the constitutive expression of MAPLC3 in SKVCR was higher, but no change of Caspase-3 and cleaved Caspase-3. (2) The ionizing radiation (IR)- induced apoptosis and autophagy were significant in both cells (P<0.05); inhibition of apoptosis with ZVAD showed no impact on survival of SKOV3 and SKVCR cells after radiation, while inhibition of autophagy significantly decreased viability in SKVCR cells, for SKVO3 cells only low level of radiation (2 Gy and 4 Gy) could decrease the viability(P<0.05). (3) ZVAD inhibited apoptosis and autophagy in both cells, 3MA inhibit apoptosis in SKOV3, and promote apoptosis in SKVCR, together with inhibition of autophagy. (4) G2/M arrest was induced by radiation in both cells; the accumulation of G2/M was more significant in SKOV3, 3MA attenuated the radiation-induced S phase delay in SKVCR. IR-induced autophagy provides a self-protective mechanism against radiotherapy in SKVCR cells, the use of autophagy inhibitor, 3MA, increases the killing effects of radiation by inhibiting autophagy and radiation- induced S phase delay, also by the increase of apoptosis, which suggests a better therapeutic strategy in drug- resistant SKVCR ovarian cancer cells

  16. Engineering Salmonella as intracellular factory for effective killing of tumour cells.

    Science.gov (United States)

    Camacho, Eva María; Mesa-Pereira, Beatriz; Medina, Carlos; Flores, Amando; Santero, Eduardo

    2016-01-01

    Salmonella have many desirable properties as antitumour-agent due to its ability to proliferate inside tumours and induce tumour regression. Additionally, this bacterium can be genetically engineered to deliver therapeutic proteins intratumourally. The main limitation of this approach is the efficient release of therapeutic molecules from intratumoural bacteria. Here we have developed an inducible autolysis system based in the lysis operon of the lambda phage that, in response to anhydrotetracycline, lysates Salmonella thus releasing its content. The system was combined with a salicylate cascade system that allows efficient production of therapeutic molecules in response to aspirin and with a sifA mutation that liberates bacteria from the vacuoles to a cytosolic location. The combination of these three elements makes this strain a putative powerful instrument in cancer treatment. We have used this engineered strain for the intracellular production and delivery of Cp53 peptide. The engineered strain is able to sequentially produce and release the cytotoxic peptide while proliferating inside tumour cells, thus inducing host cell death. Our results show that temporal separation of protein production from protein release is essential to efficiently kill tumour cells. The combined system is a further step in the engineering of more efficient bacteria for cancer therapy. PMID:27464652

  17. Cancer - What You Don't Know Can Kill You PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2010-07-22

    This 60 second PSA is based on the July 2010 CDC Vital Signs report which provides information on colorectal and breast cancer and the importance of getting screened.  Created: 7/22/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/22/2010.

  18. Cancer – What You Don't Know Can Kill You

    Centers for Disease Control (CDC) Podcasts

    2010-07-23

    This podcast is based on the July, 2010 CDC Vital Signs report which provides information on colorectal and breast cancer screening and the importance of early detection of disease.  Created: 7/23/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/23/2010.

  19. Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using {sup 149}Tb-rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Beyer, G.J.; Soloviev, D.; Buchegger, F. [Division of Nuclear Medicine, University Hospital of Geneva, 24 Rue Micheli du Crest, 1211, Geneva 14 (Switzerland); Miederer, M. [Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York (United States); Vranjes-Duric, S. [Laboratory of Radioisotopes, Vinca Institute of Nuclear Sciences, Belgrade (Czechoslovakia); Comor, J.J. [Laboratory of Physics, Vinca Institute of Nuclear Sciences, Belgrade (Czechoslovakia); Kuenzi, G.; Hartley, O. [Department of Medical Biochemistry, University Medical Center, Geneva (Switzerland); Senekowitsch-Schmidtke, R. [Clinic of Nuclear Medicine, Technical University of Munich, Munich (Germany)

    2004-04-01

    This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an intravenous graft of 5.10{sup 6} Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300 {mu}g unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%{+-}4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%{+-}2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with {sup 149}Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach. (orig.)

  20. 外磁场协同卟啉-葡聚糖磁性纳米微粒的光动力学对人膀胱癌细胞的杀伤作用%Synergetic killing effects of external magnetic fields combined with porphyrin-dextran magnetic nanoparticles on the human bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    罗道升; 米其武; 孟祥军; 高勇; 戴宇平; 邓春华

    2012-01-01

    目的:探讨外磁场协同卟啉-葡聚糖磁性纳米微粒(porphyrin-dextran magnetic nanoparticles,PDMN)的光动力学作用对人膀胱癌细胞杀伤作用的影响.方法:用化学共沉淀和氧化还原法制备PDMN,并检测其理化性质.采用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)法、流式细胞术分别观察脉冲电磁场协同PDMN的光动力学作用对人膀胱癌BIU-87细胞的杀伤作用.结果:PDMN的直径、比饱和磁化强度(saturation magnetization,Ms)分别为10 ~ 15 nm、0.20 emu/g,有效粒径为94.8nm.PDMN光动力学作用可显著抑制BIU-87细胞增值,抑制率达(17.61±2.73)%,并诱导BIU-87细胞发生明显的凋亡,凋亡率为(24.53 +5.74)%.脉冲外电磁场(5 mT)也可抑制BIU-87细胞增殖和诱导发生凋亡,且协同PDMN的光动力学作用对BIU-87细胞的生长抑制和诱导肿瘤细胞凋亡的效应均显著增强,抑制率和凋亡率分别为(28.11±4.25)%、(24.53±5.74)%,明显高于其他各组(P<0.01).结论:化学修饰后的PDMN的光动力学作用能有效地抑制人膀胱癌BIU-87细胞的增殖并诱导其凋亡,与恒定外磁场协同作用对BIU-87细胞的杀伤作用更强.%Objective: To study the synergetic killing effects of external magnetic fields combined with the photodynamic action of porphyrin-dextran iron oxide magnetic nanoparticles ( PDMN) on human bladder cancer cells in vitro. Methods: The PDMN were produced by using the chemical co-precipitation and redox process and the physicochemical properties were characterized. Methyl thiazolyl tetrazolium ( MTT) and flow cytometry were used to determine the effects of photodynamic therapy of PDMN combined with external pulsed electromagnetic fields (5 mT) on killing human bladder cancer BIU-87 cells respectively. Results: The diameters of PDMN were 10 - 15 nm and the saturation magnetization was 0. 20 emu/g. Effective diameter of PDMN was 94. 8 nm. PDMN could remarkably inhibit the proliferation and

  1. Radiation related basic cancer research : research for radiation induced tumor cell killing

    International Nuclear Information System (INIS)

    The radioresistant clones was established from human U251 glioblastoma cell line through intermittently exposed to 3 Gy gamma-radiation for six months. Treatment of SNU-16 cells with various doses of radiation, TNF alpha and PMA resulted in a decrease in cell viability. The results prove that cell death of SNU16 is a apoptosis mediated by caspase-3. We have examined the expression of bcl-2 and c-myc in cervical cancer specimens and cervical intraepithelial neoplasia (CIN) to determine the role of coexpression of bcl-3 and c-myc during progression into cervical cancer. The frequent alterations in FHIT expression in many cervical carcinomas and their cell lines suggest that FHIT gene alterations are pla a role in cervical tumorigenesis. According to these correlation between the viability and apoptosis of RD cells, the proper range of the dosage for the investigation of differentiation potency in RD cells was assessed as 1 to 3Gy

  2. Radiation related basic cancer research : research for radiation induced tumor cell killing

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Hoon; Hong, Seok Il; Cho, Kyung Ja; Kim, Byung Gi; Lee, Kee Ho; Nam, Myung Jin

    1999-04-01

    The radioresistant clones was established from human U251 glioblastoma cell line through intermittently exposed to 3 Gy gamma-radiation for six months. Treatment of SNU-16 cells with various doses of radiation, TNF alpha and PMA resulted in a decrease in cell viability. The results prove that cell death of SNU16 is a apoptosis mediated by caspase-3. We have examined the expression of bcl-2 and c-myc in cervical cancer specimens and cervical intraepithelial neoplasia (CIN) to determine the role of coexpression of bcl-3 and c-myc during progression into cervical cancer. The frequent alterations in FHIT expression in many cervical carcinomas and their cell lines suggest that FHIT gene alterations are pla a role in cervical tumorigenesis. According to these correlation between the viability and apoptosis of RD cells, the proper range of the dosage for the investigation of differentiation potency in RD cells was assessed as 1 to 3Gy.

  3. Stressing the ubiquitin-proteasome system without 20S proteolytic inhibition selectively kills cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Ravi K Anchoori

    Full Text Available Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate, and for specific signaling pathways, notably HPV E6-targeted degradation of p53 and PDZ proteins. Natural compounds with antioxidant properties including flavonoids and triterpenoids hold promise as anticancer agents by interfering with ubiquitin-dependent protein degradation. An increasing body of evidence indicates that their α-β unsaturated carbonyl system is the molecular determinant for inhibition of ubiquitin-mediated protein degradation up-stream of the catalytic sites of the 20S proteasome. Herein we report the identification and characterization of a new class of chalcone-based, potent and cell permeable chemical inhibitors of ubiquitin-dependent protein degradation, and a lead compound RAMB1. RAMB1 inhibits ubiquitin-dependent protein degradation without compromising the catalytic activities of the 20S proteasome, a mechanism distinct from that of Bortezomib. Treatment of cervical cancer cells with RAMB1 triggers unfolded protein responses, including aggresome formation and Hsp90 stabilization, and increases p53 steady state levels. RAMB1 treatment results in activation of lysosomal-dependent degradation pathways as a mechanism to compensate for increasing levels of poly-ubiquitin enriched toxic aggregates. Importantly, RAMB1 synergistically triggers cell death of cervical cancer cells when combined with the lysosome inhibitor Chloroquine.

  4. Effect of Refractory on Nonmetallic Inclusions in Al-Killed Steel

    Science.gov (United States)

    Deng, Zhiyin; Zhu, Miaoyong; Sichen, Du

    2016-10-01

    To understand the effect of refractory on the evolution of inclusions in the secondary steelmaking, steel samples were taken at different stages of the process train. Laboratory experiments were carried out using different refractories (alumina, spinel, and MgO). In the laboratory study, the types of inclusions considered were alumina, spinel, and calcium aluminate. The focus was given to Al-killed steel. The results showed that alumina refractory and spinel refractory had little effect on all the three types of inclusions, while the effect of MgO refractory depended on the activity of dissolved oxygen in liquid steel. With lower oxygen activity, alumina inclusions could transform into spinel inclusions. No evident change could be found for spinel and calcium aluminate inclusions. When the oxygen activity was high enough, spinel inclusions could not be generated from alumina inclusions. The laboratory results helped in understanding the evolution of the inclusions in the industrial process.

  5. Effect of Refractory on Nonmetallic Inclusions in Al-Killed Steel

    Science.gov (United States)

    Deng, Zhiyin; Zhu, Miaoyong; Sichen, Du

    2016-07-01

    To understand the effect of refractory on the evolution of inclusions in the secondary steelmaking, steel samples were taken at different stages of the process train. Laboratory experiments were carried out using different refractories (alumina, spinel, and MgO). In the laboratory study, the types of inclusions considered were alumina, spinel, and calcium aluminate. The focus was given to Al-killed steel. The results showed that alumina refractory and spinel refractory had little effect on all the three types of inclusions, while the effect of MgO refractory depended on the activity of dissolved oxygen in liquid steel. With lower oxygen activity, alumina inclusions could transform into spinel inclusions. No evident change could be found for spinel and calcium aluminate inclusions. When the oxygen activity was high enough, spinel inclusions could not be generated from alumina inclusions. The laboratory results helped in understanding the evolution of the inclusions in the industrial process.

  6. Chaperone-Targeting Cytotoxin and Endoplasmic Reticulum Stress-Inducing Drug Synergize to Kill Cancer Cells

    Directory of Open Access Journals (Sweden)

    Joseph M. Backer

    2009-11-01

    Full Text Available Diverse physiological and therapeutic insults that increase the amount of unfolded or misfolded proteins in the endoplasmic reticulum (ER induce the unfolded protein response, an evolutionarily conserved protective mechanism that manages ER stress. Glucose-regulated protein 78/immunoglobulin heavy-chain binding protein (GRP78/BiP is an ER-resident protein that plays a central role in the ER stress response and is the only known substrate of the proteolytic A subunit (SubA of a novel bacterial AB5 toxin. Here, we report that an engineered fusion protein, epidermal growth factor (EGF-SubA, combining EGF and SubA, is highly toxic to growing and confluent epidermal growth factor receptor-expressing cancer cells, and its cytotoxicity is mediated by a remarkably rapid cleavage of GRP78/BiP. Systemic delivery of EGF-SubA results in a significant inhibition of human breast and prostate tumor xenografts in mouse models. Furthermore, EGF-SubA dramatically increases the sensitivity of cancer cells to the ER stress-inducing drug thapsigargin, and vice versa, demonstrating the first example of mechanism-based synergism in the action of a cytotoxin and an ER-targeting drug.

  7. Mitochondrial-Targeting MET Kinase Inhibitor Kills Erlotinib-Resistant Lung Cancer Cells.

    Science.gov (United States)

    Yang, Tianming; Ng, Wai Har; Chen, Huan; Chomchopbun, Kamon; Huynh, The Hung; Go, Mei Lin; Kon, Oi Lian

    2016-08-11

    Lung cancer cells harboring activating EGFR mutations acquire resistance to EGFR tyrosine kinase inhibitors (TKIs) by activating several bypass mechanisms, including MET amplification and overexpression. We show that a significant proportion of activated MET protein in EGFR TKI-resistant HCC827 lung cancer cells resides within the mitochondria. Targeting the total complement of MET in the plasma membrane and mitochondria should render these cells more susceptible to cell death and hence provide a means of circumventing drug resistance. Herein, the mitochondrial targeting triphenylphosphonium (TPP) moiety was introduced to the selective MET kinase inhibitor PHA665752. The resulting TPP analogue rapidly localized to the mitochondria of MET-overexpressing erlotinib-resistant HCC827 cells, partially suppressed the phosphorylation (Y1234/Y1235) of MET in the mitochondrial inner membrane and was as cytotoxic and apoptogenic as the parent compound. These findings provide support for the targeting of mitochondrial MET with a TPP-TKI conjugate as a means of restoring responsiveness to chemotherapy. PMID:27563407

  8. Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand

    Science.gov (United States)

    Doherty, Rachel E.; Sazanovich, Igor V.; McKenzie, Luke K.; Stasheuski, Alexander S.; Coyle, Rachel; Baggaley, Elizabeth; Bottomley, Sarah; Weinstein, Julia A.; Bryant, Helen E.

    2016-03-01

    Photodynamic therapy that uses photosensitizers which only become toxic upon light-irradiation provides a strong alternative to conventional cancer treatment due to its ability to selectively target tumour material without affecting healthy tissue. Transition metal complexes are highly promising PDT agents due to intense visible light absorption, yet the majority are toxic even without light. This study introduces a small, photostable, charge-neutral platinum-based compound, Pt(II) 2,6-dipyrido-4-methyl-benzenechloride, complex 1, as a photosensitizer, which works under visible light. Activation of the new photosensitizer at low concentrations (0.1–1 μM) by comparatively low dose of 405 nm light (3.6 J cm‑2) causes significant cell death of cervical, colorectal and bladder cancer cell lines, and, importantly, a cisplatin resistant cell line EJ-R. The photo-index of the complex is 8. We demonstrate that complex 1 induces irreversible DNA single strand breaks following irradiation, and that oxygen is essential for the photoinduced action. Neither light, nor compound alone led to cell death. The key advantages of the new drug include a remarkably fast accumulation time (diffusion-controlled, minutes), and photostability. This study demonstrates a highly promising new agent for photodynamic therapy, and attracts attention to photostable metal complexes as viable alternatives to conventional chemotherapeutics, such as cisplatin.

  9. Selective killing of gastric cancer cells by a small molecule targeting ROS-mediated ER stress activation.

    Science.gov (United States)

    Zou, Peng; Xia, Yiqun; Chen, Tongke; Zhang, Junru; Wang, Zhe; Chen, Wenbo; Chen, Minxiao; Kanchana, Karvannan; Yang, Shulin; Liang, Guang

    2016-06-01

    Gastric cancer is one of the leading causes of cancer mortality in the world. Curcumin is a natural product with multiple pharmacological activities, while its clinical application has been limited by the poor chemical stability. We have previously designed a series of curcumin derivatives with high stability and anticancer potentials. The present study aims to identify the anti-cancer effects and mechanisms of WZ26, an analog of curcumin, in gastric cancer cells. In vitro, WZ26 showed higher chemical stability and much stronger anti-proliferative effects than curcumin, accompanied by dose-dependent induction of cell cycle arrest and apoptosis in gastric cancer cells. Mechanistically, the novel compound WZ26 induced ROS production, resulting in the activation of JNK-mitochondrial and ER stress apoptotic pathways. Blockage of ROS production totally reversed WZ26-induced JNK activation, Bcl-2/Bax decrease, ER stress activation, and final cell apoptosis in SGC-7901 cells. WZ26 also exhibited potent anti-tumor effects in human gastric cancer cell xenograft models. WZ26 could be considered as a potential chemotherapeutic agent for the treatment of advanced gastric cancer. In addition, this study also demonstrated that ROS production could be act as a vital candidate pathway for inducing tumor cell apoptosis by targeting mitochondrial and ER stress-related death pathway. © 2015 Wiley Periodicals, Inc. PMID:26086416

  10. The killing effect of 4-S-cysteaminylphenol, a newly synthesised melanin precursor, on B16 melanoma cell lines.

    OpenAIRE

    Yamada, I.; Seki, S.; Ito, S.; Suzuki, S.; Matsubara, O.; Kasuga, T.

    1991-01-01

    We have examined the killing effect of 4-S-cysteaminylphenol (4-S-CAP), a newly synthesised melanin precursor, on B16 melanoma cell lines possessing different melanin-producing activities and found it to be particularly effective in heavily melanised melanoma cells, but less so in moderately melanised melanoma cells, and having no effect on amelanotic melanoma cells and nonmelanoma cells. Thus, it was found that the killing effect of 4-S-CAP is highly dependent upon the synthesis of melanin a...

  11. Effect of Temper Rolling on Tensile Properties of Low-Si AI-Killed Sheet Steel

    Institute of Scientific and Technical Information of China (English)

    MA Qing-long; WANG Dong-cheng; LIU Hong-min; LU Hai-ming

    2009-01-01

    The tensile properties of steel after temper rolling are affected by the reduction;low-Si Al-killed sheet steel was taken to study the effect of temper rolling on the tensile properties.The results indicate that the yield strength first decreases with the increase of reduction,and then increases.The relationship between the yield strength and the reduction can be expressed using quadratic function.The tensile strength increases with the increase of the reduction,while the total elongation decreases with the increase of the reduction,and the relationship between them and the reduction can be expressed using power function.Under the same condition,the results also indicate that the yield strength and tensile strength of steels across the rolling direction are all larger than those along the rolling direction; there is no obvious distinction between the total elongation along the rolling direction and that across the rolling direction.

  12. Killing effect of coexpressing cytosine deaminase and thymidine kinase on rat vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    曹慧青; 孟宪敏; 刘冬青; 赵秀文; 丁金凤

    2004-01-01

    Background Vascular smooth muscle cell (VSMC) proliferation following arterial injury plays a critical role in a variety of vascular proliferative disorders, such as atherosclerosis and restenosis after balloon angioplasty. Herpes simplex virus-thymidine kinase (HSV-TK)/ganciclovir (GCV) and E.coli cytosine deaminase (CD)/5-fluorocytosine (5-Fc) suicide gene systems have been successfully employed in cardiovascular gene therapy, respectively. We reasoned that coexpression of both HSV-TK with CD suicide genes would lead to increased cell killing. To test this imagine, the adenoviral vectors expressing TK and/or CD genes were developed and tested on vascular smooth muscle cells. Methods Adenoviral vectors, including Ad-EF1α-CD-cytomegolovirus (CMV)-TK coexpressing both CD and TK double suicide genes, Ad-EF1α-CD and Ad-CMV-TK expressing CD and TK respectively, and control vector Ad-CMV-LacZ, were constructed and prepared with homologous recombination in RecA+E.coli cells. Integration and expression of CD and/or TK gene were identified by PCR and Western blot. Primary cultured VSMCs were infected at a multiplicity of infection (MOI) of 20 with exposure to their matching prodrugs 5-Fc and GCV. Cell mortality was measured by methyl thiazolyl tetrazolium (MTT) assays. Flow cytometry analysis was used to detect cell death. Apoptotic cells were analyzed using Hoechst 33342 fluorescence dye as a DNA probe. Genomic DNA cleavage of apoptotic VSMCs was tested by agarose gel electrophoresis. Results Recombinant adenovirus expressing CD and/or TK suicide genes were successfully constructed. Both single and double suicide genes could be integrated into adenoviral genome and expressed. Cytotoxic effects of Ad-EF1α-CD-CMV-TK double suicide genes combined with 5-Fc and GCV were higher than those of Ad-CMV-TK and Ad-EF1α-CD single gene groups. The rate of cell survival was only (9±3)% in the Ad-EF1α-CD-CMV-TK group, but (37±3)% in the Ad-CMV-TK and (46±4)% in the Ad-EF1

  13. Tetrandrine, a Compound Common in Chinese Traditional Medicine, Preferentially Kills Breast Cancer Tumor Initiating Cells (TICs In Vitro

    Directory of Open Access Journals (Sweden)

    Jessica Li

    2011-05-01

    Full Text Available Tetrandrine is a bisbenzylisoquinoline alkaloid found in Stephania tetrandra, a Chinese medicine commonly used as an anti-inflammatory. It has extensive pharmacological activity, including positive ion channel blockade and inhibition of multiple drug resistance proteins. These activities are very similar to that of salinomycin, a known drug targeting breast cancer initiation cells (TICs. Herein, we tested tetrandrine targeting of breast cancer TICs. SUM-149, an inflammatory breast cancer cell line and SUM-159, a non-inflammatory metaplastic breast cancer cell line were used in these studies. In proliferation assays using 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTS, we found that the IC50 for inhibition of proliferation is 15.3 ± 4.1 µM for SUM-149 and 24.3 ± 2.1 µM for SUM-159 cells. Tetrandrine also inhibited mammosphere formation, a surrogate for breast cancer TICs growth in vitro with IC50 around 1 µM for SUM-149 and around 2 µM for SUM-159 cells. Tetrandrine has similar effects on the mammosphere formation from cells isolated from fresh patient sample. Moreover, tetrandrine decreases the aldehyde dehydrogenase (ALDH positive population in SUM-159 by 45% ± 5.45% P = 0.005. In summary, tetrandrine demonstrates significant efficacy against in vitro surrogates for inflammatory and aggressive breast cancer TICs.

  14. Antiproliferative and proapoptotic effects of viable or heat-killed Lactobacillus paracasei IMPC2.1 and Lactobacillus rhamnosus GG in HGC-27 gastric and DLD-1 colon cell lines.

    Science.gov (United States)

    Orlando, A; Refolo, M G; Messa, C; Amati, L; Lavermicocca, P; Guerra, V; Russo, F

    2012-01-01

    Data from literature suggest the possible use of probiotics as chemopreventive agents against colon cancer, but few investigations are available on their effects on gastric cancer proliferation. In our previous study, a specific Lactobacillus, strain L. paracasei IMPC2.1, was demonstrated to colonize the human gut and positively affect fecal bacteria and biochemical parameters. The aims of the present study were to investigate the effects of L. paracasei IMPC2.1, comparing them with those of Lactobacillus rhamnosus GG (L.GG), either as viable or heat-killed cells, on cell proliferation and apoptosis in a gastric cancer (HGC-27) and a colorectal cancer cell line (DLD-1). Both the gastric and colon cancer cells were sensitive to the growth inhibition and apoptosis induction by both viable or heat-killed cells from L. paracasei IMPC2.1 and L.GG. These findings suggest the possibility for a food supplement, based on dead probiotics, including L. paracasei IMPC2.1 cells, which could represent an effective component of a functional food strategy for cancer growth inhibition, with potential for cancer prevention. PMID:23061912

  15. Selective killing of K-ras-transformed pancreatic cancer cells by targeting NAD(P)H oxidase

    Institute of Scientific and Technical Information of China (English)

    Peng Wang; Yi-Chen Sun; Wen-Hua Lu; Peng Huang; and Yumin Hu

    2015-01-01

    Introduction:Oncogenic activation of the K-ras gene occurs in>90%of pancreatic ductal carcinoma and plays a critical role in the pathogenesis of this malignancy. Increase of reactive oxygen species (ROS) has also been observed in a wide spectrum of cancers. This study aimed to investigate the mechanistic association between K-ras–induced transformation and increased ROS stress and its therapeutic implications in pancreatic cancer. Methods:ROS level, NADPH oxidase (NOX) activity and expression, and cel invasion were examined in human pancreatic duct epithelial E6E7 cel s transfected with K-rasG12V compared with parental E6E7 cel s. The cytotoxic effect and antitumor effect of capsaicin, a NOX inhibitor, were also tested in vitro and in vivo. Results:K-ras transfection caused activation of the membrane-associated redox enzyme NOX and elevated ROS generation through the phosphatidylinositol 3′-kinase (PI3K) pathway. Importantly, capsaicin preferential y inhibited the enzyme activity of NOX and induced severe ROS accumulation in K-ras–transformed cel s compared with parental E6E7 cel s. Furthermore, capsaicin effectively inhibited cel proliferation, prevented invasiveness of K-ras–transformed pancreatic cancer cel s, and caused minimum toxicity to parental E6E7 cel s. In vivo, capsaicin exhibited antitumor activity against pancreatic cancer and showed oxidative damage to the xenograft tumor cel s. Conclusions:K-ras oncogenic signaling causes increased ROS stress through NOX, and abnormal ROS stress can selectively kil tumor cel s by using NOX inhibitors. Our study provides a basis for developing a novel therapeutic strategy to effectively kil K-ras–transformed cel s through a redox-mediated mechanism.

  16. Targeting and Photodynamic Killing of Cancer Cell by Nitrogen-Doped Titanium Dioxide Coupled with Folic Acid

    Directory of Open Access Journals (Sweden)

    Jin Xie

    2016-06-01

    Full Text Available Titanium dioxide (TiO2 has attracted wide attention as a potential photosensitizer (PS in photodynamic therapy (PDT. However, bare TiO2 can only be excited by ultraviolet illumination, and it lacks specific targeting ligands, which largely impede its application. In our study, we produced nitrogen-doped TiO2 and linked it with an effective cancer cell targeting agent, folic acid (FA, to obtain N-TiO2-FA nanoconjugates. Characterization of N-TiO2-FA included Zeta potential, absorption spectra and thermogravimetric analysis. The results showed that N-TiO2-FA was successfully produced and it possessed better dispersibility in aqueous solution than unmodified TiO2. The N-TiO2-FA was incubated with human nasopharyngeal carcinoma (KB and human pulmonary adenocarcinoma (A549 cells. The KB cells that overexpress folate receptors (FR on cell membranes were used as FR-positive cancer cells, while A549 cells were used as FR-negative cells. Laser scanning confocal microscopy results showed that KB cells had a higher uptake efficiency of N-TiO2-FA, which was about twice that of A549 cells. Finally, N-TiO2-FA is of no cytotoxicity, and has a better photokilling effect on KB cells under visible light irradiation. In conclusion, N-TiO2-FA can be as high-value as a PS in cancer targeting PDT.

  17. To kill, stay or flee: the effects of lions and landscape factors on habitat and kill site selection of cheetahs in South Africa.

    Directory of Open Access Journals (Sweden)

    Susana Rostro-García

    Full Text Available Understanding how animals utilize available space is important for their conservation, as it provides insight into the ecological needs of the species, including those related to habitat, prey and inter and intraspecific interactions. We used 28 months of radio telemetry data and information from 200 kill locations to assess habitat selection at the 3rd order (selection of habitats within home ranges and 4th order (selection of kill sites within the habitats used of a reintroduced population of cheetahs Acinonyx jubatus in Phinda Private Game Reserve, South Africa. Along with landscape characteristics, we investigated if lion Panthera leo presence affected habitat selection of cheetahs. Our results indicated that cheetah habitat selection was driven by a trade-off between resource acquisition and lion avoidance, and the balance of this trade-off varied with scale: more open habitats with high prey densities were positively selected within home ranges, whereas more closed habitats with low prey densities were positively selected for kill sites. We also showed that habitat selection, feeding ecology, and avoidance of lions differed depending on the sex and reproductive status of cheetahs. The results highlight the importance of scale when investigating a species' habitat selection. We conclude that the adaptability of cheetahs, together with the habitat heterogeneity found within Phinda, explained their success in this small fenced reserve. The results provide information for the conservation and management of this threatened species, especially with regards to reintroduction efforts in South Africa.

  18. Development and evaluation of a safe and effective sugar-free herbal lollipop that kills cavity-causing bacteria

    OpenAIRE

    Hu, Chu-hong; He, Jian; Eckert, Randal; Wu, Xiao-Yang; Li, Li-na; Tian, Yan; Lux, Renate; Shuffer, Justin A; Gelman, Faina; Mentes, Janet; Spackman, Sue; Bauer, Janet; Anderson, Maxwell H.; Shi, Wen-yuan

    2011-01-01

    Dental caries (tooth decay) is caused by a specific group of cariogenic bacteria, like Streptococcus mutans, which convert dietary sugars into acids that dissolve the mineral in tooth structure. Killing cariogenic bacteria is an effective way to control or prevent tooth decay. In a previous study, we discovered a novel compound (Glycyrrhizol A), from the extraction of licorice roots, with strong antimicrobial activity against cariogenic bacteria. In the current study, we developed a method to...

  19. Effectiveness of Disinfectants in Killing Enterobacter sakazakii in Suspension, Dried on the Surface of Stainless Steel, and in a Biofilm▿

    OpenAIRE

    Kim, Hoikyung; Ryu, Jee-Hoon; Beuchat, Larry R.

    2006-01-01

    The effectiveness of 13 disinfectants used in hospitals, day-care centers, and food service kitchens in killing Enterobacter sakazakii in suspension, dried on the surface of stainless steel, and in biofilm was determined. E. sakazakii exhibited various levels of resistance to the disinfectants, depending on the composition of the disinfectants, amount and type of organic matrix surrounding cells, and exposure time. Populations of planktonic cells suspended in water (7.22 to 7.40 log CFU/ml) d...

  20. Effect of Melanin and Carotenoids of Exophiala (Wangiella) dermatitidis on Phagocytosis, Oxidative Burst, and Killing by Human Neutrophils

    OpenAIRE

    Schnitzler, Norbert; Peltroche-Llacsahuanga, Heidrun; Bestier, Nicole; Zündorf, Josef; Lütticken, Rudolf; Haase, Gerhard

    1999-01-01

    The black yeast Exophiala (Wangiella) dermatitidis is an increasingly recognized pathogen and a leading cause of severe pheohyphomycosis. Melanin is thought to contribute to the virulence of E. dermatitidis. Whereas the synthesis and the redox properties of melanin have been studied intensively, the influence of melanin and carotenoids on the phagocytosis, the oxidative burst, and the killing of E. dermatitidis by human neutrophils has not been studied. To study their effects on these phenome...

  1. The Study of Comparing the Efficiency of ZnPC-PDT and HPD-PDT in Killing LLC Lung Cancer%ZnPc和HPD介导的PDT对肺癌细胞杀伤效果的对比研究

    Institute of Scientific and Technical Information of China (English)

    李维娜; 杨继庆; 刘渊声; 文峻; 屈学民; 龙开平

    2012-01-01

    Objective: To compare the efficiency of two photosensitizers ZnPC and HPD in killing LLC lung cancer under different concentration, exposure time and power density. Explore the best parameters of ZnPc-PDT for lung cancer. Methods: This artcle selects the second generation photosensitizer ZnPc and traditional photosensitizer HPD as the research objects, applied them to the LLC lung cancer cells, uses ultraviolet spectrophotometer to measure the absorption peak values and selectes proper excitation light resources; uses inverted microscope and MTT to observe and compare the killing effects of ZnPC-PDT and HPD-PDT on LLC lung cancer cells under different photosensitizers' concentration, exposure time, and different laser power density. Results: (1) Comparing to HPD, ZnPc has a singular absorption wave peak with longer wavelength. (2)ln both cases, the effects of killing lung cancer increases with the increasing of photosensitizers1 concentration, exposure time, and different light source power density, while the effects would be saturated after reaches certain value. (3)At the same conditions, ZnPc is more effective in killing lung cancer than HPD with distinctive difference. Conclusions: ZnPc-PDT is a more effective treatment in curing lung cancer than HPD-PDT%目的:对比不同光敏剂浓度、不同光照时间和不同激光功率密度下,ZnPc和HPD对肺癌细胞的杀伤效果,探索了ZnPc-PDT的最佳工作参数.方法:分别选用ZnPc和传统光敏剂HPD为研究对象,使其作用于Lewis肺癌细胞,通过分光光度计测量其吸收峰值,选取合适的激发光源;通过倒置显微镜和MTT法的检测,对比了不同光敏剂浓度、不同光照时间及不同激光功率密度下ZnPC-PDT和HPD-PDT对LLC肺癌细胞的杀伤能力.结果:(1)ZnPc的吸收峰的波峰较HPD相对单一,且波长较长;(2)ZnPc和HPD对肺癌细胞的杀伤作用均随光敏剂浓度、光照时间、光源功率密度的增强而增强,但增大到

  2. The Effects of Arolycoricidine and Narciprimine on Tumor Cell Killing and Topoisomerase Activity

    Directory of Open Access Journals (Sweden)

    Buket Bozkurt Sarikaya

    2012-07-01

    Full Text Available In this study, narciprimine and arolycoricidine were isolated from G. rizehensis Stern (Amaryllidaceae. The structures of the alkaloids were elucidated by spectroscopic methods (1D NMR, EI-MS. Due to the previous reports on anti-cancer activity of this group of alkaloids, we investigated their effects on DNA topoisomerase reactions, which are known as the cellular targets of a number of chemotherapeutical drugs. The results revealed that arolycoricidine and narciprimine were effective in both type I and type II DNA topoisomerase reactions in a dose-dependent manner. Topoisomerase-interfering ability of these alkaloids partially correlated with cytostaticity assays, using HeLa (cervix adenocarcinoma, MCF7 (breast adenocarcinoma and A431 (skin epidermoid carcinoma cells. Our results are discussed in relation to the potential significance of these alkaloids in the course of drug-development studies.

  3. Killing of Cancer Cells by the Photoactivatable Protein Kinase C Inhibitor, Calphostin C, Involves Induction of Endoplasmic Reticulum Stress

    Directory of Open Access Journals (Sweden)

    Aparna Kaul

    2009-09-01

    Full Text Available Calphostin C (cal-C is a photoactivatable inhibitor that binds to the regulatory domain of protein kinase C (PKC and to other proteins that contain diacylglycerol/phorbol ester binding sites. Cal-C is cytotoxic against many types of cancer cells, yet the basis for this activity remains poorly understood. Here, we show that one of the earliest effects of cal-C is an impairment of glycoprotein export from the endoplasmic reticulum (ER, accompanied by formation of ER-derived vacuoles. Vacuolization of the ER is correlated with induction of an ER stress response that includes activation of c-Jun N-terminal kinase and protein kinase R-like ER kinase, as well as increased expression of CCAAT/enhancer binding protein homologous transcription factor (CHOP; GADD153. These effects of cal-C are not mimicked by staurosporine, an inhibitor of PKC catalytic activity, indicating that ER stress is due to interaction of cal-C with targets other than PKC. In conjunction with the induction of ER stress, breast carcinoma cells undergo caspase-dependent cell death with early activation of caspases 9 and 7 and cleavage of poly(ADP-ribosepolymerase. Reduction of CHOP expression by short hairpin RNA decreases the sensitivity of the cells to cal-C, suggesting that induction of apoptosis by cal-C is related, at least in part, to ER stress triggered by disruption of ER morphology and transport function. Antineoplastic drugs that work by inducting ER stress have shown promise in preclinical and clinical trials. Thus, the present findings raise the possibility that cal-C may be useful for photodynamic therapy based on induction of ER stress in some forms of cancer.

  4. Evaluation of the effects of a plasma activated medium on cancer cells

    Science.gov (United States)

    Mohades, S.; Laroussi, M.; Sears, J.; Barekzi, N.; Razavi, H.

    2015-12-01

    The interaction of low temperature plasma with liquids is a relevant topic of study to the field of plasma medicine. This is because cells and tissues are normally surrounded or covered by biological fluids. Therefore, the chemistry induced by the plasma in the aqueous state becomes crucial and usually dictates the biological outcomes. This process became even more important after the discovery that plasma activated media can be useful in killing various cancer cell lines. Here, we report on the measurements of concentrations of hydrogen peroxide, a species known to have strong biological effects, produced by application of plasma to a minimum essential culture medium. The activated medium is then used to treat SCaBER cancer cells. Results indicate that the plasma activated medium can kill the cancer cells in a dose dependent manner, retain its killing effect for several hours, and is as effective as apoptosis inducing drugs.

  5. Evaluation of the effects of a plasma activated medium on cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mohades, S.; Laroussi, M., E-mail: mlarouss@odu.edu; Sears, J.; Barekzi, N.; Razavi, H. [Plasma Engineering and Medicine Institute, Old Dominion University, Norfolk, Virginia 23529 (United States)

    2015-12-15

    The interaction of low temperature plasma with liquids is a relevant topic of study to the field of plasma medicine. This is because cells and tissues are normally surrounded or covered by biological fluids. Therefore, the chemistry induced by the plasma in the aqueous state becomes crucial and usually dictates the biological outcomes. This process became even more important after the discovery that plasma activated media can be useful in killing various cancer cell lines. Here, we report on the measurements of concentrations of hydrogen peroxide, a species known to have strong biological effects, produced by application of plasma to a minimum essential culture medium. The activated medium is then used to treat SCaBER cancer cells. Results indicate that the plasma activated medium can kill the cancer cells in a dose dependent manner, retain its killing effect for several hours, and is as effective as apoptosis inducing drugs.

  6. Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway.

    Science.gov (United States)

    Ardiani, Andressa; Gameiro, Sofia R; Kwilas, Anna R; Donahue, Renee N; Hodge, James W

    2014-10-15

    Despite recent advances in diagnosis and management, prostrate cancer remains the second most common cause of death from cancer in American men, after lung cancer. Failure of chemotherapies and hormone-deprivation therapies is the major cause of death in patients with castration-resistant prostate cancer (CRPC). Currently, the androgen inhibitors enzalutamide and abiraterone are approved for treatment of metastatic CRPC. Here we show for the first time that both enzalutamide and abiraterone render prostate tumor cells more sensitive to T cell-mediated lysis through immunogenic modulation, and that these immunomodulatory activities are androgen receptor (AR)-dependent. In studies reported here, the NAIP gene was significantly down-regulated in human prostate tumor cells treated in vitro and in vivo with enzalutamide. Functional analysis revealed that NAIP played a critical role in inducing CTL sensitivity. Amplification of AR is a major mechanism of resistance to androgen-deprivation therapy (ADT). Here, we show that enzalutamide enhances sensitivity to immune-mediated killing of prostate tumor cells that overexpress AR. The immunomodulatory properties of enzalutamide and abiraterone provide a rationale for their use in combination with immunotherapeutic agents in CRPC, especially for patients with minimal response to enzalutamide or abiraterone alone, or for patients who have developed resistance to ADT. PMID:25344864

  7. Effect of Al content on r-value and recrystallization texture of B-bearing Al-killed steel sheets

    Energy Technology Data Exchange (ETDEWEB)

    Funakawa, Y.; Inazumi, I.; Hosoya, Y. [NKK Corp., Hiroshima (Japan). Mater. and Process. Res. Center; Murayama, T.

    1998-10-01

    It has been demonstrated that boron (B) had a beneficial effect on the mechanical properties of continuously annealed Al-killed steel sheets. However, the effect of Al content on r-value in the B-bearing steels has not been well discussed yet. In this study, the effect of Al content on r-value and recrystallization texture formation was investigated for laboratory-melt B-bearing low C Al-killed steel sheets. The r-value of continuously annealed B-bearing steel increased with decreasing Al content under the same grain size. In the steels with lower Al (Al=0.005%) content, the carbide coarsening in hot-rolled sheet was more significant as compared to those with higher Al(Al=0.055%) content. The recrystallization temperature was lowered with decreasing Al content, and the development of left angle 111 right angle //ND components was accelerated while that of left angle 110 right angle //ND components was retarded. Since the increase in Al content accelerates AlN precipitation in hot-rolled sheets, B might remain as in solution and segregate to grain boundaries. On the other hand, the reduction in Al content causes preferential precipitation of BN in hot-rolled sheets. The improvement of r-value by reducing Al content in B-bearing low C steels was caused by the development of left angle 111 right angle //ND components which reduced by solute B. (orig.) 9 refs.

  8. Breast tumor cells isolated from in vitro resistance to trastuzumab remain sensitive to trastuzumab anti-tumor effects in vivo and to ADCC killing.

    Science.gov (United States)

    Kute, Timothy E; Savage, Lori; Stehle, John R; Kim-Shapiro, Jung W; Blanks, Michael J; Wood, James; Vaughn, James P

    2009-11-01

    An understanding of model systems of trastuzumab (Herceptin) resistance is of great importance since the humanized monoclonal antibody is now used as first line therapy with paclitaxel in patients with metastatic Her2 overexpressing breast cancer, and the majority of their tumors has innate resistance or develops acquired resistance to the treatment. Previously, we selected trastuzumab-resistant clonal cell lines in vitro from trastuzumab-sensitive parental BT-474 cells and showed that cloned trastuzumab-resistant cell lines maintain similar levels of the extracellular Her2 receptor, bind trastuzumab as efficiently as the parental cells, but continue to grow in the presence of trastuzumab and display cell cycle profiles and growth rates comparable to parental cells grown in the absence of trastuzumab (Kute et al. in Cytometry A 57:86-93, 2004). We now show that trastuzumab-resistant and trastuzumab-sensitive cells both surprisingly display trastuzumab-mediated growth inhibition in athymic nude mice. This demonstrates that resistance developed in vitro is not predictive of resistance in vivo. The observation that in vitro resistant cells are sensitive to trastuzumab in vivo could be explained by antibody dependent cellular cytotoxicity (ADCC). Therefore, both parental and trastuzumab-resistant cells were assayed for ADCC in real time on electroplates with and without trastuzumab in the presence of a natural killer cell line (NK-92), and granulocyte or mononuclear cellular fractions isolated from human peripheral blood. Mononuclear cells and NK-92 cells were more effective in killing both parental and trastuzumab-resistant cells in the presence of trastuzumab. Both trastuzumab-resistant cells and trastuzumab-sensitive cells showed similar susceptibility to ADCC despite displaying divergent growth responses to trastuzumab. The granulocyte fraction was able to kill these cells with equal efficacy in the presence or absence of trastuzumab. These results support a model

  9. Preferential killing of human lung cancer cell lines with mitochondrial dysfunction by nonthermal dielectric barrier discharge plasma

    OpenAIRE

    Panngom, K; Baik, K Y; Nam, M K; Han, J. H.; Rhim, H; Choi, E. H.

    2013-01-01

    The distinctive cellular and mitochondrial dysfunctions of two human lung cancer cell lines (H460 and HCC1588) from two human lung normal cell lines (MRC5 and L132) have been studied by dielectric barrier discharge (DBD) plasma treatment. This cytotoxicity is exposure time-dependent, which is strongly mediated by the large amount of H2O2 and NOx in culture media generated by DBD nonthermal plasma. It is found that the cell number of lung cancer cells has been reduced more than that of the lun...

  10. Enhanced Cancer Cell (HeLa Killing Efficacy of Mixed Αlpha and Gamma Iron Oxide Superparamagnetic Nanoparticles under Combined AC (Alternating Current Magnetic-Field and Photoexcitation

    Directory of Open Access Journals (Sweden)

    Md. Shariful Islam, Yoshihumi Kusumoto, Md. Abdulla Al-Mamun and Yuji Horie

    2011-12-01

    Full Text Available We synthesized mixed α and γ-Fe2O3 nanoparticles and investigated their toxic effects against HeLa cells under induced AC (alternating current magnetic-fields and photoexcited conditions at room temperature. The findings revealed that the cell-killing percentage was increased with increasing dose for all types of treatments. Finally, 99% cancer cells were destructed at 1.2 mL dose when exposed to combined AC magnetic-field and photoexcited conditions (T3 whereas 89 and 83 % of HeLa cells were killed under only AC magnetic-field induced (T1 or only photoexcited (T2 condition at the same dose.ABSTRAK: Campuran α dan zarah γ-Fe2O3 bersaiz nano disintesiskan dan kesan toksidnya terhadap sel HeLa dikaji dibawah aruhan medan magnet arus ulang-alik (alternating current (AC dan keadaan photoexcited (proses ransangan atom atau molekul suatu bahan dengan penyerapan tenaga sinaran pada suhu bilik. Penemuan mendedahkan bahawa peratusan sel yang musnah bertambah dengan pertambahan dos untuk semua jenis rawatan. Akhirnya, 99% sel kanser dimusnahkan pada kadar dos 1.2mL setelah didedahkan terhadap kombinasi medan magnet AC dan keadaan photoexcited (T3 dimana 89% dan 83% sel HeLa dimusnahkan dengan hanya di bawah aruhan medan magnet AC (T1 atau hanya pada keadaan photoexcited (T2 pada kadar dos yang sama.KEY WORDS : Cancer, Hyperthermia, Iron oxide nanoparticles, Heat dissipation,    Cytotoxicity, HeLa cell.

  11. Heat Killed Lactobacillus reuteri GMNL-263 Reduces Fibrosis Effects on the Liver and Heart in High Fat Diet-Hamsters via TGF-β Suppression

    Directory of Open Access Journals (Sweden)

    Wei-Jen Ting

    2015-10-01

    Full Text Available Obesity is one of the major risk factors for nonalcoholic fatty liver disease (NAFLD, and NAFLD is highly associated with an increased risk of cardiovascular disease (CVD. Scholars have suggested that certain probiotics may significantly impact cardiovascular health, particularly certain Lactobacillus species, such as Lactobacillus reuteri GMNL-263 (Lr263 probiotics, which have been shown to reduce obesity and arteriosclerosis in vivo. In the present study, we examined the potential of heat-killed bacteria to attenuate high fat diet (HFD-induced hepatic and cardiac damages and the possible underlying mechanism of the positive effects of heat-killed Lr263 oral supplements. Heat-killed Lr263 treatments (625 and 3125 mg/kg-hamster/day were provided as a daily supplement by oral gavage to HFD-fed hamsters for eight weeks. The results show that heat-killed Lr263 treatments reduce fatty liver syndrome. Moreover, heat-killed Lactobacillus reuteri GMNL-263 supplementation in HFD hamsters also reduced fibrosis in the liver and heart by reducing transforming growth factor β (TGF-β expression levels. In conclusion, heat-killed Lr263 can reduce lipid metabolic stress in HFD hamsters and decrease the risk of fatty liver and cardiovascular disease.

  12. Tumor cell killing effect of boronated dipeptide. Boromethylglycylphenylalanine on boron neutron capture therapy for malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Takagaki, Masao; Ono, Koji; Masunaga, Shinichiro; Kinashi, Yuko; Kobayashi, Toru [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.; Oda, Yoshifumi; Kikuchi, Haruhiko; Spielvogel, B.F.

    1994-03-01

    The killing effect of Boron Neutron Capture Therapy; BNCT, is dependant on the boron concentration ratio of tumor to normal brain (T/N ratio), and also that of tumor to blood (T/B ratio). The clinical boron carrier of boro-captate (BSH) showed the large T/N ratio of ca. 8, however the T/B ratio was around 1, which indicated nonselective accumulation into tumor. Indeed high boron concentration of blood restrict the neutron irradiation dose in order to circumvent the normal endothelial damage, especially in the case of deeply seated tumor. Phenylalanine analogue of para borono-phenylalanine (BPA) is an effective boron carrier on BNCT for malignant melanoma. For the BNCT on brain tumors, however, BPA concentration in normal brain was reported to be intolerably high. In order to improve the T/N ratio of BPA in brain, therefore, a dipeptide of boromethylglycylphenylalanine (BMGP) was synthesized deriving from trimethylglycine conjugated with BPA. It is expected to be selectively accumulated into tumor with little uptake into normal brain. Because a dipeptide might not pass through the normal blood brain barrier (BBB). Its killing effect on cultured glioma cell, T98G, and its distribution in rat brain bearing 9L glioma have been investigated in this paper. The BNCT effect of BMGP on cultured cells was nearly triple in comparison with DL-BPA. The neutron dose yielding 1% survival ratio were 7x10{sup 12}nvt for BMGP and 2x10{sup 13}nvt for BPA respectively on BNCT after boron loading for 16 hrs in the same B-10 concentration of 20ppm. Quantitative study of boron concentration via the {alpha}-auto radiography and the prompt gamma ray assay on 9L brain tumor rats revealed that T/N ratio and T/B ratio are 12.0 and 3.0 respectively. Those values are excellent for BNCT use. (author).

  13. Alternative treatments for melanoma: targeting BCL-2 family members to de-bulk and kill cancer stem cells

    OpenAIRE

    Mukherjee, Nabanita; Schwan, Josianna V.; Fujita, Mayumi; Norris, David A.; Shellman, Yiqun G.

    2015-01-01

    For the first time new treatments in melanoma have produced significant responses in advanced diseases, but 30–90% of melanoma patients do not respond or eventually relapse after the initial response to the current treatments. The resistance of these melanomas is likely due to tumor heterogeneity, which may be explained by models such as the stochastic, hierarchical, and phenotype-switching models. This review will discuss the recent advancements in targeting BCL-2 family members for cancer t...

  14. 5-Fluorouracil-loaded polylactic acid nanoparticles have a killing effect on gastric cancer cell lines in vitro%5-氟尿嘧啶聚乳酸载药纳米微粒对胃癌细胞株的体外杀伤作用

    Institute of Scientific and Technical Information of China (English)

    李晓利; 牛敏; 张铭; 张娜娜; 施瑶

    2015-01-01

    背景:5-氟尿嘧啶在胃癌治疗中占据重要地位,但是长期服用容易出现骨髓抑制、白细胞减少等不良反应。聚乳酸及共聚物载药微粒材料生物相容性较高,分解物不会在机体内发生聚集。  目的:探讨聚乳酸载药纳米微粒对胃癌细胞株的体外杀伤作用机制。  方法:选取10只小鼠进行实验,利用超声乳化方法制备5-氟尿嘧啶聚乳酸载药纳米微粒,并采用噻唑蓝比色法配制1×10-7,1×10-6,1×10-5,1×10-4 mol/L的5-氟尿嘧啶聚乳酸载药纳米微粒,检测其对小鼠胃癌细胞的体外杀伤效应,并且计算出药物的抑制率浓度以及对胃癌细胞的生长抑制能力等以及凋亡的诱导作用。  结果与结论:透射电镜下观察5-氟尿嘧啶聚乳酸载药纳米微粒:形态完好,分布相对均匀,不出现粘连等现象,用药24 h药物浓度可达到50%,72 h后能够达到62.9%;不同浓度下单一5-氟尿嘧啶和5-氟尿嘧啶聚乳酸载药纳米微粒和小鼠胃癌细胞联合培养48 h后,细胞的活性随着药物浓度的提高出现下降趋势,并且5-氟尿嘧啶聚乳酸载药纳米微粒细胞抑制能力显著高于5-氟尿嘧啶(P OBJECTIVE:To investigate the in vitro cytotoxicity mechanism of 5-fluorouracil-loaded polylactic acid nanoparticles on gastric cancer cel lines. METHODS:Ten mice were selected in this study. 5-fluorouracil-loaded polylactic acid nanoparticles (1×10-7, 1×10-6, 1×10-5, 1×10-4 mol/L) were prepared using ultrasonic emulsification method. Kiling effect of polylactic acid nanoparticles on gastric cancer cel lines in vitrowere detected. Then, the inhibition rate was calculated at different concentrations. RESULTS AND CONCLUSIONS: Under the transmission electron microscope, 5-fluorouracil-loaded polylactic acid nanoparticles had good shape and relatively evenly distributed with no adhesions. After drug administration, the drug concentration was

  15. Xenoantigen, an αGal epitope-expression construct driven by the hTERT-promoter, specifically kills human pancreatic cancer cell line

    Directory of Open Access Journals (Sweden)

    Fuchinoue Shohei

    2002-10-01

    Full Text Available Abstract Background We previously reported the usefulness of the αGal epitope as a target molecule for gene therapy against cancer. To induce cancer cell specific transcription of the αGal epitope, an expression vector which synthesizes the αGal epitope under the control of a promoter region of the human telomerase reverse transcriptase (hTERT, NK7, was constructed. Methods NK7 was transfected into a human pancreatic carcinoma cell line, MIA cells, and telomerase-negative SUSM-1 cells served controls. Expression of the αGal epitope was confirmed by flow cytometry using IB4 lectin. The susceptibility of transfected MIA cells to human natural antibodies, was examined using a complement-dependent cytotoxic cross-match test (CDC and a flow cytometry using annexin V. Results The αGal epitope expression was detected only on the cell surfaces of NK7-transfected MIA cells, i.e., not on naive MIA cells or telomerase negative SUSM-1 cells. The CDC results indicated that MIA cells transfected with NK7 are susceptible to human natural antibody-mediated cell killing, and the differences, as compared to NK-7 transfected telomerase negative SUSM-1 cells or telomerase positive naïve MIA cells, were statistically significant. The flow cytometry using annexin V showed a higher number of the apoptotic cells in NK-7 transfected MIA cells than in naïve MIA cells. Conclusions The results suggest that αGal epitope-expression, under the control of the hTERT-promoter, may be useful in cancer specific gene therapy.

  16. Anti-Cancer Effect of Angelica Sinensis on Women’s Reproductive Cancer

    Directory of Open Access Journals (Sweden)

    Hong-Hong Zhu

    2012-06-01

    Full Text Available Objective: Danggui, the root of Angelica Sinensis, has traditionally been used for the treatment of women’s reproductive disorders in China for thousands of years. This study was to determine whether Danggui have potential anti-cancer effect on women’s cancer and its potential mechanism. Methods: Danggui was extracted by ethanol. The Cell Titer 96® Aqueous Non-Radioactive Cell Proliferation Assay was used to compare the effects of Danggui on human breast (MCF-7 and 7368 and cervical (CaSki and SiHa cancer cells with its effects on normal fibroblasts (HTB-125. A revised Ames test was used to test for antimutagenicity. The standard strains of Salmonella typhimarium (TA 100 and 102 were used in the test. Methyl methane sulfonate (MMS and UV light were used as positive mutagen controls and ethanol and double distilled water (DDW as controls. The SAS statistical software was used to analyze the data. Results: Danggui was found to be much more toxic to all cancer cell lines tested than to normal fibroblasts. There was a significant negative dose-effect relationship between Danggui and cancer cell viability. Average viability of MCF-7 was 69.5%, 18.4%, 5.7%, 5.7%, and 5.0% of control for Danggui doses 0.07, 0.14, 0.21, 0.32, and 0.64 ug/ul, respectively, with a Ptrend < 0.0001. Half maximal inhibitory dose (ID50 of Danggui for cancer cell lines MCF-7, CaSki, SiHa and CRL-7368 was 0.10, 0.09, 0.10 and 0.07 ug/ul, Functional Foods in Health and Disease 2012, 2(6:242-250respectively. For the normal fibroblasts, ID50 was 0.58 ug/ul. At a dose of 0.32 ug/ul, Danggui killed over 90% of the cells in each cancer cell line, but at the same dose, only 12.3 % of the normal HTB-125 cells were killed. Revertants per plate of TA 100 decreased with the introduction of increasing doses of Danggui extracts with a Ptrend < 0.0001 when UV light was used as a mutagen. There was no difference in revertants per plate between ethanol and DDW control groups. Conclusions

  17. Inhibiting WEE1 Selectively Kills Histone H3K36me3-Deficient Cancers by dNTP Starvation.

    Science.gov (United States)

    Pfister, Sophia X; Markkanen, Enni; Jiang, Yanyan; Sarkar, Sovan; Woodcock, Mick; Orlando, Giulia; Mavrommati, Ioanna; Pai, Chen-Chun; Zalmas, Lykourgos-Panagiotis; Drobnitzky, Neele; Dianov, Grigory L; Verrill, Clare; Macaulay, Valentine M; Ying, Songmin; La Thangue, Nicholas B; D'Angiolella, Vincenzo; Ryan, Anderson J; Humphrey, Timothy C

    2015-11-01

    Histone H3K36 trimethylation (H3K36me3) is frequently lost in multiple cancer types, identifying it as an important therapeutic target. Here we identify a synthetic lethal interaction in which H3K36me3-deficient cancers are acutely sensitive to WEE1 inhibition. We show that RRM2, a ribonucleotide reductase subunit, is the target of this synthetic lethal interaction. RRM2 is regulated by two pathways here: first, H3K36me3 facilitates RRM2 expression through transcription initiation factor recruitment; second, WEE1 inhibition degrades RRM2 through untimely CDK activation. Therefore, WEE1 inhibition in H3K36me3-deficient cells results in RRM2 reduction, critical dNTP depletion, S-phase arrest, and apoptosis. Accordingly, this synthetic lethality is suppressed by increasing RRM2 expression or inhibiting RRM2 degradation. Finally, we demonstrate that WEE1 inhibitor AZD1775 regresses H3K36me3-deficient tumor xenografts. PMID:26602815

  18. Specific targeted killing of ErbB2 positive breast cancer by retrovirus-mediated Immunocaspase-3 secreting T cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lihong; YANG An-gang; JIA Lintao; ZHAO Jing; XU Yanming; WEN Weihong; BAO Wei; CAO Yunxin; SU Chengzhi; WANG Chengji

    2004-01-01

    In this study, Immunocaspase-3 gene was transfected into Jurkat T lymphocytes and the targeted proapoptotic protein Immunocaspase-3 was stably secreted.Its entry to ErbB2 positive SKBr3 breast carcinoma cell line was observed by indirect immunofluorescence staining.Growth of SKBr3 cells was significantly inhibited when they were cultured with medium containing Immunocaspase-3.Next, Immunocaspase-3 gene was cloned into retrovirus vector pLNCX, which was then transfected into PA317 cells to package. Packaged cells producing high titer pseudoviruses were acquired and the pseudoviruses were harvested to infect PBMCs, which had been stimulated to division. The latter were selected and administered to nude mice bearing SKBr3 tumors through tail vein. The results showed that the treatment contributed to an inhibition of tumor growth and prolonged the lifetime of nude mice bearing SKBr3 tumor.The efficiency of inhibition of tumor reached 73.25%, and the average lifetime of treated nude mice was 80.95% longer than that of control group. Immunohistochemical examination revealed the exclusive distribution of Immunocaspase-3proteins only in the tumor tissue samples; and TUNEL assay confirmed the occurrence of apoptosis in tumor cells. The present study suggests that Immunocaspase-3 secreted by T lymphocytes can selectively bind and enter into ErbB2 positive breast cancer cells, where it exhibits a proapoptotic activity and causes tumor suppression in an in vivo tumor model.

  19. A time to kill when is leadership targeting an effective counterterrorism strategy

    OpenAIRE

    Schliep, Randy D.

    2007-01-01

    lts. This study will argue that leadership targeting may be an effective strategy, but only under specific conditions. It is critical to the security of the United States, for strategic and operational planners, policy makers, and executives, to understand the appropriate environment for undertaking a leadership targeting strategy. This study provides a framework for analyzing the effectiveness of leadership targeting based on critical components of leadership.

  20. Mast cell toll-like receptor 2 signaling is crucial for effective killing of Francisella tularensis1

    Science.gov (United States)

    Rodriguez, Annette R.; Yu, Jieh-Juen; Guentzel, M. N.; Navara, Christopher S.; Klose, Karl E.; Forsthuber, Thomas G.; Chambers, James P.; Berton, Michael T.; Arulanandam, Bernard P

    2012-01-01

    Toll-like receptor (TLR) signaling is critical for early host defense against pathogens, but the contribution of mast cell TLR-mediated mechanisms and subsequent effector functions during pulmonary infection is largely unknown. We have previously demonstrated that mast cells, through the production of IL-4, effectively control Francisella tularensis replication. In this study, the highly human virulent strain of F. tularensis SCHU S4 and the Live Vaccine Strain (LVS) were utilized to investigate the contribution of mast cell-TLR regulation of Francisella. Mast cells required TLR2 for effective bacterial killing, regulation of the hydrolytic enzyme cathepsin L, and for coordination and trafficking of MHCII and lysosomal associated membrane protein 2 (LAMP2). Infected TLR2−/− mast cells, in contrast to WT and TLR4−/−, lacked detectable IL-4 and displayed increased cell death with a 2–3 log increase of F. tularensis replication, but could be rescued with recombinant IL-4 treatment. Importantly, MHCII and LAMP2 localization with labeled F. tularensis in the lungs was greater in WT than in TLR2−/− mice. These results provide evidence for the important effector contribution of mast cells and TLR2-mediated signaling on early innate processes in the lung following pulmonary F. tularensis infection and provide additional insight into possible mechanisms by which intracellular pathogens modulate respiratory immune defenses. PMID:22529298

  1. Evaluation of the speed of kill, effects on reproduction, and effectiveness in a simulated infested-home environment of sarolaner (Simparica™) against fleas on dogs.

    Science.gov (United States)

    Six, Robert H; Becskei, Csilla; Carter, Lori; Gale, Boyd; Young, David R; Mahabir, Sean P; Chapin, Sara; Myers, Melanie R

    2016-05-30

    Four studies were conducted to evaluate the speed of kill, effect on egg production, and efficacy in a simulated infested-home environment of a novel isoxazoline, sarolaner (Simparica™, Zoetis), against fleas on dogs. Individually identified and housed, purpose-bred Beagles were used in each study and were allocated randomly to groups based on pretreatment parasite counts. In two speed of kill studies, groups of dogs infested with 100 fleas prior to treatment were treated orally with placebo or sarolaner tablets providing the minimum dose of 2mg/kg and then re-infested with fleas weekly for five weeks post-treatment. Comb counts were conducted to determine the numbers of viable fleas at one to three, four, eight and 12h after treatment and each subsequent infestation. In the egg production study, sarolaner- and placebo-treated dogs were similarly challenged with fleas and at 48h after each infestation the dogs were housed for 20h in cages allowing the collection and counting of all flea eggs produced during this period. Collected eggs were incubated to evaluate hatch and development to adults. The last study used dogs housed in a flea-infested simulated-home environment. Dogs were allocated to treatment with either placebo or sarolaner tablets providing a dose of 2mg/kg once a month for three treatments. Flea infestations were assessed by comb counts (fleas were replaced on the dogs) on Days 14, 30, 44, 60, 74 and 90. The speed of kill studies demonstrated that a single 2mg/kg oral dose of sarolaner started killing fleas within three to four hours after treatment or subsequent re-infestations for up to a month, and achieved ≥98% control of fleas by eight hours after treatment or re-infestation for 28 days. In the study to assess effects on flea reproduction, a single oral treatment of sarolaner resulted in the complete cessation of egg-laying for 35 days. This rapid kill of fleas and inhibition of reproduction were confirmed in a simulated-home environment

  2. Cryotherapy for prostate cancer

    Science.gov (United States)

    Cryotherapy uses very cold temperatures to freeze and kill prostate cancer cells. The goal of cryosurgery is ... Possible short-term side effects of cryotherapy for prostate ... of the penis or scrotum Problems controlling your bladder (more ...

  3. Relative biological effect of high Z, high LET charged particles for spermatogonial killing

    International Nuclear Information System (INIS)

    The effects of high LET radiations produced with accelerated heavy-ion beams on weight loss of the mouse testes have been examined. It is assumed that weight loss is due primarily to cell death in the germinal epithelium. Results indicate that little or no recovery of sublethal injury occurs in this cell renewal system. Generally, the RBE rises continuously and monotonically for all LET values associated with helium and carbon from 6 to 100 keV/μm. On the other hand, the data for neon and argon do not appear to fit. From the standpoint of the radiobiology of heavy ions, the most significant observation is that LET alone does not account for variation in radiation response of the spermatogonial population

  4. Effects of vancomycin versus nafcillin in enhancing killing of methicillin-susceptible Staphylococcus aureus causing bacteremia by human cathelicidin LL-37.

    Science.gov (United States)

    Le, J; Dam, Q; Schweizer, M; Thienphrapa, W; Nizet, V; Sakoulas, G

    2016-09-01

    Recent studies have demonstrated that anti-staphylococcal beta-lactam antibiotics, like nafcillin, render methicillin-resistant Staphylococcus aureus (MRSA) more susceptible to killing by innate host defense peptides (HDPs), such as cathelicidin LL-37. We compared the effects of growth in 1/4 minimum inhibitory concentration (MIC) of nafcillin or vancomycin on the LL-37 killing of 92 methicillin-susceptible S. aureus (MSSA) isolates. For three randomly selected strains among these, we examined the effects of nafcillin, vancomycin, daptomycin, or linezolid on LL-37 killing and autolysis. Growth in the presence of subinhibitory nafcillin significantly enhanced LL-37 killing of MSSA compared to vancomycin and antibiotic-free controls. Nafcillin also reduced MSSA production of the golden staphylococcal pigment staphyloxanthin in 39 % of pigmented strains vs. 14 % for vancomycin. Among the antibiotics tested, only nafcillin resulted in significantly increased MSSA autolysis. These studies point to additional mechanisms of anti-staphylococcal activity of nafcillin beyond direct bactericidal activity, properties that vancomycin and other antibiotic classes do not exhibit. The ability of nafcillin to enhance sensitivity to innate HDPs may contribute to its superior effectiveness against MSSA, as suggested by studies comparing clinical outcomes to vancomycin treatment. PMID:27234592

  5. Killing effect of Chinese hamster V79 cells exposed to accelerated carbon ions and RBE determination

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Survival curves of Chinese hamster V79 cells exposed to accclerated carbon ions with linear energy transfers of 125.5, 200 and 700 keV/μm were measured, respectively. Inactivation cross sections corresponding to the irradiation above were deduced from the V79 cell survival curves. They are 7.86±0.17, 10.44±1.11 and 32.32±3.58 μm2 in turn. With the surviving response of V79 cells to 60Co γ-rays as a reference value, relative biological effectiveness at 10%, 20%, 50% and 80% survival levels were given for the accelerated carbon ions. The results showed that carbon ions with LET of 125.5 keV/μm had a higher value of RBE at all the four survival levels than the carbon ions with other LETs. It was prompted that the maximum value of RBE for the V79 cell surviving as the biological endpoint emerged at the LET below 200 keV/μm for carbon ions.

  6. Transferrin coupled azanthraquinone enhances the killing effect on trypanosomes. The role of lysosomal mannosidase

    Directory of Open Access Journals (Sweden)

    Nok A.J.

    2002-12-01

    Full Text Available Partially purified azanthraquinone (AQ extract from Mitracarpus scaber was coupled to bovine transferrin (Tf using azidophenyl glyoxal (APG. The AQ-APG-Tf conjugate was found to possess an enhanced in vitro trypanocidal activity against Trypanosoma congolense and T. brucei brucei. At low concentrations of 0.39-90 mg/ml, the conjugate diminished the growth of T. congolense and T. b. brucei dose dependently at the logarithmic phase. Both parasites were more sensitive to AQ-APG-Tf than to the free (AQ extract. Growth inhibition on the parasites by the free extract was observed at 20-200 mg/ml. The total activity of the lysosomal enzyme a-mannosidase was reduced in the T. congolense cells treated with AQ-APG-Tf in a dose related pattern. However, the activity of the mannosidase in the T. b. brucei treated cells is less affected. The AQ-APG-Tf is more effective on a mannosidase than free AQ, eight and four fold for T. congolense and T. b. brucei respectively. The results are discussed as regards the potency of using transferrin as suitable drug carrier in the chemotherapy of Human sleeping sickness.

  7. Killing effect of Chinese hamster V79 cells exposed to accelerated carbon ions and RBE determination

    Institute of Scientific and Technical Information of China (English)

    LIQiang; ZHOUGuang-Ming; 等

    2002-01-01

    Survival curves of Chinese hamster V79 cells exposed to accelerated carbon ions with linear energy transfers of 125.5,200 and 700keV/um were measured,respectively,Inactivation cross sections corresponding to the irradiation above were deduced from the V79 cell survival curves.They are 7.86±0.17,10.44±1.11 and 32.32±3.59um2 in turn.With the surviving response of V79 cells to 60Co γ-rays as a reference value,relative biological effectiveness at 10%,20%,50%and 80% survival levels were given for the accelerated carbon ions,The results showed that carbon ions with LET of 125.5keV/um had a higher value of RBE at all the four survival levels than the carbon ions with other LETs.It was prompted that the maximum value of RBE for the V79 cell surviving as the biological endpoint emerged at the LET below 200keV/um for carbon ions.

  8. Effect of sociality and season on gray wolf (Canis lupus foraging behavior: implications for estimating summer kill rate.

    Directory of Open Access Journals (Sweden)

    Matthew C Metz

    Full Text Available BACKGROUND: Understanding how kill rates vary among seasons is required to understand predation by vertebrate species living in temperate climates. Unfortunately, kill rates are only rarely estimated during summer. METHODOLOGY/PRINCIPAL FINDINGS: For several wolf packs in Yellowstone National Park, we used pairs of collared wolves living in the same pack and the double-count method to estimate the probability of attendance (PA for an individual wolf at a carcass. PA quantifies an important aspect of social foraging behavior (i.e., the cohesiveness of foraging. We used PA to estimate summer kill rates for packs containing GPS-collared wolves between 2004 and 2009. Estimated rates of daily prey acquisition (edible biomass per wolf decreased from 8.4±0.9 kg (mean ± SE in May to 4.1±0.4 kg in July. Failure to account for PA would have resulted in underestimating kill rate by 32%. PA was 0.72±0.05 for large ungulate prey and 0.46±0.04 for small ungulate prey. To assess seasonal differences in social foraging behavior, we also evaluated PA during winter for VHF-collared wolves between 1997 and 2009. During winter, PA was 0.95±0.01. PA was not influenced by prey size but was influenced by wolf age and pack size. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that seasonal patterns in the foraging behavior of social carnivores have important implications for understanding their social behavior and estimating kill rates. Synthesizing our findings with previous insights suggests that there is important seasonal variation in how and why social carnivores live in groups. Our findings are also important for applications of GPS collars to estimate kill rates. Specifically, because the factors affecting the PA of social carnivores likely differ between seasons, kill rates estimated through GPS collars should account for seasonal differences in social foraging behavior.

  9. Assessing road effects on bats: the role of landscape, road features, and bat activity on road-kills

    OpenAIRE

    Medinas, Denis; Marques, João Tiago; Mira, António

    2013-01-01

    Recent studies suggest that roads can significantly impact bat populations. Though bats are one of the most threatened groups of European vertebrates, studies aiming to quantify bat mortality and determine the main factors driving it remain scarce. Between March 16 and October 31 of 2009, we surveyed road-killed bats daily along a 51-km-long transect that incorporates different types of roads in southern Portugal. We found 154 road-killed bats of 11 species. The two most common species in the...

  10. Cytotoxic macrophage-released tumour necrosis factor-alpha (TNF-α) as a killing mechanism for cancer cell death after cold plasma activation

    Science.gov (United States)

    Kaushik, Nagendra Kumar; Kaushik, Neha; Min, Booki; Choi, Ki Hong; Hong, Young June; Miller, Vandana; Fridman, Alexander; Choi, Eun Ha

    2016-03-01

    The present study aims at studying the anticancer role of cold plasma-activated immune cells. The direct anti-cancer activity of plasma-activated immune cells against human solid cancers has not been described so far. Hence, we assessed the effect of plasma-treated RAW264.7 macrophages on cancer cell growth after co-culture. In particular, flow cytometer analysis revealed that plasma did not induce any cell death in RAW264.7 macrophages. Interestingly, immunofluorescence and western blot analysis confirmed that TNF-α released from plasma-activated macrophages acts as a tumour cell death inducer. In support of these findings, activated macrophages down-regulated the cell growth in solid cancer cell lines and induced cell death in vitro. Together our findings suggest plasma-induced reactive species recruit cytotoxic macrophages to release TNF-α, which blocks cancer cell growth and can have the potential to contribute to reducing tumour growth in vivo in the near future.

  11. Cytotoxic macrophage-released tumour necrosis factor-alpha (TNF-α) as a killing mechanism for cancer cell death after cold plasma activation

    International Nuclear Information System (INIS)

    The present study aims at studying the anticancer role of cold plasma-activated immune cells. The direct anti-cancer activity of plasma-activated immune cells against human solid cancers has not been described so far. Hence, we assessed the effect of plasma-treated RAW264.7 macrophages on cancer cell growth after co-culture. In particular, flow cytometer analysis revealed that plasma did not induce any cell death in RAW264.7 macrophages. Interestingly, immunofluorescence and western blot analysis confirmed that TNF-α released from plasma-activated macrophages acts as a tumour cell death inducer. In support of these findings, activated macrophages down-regulated the cell growth in solid cancer cell lines and induced cell death in vitro. Together our findings suggest plasma-induced reactive species recruit cytotoxic macrophages to release TNF-α, which blocks cancer cell growth and can have the potential to contribute to reducing tumour growth in vivo in the near future. (paper)

  12. Solubilization of Poorly Soluble PDT Agent, Meso-tetraphenylporphin, in Plain or Immunotargeted PEG-PE Micelles Results in Dramatically Improved Cancer Cell Killing in Vitro

    OpenAIRE

    Roby, Aruna; Erdogan, Suna; Torchilin, Vladimir P.

    2005-01-01

    Poorly soluble photodynamic therapy (PDT) agent, meso-tetratphenylporphine (TPP), was effectively solubilized using non-targeted and tumor-targeted polymeric micelles prepared of polyethylene glycol/phosphatidyl ethanolamine conjugate (PEG-PE). Encapsulation of TPP into PEG-PE-based micelles and immunomicelles (bearing an anti-cancer monoclonal 2C5 antibody) resulted in significantly improved anticancer effects of the drug at PDT conditions against murine (LLC, B16) and human (MCF-7, BT20) ca...

  13. How to kill creativity.

    Science.gov (United States)

    Amabile, T M

    1998-01-01

    In today's knowledge economy, creativity is more important than ever. But many companies unwittingly employ managerial practices that kill it. How? By crushing their employees' intrinsic motivation--the strong internal desire to do something based on interests and passions. Managers don't kill creativity on purpose. Yet in the pursuit of productivity, efficiency, and control--all worthy business imperatives--they undermine creativity. It doesn't have to be that way, says Teresa Amabile. Business imperatives can comfortably coexist with creativity. But managers will have to change their thinking first. Specifically, managers will need to understand that creativity has three parts: expertise, the ability to think flexibly and imaginatively, and motivation. Managers can influence the first two, but doing so is costly and slow. It would be far more effective to increase employees' intrinsic motivation. To that end, managers have five levers to pull: the amount of challenge they give employees, the degree of freedom they grant around process, the way they design work groups, the level of encouragement they give, and the nature of organizational support. Take challenge as an example. Intrinsic motivation is high when employees feel challenged but not overwhelmed by their work. The task for managers, therefore, becomes matching people to the right assignments. Consider also freedom. Intrinsic motivation--and thus creativity--soars when managers let people decide how to achieve goals, not what goals to achieve. Managers can make a difference when it comes to employee creativity. The result can be truly innovative companies in which creativity doesn't just survive but actually thrives.

  14. Evolution of coalitionary killing.

    Science.gov (United States)

    Wrangham, R W

    1999-01-01

    Warfare has traditionally been considered unique to humans. It has, therefore, often been explained as deriving from features that are unique to humans, such as the possession of weapons or the adoption of a patriarchal ideology. Mounting evidence suggests, however, that coalitional killing of adults in neighboring groups also occurs regularly in other species, including wolves and chimpanzees. This implies that selection can favor components of intergroup aggression important to human warfare, including lethal raiding. Here I present the principal adaptive hypothesis for explaining the species distribution of intergroup coalitional killing. This is the "imbalance-of-power hypothesis," which suggests that coalitional killing is the expression of a drive for dominance over neighbors. Two conditions are proposed to be both necessary and sufficient to account for coalitional killing of neighbors: (1) a state of intergroup hostility; (2) sufficient imbalances of power between parties that one party can attack the other with impunity. Under these conditions, it is suggested, selection favors the tendency to hunt and kill rivals when the costs are sufficiently low. The imbalance-of-power hypothesis has been criticized on a variety of empirical and theoretical grounds which are discussed. To be further tested, studies of the proximate determinants of aggression are needed. However, current evidence supports the hypothesis that selection has favored a hunt-and-kill propensity in chimpanzees and humans, and that coalitional killing has a long history in the evolution of both species. PMID:10601982

  15. Photo activation of HPPH encapsulated in “Pocket” liposomes triggers multiple drug release and tumor cell killing in mouse breast cancer xenografts

    Directory of Open Access Journals (Sweden)

    Sine J

    2014-12-01

    Full Text Available Jessica Sine,1,* Cordula Urban,2,* Derek Thayer,1 Heather Charron,2 Niksa Valim,2 Darrell B Tata,3 Rachel Schiff,4 Robert Blumenthal,1 Amit Joshi,2 Anu Puri1 1Membrane Structure and Function Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute – Frederick, Frederick, MD, USA; 2Department of Radiology, Baylor College of Medicine, Houston, TX, USA; 3US Food and Drug Administration, CDRH/OSEL/Division of Physics, White Oak Campus, MD, USA; 4Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA *These authors contributed equally to this work Abstract: We recently reported laser-triggered release of photosensitive compounds from liposomes containing dipalmitoylphosphatidylcholine (DPPC and 1,2 bis(tricosa-10,12-diynoyl-sn-glycero-3-phosphocholine (DC8,9PC. We hypothesized that the permeation of photoactivated compounds occurs through domains of enhanced fluidity in the liposome membrane and have thus called them “Pocket” liposomes. In this study we have encapsulated the red light activatable anticancer photodynamic therapy drug 2-(1-Hexyloxyethyl-2-devinyl pyropheophorbide-a (HPPH (Ex/Em410/670 nm together with calcein (Ex/Em490/517 nm as a marker for drug release in Pocket liposomes. A mole ratio of 7.6:1 lipid:HPPH was found to be optimal, with >80% of HPPH being included in the liposomes. Exposure of liposomes with a cw-diode 660 nm laser (90 mW, 0–5 minutes resulted in calcein release only when HPPH was included in the liposomes. Further analysis of the quenching ratios of liposome-entrapped calcein in the laser treated samples indicated that the laser-triggered release occurred via the graded mechanism. In vitro studies with MDA-MB-231-LM2 breast cancer cell line showed significant cell killing upon treatment of cell-liposome suspensions with the laser. To assess in vivo efficacy, we implanted MDA-MB-231-LM2 cells containing the luciferase gene along the mammary fat pads

  16. MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells

    Science.gov (United States)

    Kosmacek, Elizabeth A.; Chatterjee, Arpita; Tong, Qiang; Lin, Chi; Oberley, Rebecca E.

    2016-01-01

    Manganese porphyrins have been shown to be potent radioprotectors in a variety of cancer models. However, the mechanism as to how these porphyrins protect normal tissues from radiation damage still remains largely unknown. In the current study, we determine the effects of the manganese porphyrin, MnTnBuOE-2-PyP, on primary colorectal fibroblasts exposed to irradiation. We found that 2 Gy of radiation enhances the fibroblasts' ability to contract a collagen matrix, increases cell size and promotes cellular senesence. Treating fibroblasts with MnTnBuOE-2-PyP significantly inhibited radiation-induced collagen contraction, preserved cell morphology and also inhibited cellular senescence. We further showed that MnTnBuOE-2-PyP enhanced the overall viability of the fibroblasts following exposure to radiation but did not protect colorectal cancer cell viability. Specifically, MnTnBuOE-2-PyP in combination with irradiation, caused a significant decrease in tumor clonogenicity. Since locally advanced rectal cancers are treated with chemoradiation therapy followed by surgery and non-metastatic anal cancers are treated with chemoradiation therapy, we also investigated the effects of MnTnBuOE-2-PyP in combination with radiation, 5-fluorouracil with and without Mitomycin C. We found that MnTnBuOE-2-PyP in combination with Mitomycin C or 5-fluorouracil further enhances those compounds' ability to suppress tumor cell growth. When MnTnBuOE-2-PyP was combined with the two chemotherapeutics and radiation, we observed the greatest reduction in tumor cell growth. Therefore, these studies indicate that MnTnBuOE-2-PyP could be used as a potent radioprotector for normal tissue, while at the same time enhancing radiation and chemotherapy treatment for rectal and anal cancers. PMID:27119354

  17. Predicting In Silico Which Mixtures of the Natural Products of Plants Might Most Effectively Kill Human Leukemia Cells?

    Directory of Open Access Journals (Sweden)

    Hany A. El-Shemy

    2013-01-01

    Full Text Available The aim of the analysis of just 13 natural products of plants was to predict the most likely effective artificial mixtures of 2-3 most effective natural products on leukemia cells from over 364 possible mixtures. The natural product selected included resveratrol, honokiol, chrysin, limonene, cholecalciferol, cerulenin, aloe emodin, and salicin and had over 600 potential protein targets. Target profiling used the Ontomine set of tools for literature searches of potential binding proteins, binding constant predictions, binding site predictions, and pathway network pattern analysis. The analyses indicated that 6 of the 13 natural products predicted binding proteins which were important targets for established cancer treatments. Improvements in effectiveness were predicted for artificial combinations of 2 or 3 natural products. That effect might be attributed to drug synergism rather than increased numbers of binding proteins bound (dose effects. Among natural products, the combinations of aloe emodin with mevinolin and honokiol were predicted to be the most effective combination for AML-related predicted binding proteins. Therefore, plant extracts may in future provide more effective medicines than the single purified natural products of modern medicine, in some cases.

  18. Deprive to kill: Glutamine closes the gate to anticancer monocarboxylic drugs

    OpenAIRE

    Cardaci, Simone; Ciriolo, Maria Rosa

    2012-01-01

    Killing properties of antitumor drugs can be enhanced by strategies targeting biochemical adaptations of cancer cells. Recently, we reported that depriving cancer cells of glutamine is a feasible approach to enhance antitumor effects of the alkylating analog of pyruvic acid, 3-bromopyruvate, which rely on the induction of autophagic cell death by metabolic-oxidative stress. 3-bromopyruvate chemopotentiation is the result of its increased intracellular uptake mediated by the monocarboxylate tr...

  19. Effects of killing Helicobacter pylori quadruple therapy on peptic ulcer: A randomized double-blind clinical trial

    Institute of Scientific and Technical Information of China (English)

    Li-Ying Feng; Xi-Xian Yao; Shu-Lin Jiang

    2005-01-01

    AIM: To study the therapeutic efficacy of a Chinese and Western integrated regimen, killing Helicobacter pylori quadruple therapy on H pylori-associated peptic ulcers(PU).METHODS: With prospective and double-blind controlled method, seventy-five active PU patients with H pylori infection were randomized to receive one of the following three regimens: (1) new triple therapy (group A:lansoprazole 30 mg qd, plus clarithromycin 250 mg bid,plus amoxycillin 500 mg tid, each for 10 d); (2) killing Hp quadruple therapy(group B: the three above drugs plus killing H pylori capsule 6 capsules bid for 4 wk) and (3)placebo(group C: gastropine 3 tablets bid for 4 wk).H pylori eradication and ulcer healing quality were evaluated under an endoscope 4 wk after treatment. The patients were followed up for 5 years.RESULTS: Both the healing rate of PU and H pylori eradication rate in group B were significantly higher than those in group C (100% and 96.4% vs 20% and 0%,respectively, P<0.005), but there was no significant difference compared to those in group A (88% and92%, P>0.05). The healing quality of ulcer in group B was superior to that in groups C and A (P<0.05). The recurrence rate of PU in group B (4%) was lower than that in group A (10%) and group C (100%, P<0.01).CONCLUSION: Killing Helicobacter pylori quadruple therapy can not only promote the eradication of H pylori and healing quality of ulcer but also reduce recurrence rate of ulcer.

  20. Effects of Rhodomyrtus tomentosa Extract on Killing Activity of Human Neutrophils and Membrane Integrity of Enterohaemorrhagic Escherichia coli O157:H7

    Directory of Open Access Journals (Sweden)

    Jutharat Hmoteh

    2016-05-01

    Full Text Available Enterohaemorrhagic Escherichia coli (E. coli O157:H7 is one of the most virulent causative agents of foodborne disease. Use of antibiotics for the treatment against E. coli O157:H7 infection leads to hemolytic uremic syndrome. The present study evaluated the potential of ethanolic leaf extract of a medicinal plant, Rhodomyrtus tomentosa in enhancing the killing activity of human neutrophils against E. coli O157:H7. In addition, the effects of the extract on membrane permeability of the organisms were studied. In the killing assay, percentage survival of the bacterial cells after being exposed to human neutrophils in the presence of various concentrations of the extract were determined. At 45 min, percentage survival of E. coli O157:H7 and E. coli ATCC 25922 after treated with neutrophils in the presence of the extract at 125–250 µg/mL was 58.48%–50.28% and 69.13%–35.35%, respectively. Furthermore, upon treatment with R. tomentosa at 250 µg/mL uptake of crystal violet by E. coli O157:H7 and E. coli ATCC 25922 was increased to 40.07% and 36.16%, respectively. Therefore, it is suggested that the extract exhibited dual effects as immunostimulant and membrane permeabilizing agent perhaps resulted in enhancing the killing activity of neutrophils against the organisms.

  1. How electroshock weapons kill!

    Science.gov (United States)

    Lundquist, Marjorie

    2010-03-01

    Growing numbers of law enforcement officers now carry an electroshock weapon (ESW). Over 500 U.S. deaths have followed ESW use in the past 26 years; over 450 of these deaths followed use of an electromuscular disruptor in the past 9 years. Most training courses teach that ESWs are safe; that they can kill only by the direct effect of electric current on the heart; and that a death following use of an ESW always has some other cause. All these teachings are false! The last was disproved by Lundquist.^1 Williams^2 ruled out direct electrical effects as a cause of almost all the 213 deaths he studied, leaving disruption of normal physiological processes as the only alternative explanation. Careful study of all such deaths identifies 4 different ways that death has or could have been brought about by the ESW: kidney failure following rhabdomyolysis [rare]; cardiac arrest from hyperkalemia following rhabdomyolysis [undocumented]; lactic acid-induced ventricular fibrillation [conclusive proof impossible]; and [most common] anoxia from so much lactic acid in the circulating blood that it acts as an oxygen scavenger, continuously depleting the blood of oxygen until most of the lactate has been metabolized. ^1M. Lundquist, BAPS 54(1) K1.270(2009). ^2Howard E. Williams, Taser Electronic Control Devices and Sudden In-Custody Death, 2008.

  2. Are lead-free hunting rifle bullets as effective at killing wildlife as conventional lead bullets? A comparison based on wound size and morphology

    Energy Technology Data Exchange (ETDEWEB)

    Trinogga, Anna, E-mail: anna_trinogga@gmx.de; Fritsch, Guido; Hofer, Heribert; Krone, Oliver

    2013-01-15

    Fragmentation of the lead core of conventional wildlife hunting rifle bullets causes contamination of the target with lead. The community of scavenger species which feed on carcasses or viscera discarded by hunters are regularly exposed to these lead fragments and may die by acute or chronic lead intoxication, as demonstrated for numerous species such as white-tailed eagles (Haliaeetus albicilla) where it is among the most important sources of mortality. Not only does hunting with conventional ammunition deposit lead in considerable quantities in the environment, it also significantly delays or threatens the recovery of endangered raptor populations. Although lead-free bullets might be considered a suitable alternative that addresses the source of these problems, serious reservations have been expressed as to their ability to quickly and effectively kill a hunted animal. To assess the suitability of lead-free projectiles for hunting practice, the wounding potential of conventional bullets was compared with lead-free bullets under real life hunting conditions. Wound dimensions were regarded as good markers of the projectiles' killing potential. Wound channels in 34 killed wild ungulates were evaluated using computed tomography and post-mortem macroscopical examination. Wound diameters caused by conventional bullets did not differ significantly to those created by lead-free bullets. Similarly, the size of the maximum cross-sectional area of the wound was similar for both bullet types. Injury patterns suggested that all animals died by exsanguination. This study demonstrates that lead-free bullets are equal to conventional hunting bullets in terms of killing effectiveness and thus equally meet the welfare requirements of killing wildlife as painlessly as possible. The widespread introduction and use of lead-free bullets should be encouraged as it prevents environmental contamination with a seriously toxic pollutant and contributes to the conservation of a wide

  3. When CO2 kills: effects of magmatic CO2 flux on belowground biota at Mammoth Mountain, CA

    Science.gov (United States)

    McFarland, J.; Waldrop, M. P.; Mangan, M.

    2011-12-01

    The biomass, composition, and activity of the soil microbial community is tightly linked to the composition of the aboveground plant community. Microorganisms in aerobic surface soils, both free-living and plant-associated are largely structured by the availability of growth limiting carbon (C) substrates derived from plant inputs. When C availability declines following a catastrophic event such as the death of large swaths of trees, the number and composition of microorganisms in soil would be expected to decline and/or shift to unique microorganisms that have better survival strategies under starvation conditions. High concentrations of volcanic cold CO2 emanating from Mammoth Mountain near Horseshoe Lake on the southwestern edge of Long Valley Caldera, CA has resulted in a large kill zone of tree species, and associated soil microbial species. In July 2010, we assessed belowground microbial community structure in response to disturbance of the plant community along a gradient of soil CO2 concentrations grading from 80% (no plant life). We employed a microbial community fingerprinting technique (automated ribosomal intergenic spacer analysis) to determine changes in overall community composition for three broad functional groups: fungi, bacteria, and archaea. To evaluate changes in ectomycorrhizal fungal associates along the CO2 gradient, we harvested root tips from lodgepole pine seedlings collected in unaffected forest as well as at the leading edge of colonization into the kill zone. We also measured soil C fractions (dissolved organic C, microbial biomass C, and non-extractable C) at 10 and 30 cm depth, as well as NH4+. Not surprisingly, our results indicate a precipitous decline in soil C, and microbial C with increasing soil CO2; phospholipid fatty acid analysis in conjunction with community fingerprinting indicate both a loss of fungal diversity as well as a dramatic decrease in biomass as one proceeds further into the kill zone. This observation was

  4. Chemical surface modification of porous silicon nanoparticles for cancer therapy

    OpenAIRE

    Wang, Chang-Fang

    2015-01-01

    Anticancer drugs inhibit the cancer growth by killing the rapidly dividing cancer cells. However, anticancer drugs also kill the dividing healthy cells and cause severe damage to healthy tissues. More specific delivery of the cancer drugs to the cancer tissue can increase the drug delivery efficiency and reduce the drug s side effects. Nanocarriers can increase the solubility of poorly-water soluble anticancer drugs and be modified for targeted drug delivery and theranostic applications. For ...

  5. Analysing the Wrongness of Killing

    DEFF Research Database (Denmark)

    Di Nucci, Ezio

    2016-01-01

    This article provides an in-depth analysis of the wrongness of killing by comparing different versions of three influential views: the traditional view that killing is always wrong; the liberal view that killing is wrong if and only if the victim does not want to be killed; and Don Marquis‟ future...

  6. Effects of bortezomib in sensitizing human prostate cancer cell lines to NK-mediated cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Wei Hu; Rui-Rui Zheng; Hui-Xia Cui; Dan Yue; Yong Wang; You-Hong Jiang

    2012-01-01

    The proteasome inhibitor,bortezomib,has been demonstrated to sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis.Natural killer (NK) cells represent potent antitumor effector cells.They also express TRAIL.Therefore.we investigated whether bortezomib could sensitize tumor cells to NK cell-mediated killing,and have the same effect in human prostate cancer cell lines (LNCaP and DU145).We found that bortezomib strongly inhibits proliferation in both cell lines.Furthermore,compared with LNCaP cells,DU 145 cells are more sensitive to bortezomib-induced apoptosis.However,bortezomib is unable to sensitize these two cell lines to NK cell-mediated killing in short-term assays.In long-term assays,we found that killing mediated by activated NK cells following bortezornib treatment leads to greater antitumor effects than either treatment alone.In addition,treatment with bortezomib causes these cells to upregulate apoptosis-related mRNA as well as death receptors and downregulate the major histocompatibility class (MHC)-Ⅰ molecule on the cell surface of DU145 cells.In contrast,LNCaP cells are not sensitized by this treatment.Death receptors and the MHC-Ⅰ molecule did not change in this cell line.These-data suggest that bortezomib can be used to sensitize prostate cancer cells to NK cell-mediated killing and improve current cancer therapies.This therapeutic strategy may be more effective in patients with androgen-insensitive prostate cancer.

  7. Gadolinium-loaded chitosan nanoparticles for neutron-capture therapy: Influence of micrometric properties of the nanoparticles on tumor-killing effect.

    Science.gov (United States)

    Ichikawa, Hideki; Uneme, Takeshi; Andoh, Tooru; Arita, Yuya; Fujimoto, Takuya; Suzuki, Minoru; Sakurai, Yoshinori; Shinto, Hiroyuki; Fukasawa, Tomonori; Fujii, Fumihiko; Fukumori, Yoshinobu

    2014-06-01

    As a nanoparticulate device for controlled delivery of Gd in NCT, the authors have developed gadolinium-loaded chitosan nanoparticles (Gd-nanoCPs). In the present study, influence of micrometric properties such as particle size, particle-surface charge and Gd content of Gd-nanoCPs on tumor-killing effect by Gd-NCT was investigated with Gd-nanoCPs. Two types of Gd-nanoCPs with different mean particle size, zeta potential and Gd-content (Gd-nanoCP-400; 391nm, 28mV, 9wt% and Gd-nanoCP-200; 214nm, 19mV, 24wt%) could be prepared by using chitosans with different molecular weights. Gd-nanoCPs incorporating 1.2mg of natural Gd were injected intratumorally once or twice to mice subcutaneously-bearing B16F10 melanoma. Eight hours after the last administration, thermal neutron was irradiated to tumor region of the mice. Remarkable tumor-growth was observed in both hot and cold control groups. In contrast, Gd-NCT groups showed significant tumor-growth suppression effect, though their efficacy was found to depend on the micrometric properties of Gd-nanoCPs. In particular, the Gd-nanoCP-200 exhibited stronger tumor-killing effect than the Gd-nanoCP-400 at the same Gd dose and it was still similar to Gd-nanoCP-400 in tumor-growth suppressing effect even at the half of Gd dose of Gd-nanoCP-400. This significance in tumor-killing effect would be ascribed from a higher Gd retention in the tumor tissue and an improved distribution of Gd with intratumorally administered Gd-nanoCP-200. Indeed, the Gd concentration in tumor tissue at the time corresponding to the onset of thermal neutron irradiation was determined to be significantly higher in Gd-nanoCP-200, compared with Gd-nanoCP-400. These results demonstrated that appropriate modification of Gd-nanoCPs in micrometric properties would be an effective way to improve the retention of Gd in the tumor tissue after intratumoral injection, leading to the enhanced tumor-killing effect in Gd-NCT.

  8. Carbofuran - A New and Effective Method of Illegal Killing of Otters (Lutra lutra in the Czech Republic

    Directory of Open Access Journals (Sweden)

    Václav Hlaváč

    2010-10-01

    Full Text Available Carbofuran - a poison recently used to illegally kill otters - is described from the Czech Republic. Six different cases of illegal poisoning of otters have been discovered since 2006 with a total number of 14 killed individuals. Apart from otters, many other animals - namely raptors and other carnivores - have been poisoned by carbofuran in the Czech Republic as well. The poisoning substance is now banned in the EU, however, it has been widely used in agriculture as insecticide and large supplies are generally available. This fact together with relative ease of using it can pose a threat to otter population, especially in areas with raising conflict between otter protection and fish farming. Therefore, it is important to report any suspicious cases of dead wildlife, to immediately carry out laboratory testing in such cases, and to inform relevant officials including the police. It will help monitor the problem and raise local awareness, and could possibly help to catch some persecutors. Taking these actions should be the first step in trying to stop poisoning wildlife by carbofuran.

  9. Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B

    DEFF Research Database (Denmark)

    Skov, Søren; Pedersen, Marianne Terndrup; Andresen, Lars;

    2005-01-01

    We show that histone deacetylase (HDAC) inhibitors lead to functional expression of MHC class I-related chain A and B (MICA/B) on cancer cells, making them potent targets for natural killer (NK) cell-mediated killing through a NK group 2, member D (NKG2D) restricted mechanism. Blocking either...... apoptosis or oxidative stress caused by HDAC inhibitor treatment did not affect MICA/B expression, suggesting involvement of a separate signal pathway not directly coupled to induction of cell death. HDAC inhibitor treatment induced glycogen synthase kinase-3 (GSK-3) activity and down-regulation of GSK-3...... by small interfering RNA or by different inhibitors showed that GSK-3 activity is essential for the induced MICA/B expression. We thus present evidence that cancer cells which survive the direct induction of cell death by HDAC inhibitors become targets for NKG2D-expressing cells like NK cells, gammadelta T...

  10. Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway

    OpenAIRE

    Ardiani, Andressa; Gameiro, Sofia R.; Kwilas, Anna R.; Donahue, Renee N.; Hodge, James W.

    2014-01-01

    Despite recent advances in diagnosis and management, prostrate cancer remains the second most common cause of death from cancer in American men, after lung cancer. Failure of chemotherapies and hormone-deprivation therapies is the major cause of death in patients with castration-resistant prostate cancer (CRPC). Currently, the androgen inhibitors enzalutamide and abiraterone are approved for treatment of metastatic CRPC. Here we show for the first time that both enzalutamide and abiraterone r...

  11. Cost-effectiveness of colorectal cancer screening

    NARCIS (Netherlands)

    I. Lansdorp-Vogelaar (Iris); A.B. Knudsen (Amy); H. Brenner (Hermann)

    2011-01-01

    textabstractColorectal cancer is an important public health problem. Several screening methods have been shown to be effective in reducing colorectal cancer mortality. The objective of this review was to assess the cost-effectiveness of the different colorectal cancer screening methods and to determ

  12. Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers

    Directory of Open Access Journals (Sweden)

    van Haard Paul MM

    2011-03-01

    Full Text Available Abstract Background Ovarian cancer remains the leading cause of death from gynaecological malignancy. More than 60% of the patients are presenting the disease in stage III or IV. In spite of combination of chemotherapy and surgery the prognosis stays poor for therapy regimen. Methods The leaves of a plant endemic to Australia, Calomeria amaranthoides, were extracted and then fractionated by column chromatography. In vitro cytotoxicity tests were performed with fractions of the plant extract and later with an isolated compound on ovarian cancer cell lines, as well as normal fibroblasts at concentrations of 1-100 μg/mL (crude extract and 1-10 μg/mL (compound. Cytotoxicity was measured after 24, 48 and 72 hours by using a non-fluorescent substrate, Alamar blue. In vivo cytotoxicity was tested on ascites, developed in the abdomen of nude mice after inoculation with human OVCAR3 cells intraperitoneally. The rate of change in abdomen size for the mice was determined by linear regression and statistically evaluated for significance by the unpaired t test. Results Two compounds were isolated by chromatographic fractionation and identified by 1H-NMR, 13C-NMR and mass spectrometry analyses, EPD, an α-methylene sesquiterpene lactone of the eremophilanolide subtype, and EPA, an α-methylene carboxylic acid. Cytotoxicity of EPD for normal fibroblasts at all time points IC50 was greater than 10 μg/mL, whereas, for OVCAR3 cells at 48 hours IC50 was 5.3 μg/mL (95% confidence interval 4.3 to 6.5 μg/mL. Both, the crude plant extract as well as EPD killed the cancer cells at a final concentration of 10 μg/mL and 5 μg/mL respectively, while in normal cells only 20% cell killing effect was observed. EPA had no cytotoxic effects. Changes in abdomen size for control versus Cisplatin treated mice were significantly different, P = 0.023, as were control versus EPD treated mice, P = 0.025, whereas, EPD versus Cisplatin treated mice were not significantly

  13. Technical Aspects of Cyber Kill Chain

    OpenAIRE

    Yadav, Tarun; Mallari, Rao Arvind

    2016-01-01

    Recent trends in targeted cyber-attacks has increased the interest of research in the field of cyber security. Such attacks have massive disruptive effects on rganizations, enterprises and governments. Cyber kill chain is a model to describe cyber-attacks so as to develop incident response and analysis capabilities. Cyber kill chain in simple terms is an attack chain, the path that an intruder takes to penetrate information systems over time to execute an attack on the target. This paper broa...

  14. In Vitro Photodynamic Effect of Phycocyanin against Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Subramaniyan Bharathiraja

    2016-11-01

    Full Text Available C-phycocyanin, a natural blue-colored pigment-protein complex was explored as a novel photosensitizer for use in low-level laser therapy under 625-nm laser illumination. C-phycocyanin produced singlet oxygen radicals and the level of reactive oxygen species (ROS were raised in extended time of treatment. It did not exhibit any visible toxic effect in the absence of light. Under 625-nm laser irradiation, c-phycocyanin generated cytotoxic stress through ROS induction, which killed MDA-MB-231 breast cancer cells depending on concentrations. Different fluorescent staining of laser-treated cells explored apoptotic cell death characteristics like the shrinking of cells, cytoplasmic condensation, nuclei cleavage, and the formation of apoptotic bodies. In conclusion, phycocyanin is a non-toxic fluorescent pigment that can be used in low-level light therapy.

  15. It's not just conflict that motivates killing of orangutans.

    Directory of Open Access Journals (Sweden)

    Jacqueline T Davis

    Full Text Available We investigated why orangutans are being killed in Kalimantan, Indonesia, and the role of conflict in these killings. Based on an analysis of interview data from over 5,000 respondents in over 450 villages, we also assessed the socio-ecological factors associated with conflict and non-conflict killings. Most respondents never kill orangutans. Those who reported having personally killed an orangutan primarily did so for non-conflict reasons; for example, 56% of these respondents said that the reason they had killed an orangutan was to eat it. Of the conflict-related reasons for killing, the most common reasons orangutans were killed was fear of orangutans or in self-defence. A similar pattern was evident among reports of orangutan killing by other people in the villages. Regression analyses indicated that religion and the percentage of intact forest around villages were the strongest socio-ecological predictors of whether orangutans were killed for conflict or non-conflict related reasons. Our data indicate that between 44,170 and 66,570 orangutans were killed in Kalimantan within the respondents' active hunting lifetimes: between 12,690 and 29,024 for conflict reasons (95%CI and between 26,361 and 41,688 for non-conflict reasons (95% CI. These findings confirm that habitat protection alone will not ensure the survival of orangutans in Indonesian Borneo, and that effective reduction of orangutan killings is urgently needed.

  16. Cryptococcus neoformans modulates extracellular killing by neutrophils

    Directory of Open Access Journals (Sweden)

    Asfia eQureshi

    2011-09-01

    Full Text Available We recently established a key role for host sphingomyelin synthase (SMS in the regulation of the killing activity of neutrophils against Cryptococcus neoformans. In this work, we studied the effect of C. neoformans on the killing activity of neutrophils and whether SMS would still be a player against C. neoformans in immunocompromised mice lacking T and NK cells (Tgε26 mice. To this end, we analyzed whether C. neoformans would have any effect on neutrophil survival and killing in vitro and in vivo. We show that unlike C. albicans, neither the presence nor the capsule size of C. neoformans cells have any effect on neutrophil viability. Interestingly, melanized C. neoformans cells totally abrogated the killing activity of neutrophils. Next, we monitored how exposure of neutrophils to C. neoformans cells would interfere with any further killing activity of the medium and found that pre-incubation with live but not heat-killed fungal cells significantly inhibits further killing activity of the medium. We next studied whether activation of SMS at the site of C. neoformans infection is dependent on T and NK cells. Using matrix-assisted laser desorption-ionization (MALDI tissue imaging in infected lung we found that similarly to previous observations in the isogenic wild type CBA/J mice, SM 16:0 levels are significantly elevated at the site of infection in mice lacking T and NK cells but only at early time points. This study highlights that C. neoformans may negatively regulate the killing activity of neutrophils and that SMS activation in neutrophils appears to be partially independent of T and/or NK cells.

  17. Theriocide: Naming Animal Killing

    Directory of Open Access Journals (Sweden)

    Piers Beirne

    2014-08-01

    Full Text Available In this essay I recommend ‘theriocide’ as the name for those diverse human actions that cause the deaths of animals. Like the killing of one human by another, theriocide may be socially acceptable or unacceptable, legal or illegal. It may be intentional or unintentional and may involve active maltreatment or passive neglect. Theriocide may occur one-on-one, in small groups or in large-scale social institutions. The numerous and sometimes intersecting sites of theriocide include intensive rearing regimes; hunting and fishing; trafficking; vivisection; militarism; pollution; and human-induced climate change. If the killing of animals by humans is as harmful to them as homicide is to humans, then the proper naming of such deaths offers a remedy, however small, to the extensive privileging of human lives over those of other animals. Inevitably, the essay leads to a shocking question: Is theriocide murder?

  18. HPMA copolymer-based combination therapy toxic to both prostate cancer stem/progenitor cells and differentiated cells induces durable anti-tumor effects

    Science.gov (United States)

    Zhou, Yan; Yang, Jiyuan; Rhim, Johng S.; Kopeček, Jindřich

    2013-01-01

    Current treatments for prostate cancer are still not satisfactory, often resulting in tumor regrowth and metastasis. One of the main reasons for the ineffective anti-prostate cancer treatments is the failure to deplete cancer stem-like cells (CSCs) - a subset of cancer cells with enhanced tumorigenic capacity. Thus, combination of agents against both CSCs and bulk tumor cells may offer better therapeutic benefits. Several molecules with anti-cancer stem/progenitor cell activities have been under preclinical evaluations. However, their low solubility and nonspecific toxicity limit their clinical translation. Herein, we designed a combination macromolecular therapy containing two drug conjugates: HPMA copolymer-cyclopamine conjugate (P-CYP) preferentially toxic to cancer stem/progenitor cells, and HPMA copolymer-docetaxel conjugate (P-DTX) effective in debulking the tumor mass. Both conjugates were synthesized using RAFT (reversible addition-fragmentation chain transfer) polymerization resulting in narrow molecular weight distribution. The killing effect of the two conjugates against bulk tumor cells and CSCs were evaluated in vitro and in vivo. In PC-3 or RC-92a/hTERT prostate cancer cells, P-CYP preferentially kills and impairs the function of CD133+ prostate cancer stem/progenitor cells; P-DTX was able to kill bulk tumor cells instead of CSCs. In PC-3 xenograft mice model, combination of P-DTX and P-CYP showed the most effective and persistent tumor growth inhibitory effect. In addition, residual tumors contained less CD133+ cancer cells following combination or P-CYP treatments, indicating selective killing of cancer cells with stem/progenitor cell properties. PMID:24041709

  19. Theriocide: Naming Animal Killing

    OpenAIRE

    Piers Beirne

    2014-01-01

    In this essay I recommend ‘theriocide’ as the name for those diverse human actions that cause the deaths of animals. Like the killing of one human by another, theriocide may be socially acceptable or unacceptable, legal or illegal. It may be intentional or unintentional and may involve active maltreatment or passive neglect. Theriocide may occur one-on-one, in small groups or in large-scale social institutions. The numerous and sometimes intersecting sites of theriocide include intensive rear...

  20. Allele-specific cancer cell killing in vitro and in vivo targeting a single-nucleotide polymorphism in POLR2A

    NARCIS (Netherlands)

    O.R.F. Mook; F. Baas; M.B. de Wissel; K. Fluiter

    2009-01-01

    Cancer is one of the diseases for which RNA interference is a potential therapeutic approach. Genes involved in the promotion or maintenance of tumor growth are obvious targets for RNAi. RNAi is also considered an attractive additional approach to conventional chemotherapy for cancer treatment. More

  1. EFFECTS OF THERMAL MODIFICATION ON MECHANICAL AND SWELLING PROPERTIES AND COLOR CHANGE OF LUMBER KILLED BY MOUNTAIN PINE BEETLE

    Directory of Open Access Journals (Sweden)

    Jiabin Cai,

    2012-06-01

    Full Text Available To extend the application of mountain pine beetle (MPB killed lumber for decking, siding, and landscaping materials, it is essential to improve its dimensional stability. Thermal treatment is one of the well-established processes used to improve wood stability by modifying chemical compounds and masking blue-stains by darkening the fibre color. In this study, the MPB lumber was subjected to thermal treatment at three temperatures (195, 205, or 215°C and three exposure times (1.5, 2, or 3 h. Based on Duncan's multiple range test, the results indicated that the volumetric swelling after thermal treatment, either from oven-dry to air-conditioned or from oven-dry to water-saturated, was significantly reduced after thermal treatment. Modulus of elasticity was increased when specimens were treated at a temperature of 195°C, and then decreased as the temperature increased. Modulus of rupture was significantly reduced as treatment temperature increased. The hardness of lumber thermal-treated at 195°C was significantly increased compared to that of the untreated lumber. At higher temperatures, hardness started to decrease slightly. With the treatment temperature increasing to 215°C for 3 h, the color difference between stained and clear wood was reduced by 75%. As a result, the blue-stains vanished gradually.

  2. Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

    International Nuclear Information System (INIS)

    Introduction: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium(188Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. Methods: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi 188Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188Re-labeled non-specific IgM. Results: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. Conclusions: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers

  3. Photo activation of HPPH encapsulated in “Pocket” liposomes triggers multiple drug release and tumor cell killing in mouse breast cancer xenografts

    OpenAIRE

    Sine J; Urban C.; Thayer D; Charron H; Valim N; Tata DB; Schiff R; Blumenthal R; Joshi A; Puri A

    2014-01-01

    Jessica Sine,1,* Cordula Urban,2,* Derek Thayer,1 Heather Charron,2 Niksa Valim,2 Darrell B Tata,3 Rachel Schiff,4 Robert Blumenthal,1 Amit Joshi,2 Anu Puri1 1Membrane Structure and Function Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute – Frederick, Frederick, MD, USA; 2Department of Radiology, Baylor College of Medicine, Houston, TX, USA; 3US Food and Drug Administration, CDRH/OSEL/Division of Physics, White Oak Campus, MD, USA; 4Lester and ...

  4. Photo activation of HPPH encapsulated in “Pocket” liposomes triggers multiple drug release and tumor cell killing in mouse breast cancer xenografts

    OpenAIRE

    Puri, Anu

    2014-01-01

    Jessica Sine,1,* Cordula Urban,2,* Derek Thayer,1 Heather Charron,2 Niksa Valim,2 Darrell B Tata,3 Rachel Schiff,4 Robert Blumenthal,1 Amit Joshi,2 Anu Puri1 1Membrane Structure and Function Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute – Frederick, Frederick, MD, USA; 2Department of Radiology, Baylor College of Medicine, Houston, TX, USA; 3US Food and Drug Administration, CDRH/OSEL/Division of Physics, White Oak Campus, MD, USA; 4Lester ...

  5. Charged conformal Killing spinors

    Energy Technology Data Exchange (ETDEWEB)

    Lischewski, Andree, E-mail: lischews@mathematik.hu-berlin.de [Humboldt-Universität zu Berlin, Institut für Mathematik, Rudower Chaussee 25, Room 1.310, D12489 Berlin (Germany)

    2015-01-15

    We study the twistor equation on pseudo-Riemannian Spin{sup c}-manifolds whose solutions we call charged conformal Killing spinors (CCKSs). We derive several integrability conditions for the existence of CCKS and study their relations to spinor bilinears. A construction principle for Lorentzian manifolds admitting CCKS with nontrivial charge starting from CR-geometry is presented. We obtain a partial classification result in the Lorentzian case under the additional assumption that the associated Dirac current is normal conformal and complete the classification of manifolds admitting CCKS in all dimensions and signatures ≤5 which has recently been initiated in the study of supersymmetric field theories on curved space.

  6. Ecological Therapy for Cancer: Defining Tumors Using an Ecosystem Paradigm Suggests New Opportunities for Novel Cancer Treatments1

    OpenAIRE

    Kenneth J Pienta; McGregor, Natalie; Axelrod, Robert; Axelrod, David E

    2008-01-01

    We propose that there is an opportunity to devise new cancer therapies based on the recognition that tumors have properties of ecological systems. Traditionally, localized treatment has targeted the cancer cells directly by removing them (surgery) or killing them (chemotherapy and radiation). These modes of therapy have not always been effective because many tumors recur after these therapies, either because not all of the cells are killed (local recurrence) or because the cancer cells had al...

  7. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties.

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues.

  8. Anti-protozoal and anti-bacterial antibiotics that inhibit protein synthesis kill cancer subtypes enriched for stem cell-like properties

    Science.gov (United States)

    Cuyàs, Elisabet; Martin-Castillo, Begoña; Corominas-Faja, Bruna; Massaguer, Anna; Bosch-Barrera, Joaquim; Menendez, Javier A

    2015-01-01

    Key players in translational regulation such as ribosomes might represent powerful, but hitherto largely unexplored, targets to eliminate drug-refractory cancer stem cells (CSCs). A recent study by the Lisanti group has documented how puromycin, an old antibiotic derived from Streptomyces alboniger that inhibits ribosomal protein translation, can efficiently suppress CSC states in tumorspheres and monolayer cultures. We have used a closely related approach based on Biolog Phenotype Microarrays (PM), which contain tens of lyophilized antimicrobial drugs, to assess the chemosensitivity profiles of breast cancer cell lines enriched for stem cell-like properties. Antibiotics directly targeting active sites of the ribosome including emetine, puromycin and cycloheximide, inhibitors of ribosome biogenesis such as dactinomycin, ribotoxic stress agents such as daunorubicin, and indirect inhibitors of protein synthesis such as acriflavine, had the largest cytotoxic impact against claudin-low and basal-like breast cancer cells. Thus, biologically aggressive, treatment-resistant breast cancer subtypes enriched for stem cell-like properties exhibit exacerbated chemosensitivities to anti-protozoal and anti-bacterial antibiotics targeting protein synthesis. These results suggest that old/existing microbicides might be repurposed not only as new cancer therapeutics, but also might provide the tools and molecular understanding needed to develop second-generation inhibitors of ribosomal translation to eradicate CSC traits in tumor tissues. PMID:25970790

  9. Effects of External Electric Field on AlN Precipitation and Recrystallization Texture of Deep-drawing 08Al Killed Steel Sheet

    Institute of Scientific and Technical Information of China (English)

    Xiang ZHAO; Zhuochao HU; Liang ZUO

    2006-01-01

    The effects of an electric field on AlN precipitation and recrystallization texture were investigated. Cold-rolled 08Al killed steel sheets were annealed at 550℃ according to the two-step processes, for various maintaining times, with and without applying an electric field. It was found that the electric field promotes the precipitation of the second phase (AlN particles), strengthens the γ-fiber and weakens the α-fiber texture component in the recrystallized specimens. A possible explanation for the reinforcement of γ-fiber texture by the electric field is that the second phase AlN particle promotes the growth of γ-fiber at the expense of differently oriented grains.

  10. Cancer Basics

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  11. Killing Spinors -- Beyond Supergravity

    CERN Document Server

    Palomo-Lozano, Alberto

    2012-01-01

    This is a doctoral thesis on the application of techniques originally developed in the programme of characterisation of supersymmetric solutions to Supergravity theories, to finding alternative backgrounds. We start by discussing the concept of a Killing spinor, and how these are paramount to the process of classifying of these aforementioned supersymmetric solutions. Moreover, these geometric objects also have applications when considered in different scenarios (the 'beyond' in the title). In particular, techniques based on a parallelising rule for a spinorial field can be used for obtaining solutions to Einstein-Maxwell-De Sitter theories, as well as a (partial) classification of Lorentzian Einstein-Weyl manifolds, a problem of geometrical interest. The annexe contain an introduction and summary in Spanish language. The appendices discuss the tensorial and spinorial conventions employed, some relevant geometrical information on the scalar manifolds for the matter contents of interest, as well as for the nul...

  12. Generation of more effective cancer vaccines

    Science.gov (United States)

    Fenoglio, Daniela; Traverso, Paolo; Parodi, Alessia; Kalli, Francesca; Zanetti, Maurizio; Filaci, Gilberto

    2013-01-01

    Cancer vaccines represent a promising therapeutic approach for which prime time is imminent. However, clinical efficacy must be improved in order for cancer vaccines to become a valid alternative or complement to traditional cancer treatments. Considerable efforts have been undertaken so far to better understand the fundamental requirements for clinically-effective cancer vaccines. Recent data emphasize that important requirements, among others, are (1) the use of multi-epitope immunogens, possibly deriving from different tumor antigens; (2) the selection of effective adjuvants; (3) the association of cancer vaccines with agents able to counteract the regulatory milieu present in the tumor microenvironment; and (4) the need to choose the definitive formulation and regimen of a vaccine after accurate preliminary tests comparing different antigen formulations. The first requirement deals with issues related to HLA restriction of tumor antigen presentation, as well as usefulness of tumor antigen spreading and counteraction of immune escape phenomena, linked to tumor antigen down-modulation, for an effective anti-cancer immune response. The second point underscores the necessity of optimal activation of innate immunity to achieve an efficient adaptive anti-cancer immune response. The third point focuses on the importance to inhibit subsets of regulatory cells. The last requirement stresses the concept that the regimen and formulation of the vaccine impacts profoundly on cancer vaccine efficacy. A new generation of cancer vaccines, provided with both immunological and clinical efficacy, will hopefully soon address these requirements. PMID:23978951

  13. Killing Symmetry on Finsler Manifold

    CERN Document Server

    Ootsuka, Takayoshi; Ishida, Muneyuki

    2016-01-01

    Killing vector fields $K$ are defined on Finsler manifold. The Killing symmetry is reformulated simply as $\\delta K^\\flat =0$ by using the Killing non-linear 1-form $K^\\flat$ and the spray operator $\\delta$ with the Finsler non-linear connection. $K^\\flat$ is related to the generalization of Killing tensors on Finsler manifold, and the condition $\\delta K^\\flat =0$ gives an analytical method of finding higher derivative conserved quantities, which may be called hidden conserved quantities. We show two examples: the Carter constant on Kerr spacetime and the Runge-Lentz vectors in Newtonian gravity.

  14. The Effect of Radiation on the Immune Response to Cancers

    Directory of Open Access Journals (Sweden)

    Bonggoo Park

    2014-01-01

    Full Text Available In cancer patients undergoing radiation therapy, the beneficial effects of radiation can extend beyond direct cytotoxicity to tumor cells. Delivery of localized radiation to tumors often leads to systemic responses at distant sites, a phenomenon known as the abscopal effect which has been attributed to the induction and enhancement of the endogenous anti-tumor innate and adaptive immune response. The mechanisms surrounding the abscopal effect are diverse and include trafficking of lymphocytes into the tumor microenvironment, enhanced tumor recognition and killing via up-regulation of tumor antigens and antigen presenting machinery and, induction of positive immunomodulatory pathways. Here, we discuss potential mechanisms of radiation-induced enhancement of the anti-tumor response through its effect on the host immune system and explore potential combinational immune-based strategies such as adoptive cellular therapy using ex vivo expanded NK and T cells as a means of delivering a potent effector population in the context of radiation-enhanced anti-tumor immune environment.

  15. Paclitaxel Combined with Inhibitors of Glucose and Hydroperoxide Metabolism Enhances Breast Cancer Cell Killing Via H2O2-Mediated Oxidative Stress

    OpenAIRE

    Hadzic, Tanja; Aykin-Burns, Nükhet; Zhu, Yueming; Coleman, Mitchell C.; Leick, Katie; Jacobson, Geraldine M.; Douglas R Spitz

    2010-01-01

    Cancer cells (relative to normal cells) demonstrate alterations in oxidative metabolism characterized by increased steady-state levels of reactive oxygen species [i.e. hydrogen peroxide, H2O2] that may be compensated for by increased glucose metabolism but the therapeutic significance of these observations is unknown. In the current study, inhibitors of glucose [i.e., 2-deoxy-D-glucose, 2DG] and hydroperoxide [i.e., L-buthionine-S, R-sulfoximine, BSO] metabolism were utilized in combination w...

  16. Unraveling the mystery of enhanced cell-killing effect around the Bragg peak region of a double irradiation source 9C-ion beam

    Institute of Scientific and Technical Information of China (English)

    LI Qiang; Y. Furusawa; M. Kanazawa; A. Kitagawa

    2005-01-01

    An enhanced cell-killing effect at the penetration depths around the Bragg peak of a β-delayed particle decay 9C-ion beam has been observed in our preceding radiobiological experiments in comparison with a therapeutic 12C beam under the same conditions, and RBE values of the 9C beam were revealed to be higher than those of the comparative 12C beam by a factor of up to 2. This study is aimed at investigating the biophysical mechanisms underlying the important experimental phenomenon. First of all, a model for calculating the stopping probability density of the experimentally applied 9C beam is worked out, where all determinants such as the initial momentum spread of the 9C beam, the fluence attenuation with penetration depth due to the projectile-target nuclear reaction and the energy straggling effect are taken into account. On the basis of the calculated 9C-ion stopping distribution, it has been found that the area corresponding to the enhanced cell-killing effect of the 9C beam appears at the stopping region of the incident 9C ions. The stopping 9C-ion density in depth, then, is derived from the calculated probability density. Moreover, taking entrance dose 1 Gy for the 9C beam as an example, the average stopping 9C-ion numbers per cell at various depths are deduced. Meanwhile, the mean lethal damage events induced by the 9C and comparative 12C beams at the depths with almost equal dose-averaged LETs are derived from the measured cell surviving fractions at these depths for the 9C and 12C beams. Under the condition of the same absorbed doses, there are indeed good agreements between the average stopping 9C-ion number pre cell and the difference of the mean lethal damage events between the 9C and 12C beams at the depths of similar dose-averaged LETs. It can be inferred that if a 9C ion comes to rest in a cell, the cell would undergo dying. In view of the decay property of 9C nuclide, clustered damage would be caused in the cell by the emitted low-energy particles

  17. Photothermal effects of multi-walled carbon nanotubes on the viability of BT-474 cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Hung-Tao [Department of Materials Science and Engineering, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Wang, Tsung-Pao [Department of Medical Science, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Lee, Chi-Young [Department of Materials Science and Engineering, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Tai, Nyan-Hwa, E-mail: nhtai@mx.nthu.edu.tw [Department of Materials Science and Engineering, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Chang, Hwan-You, E-mail: hychang@mx.nthu.edu.tw [Department of Medical Science, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China)

    2013-03-01

    Functionalized multi-walled carbon nanotubes (f-MWCNTs) were conjugated to an antibody of BT-474 cancer cells (f-MWCNTs-ab), and the photothermal effect of the f-MWCNTs-ab for BT-474 cancer cell destruction was demonstrated. After near-infrared irradiation, the f-MWCNTs-ab were more capable of killing cancer cells and possessed higher cell specificity than f-MWCNTs. Quantitative results showed that the viability of the cancer cells was affected by the concentration of the f-MWCNTs-ab solution, irradiation time, and settling time after irradiation. The membrane impermeable fluorescence dye ethidium bromide was used to detect cell viability after near-infrared irradiation, and the results agreed with those obtained from the Alamar Blue cell viability assay. The EtBr fluorescence results suggest that the cell membrane, attached to f-MWCNTs-ab, was damaged after irradiation, which led to cell death and necrosis. Using confocal microscopy, a few f-MWCNTs-ab were detected in the cell, indicating the endocytosis effect. The results not only explain the improved efficiency of thermotherapy but also indicate that necrosis may result from protein denaturation attributing to the heated f-MWCNTs-ab in the cell. Highlights: Black-Right-Pointing-Pointer f-MWCNTs conjugated with anti-HER2 antibody by chemical method. Black-Right-Pointing-Pointer Kill breast cancer cells by using low dose f-MWCNTs-ab due to photothermal effect. Black-Right-Pointing-Pointer Use EtBr fluorescent to prove that the cell membrane was broken by heated f-MWCNTs. Black-Right-Pointing-Pointer Few f-MWCNTs-ab were detected in the cell indicating the endocytosis effect. Black-Right-Pointing-Pointer Necrosis may result from protein denaturation due to contact with the heated CNTs.

  18. Comparative effectiveness in esophagogastric cancer.

    Science.gov (United States)

    Knab, Lawrence M; Belotte, Jim; Munshi, Hidayatullah G; Bentrem, David J

    2015-01-01

    Cancer of the esophagus and the gastroesophageal junction (GEJ) continues to have a dismal prognosis, with the incidence of esophageal cancer increasing in the United States. Although radical resection was initially the primary treatment for this disease process, systemic chemotherapy and radiation have been shown to play a role in prolonging survival in most patient populations. This chapter explores the evidence that guides treatment for esophageal and GEJ cancer today. Chemotherapy and radiation therapy were introduced as treatment modalities for esophageal and GEJ cancers when it became evident that surgical therapy alone provided poor long-term survival rates. A variety of treatment strategies have been explored including preoperative (neoadjuvant) and postoperative (adjuvant) chemotherapy, with and without radiation. The evidence suggests that neoadjuvant chemotherapy or chemoradiotherapy provides better outcomes compared to surgery alone for esophageal, GEJ, and gastric cancers. Studies indicate a trend towards improved survival when neoadjuvant chemoradiotherapy is compared to chemotherapy alone. When patients have undergone resection with node-positive disease without receiving neoadjuvant therapy, some form of adjuvant treatment is recommended. This chapter also explores the surgical management of esophageal, GEJ, and gastric cancers including the extent of the gastric lymph node dissection. It also includes a discussion about adherence to national guidelines in terms of gastric cancer treatment and esophageal and gastric lymph node examinations.

  19. Killing curve activity of ciprofloxacin is comparable to synergistic effect of beta-lactam-tobramycin combinations against Haemophilus species endocarditis strains

    DEFF Research Database (Denmark)

    Westh, H; Frimodt-Møller, N; Gutschik, E;

    1992-01-01

    Nine Haemophilus species strains, all beta-lactamase negative, isolated from patients with endocarditis were tested in killing curve experiments. Antibiotics used were penicillin, amoxicillin, aztreonam alone and in combination with tobramycin, as well as ciprofloxacin alone. Synergism between beta...

  20. Can a penny kill you?

    OpenAIRE

    Hili, Alexander; Duca, Edward

    2015-01-01

    A long-standing urban legend suggests that a penny dropped from a great height, let's say the Empire State Building, kills. The penny should speed up and pass through a person's skull easily. http://www.um.edu.mt/think/can-a-penny-kill-you/

  1. "The Killing Fields" of Innovation

    DEFF Research Database (Denmark)

    Ingerslev, Karen

    2014-01-01

    to clustering of ideas, a design strategy which seemed to kill unique ideas. The reframing of innovation as a radical endeavor killed learning from others for being not innovative. The findings of this paper supplement theories of deliberate killing of ideas by suggesting framing, design and facilitation......This paper points to seemingly contradicted processes of framing innovation, idea generation and killing ideas. It reports from a yearlong innovation project, where health care professionals explored problems and tested ideas for solutions, regarding a future downsizing of the case hospital....... Theories in various ways describe the opening and closing phases of innovation. Exploration and idea generation opens a field of interest, which is then closed by making choices of ideas to further explore in the next opening phase. These choices deliberately kill a lot of ideas. In the innovation project...

  2. What Doesn't Kill You Makes You Wary? Effect of Repeated Culling on the Behaviour of an Invasive Predator

    OpenAIRE

    Isabelle M. Côté; Darling1, Emily S.; Luis Malpica-Cruz; Smith, Nicola S.; Green, Stephanie J.; Jocelyn Curtis-Quick; Craig Layman

    2014-01-01

    As a result of being hunted, animals often alter their behaviour in ways that make future encounters with predators less likely. When hunting is carried out for conservation, for example to control invasive species, these behavioural changes can inadvertently impede the success of future efforts. We examined the effects of repeated culling by spearing on the behaviour of invasive predatory lionfish (Pterois volitans/miles) on Bahamian coral reef patches. We compared the extent of concealment ...

  3. Dose-rate effects in mammalian cells in culture. III. Comparison of cell killing and cell proliferation during continuous irradiation for six different cell lines

    International Nuclear Information System (INIS)

    The effects of continuous irradiation over a wide range of dose rates were studied for six different mammalian cell lines in regard to cell survival and proliferation. Cell lines were chosen in which such characteristics as population doubling time, chromosome number, DNA content, acute dose-survival curve parameters, and division delay were as diverse as possible. There was no correlation between the minimum dose rate necessary to stop cell population growth and any of the above listed characteristics, with the exception of division delay following acute doses. In general, the longer the division delay (min/rad), the lower the dose rate required to stop cell population growth. The effects of cell-cycle redistribution during continuous irradiaton in regard to cell survival were dramatic. In some cases a reduction in dose rate resulted in an increase in cell killing for a given total dose. This occurred only when dose rates were sufficient to stop cell population growth and after exposure times sufficient to allow for the occurrence of cell-cycle redistribution

  4. Gabapentin, an Analgesic Used Against Cancer-Associated Neuropathic Pain: Effects on Prostate Cancer Progression in an In Vivo Rat Model.

    Science.gov (United States)

    Bugan, Ilknur; Karagoz, Zeynep; Altun, Seyhan; Djamgoz, Mustafa B A

    2016-03-01

    A major problem associated with clinical management of cancer is controlling the accompanying pain, and various analgesics are in common use for this purpose. Recent evidence suggests that some of the targets of analgesics, such as ion channels and receptors, may also be involved in the cancer process, thereby raising the possibility that such use of some analgesics may impact upon cancer itself. The main aim of this study was to determine whether gabapentin, a common adjuvant analgesic in current use against cancer-associated neuropathic pain, would affect tumour development and progression in vivo. The Dunning rat model of prostate cancer was used. Strongly metastatic Mat-LyLu cells were implanted subcutaneously into syngeneic Copenhagen rats which were then treated every other day with 4.6-16.8 μg/kg gabapentin by gavage. Primary tumourigenesis was monitored daily. Lung metastases were counted and measured after killing the rats 21 days later. Gabapentin had no effect on primary tumourigenesis but produced dose-dependent effects on lung metastasis. Whilst 4.6 μg/kg had no effect, 9.1 μg/kg gabapentin decreased the number of lung metastases significantly by 64%. In contrast, 16.8 μg/kg gabapentin promoted metastasis significantly by 112% and showed a strong tendency to shorten mean survival time. It is concluded that gabapentin prescribed to cancer patients against pain could impact upon the cancer process itself.

  5. IAP antagonists sensitize murine osteosarcoma cells to killing by TNFα

    Science.gov (United States)

    Shekhar, Tanmay M.; Miles, Mark A.; Gupte, Ankita; Taylor, Scott; Tascone, Brianna; Walkley, Carl R.; Hawkins, Christine J.

    2016-01-01

    Outcomes for patients diagnosed with the bone cancer osteosarcoma have not improved significantly in the last four decades. Only around 60% of patients and about a quarter of those with metastatic disease survive for more than five years. Although DNA-damaging chemotherapy drugs can be effective, they can provoke serious or fatal adverse effects including cardiotoxicity and therapy-related cancers. Better and safer treatments are therefore needed. We investigated the anti-osteosarcoma activity of IAP antagonists (also known as Smac mimetics) using cells from primary and metastatic osteosarcomas that arose spontaneously in mice engineered to lack p53 and Rb expression in osteoblast-derived cells. The IAP antagonists SM-164, GDC-0152 and LCL161, which efficiently target XIAP and cIAPs, sensitized cells from most osteosarcomas to killing by low levels of TNFα but not TRAIL. RIPK1 expression levels and activity correlated with sensitivity. RIPK3 levels varied considerably between tumors and RIPK3 was not required for IAP antagonism to sensitize osteosarcoma cells to TNFα. IAP antagonists, including SM-164, lacked mutagenic activity. These data suggest that drugs targeting XIAP and cIAP1/2 may be effective for osteosarcoma patients whose tumors express abundant RIPK1 and contain high levels of TNFα, and would be unlikely to provoke therapy-induced cancers in osteosarcoma survivors. PMID:27129149

  6. Effectiveness of Linezolid, 127I-Linezolid and 131I-Linezolid Against Methicillin-Susceptible Staphylococcus Aureus by Time Kill Curve Methods

    Directory of Open Access Journals (Sweden)

    Hasan Demiroğlu

    2015-02-01

    Full Text Available Objective: Linezolid (LNZ is one of the most effective treatments against Gram positive bacteria. However LNZ resistant intermediate strains have recently emerged in worldwide. The aim of the study was to compare the minimum inhibitory concentration (MIC, minimum bactericidal concentration (MBC and minimum biofilm inhibitory concentration (MBIC of LNZ, 127I-LNZ and 131I-LNZ against methicillin susceptible Staphylococcus aureus ATCC 35556 (MSSA biofilms. Methods: LNZ radiolabeled with 131I and cold labeling study with 127I was performed. Radiolabeling and inactive labeling quality-control studies of LNZ were carried out by using TLC (Thin Layer Radiochromatography and HPLC (High Pressure Liquid Chromatography. LNZ, 127I-LNZ and 131I-LNZ against biofilm-forming MSSA was investigated, using a twofold serial broth microtiter method, biofilm challenge, and bacterial count recovery. Results: The binding yield was obtained to be about 86±2% for radiolabeled LNZ. Minimal inhibitory concentration (MIC and minimal bactericidal concentration for LNZ, 127I-LNZ and 131I-LNZ ranged from 1 to 2 µg/mL respectively. In time-kill studies LNZ, 127I-LNZ and 131I-LNZ were bactericidal against staphylococci, producing ≥3 Log10 decrease in viable counts (cfu/mL within 6 h at 2xMIC. Following the biofilm formation on polystyrene U-bottom microtiter plates to investigate the minimal biofilm inhibitory concentration (MBIC of LNZ, 127I-LNZ and 131I-LNZ was defined as the minimal concentration of antibiotic required to inhibite the biofilm. None of the LNZ, 127I-LNZ and 131I-LNZ killed 100% of biofilm associated cells. Mean cell survival in biofilms treated with 64 µg/mL LNZ, 127I-LNZ and 131I-LNZ (64 µg/mL was 48%, 49%, and 33%, respectively. Conclusion: Our results show that radiolabeled Linezolid demonstrated that 24 h of exposure to 64 µg/mL, promise in treating biofilm producing Staphylococcus aureus.

  7. Nanoassemblies Based on Supramolecular Complexes of Nonionic Amphiphilic Cyclodextrin and Sorafenib as Effective Weapons to Kill Human HCC Cells.

    Science.gov (United States)

    Bondì, Maria Luisa; Scala, Angela; Sortino, Giuseppe; Amore, Erika; Botto, Chiara; Azzolina, Antonina; Balasus, Daniele; Cervello, Melchiorre; Mazzaglia, Antonino

    2015-12-14

    Sorafenib (Sor), an effective chemiotherapeutic drug utilized against hepatocellular carcinoma (HCC), robustly interacts with nonionic amphiphilic cyclodextrin (aCD, SC6OH), forming, in aqueous solution, supramolecular complexes that behave as building blocks of highly water-dispersible colloidal nanoassemblies. SC6OH/Sor complex has been characterized by complementary spectroscopic techniques, such as UV-vis, steady-state fluorescence and anisotropy, resonance light scattering and (1)H NMR. The spectroscopic evidences and experiments carried out in the presence of an adamantane derivative, which competes with drug for CD cavity, agree with the entrapment of Sor in aCD, pointing out the role of the aCD cavity in the interaction between drug and amphiphile. Nanoassemblies based on SC6OH/Sor display size of ∼200 nm, negative zeta-potential (ζ = -11 mV), and both maximum loading capacity (LC ∼ 17%) and entrapment efficiency (EE ∼ 100%). Kinetic release profiles show a slower release of Sor from nanoassemblies with respect to the free drug. SC6OH/Sor nanoassemblies have very low hemolytic activity and high efficiency in vitro in decreasing cell growth and viability of HCC cell lines, such as HepG2, Hep3B, and PLC/PRF/5, opening promising chances to their in vivo applications. PMID:26528591

  8. Double suicide genes selectively kill human umbilical vein endothelial cells

    Directory of Open Access Journals (Sweden)

    Liu Lunxu

    2011-02-01

    Full Text Available Abstract Background To construct a recombinant adenovirus containing CDglyTK double suicide genes and evaluate the killing effect of the double suicide genes driven by kinase domain insert containing receptor (KDR promoter on human umbilical vein endothelial cells. Methods Human KDR promoter, Escherichia coli (E. coli cytosine deaminase (CD gene and the herpes simplex virus-thymidine kinase (TK gene were cloned using polymerase chain reaction (PCR. Plasmid pKDR-CDglyTK was constructed with the KDR promoter and CDglyTK genes. A recombinant adenoviral plasmid AdKDR-CDglyTK was then constructed and transfected into 293 packaging cells to grow and harvest adenoviruses. KDR-expressing human umbilical vein endothelial cells (ECV304 and KDR-negative liver cancer cell line (HepG2 were infected with the recombinant adenoviruses at different multiplicity of infection (MOI. The infection rate was measured by green fluorescent protein (GFP expression. The infected cells were cultured in culture media containing different concentrations of prodrugs ganciclovir (GCV and/or 5-fluorocytosine (5-FC. The killing effects were measured using two different methods, i.e. annexin V-FITC staining and terminal transferase-mediated dUTP nick end-labeling (TUNEL staining. Results Recombinant adenoviruses AdKDR-CDglyTK were successfully constructed and they infected ECV304 and HepG2 cells efficiently. The infection rate was dependent on MOI of recombinant adenoviruses. ECV304 cells infected with AdKDR-CDglyTK were highly sensitive to GCV and 5-FC. The cell survival rate was dependent on both the concentration of the prodrugs and the MOI of recombinant adenoviruses. In contrast, there were no killing effects in the HepG2 cells. The combination of two prodrugs was much more effective in killing ECV304 cells than GCV or 5-FC alone. The growth of transgenic ECV304 cells was suppressed in the presence of prodrugs. Conclusion AdKDR-CDglyTK/double prodrog system may be a useful

  9. What doesn't kill you makes you wary? Effect of repeated culling on the behaviour of an invasive predator.

    Directory of Open Access Journals (Sweden)

    Isabelle M Côté

    Full Text Available As a result of being hunted, animals often alter their behaviour in ways that make future encounters with predators less likely. When hunting is carried out for conservation, for example to control invasive species, these behavioural changes can inadvertently impede the success of future efforts. We examined the effects of repeated culling by spearing on the behaviour of invasive predatory lionfish (Pterois volitans/miles on Bahamian coral reef patches. We compared the extent of concealment and activity levels of lionfish at dawn and midday on 16 coral reef patches off Eleuthera, The Bahamas. Eight of the patches had been subjected to regular daytime removals of lionfish by spearing for two years. We also estimated the distance at which lionfish became alert to slowly approaching divers on culled and unculled reef patches. Lionfish on culled reefs were less active and hid deeper within the reef during the day than lionfish on patches where no culling had occurred. There were no differences at dawn when removals do not take place. Lionfish on culled reefs also adopted an alert posture at a greater distance from divers than lionfish on unculled reefs. More crepuscular activity likely leads to greater encounter rates by lionfish with more native fish species because the abundance of reef fish outside of shelters typically peaks at dawn and dusk. Hiding deeper within the reef could also make remaining lionfish less likely to be encountered and more difficult to catch by spearfishers during culling efforts. Shifts in the behaviour of hunted invasive animals might be common and they have implications both for the impact of invasive species and for the design and success of invasive control programs.

  10. What doesn't kill you makes you wary? Effect of repeated culling on the behaviour of an invasive predator.

    Science.gov (United States)

    Côté, Isabelle M; Darling, Emily S; Malpica-Cruz, Luis; Smith, Nicola S; Green, Stephanie J; Curtis-Quick, Jocelyn; Layman, Craig

    2014-01-01

    As a result of being hunted, animals often alter their behaviour in ways that make future encounters with predators less likely. When hunting is carried out for conservation, for example to control invasive species, these behavioural changes can inadvertently impede the success of future efforts. We examined the effects of repeated culling by spearing on the behaviour of invasive predatory lionfish (Pterois volitans/miles) on Bahamian coral reef patches. We compared the extent of concealment and activity levels of lionfish at dawn and midday on 16 coral reef patches off Eleuthera, The Bahamas. Eight of the patches had been subjected to regular daytime removals of lionfish by spearing for two years. We also estimated the distance at which lionfish became alert to slowly approaching divers on culled and unculled reef patches. Lionfish on culled reefs were less active and hid deeper within the reef during the day than lionfish on patches where no culling had occurred. There were no differences at dawn when removals do not take place. Lionfish on culled reefs also adopted an alert posture at a greater distance from divers than lionfish on unculled reefs. More crepuscular activity likely leads to greater encounter rates by lionfish with more native fish species because the abundance of reef fish outside of shelters typically peaks at dawn and dusk. Hiding deeper within the reef could also make remaining lionfish less likely to be encountered and more difficult to catch by spearfishers during culling efforts. Shifts in the behaviour of hunted invasive animals might be common and they have implications both for the impact of invasive species and for the design and success of invasive control programs. PMID:24705447

  11. Nexavar/Stivarga and viagra interact to kill tumor cells.

    Science.gov (United States)

    Tavallai, Mehrad; Hamed, Hossein A; Roberts, Jane L; Cruickshanks, Nichola; Chuckalovcak, John; Poklepovic, Andrew; Booth, Laurence; Dent, Paul

    2015-09-01

    We determined whether the multi-kinase inhibitor sorafenib or its derivative regorafenib interacted with phosphodiesterase 5 (PDE5) inhibitors such as Viagra (sildenafil) to kill tumor cells. PDE5 and PDGFRα/β were over-expressed in liver tumors compared to normal liver tissue. In multiple cell types in vitro sorafenib/regorafenib and PDE5 inhibitors interacted in a greater than additive fashion to cause tumor cell death, regardless of whether cells were grown in 10 or 100% human serum. Knock down of PDE5 or of PDGFRα/β recapitulated the effects of the individual drugs. The drug combination increased ROS/RNS levels that were causal in cell killing. Inhibition of CD95/FADD/caspase 8 signaling suppressed drug combination toxicity. Knock down of ULK-1, Beclin1, or ATG5 suppressed drug combination lethality. The drug combination inactivated ERK, AKT, p70 S6K, and mTOR and activated JNK. The drug combination also reduced mTOR protein expression. Activation of ERK or AKT was modestly protective whereas re-expression of an activated mTOR protein or inhibition of JNK signaling almost abolished drug combination toxicity. Sildenafil and sorafenib/regorafenib interacted in vivo to suppress xenograft tumor growth using liver and colon cancer cells. From multiplex assays on tumor tissue and plasma, we discovered that increased FGF levels and ERBB1 and AKT phosphorylation were biomarkers that were directly associated with lower levels of cell killing by 'rafenib + sildenafil. Our data are now being translated into the clinic for further determination as to whether this drug combination is a useful anti-tumor therapy for solid tumor patients. PMID:25704960

  12. A translation inhibitor identified in a Drosophila screen enhances the effect of ionizing radiation and taxol in mammalian models of cancer

    Directory of Open Access Journals (Sweden)

    Mara Gladstone

    2012-05-01

    We described previously a screening protocol in Drosophila melanogaster that allows us to identify small molecules that increase the killing effect of ionizing radiation in vivo in a multicellular context. The ability of this screen to identify agents that enhance the effect of radiation in human cancer models has been validated in published proof-of-concept studies. Here we describe an agent, identified by screening through two National Cancer Institute (NCI small molecule libraries in Drosophila, that increases the effect of radiation. This agent, Bouvardin (NSC 259968, inhibits the elongation step of protein synthesis. We find that Bouvardin enhances the killing effect of X-rays in both Drosophila larvae and in human cancer cells. More detailed analysis showed that Bouvardin also increases the effect of radiation in clonogenic assays and in human cancer xenografts in mice. Finally, we present data that Bouvardin can also increase the efficacy of taxol. Regulation of translation is important to cancer biology. Current therapies target every aspect of cancer cell proliferation from growth factor signaling to cell division, with the exception of translation elongation. Our identification of Bouvardin as an enhancer of radio- and chemo-therapeutic agents suggests that targeting this niche has the potential to improve existing cancer therapies.

  13. The effects of active dried and killed dried yeast on subacute ruminal acidosis, ruminal fermentation, and nutrient digestibility in beef heifers.

    Science.gov (United States)

    Vyas, D; Uwizeye, A; Mohammed, R; Yang, W Z; Walker, N D; Beauchemin, K A

    2014-02-01

    The study addressed the importance of yeast (Saccharomyces cerevisiae) viability for reducing the incidence of subacute ruminal acidosis (SARA) and improving total tract nutrient digestibility in beef heifers. Six ruminally cannulated beef heifers (680 ± 50 kg BW) were used in a replicated 3 × 3 Latin square design and were fed a diet consisting of 40% barley silage, 10% chopped grass hay, and 50% barley grain-based concentrate (DM basis). Treatments were 1) no yeast (Control), 2) active dried yeast (ADY; 4 g providing 10(10) cfu/g; AB Vista, Marlborough, UK), and 3) killed dried yeast (KDY; 4 g autoclaved ADY). The treatments were directly dosed via the ruminal cannula daily at the time of feeding. The periods consisted of 2 wk of adaptation (d 1 to 14) and 7 d of measurements (d 15 to 21). Ruminal pH was continuously measured (d 15 to 21) using an indwelling system. Ruminal contents were sampled on d 15 and 17 at 0, 3, 6, 9, and 12 h after feeding. Total tract nutrient digestibility was measured using an external marker (YbCl3) from d 15 to 19. No treatment difference was observed for DMI (P = 0.86). Yeast supplementation (ADY and KDY) tended to increase total tract digestibility of starch (P = 0.07) whereas no effects were observed on digestibility of other nutrients. Both ADY and KDY elevated minimum (P yeast supplementation was effective in reducing time that ruminal pH was below 5.8 (P 0.10); however, the proportion of Ruminococcus flavefaciens in solid fraction of digesta was greater with KDY (P = 0.05). The study demonstrates the positive effects of yeast, irrespective of its viability, in reducing the severity of SARA. However, further studies are required to evaluate the importance of yeast viability for other dietary conditions, particularly when the risk of acidosis is high.

  14. Effectiveness of attract-and-kill systems using methyl eugenol incorporated with neonicotinoid insecticides against the oriental fruit fly (Diptera: Tephritidae).

    Science.gov (United States)

    Chuang, Yi-Yuan; Hou, Roger F

    2008-04-01

    Laboratory bioassays and field trials were conducted to evaluate an "attract-and-kill" system using methyl eugenol (ME) with neonicotinoid insecticides against male oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). In laboratory bioassays, mortality of male flies resulting from the conventional toxicant, naled was 98.3-100% at 24 through 72 h after treatment, whereas the neonicotinoid insecticides imidacloprid and acetamiprid caused only approximately 60-80% at 24 through 72 h after treatment. In the assays of residual effect, naled was persistent up to 96 wk, whereas imidacloprid or acetamiprid was persistent up to 150 wk, resulting in 38.9 or 61.2% male mortality, respectively. Imidacloprid, in particular, caused a delayed lethal effect on flies. In another experiment, male mortality within 28 wk from clothianidin, another neonicotinoid insecticide, was approximately 80% after exposure for 24 h, suggesting a delayed lethal effect similar to those treated with imidacloprid, and mortality was up to 91.8%, if observed, 72 h after treatment. In field trials, attractiveness was similar between ME alone and ME incorporated with naled or neonicotinoids, indicating that addition of these insecticides to ME in traps is not repellent to B. dorsalis males. Using an improved wick-typed trap with longer attractiveness for simulating field application, addition of imidacloprid or acetamiprid maintained 40.1 or 64.3% male mortality, respectively, when assayed once every 2 wk from traps placed in orchards for 42 wk without changing the poison, whereas incorporation with naled resulted in as high as 98.1% after 34 wk and approximately 80% at 42 wk, indicating that persistence is increased compared with sugarcane fiberboard blocks for carrying poison attractants. This study also suggests that neonicotinoid insecticides could be used as an alternative for broad-spectrum insecticides as toxicants in fly traps. PMID:18459398

  15. HER2-Specific T Lymphocytes Kill both Trastuzumab-Resistant and Trastuzumab-Sensitive Breast Cell Lines In Vitro

    Institute of Scientific and Technical Information of China (English)

    Xiao-lin Lin; Xu Liang; Tao Shen; Jun Ren; Xiao-li Wang; Bo Ma; Jun Jia; Ying Yan; Li-jun Di; Yan-hua Yuan; Feng-ling Wan; Yuan-li Lu

    2012-01-01

    Objective:Although the development of trastuzumab has improved the outlook for women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer,the resistance to anti-HER2 therapy is a growing clinical dilemma.We aim to determine whether HER2-specific T cells generated from dendritic cells (DCs) modified with HER2 gene could effectively kill the HER2-positive breast cancer cells,especially the trastuzumab-resistant cells.Methods:The peripheral blood mononuclear cells (PBMCs) from healthy donors,whose HLA haplotypes were compatible with the tumor cell lines,were transfected with reconstructive human adeno-association virus (rhAAV/HER2) to obtain the specific killing activities of T cells,and were evaluated by lactate dehydrogenase (LDH)releasing assay.Results:Trastuzumab produced a significant inhibiting effect on SK-BR-3,the IC50 was 100ng/ml.MDA-MB-453 was resistant to trastuzumab even at a concentration of 10,000 ng/ml in vitro.HER2-specific T lymphocytes killed effectively SK-BR-3 [(69.86±13.41)%] and MDA-MB-453 [(78.36±10.68)%] at 40:1 (effector:target ratio,E:T),but had no significant cytotoxicity against HER2-negative breast cancer cell lines MDA-MB-231 or MCF-7 (less than 10%).Conclusion:The study showed that HER2-specific T lymphocytes generated from DCs modified by rhAAV/HER2 could kill HER2-positive breast cancer cell lines in a HER2-dependent manner,and result in significantly high inhibition rates on the intrinsic trastuzumab-resistant cell line MDA-MB-453 and the tastuzumab-sensitive cell line SK-BR-3.These results imply that this immunotherapy might be a potential treatment to HER2-positive breast cancer.

  16. Effects of proteasome inhibitors on bone cancer

    OpenAIRE

    Terpos, Evangelos; Christoulas, Dimitrios

    2013-01-01

    Bone metastasis is a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer, while bone disease is also the characteristic clinical feature of multiple myeloma. Skeletal-related events can be devastating, with major effect on the quality of life and survival. Bisphosphonates are the mainstay of therapeutic management of bone disease of solid tumors and myeloma, and denosumab has recently been approved for patients with bone metastases. Both...

  17. Phantom metrics with Killing spinors

    Directory of Open Access Journals (Sweden)

    W.A. Sabra

    2015-11-01

    Full Text Available We study metric solutions of Einstein–anti-Maxwell theory admitting Killing spinors. The analogue of the IWP metric which admits a space-like Killing vector is found and is expressed in terms of a complex function satisfying the wave equation in flat (2+1-dimensional space–time. As examples, electric and magnetic Kasner spaces are constructed by allowing the solution to depend only on the time coordinate. Euclidean solutions are also presented.

  18. Investigating CTL mediated killing with a 3D cellular automaton.

    Directory of Open Access Journals (Sweden)

    Frederik Graw

    2009-08-01

    Full Text Available Cytotoxic T lymphocytes (CTLs are important immune effectors against intra-cellular pathogens. These cells search for infected cells and kill them. Recently developed experimental methods in combination with mathematical models allow for the quantification of the efficacy of CTL killing in vivo and, hence, for the estimation of parameters that characterize the effect of CTL killing on the target cell populations. It is not known how these population-level parameters relate to single-cell properties. To address this question, we developed a three-dimensional cellular automaton model of the region of the spleen where CTL killing takes place. The cellular automaton model describes the movement of different cell populations and their interactions. Cell movement patterns in our cellular automaton model agree with observations from two-photon microscopy. We find that, despite the strong spatial nature of the kinetics in our cellular automaton model, the killing of target cells by CTLs can be described by a term which is linear in the target cell frequency and saturates with respect to the CTL levels. Further, we find that the parameters describing CTL killing on the population level are most strongly impacted by the time a CTL needs to kill a target cell. This suggests that the killing of target cells, rather than their localization, is the limiting step in CTL killing dynamics given reasonable frequencies of CTL. Our analysis identifies additional experimental directions which are of particular importance to interpret estimates of killing rates and could advance our quantitative understanding of CTL killing.

  19. Effect of Regulation of HSV-tk Gene Expression and Tumor Killed Activity with a Single Tetracycline-regulatable Plasmid Vector on HeLa Cells

    Institute of Scientific and Technical Information of China (English)

    WANG Qian; DU Zhen-wu; MA Qing-shan; ZHANG Yu-cheng; WU Xiao-dong; YANG Shao-juan; WANG Ya-li; ZHANG Gui-zhen

    2009-01-01

    To construct a single tetracycline-regulatable plasmid vector based on the double tetracycline-regulatable plasmid vector system for regulating HSV-tk gene expression so as to effectively kill HeLa cells. Two tetracycline operator(TetO2) was cloned into pcDNA3.1 and a cassette was made for a cytomegalovirus-type 2 tetracycline oper-ator(CMV-TetO2) promoter, and the obtained vector was named pcDNA3.1-CMV-TetO2. Herpes simplex virus thy-midine kinase(HSV-tk) gene and tetracycline repressor(TR) gene were cloned into pcDNA3.1-CMV-TetO2 and the two genes were linked with internal ribosome entry site(IRES) to gain a vector named pcDNA3.1-CMV-TetO2-HSV-tk-IRES-TR. The HeLa cells were stablly transfected with pcDNA3.1-CMV-TetO2-HSV-tk-IRES-TR plasmid. The expression of HSV-tk and TR were detected by RT-PCR, the tumorcidal activity of HSV-tk/GCV was determined by MTT assay. In Hela cells transfected with the above plasmid vector, HSV-tk gene and TR gene can be expressed lowly and the concentration of GCV producing a 50% decrease in cell viability was about 50 ug/mL without adding deoxycycline; in contrast, the expessions of HSV-tk gene and TR gene increased significantly and the concentration of GCV producing a 50% decrease in cell viability was about 5 u,g/mL with adding deoxycycline. Therefore tetracycline can regulate the expression and tumorcidal activity of HSV-tk gene in HeLa cells with this single plasmid vector.

  20. Effects of AlMnCa and AlMnFe Alloys on Deoxidization of Low Carbon and Low Silicon Aluminum Killed Steels

    Institute of Scientific and Technical Information of China (English)

    ZHAN Dong-ping; ZHANG Hui-shu; JIANG Zhou-hua

    2008-01-01

    To confirm the effects of AlMnCa and AIMnFe alloys on the deoxidization and modification of Al2O3 inclu-sions, experiments of 4-heat low carbon and low silicon aluminum killed steels deoxidized by AlMnCa and AlMnFe alloys were done in a MoSi2 furnace at 1 873 K. It is found that the 1# A1MnCa alloy has the best ability of deoxidi-zation and modification of Al2 O3 inclusions than 2# A1MnCa and A1MnFe alloys. Steel A deoxidized by 1# AlMnCa alloy has the lowest total oxygen content in the terminal steel, which is 37 × 10-6. Most of the inclusions in the steel deoxidized by 1# AIMnCa alloy are spherical CaO-containing compound inclusions, and 89. 1% of them are smaller than 10 μm. The diameter of the inclusion bigger than 50 μm is not found in the final steels deoxidized by AlMnCa alloys. Whereas, for the steels deoxidized by AlMnFe alloys, most inclusions in the terminal steel are Al2O3 or Al2O3-MnO inclusions, and a few of them are spherical, and only 76. 8% of them are smaller than 10 μm. Some in-clusions bigger than 50 μm are found in the steel D deoxidized by AlMnFe alloy.

  1. Galectin-9 Signaling through TIM-3 Is Involved in Neutrophil-Mediated Gram-Negative Bacterial Killing: An Effect Abrogated within the Cystic Fibrosis Lung

    Science.gov (United States)

    Vega-Carrascal, Isabel; Bergin, David A.; McElvaney, Oliver J.; McCarthy, Cormac; Banville, Nessa; Pohl, Kerstin; Hirashima, Mitsuomi; Kuchroo, Vijay K.; Reeves, Emer P.; McElvaney, Noel G.

    2016-01-01

    The T cell Ig and mucin domain–containing molecule (TIM) family of receptors have emerged as potential therapeutic targets to correct abnormal immune function in chronic inflammatory conditions. TIM-3 serves as a functional receptor in structural cells of the airways and via the ligand galectin-9 (Gal-9) can modulate the inflammatory response. The aim of this study was to investigate TIM-3 expression and function in neutrophils, focusing on its potential role in cystic fibrosis (CF) lung disease. Results revealed that TIM-3 mRNA and protein expression values of circulating neutrophils were equal between healthy controls (n = 20) and people with CF (n = 26). TIM-3 was detected on resting neutrophil membranes by FACS analysis, and expression levels significantly increased post IL-8 or TNF-α exposure (p < 0.05). Our data suggest a novel role for TIM-3/Gal-9 signaling involving modulation of cytosolic calcium levels. Via TIM-3 interaction, Gal-9 induced neutrophil degranulation and primed the cell for enhanced NADPH oxidase activity. Killing of Pseudomonas aeruginosa was significantly increased upon bacterial opsonization with Gal-9 (p < 0.05), an effect abrogated by blockade of TIM-3 receptors. This mechanism appeared to be Gram-negative bacteria specific and mediated via Gal-9/ LPS binding. Additionally, we have demonstrated that neutrophil TIM-3/Gal-9 signaling is perturbed in the CF airways due to proteolytic degradation of the receptor. In conclusion, results suggest a novel neutrophil defect potentially contributing to the defective bacterial clearance observed in the CF airways and suggest that manipulation of the TIM-3 signaling pathway may be of therapeutic value in CF, preferably in conjunction with antiprotease treatment. PMID:24477913

  2. Methylisoindigo preferentially kills cancer stem cells by interfering cell metabolism via inhibition of LKB1 and activation of AMPK in PDACs.

    Science.gov (United States)

    Cheng, Xinlai; Kim, Jee Young; Ghafoory, Shahrouz; Duvaci, Tijen; Rafiee, Roya; Theobald, Jannick; Alborzinia, Hamed; Holenya, Pavlo; Fredebohm, Johannes; Merz, Karl-Heinz; Mehrabi, Arianeb; Hafezi, Mohammadreza; Saffari, Arash; Eisenbrand, Gerhard; Hoheisel, Jörg D; Wölfl, Stefan

    2016-06-01

    Pancreatic ductal adenocarcinoma (PDAC) clinically has a very poor prognosis. No small molecule is available to reliably achieve cures. Meisoindigo is chemically related to the natural product indirubin and showed substantial efficiency in clinical chemotherapy for CML in China. However, its effect on PDAC is still unknown. Our results showed strong anti-proliferation effect of meisoindigo on gemcitabine-resistant PDACs. Using a recently established primary PDAC cell line, called Jopaca-1 with a larger CSCs population as model, we observed a reduction of CD133+ and ESA+/CD44+/CD24+ populations upon treatment and concomitantly a decreased expression of CSC-associated genes, and reduced cellular mobility and sphere formation. Investigating basic cellular metabolic responses, we detected lower oxygen consumption and glucose uptake, while intracellular ROS levels increased. This was effectively neutralized by the addition of antioxidants, indicating an essential role of the cellular redox balance. Further analysis on energy metabolism related signaling revealed that meisoindigo inhibited LKB1, but activated AMPK. Both of them were involved in cellular apoptosis. Additional in situ hybridization in tissue sections of PDAC patients reproducibly demonstrated co-expression and -localization of LKB1 and CD133 in malignant areas. Finally, we detected that CD133+/CD44+ were more vulnerable to meisoindigo, which could be mimicked by LKB1 siRNAs. Our results provide the first evidence, to our knowledge, that LKB1 sustains the CSC population in PDACs and demonstrate a clear benefit of meisoindigo in treatment of gemcitabine-resistant cells. This novel mechanism may provide a promising new treatment option for PDAC. PMID:26887594

  3. Targeting Cancer Metabolism - Revisiting the Warburg Effects.

    Science.gov (United States)

    Tran, Quangdon; Lee, Hyunji; Park, Jisoo; Kim, Seon-Hwan; Park, Jongsun

    2016-07-01

    After more than half of century since the Warburg effect was described, this atypical metabolism has been standing true for almost every type of cancer, exhibiting higher glycolysis and lactate metabolism and defective mitochondrial ATP production. This phenomenon had attracted many scientists to the problem of elucidating the mechanism of, and reason for, this effect. Several models based on oncogenic studies have been proposed, such as the accumulation of mitochondrial gene mutations, the switch from oxidative phosphorylation respiration to glycolysis, the enhancement of lactate metabolism, and the alteration of glycolytic genes. Whether the Warburg phenomenon is the consequence of genetic dysregulation in cancer or the cause of cancer remains unknown. Moreover, the exact reasons and physiological values of this peculiar metabolism in cancer remain unclear. Although there are some pharmacological compounds, such as 2-deoxy-D-glucose, dichloroacetic acid, and 3-bromopyruvate, therapeutic strategies, including diet, have been developed based on targeting the Warburg effect. In this review, we will revisit the Warburg effect to determine how much scientists currently understand about this phenomenon and how we can treat the cancer based on targeting metabolism. PMID:27437085

  4. Targeting Cancer Metabolism - Revisiting the Warburg Effects

    Science.gov (United States)

    Tran, Quangdon; Lee, Hyunji; Park, Jisoo; Kim, Seon-Hwan; Park, Jongsun

    2016-01-01

    After more than half of century since the Warburg effect was described, this atypical metabolism has been standing true for almost every type of cancer, exhibiting higher glycolysis and lactate metabolism and defective mitochondrial ATP production. This phenomenon had attracted many scientists to the problem of elucidating the mechanism of, and reason for, this effect. Several models based on oncogenic studies have been proposed, such as the accumulation of mitochondrial gene mutations, the switch from oxidative phosphorylation respiration to glycolysis, the enhancement of lactate metabolism, and the alteration of glycolytic genes. Whether the Warburg phenomenon is the consequence of genetic dysregulation in cancer or the cause of cancer remains unknown. Moreover, the exact reasons and physiological values of this peculiar metabolism in cancer remain unclear. Although there are some pharmacological compounds, such as 2-deoxy-D-glucose, dichloroacetic acid, and 3-bromopyruvate, therapeutic strategies, including diet, have been developed based on targeting the Warburg effect. In this review, we will revisit the Warburg effect to determine how much scientists currently understand about this phenomenon and how we can treat the cancer based on targeting metabolism. PMID:27437085

  5. Enhanced Antiproliferative Effect of Carboplatin in Cervical Cancer Cells Utilizing Folate-Grafted Polymeric Nanoparticles

    Science.gov (United States)

    Ji, Jing; Zuo, Ping; Wang, Yue-Ling

    2015-11-01

    Carboplatin (CRB) possesses superior anticancer effect in cervical cancer cells with lower incidence of side effects compared to that of cisplatin. However, CRB suffers from severe side effects due to undesirable tissue distributions which contribute to the low therapeutic efficacy. Here, we report a unique folic acid-conjugated chitosan-coated poly( d- l-lactideco-glycolide) (PLGA) nanoparticles (FPCC) prepared for the selective delivery of carboplatin to the cervical cancer cells. The particles were nanosized and spherical shaped with size less than cancerous, HeLa cells owing to ligand-receptor (FA-FR-α) recognition. Consistently, FPCC showed superior cytotoxic effect than any other formulations. The IC50 (concentration of the drug required to kill 50 % of the cells) value of FPCC was 0.65 μg/ml while it was 1.08, 1.56, and 2.35 μg/ml for PCC, PLGA NP, and free CRB, respectively. Consistent with the cytotoxicity assay, FPCC induced higher fraction of early as well as late apoptosis cells. Especially, FPCC induced nearly 45 % of early apoptosis cells and more than 35 % in late apoptosis. Therefore, we propose that folate-conjugated nanoparticles might have potential applications in cervical cancer therapy.

  6. 等离子体臭氧对水中微生物的杀灭作用%Study on killing effect on microorganisms in water by plasmas ozone

    Institute of Scientific and Technical Information of China (English)

    顾春英; 薛广波; 居喜娟

    2001-01-01

    Objective To study killing effect of plasmas ozo ne water on microorganisms by plasmas ozone disinfection solution through plasma s ozone resulting from discharge along surface disinfection solution produced by machine and its effect factors. Methods Quantitative solut ion test was used to study killing action of plasmas ozone disinfection water to E. coli and staphyrococcus aureus, and to study its eff ect factors. Results Plasmas ozone water could kill 99.9% E. coli and staphyrococcus aureus after 15 min. The kill ing effect was affected by organism. With the increasing of organism concertrat ion, the killing efficacy increased. Conclusions Plasmas ozone can effectively kill microorgnisms in water and the efficacy was affected by org anism.%目的 通过沿面放电等离子体臭氧消毒液发生器 发生的等离子体臭氧消毒水来研究等离子体臭氧对水中微生物的杀灭效果及影响因素。方法 采用悬液定量消毒试验法来研究等离子体臭氧消毒水对金黄色葡萄球菌 和大肠杆菌的杀灭作用,并测试了有机物对其消毒效果的影响。结果 等 离子体臭氧对水中的大肠杆菌和金黄色葡萄球菌作用15 min,杀灭率达99.9%以上,而臭 氧浓度为1.0 mg*L-1,其杀菌作用受有机物的影响,有机物浓度越高对消 毒效果影响越大。结论 等离子体臭氧可以有效杀灭水中的细菌繁殖体, 其杀灭效果受有机物影响。

  7. Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP

    OpenAIRE

    Chen, Yong; Liu, Ju Mei; Xiong, Xin Xin; Qiu, Xin Yao; Pan, Feng; Liu, Di; Lan, Shu Jue; Jin, Si; Yu, Shang Bin; Chen, Xiao Qian

    2015-01-01

    Hepatocellular carcinomas (HCC) are highly malignant and aggressive tumors lack of effective therapeutic drugs. Piperlongumine (PL), a natural product isolated from longer pepper plants, is recently identified as a potent cytotoxic compound highly selective to cancer cells. Here, we reported that PL specifically suppressed HCC cell migration/invasion via endoplasmic reticulum (ER)-MAPKs-CHOP signaling pathway. PL selectively killed HCC cells but not normal hepatocytes with an IC50 of 10-20 μM...

  8. HAMLET kills tumor cells by apoptosis: structure, cellular mechanisms, and therapy.

    Science.gov (United States)

    Gustafsson, Lotta; Hallgren, Oskar; Mossberg, Ann-Kristin; Pettersson, Jenny; Fischer, Walter; Aronsson, Annika; Svanborg, Catharina

    2005-05-01

    New cancer treatments should aim to destroy tumor cells without disturbing normal tissue. HAMLET (human alpha-lactalbumin made lethal to tumor cells) offers a new molecular approach to solving this problem, because it induces apoptosis in tumor cells but leaves normal differentiated cells unaffected. After partial unfolding and binding to oleic acid, alpha-lactalbumin forms the HAMLET complex, which enters tumor cells and freezes their metabolic machinery. The cells proceed to fragment their DNA, and they disintegrate with apoptosis-like characteristics. HAMLET kills a wide range of malignant cells in vitro and maintains this activity in vivo in patients with skin papillomas. In addition, HAMLET has striking effects on human glioblastomas in a rat xenograft model. After convection-enhanced delivery, HAMLET diffuses throughout the brain, selectively killing tumor cells and controlling tumor progression without apparent tissue toxicity. HAMLET thus shows great promise as a new therapeutic with the advantage of selectivity for tumor cells and lack of toxicity.

  9. Killing, letting die and euthanasia.

    Science.gov (United States)

    Husak, D N

    1979-12-01

    Medical ethicists debate whether or not the moral assessment of cases of euthanasia should depend on whether the patient is 'killed' or 'allowed to die'. The usual presupposition is that a clear distinction between killing and letting die can be drawn so that this substantive question is not begged. I contend that the categorisation of cases of instances of killing rather than as instances of letting die depends in part on a prior moral assessment of the case. Hence is it trivially rather than substantively true that the distinction has moral significance. But even if a morally neutral (ie non-question begging) distinction could be drawn, its application to the euthanasia controversy is problematic. I illustrate the difficulties of employing this distinction to reach moral conclusions by critically discussing Philippa Foot's recent treatment of euthanasia. I conclude that even if an act of euthanasia is an instance of killing, and there exists a prima facie moral duty not to kill, and no more stringent duty overrides this duty, one still cannot determine such an act to be morally impermissible.

  10. Amphibian road kills: a global perspective

    OpenAIRE

    Puky, Miklós

    2005-01-01

    Transportation infrastructure is a major factor determining land use forms. As global changes in this factor are the most important for biodiversity, roads fundamentally influence wildlife. The effect of roads on wildlife has been categorized in several ways resulting in six to ten categories with road kill as an obvious and important component, and amphibians are greatly affected by this factor. As this animal group has been documented to decline from multiple threats worldwide, the study an...

  11. A STUDY ON THE TREATMENT OF GASTRIC CANCER BY CD GENE COMBINED WITH 5-FC IN VITRO AND IN VIVO

    Institute of Scientific and Technical Information of China (English)

    郭善禹; 顾琴龙; 朱正纲; 林言箴

    2001-01-01

    To study the killing effect of suicide gene CD on mouse gastric cancer. Methods: CD gene was transduced with the retroviral vector. The killing effect and bystander effect of CD gene on mouse gastric cancer cell line MFC were observed. The mouse gastric cancer model was used for in vivo study. The CD gene containing virus was injected into the tumors. The volumes of the tumors in every group were measured in time. Results: Significant killing effect and bystander effect were observed by CD gene in vitro, 70~80% cell death resulting from 20% of CD gene transduction. In vivo, CD/5-Fc caused tumor to diminution. Conclusion: CD/5-Fc system has significant killing effect on mouse gastric cancer

  12. A Near-Infrared Triggered Nanophotosensitizer Inducing Domino Effect on Mitochondrial Reactive Oxygen Species Burst for Cancer Therapy.

    Science.gov (United States)

    Yu, Zhengze; Sun, Qiaoqiao; Pan, Wei; Li, Na; Tang, Bo

    2015-11-24

    Photodynamic therapy (PDT) is a well-established modality for cancer therapy, which locally kills cancer cells when light irradiates a photosensitizer. However, conventional PDT is often limited by the extremely short lifespan and severely limited diffusion distance of reactive oxygen species (ROS) generated by photosensitizer, as well as the penetration depth of visible light activation. Here, we develop a near-infrared (NIR) triggered nanophotosensitizer based on mitochondria targeted titanium dioxide-coated upconversion nanoparticles for PDT against cancer. When irradiated by NIR laser, the nanophotosensitizer could produce ROS in mitochondria, which induced the domino effect on ROS burst. The overproduced ROS accumulated in mitochondria, resulting in mitochondrial collapse and irreversible cell apoptosis. Confocal fluorescence imaging indicated that the mitochondrial targeting and real-time imaging of ROS burst could be achieved in living cells. The complete removal of tumor in vivo confirmed the excellent therapeutic effect of the nanophotosensitizer.

  13. Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer

    Science.gov (United States)

    2011-07-14

    Bladder Cancer; Cervical Cancer; Colorectal Cancer; Endometrial Cancer; Gastrointestinal Complications; Long-term Effects Secondary to Cancer Therapy in Adults; Ovarian Cancer; Prostate Cancer; Radiation Toxicity; Sarcoma; Testicular Germ Cell Tumor; Vaginal Cancer

  14. Hemagglutinating virus of Japan envelope (HVJ-E) can enhance the immune responses of swine immunized with killed PRRSV vaccine

    International Nuclear Information System (INIS)

    Highlights: ► We investigated the immunoadjuvant effects of HVJ-E on killed PRRSV vaccine. ► HVJ-E enhanced the humoral and cellular responses of the piglets to PRRSV. ► It is suggested that HVJ-E could be developed as a new-type adjuvant for mammals. -- Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically detrimental pig pathogen that causes significant losses for the pig industry. The immunostimulatory effects of hemagglutinating virus of Japan envelope (HVJ-E) in cancer therapy and the adjuvant efficacy of HVJ-E have been previously evaluated. The objective of this study was to investigate the adjuvant effects of HVJ-E on immunization with killed PRRSV vaccine, and to evaluate the protective effects of this immunization strategy against virulent PRRSV infection in piglets. Next, the PRRSV-specific antibody response, lymphocyte proliferation, PRRSV-specific IL-2, IL-10 and IFN-γ production, and the overall protection efficacy were evaluated to assess the immune responses of the piglets. The results showed that the piglets inoculated simultaneously with killed PRRSV vaccine and HVJ-E had a significantly stronger immune response than those inoculated with killed PRRSV vaccine alone. Our results suggest that HVJ-E could be employed as an effective adjuvant to enhance the humoral and cellular responses of piglets to PRRSV.

  15. Late endocrine effects of childhood cancer.

    Science.gov (United States)

    Rose, Susan R; Horne, Vincent E; Howell, Jonathan; Lawson, Sarah A; Rutter, Meilan M; Trotman, Gylynthia E; Corathers, Sarah D

    2016-06-01

    The cure rate for paediatric malignancies is increasing, and most patients who have cancer during childhood survive and enter adulthood. Surveillance for late endocrine effects after childhood cancer is required to ensure early diagnosis and treatment and to optimize physical, cognitive and psychosocial health. The degree of risk of endocrine deficiency is related to the child's sex and their age at the time the tumour is diagnosed, as well as to tumour location and characteristics and the therapies used (surgery, chemotherapy or radiation therapy). Potential endocrine problems can include growth hormone deficiency, hypothyroidism (primary or central), adrenocorticotropin deficiency, hyperprolactinaemia, precocious puberty, hypogonadism (primary or central), altered fertility and/or sexual function, low BMD, the metabolic syndrome and hypothalamic obesity. Optimal endocrine care for survivors of childhood cancer should be delivered in a multidisciplinary setting, providing continuity from acute cancer treatment to long-term follow-up of late endocrine effects throughout the lifespan. Endocrine therapies are important to improve long-term quality of life for survivors of childhood cancer. PMID:27032982

  16. Antiproton radiation found effective in cancer research

    CERN Multimedia

    2003-01-01

    "An international collaboration of scientists has completed the first ever antiproton beam experiments designed to reveal the biological effectiveness of antiproton radiation in terminating cells used for cancer research...PBar Labs assembled the collaboration at CERN (European Organization for Nuclear Research in Geneva) to perform the measurements" (1 page).

  17. Effects of Brassicaceae Isothiocyanates on Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Silvia Novío

    2016-05-01

    Full Text Available Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models.

  18. Neurocognitive Effects of Treatment for Childhood Cancer

    Science.gov (United States)

    Butler, Robert W.; Haser, Jennifer K.

    2006-01-01

    We review research on the neuropsychological effects that central nervous system (CNS) cancer treatments have on the cognitive abilities of children and adolescents. The authors focus on the two most common malignancies of childhood: leukemias and brain tumors. The literature review is structured so as to separate out earlier studies, generally…

  19. Improving photodynamic inactivation of bacteria in dentistry: highly effective and fast killing of oral key pathogens with novel tooth-colored type-II photosensitizers.

    Science.gov (United States)

    Späth, Andreas; Leibl, Christoph; Cieplik, Fabian; Lehner, Karin; Regensburger, Johannes; Hiller, Karl-Anton; Bäumler, Wolfgang; Schmalz, Gottfried; Maisch, Tim

    2014-06-26

    Increasing antibiotic resistances in microorganisms create serious problems in public health. This demands alternative approaches for killing pathogens to supplement standard treatment methods. Photodynamic inactivation of bacteria (PIB) uses light activated photosensitizers (PS) to generate reactive oxygen species immediately upon illumination, inducing lethal phototoxicity. Positively charged phenalen-1-one derivatives are a new generation of PS for light-mediated killing of pathogens with outstanding singlet oxygen quantum yield ΦΔ of >97%. Upon irradiation with a standard photopolymerizer light (bluephase C8, 1260 ± 50 mW/cm(2)) the PS showed high activity against the oral key pathogens Enterococcus faecalis, Actinomyces naeslundii, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans. At a concentration of 10 μM, a maximum efficacy of more than 6 log10 steps (≥ 99.9999%) of bacteria killing is reached in less than 1 min (light dose 50 J/cm(2)) after one single treatment. The pyridinium substituent as positively charged moiety is especially advantageous for antimicrobial action. PMID:24884918

  20. Killing Effects of Ozone on Pathogens in Mineral Water%臭氧对矿泉水中致病菌的杀灭效果

    Institute of Scientific and Technical Information of China (English)

    张永清; 吴清平; 张菊梅; 郭伟鹏; 彭飞艇; 杨秀华

    2014-01-01

    采用悬液定量杀菌和流动杀菌的方法,对铜绿假单胞菌(Pseudomonas aeruginosa)、粪链球菌(Strep-tococcus faecium)和大肠杆菌(Escherichia coli)的臭氧消毒效果进行了研究。结果表明,悬液定量杀菌试验中,臭氧浓度0.36 mg/L,作用10 min后,铜绿假单胞菌存活率小于1.0%;臭氧浓度0.31 mg/L,作用3 min后,粪链球菌存活率小于0.1%;臭氧浓度在0.45 mg/L及以上,作用10 min后,大肠杆菌存活率在2.0%以下。流动杀菌试验中,臭氧浓度0.20~0.60 mg/L,作用3 min后,大肠杆菌、铜绿假单胞菌和粪链球菌的存活率在0.01%以下,即杀灭率在99.99%以上。%Both suspension quantitative germicidal test and flow germicidal test were used to study disinfection effects of ozone on the Pseudomonas aeruginosa, Streptococcus faecium and Escherichia coli. The suspension quantitative germicidal test found that the survival rate of Pseudomonas aeruginosa treated with 0.36 mg/L of ozone for 10 min was less than 1.0%, and that of Streptococcus faecium reacted with 0.31 mg/L of ozone for 10 min was less than 0.1%. When the ozone was more than 0.45 mg/L and the time was 10 min, the survival rates of Escherichia coli was under 2.0%. The results of the flow germicidal test showed that the probability of survivability of Escherichia coli, Pseudomonas aeruginosa and Streptococcus faecium treated with 0.20-0.60 mg/L of ozone for 3 min were under 0.01%, with the killing rates of more than 99.99%.

  1. Heparanase multiple effects in cancer.

    Science.gov (United States)

    Nadir, Yona; Brenner, Benjamin

    2014-05-01

    Heparanase is an endo-β-D-glucuronidase that is capable of cleaving heparan sulfate side chains of heparan sulfate proteoglycans on cell surfaces and the extracellular matrix, activity that is strongly implicated in tumor metastasis and angiogenesis. Apart of its well characterized enzymatic activity, heparanase was noted to exert also enzymatic-independent functions. Among these are the up-regulation of vascular endothelial growth factor (VEGF)-A, VEGF-C and activation of intra-cellular signaling involved in cell survival and proliferation. We had earlier demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. We had shown that heparanase up-regulated the expression of the blood coagulation initiator- tissue factor (TF) and interacted with the tissue factor pathway inhibitor (TFPI) on the cell surface membrane of endothelial and tumor cells, leading to dissociation of TFPI and resulting in increased cell surface coagulation activity. Moreover, we have demonstrated that heparanase directly enhanced TF activity which led to increased factor Xa production and subsequent activation of the coagulation system. Taking into account the prometastatic, pro-angiogenic and pro-coagulant functions of heparanase, over-expression in human malignancies and abundance in platelets, implies that heparanase is potentially a good target for cancer therapy. PMID:24862152

  2. Chemically unassisted phototherapy: dose effects via real-time optical monitoring of cancer cells

    Science.gov (United States)

    Landry, Sylvie; Keeler, Werden

    2010-03-01

    Ultraviolet (UV) light and short wavelength visible (VIS) light have been used to kill pathogens for many years. Although the adverse effects of UV radiation on living cells have been extensively studied using biochemical and biomolecular techniques, most of the light therapies used for medical treatment are chemically assisted (i.e., photodynamic therapy). However, the use of light alone could prove both cost and therapeutically effective as an alternative treatment modality for localized diseases. In this study, real-time oblique incidence reflection (OIR) microscopy and image analysis were used to visualize and quantify the effects of chemically unassisted light therapy on untagged live cancer cells in vitro. The incident radiation fluence (in mJ/cm^2) required to induce cell death was determined for selected quasi-monochromatic UV to VIS wavelengths ranging from 275nm to 460nm. A predictive mathematical equation quantifying the lethal fluence as a function of wavelength will be discussed.

  3. 33 CFR 117.801 - Newtown Creek, Dutch Kills, English Kills and their tributaries.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Newtown Creek, Dutch Kills....801 Newtown Creek, Dutch Kills, English Kills and their tributaries. (a) The following requirements apply to all bridges across Newtown Creek, Dutch Kills, English Kills, and their tributaries: (1)...

  4. Effect of Nitric Oxide on Esophageal Cancer Cell Line TE-1

    Institute of Scientific and Technical Information of China (English)

    Guo-gui Sun; Wan-ning Hu; Jun Zhang; Cheng-lin Li; Cong-rong Yang

    2013-01-01

    Objective To investigate the radiosensitizing effect of nitric oxide (NO) combined with radiation on esophageal cancer cell line TE-1. Methods Methyl thiazolyl tetrazolium (MTT) assay was used to assess the effects of NO and radia-tion on TE-1 cells regarding inhibition of cell proliferation. Flow cytometry was used to examine the effect of NO and radiation on cell apoptosis and cycle. Reverse transcription polymerase chine reaction and Western blot were used to evaluete the effect of NO on mRNA and protein expression of manganese superoxide dismutase (MnSOD). Results NO inhibited the proliferation of TE-1 cells while significantly enhancing their radiosensitiv-ity. The application of NO combined with radiation significantly increased the apoptosis rate and G2/M phase proportion of TE-1 cells,with substantial decreases in the MnSOD mRNA and protein expression levels. Conclusions NO reduces the MnSOD mRNA and protein expression levels by affecting TE-1 cell cycle,further inhibiting the apoptosis of esophageal cancer cells and enhancing the killing effect of radiation on esophageal cancer cells.

  5. Effects of recombinant epidermal growth factor receptor antisense adenovirus combined with irradiation on breast cancer cells

    International Nuclear Information System (INIS)

    Objective: To investigate the effects of a recombinant antisense adenovirus for epidermal growth factor receptor (EGFR) combined with irradiation on breast cancer cells. Methods: Human EGFR cDNA fragment was subcloned in the opposite orientation to the cytomegaloviral promoter and inserted into a E1/E3-deleted type 5 adenoviral vector to obtain AdE5 construct which expresses EGFR antisense RNA. Combined with γ-ray irradiation, its effects on clonogenicity and cell cycle phase distribution were studied in a human breast cancer line MDA-MB-23. Results: EGFR protein expression was dramatically inhibited in MDA-MB-231 cells after AdE5 infection. The post-irradiation clonogenicity was reduced by AdE5 in a viral and irradiation dose-dependent manner. Further cytometric analysis showed that AdE5 infection at a MOI of 300 pfu/cell induced a cell cycle progression from radio-resistant G0 + G1 phases to radiosensitive G2 + M phases, resulting in a synergistic effect after combination of these two treatments. Conclusions: The transduction of EGFR antisense RNA by adenoviral vector is effective for antisense strategy targeting EGFR, and increases the cell-killing effect of ionizing radiation on breast cancer cells.(authors)

  6. To Kill For An Image

    DEFF Research Database (Denmark)

    Fausing, Bent

    Images can provide both an overview and insight, but also the opposite. This ambivalence has become an even bigger part of the nature of the image, of what is an Image? Today we kill for an image, seen from afar on a screen and captured by a drone. The time also asks: Should it be big data...

  7. Second Cancers After Fractionated Radiotherapy: Stochastic Population Dynamics Effects

    Science.gov (United States)

    Sachs, Rainer K.; Shuryak, Igor; Brenner, David; Fakir, Hatim; Hahnfeldt, Philip

    2007-01-01

    When ionizing radiation is used in cancer therapy it can induce second cancers in nearby organs. Mainly due to longer patient survival times, these second cancers have become of increasing concern. Estimating the risk of solid second cancers involves modeling: because of long latency times, available data is usually for older, obsolescent treatment regimens. Moreover, modeling second cancers gives unique insights into human carcinogenesis, since the therapy involves administering well characterized doses of a well studied carcinogen, followed by long-term monitoring. In addition to putative radiation initiation that produces pre-malignant cells, inactivation (i.e. cell killing), and subsequent cell repopulation by proliferation can be important at the doses relevant to second cancer situations. A recent initiation/inactivation/proliferation (IIP) model characterized quantitatively the observed occurrence of second breast and lung cancers, using a deterministic cell population dynamics approach. To analyze ifradiation-initiated pre-malignant clones become extinct before full repopulation can occur, we here give a stochastic version of this I I model. Combining Monte Carlo simulations with standard solutions for time-inhomogeneous birth-death equations, we show that repeated cycles of inactivation and repopulation, as occur during fractionated radiation therapy, can lead to distributions of pre-malignant cells per patient with variance >> mean, even when pre-malignant clones are Poisson-distributed. Thus fewer patients would be affected, but with a higher probability, than a deterministic model, tracking average pre-malignant cell numbers, would predict. Our results are applied to data on breast cancers after radiotherapy for Hodgkin disease. The stochastic IIP analysis, unlike the deterministic one, indicates: a) initiated, pre-malignant cells can have a growth advantage during repopulation, not just during the longer tumor latency period that follows; b) weekend

  8. Adenoviral delivery of pan-caspase inhibitor p35 enhances bystander killing by P450 gene-directed enzyme prodrug therapy using cyclophosphamide+

    International Nuclear Information System (INIS)

    Cytochrome P450-based suicide gene therapy for cancer using prodrugs such as cyclophosphamide (CPA) increases anti-tumor activity, both directly and via a bystander killing mechanism. Bystander cell killing is essential for the clinical success of this treatment strategy, given the difficulty of achieving 100% efficient gene delivery in vivo using current technologies. Previous studies have shown that the pan-caspase inhibitor p35 significantly increases CPA-induced bystander killing by tumor cells that stably express P450 enzyme CYP2B6 (Schwartz et al, (2002) Cancer Res. 62: 6928-37). To further develop this approach, we constructed and characterized a replication-defective adenovirus, Adeno-2B6/p35, which expresses p35 in combination with CYP2B6 and its electron transfer partner, P450 reductase. The expression of p35 in Adeno-2B6/p35-infected tumor cells inhibited caspase activation, delaying the death of the CYP2B6 'factory' cells that produce active CPA metabolites, and increased bystander tumor cell killing compared to that achieved in the absence of p35. Tumor cells infected with Adeno-2B6/p35 were readily killed by cisplatin and doxorubicin, indicating that p35 expression is not associated with acquisition of general drug resistance. Finally, p35 did not inhibit viral release when the replication-competent adenovirus ONYX-017 was used as a helper virus to facilitate co-replication and spread of Adeno-2B6/p35 and further increase CPA-induced bystander cell killing. The introduction of p35 into gene therapeutic regimens constitutes an effective approach to increase bystander killing by cytochrome P450 gene therapy. This strategy may also be used to enhance other bystander cytotoxic therapies, including those involving the production of tumor cell toxic protein products

  9. Spatio-temporal analysis of tamoxifen-induced bystander effects in breast cancer cells using microfluidics.

    Science.gov (United States)

    Rios-Mondragon, Ivan; Wang, Xiang; Gerdes, Hans-Hermann

    2012-06-01

    The bystander effect in cancer therapy is the inhibition or killing of tumor cells that are adjacent to those directly affected by the agent used for treatment. In the case of chemotherapy, little is known as to how much and by which mechanisms bystander effects contribute to the elimination of tumor cells. This is mainly due to the difficulty to distinguish between targeted and bystander cells since both are exposed to the pharmaceutical compound. We here studied the interaction of tamoxifen-treated human breast cancer MCF-7 cells with their neighboring counterparts by exploiting laminar flow patterning in a microfluidic chip to ensure selective drug delivery. The spatio-temporal evolution of the bystander response in non-targeted cells was analyzed by measuring the mitochondrial membrane potential under conditions of free diffusion. Our data show that the bystander response is detectable as early as 1 hour after drug treatment and reached effective distances of at least 2.8 mm. Furthermore, the bystander effect was merely dependent on diffusible factors rather than cell contact-dependent signaling. Taken together, our study illustrates that this microfluidic approach is a promising tool for screening and optimization of putative chemotherapeutic drugs to maximize the bystander response in cancer therapy. PMID:23750189

  10. Effects of residential radon on cancer incidence

    International Nuclear Information System (INIS)

    Radon activity concentrations of 1077 homes were surveyed in two villages of Northern Hungary to obtain the yearly averages. The distribution of indoor radon activity concentrations covered a wide range. Cancer incidences of all the 2680 inhabitants for the last 30 years were also studied in these villages in order to establish a possible correlation with radon exposure. The methods applied in the analysis allow to draw up statistically supported statements concerning the relative cancer risks of different radon level groups. The results show that among non-smoking middle-aged women the frequency of cancer, regardless to tumor types, is lower for those who live in residential radon activity concentrations of a level between 110 and 185 Bq x m-3 compared to those living in radon levels outside this range. A minimum value in the cancer frequency exists at a level of significance p<0.008 (determined with the help of Fisher's test). In general, the present study corroborates the outcome of other studies demonstrating the existence of a biopositive effect, and suggests a wider concept of radon health effects. (author)

  11. Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells

    Science.gov (United States)

    Deng, Senyi; Wu, Qinjie; Zhao, Yuwei; Zheng, Xin; Wu, Ni; Pang, Jing; Li, Xuejing; Bi, Cheng; Liu, Xinyu; Yang, Li; Liu, Lei; Su, Weijun; Wei, Yuquan; Gong, Changyang

    2015-03-01

    Circulating tumor cells (CTCs) play a crucial role in tumor metastasis, but it is rare for any chemotherapy regimen to focus on killing CTCs. Herein, we describe doxorubicin (Dox) micelles that showed anti-metastatic activity by killing CTCs. Dox micelles with a small particle size and high encapsulation efficiency were obtained using a pH-induced self-assembly method. Compared with free Dox, Dox micelles exhibited improved cytotoxicity, apoptosis induction, and cellular uptake. In addition, Dox micelles showed a sustained release behavior in vitro, and in a transgenic zebrafish model, Dox micelles exhibited a longer circulation time and lower extravasation from blood vessels into surrounding tissues. Anti-tumor and anti-metastatic activities of Dox micelles were investigated in transgenic zebrafish and mouse models. In transgenic zebrafish, Dox micelles inhibited tumor growth and prolonged the survival of tumor-bearing zebrafish. Furthermore, Dox micelles suppressed tumor metastasis by killing CTCs. In addition, improved anti-tumor and anti-metastatic activities were also confirmed in mouse tumor models, where immunofluorescent staining of tumors indicated that Dox micelles induced more apoptosis and showed fewer proliferation-positive cells. There were decreased side effects in transgenic zebrafish and mice after administration of Dox micelles. In conclusion, Dox micelles showed stronger anti-tumor and anti-metastatic activities and decreased side effects both in vitro and in vivo, which may have potential applications in cancer therapy.

  12. Synergistic antitumor effect of TRATL and doxorubicin on colon cancer cell line SW480

    Institute of Scientific and Technical Information of China (English)

    Li-Hong Xu; Chang-Sheng Deng; You-Qing Zhu; Shi-Quan Liu; Dong-Zhou Liu

    2003-01-01

    AIM: TRAIL (tumor necrosis factor-related apoptosisinducing ligand) has been reported to specifically induce apoptosis of cancer cells although only a small percentage of cell lines were sensitive to it. Cell lines not responding to TRAIL in vitro were said to be more prone to apoptosis when TRAIL was combined with another anticancer agent.Generally, factors affecting drug-sensitivity involve many apoptosis-related proteins, including p53. The expression of wild-type p53 gene was proposed as an important premise for tumor cells responding to chemotherapy. The present study was to investigate the cell killing action of TRAIL on colon cancer cell line SW480, its synergistic effect with doxorubicin, and the possible mechanisms. METHODS: SW480 cells were cultured in the regular condition and incubated with different levels of agents.Morphologic changes in these cells after treatment were observed under phase-contrast microscope and cytotoxicity by TRAIL alone and in combination with doxorubicin was quantified by a 1-day microculture tetrazolium dye (MTT)assay. In addition, flow cytometry assay (FCM) and transmission electron microscopy were used to detectapoptosis among these cells. Variation of p53 protein level among different groups according to concentrations of agents was measured by Western blot assay.RESULTS: (1) SW480 cells were not sensitive to TRAIL,with IC50>1 mg@L1 and dose-independent cytotoxicity. (2)SW480 cells were sensitive to doxorubicin at a certain degree,with dose-dependent cytotoxicity and IC50=65.25+3.48μmol@L-1. (3) TRAIL could synergize with doxorubicin to kill SW480 cells effectively, which was represented by the boosted killing effect of doxorubicin on theses cells. IC50 of doxorubicin against SW480 cells sharply reduced when it was combined with TRAIL. (4) Subtoxic TRAIL (100 μg.L-1),combined with subtoxic doxorubicin (0.86 μmol@L1), could kill SW480 cells sufficiently. Cytotoxicity by MTT assay arrived at 80.12+2.67%, which was

  13. Tobacco and Cancer

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  14. Effects of capsid-modified oncolytic adenoviruses and their combinations with gemcitabine or silica gel on pancreatic cancer.

    Science.gov (United States)

    Kangasniemi, Lotta; Parviainen, Suvi; Pisto, Tommi; Koskinen, Mika; Jokinen, Mika; Kiviluoto, Tuula; Cerullo, Vincenzo; Jalonen, Harry; Koski, Anniina; Kangasniemi, Anna; Kanerva, Anna; Pesonen, Sari; Hemminki, Akseli

    2012-07-01

    Conventional cancer treatments often have little impact on the course of advanced pancreatic cancer. Although cancer gene therapy with adenoviruses is a promising developmental approach, the primary receptor is poorly expressed in pancreatic cancers which might compromise efficacy and thus targeting to other receptors could be beneficial. Extended stealth delivery, combination with standard chemotherapy or circumvention of host antiadenoviral immune response might improve efficacy further. In this work, capsid-modified adenoviruses were studied for transduction of cell lines and clinical normal and tumor tissue samples. The respective oncolytic viruses were tested for oncolytic activity in vitro and in vivo. Survival was studied in a peritoneally disseminated pancreas cancer model, with or without concurrent gemcitabine while silica implants were utilized for extended intraperitoneal virus delivery. Immunocompetent mice and Syrian hamsters were used to study the effect of silica mediated delivery on antiviral immune responses and subsequent in vivo gene delivery. Capsid modifications selectively enhanced gene transfer to malignant pancreatic cancer cell lines and clinical samples. The respective oncolytic viruses resulted in increased cell killing in vitro, which translated into a survival benefit in mice. Early proinfammatory cytokine responses and formation of antiviral neutralizing antibodies was partially avoided with silica implants. The implant also shielded the virus from pre-existing neutralizing antibodies, while increasing the pancreas/liver gene delivery ratio six-fold. In conclusion, capsid modified adenoviruses would be useful for testing in pancreatic cancer trials. Silica implants might increase the safety and efficacy of the approach.

  15. Intracellular effects of atmospheric-pressure plasmas on melanoma cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ishaq, M., E-mail: ishaqmusarat@gmail.com [Peter MacCallum Cancer Centre, East Melbourne, VIC 3002 (Australia); Comonwealth Scientific and Industrial Research Organization, Sydney, New South Wales (Australia); Bazaka, K. [Institute for Health and Biomedical Innovation, School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD 4000 (Australia); Ostrikov, K. [Comonwealth Scientific and Industrial Research Organization, Sydney, New South Wales (Australia); Institute for Health and Biomedical Innovation, School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD 4000 (Australia)

    2015-12-15

    Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown as a promising tool for cancer treatment. The mechanism of the plasma action is attributed to generation of reactive oxygen and nitrogen species, electric fields, charges, and photons. The relative importance of different modes of action of atmospheric-pressure plasmas depends on the process parameters and specific treatment objects. Hence, an in-depth understanding of biological mechanisms that underpin plasma-induced death in cancer cells is required to optimise plasma processing conditions. Here, the intracellular factors involved in the observed anti-cancer activity in melanoma Mel007 cells are studied, focusing on the effect of the plasma treatment dose on the expression of tumour suppressor protein TP73. Over-expression of TP73 causes cell growth arrest and/or apoptosis, and hence can potentially be targeted to enhance killing efficacy and selectivity of the plasma treatment. It is shown that the plasma treatment induces dose-dependent up-regulation of TP73 gene expression, resulting in significantly elevated levels of TP73 RNA and protein in plasma-treated melanoma cells. Silencing of TP73 expression by means of RNA interference inhibited the anticancer effects of the plasma, similar to the effect of caspase inhibitor z-VAD or ROS scavenger N-acetyl cysteine. These results confirm the role of TP73 protein in dose-dependent regulation of anticancer activity of atmospheric-pressure plasmas.

  16. Intracellular effects of atmospheric-pressure plasmas on melanoma cancer cells

    Science.gov (United States)

    Ishaq, M.; Bazaka, K.; Ostrikov, K.

    2015-12-01

    Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown as a promising tool for cancer treatment. The mechanism of the plasma action is attributed to generation of reactive oxygen and nitrogen species, electric fields, charges, and photons. The relative importance of different modes of action of atmospheric-pressure plasmas depends on the process parameters and specific treatment objects. Hence, an in-depth understanding of biological mechanisms that underpin plasma-induced death in cancer cells is required to optimise plasma processing conditions. Here, the intracellular factors involved in the observed anti-cancer activity in melanoma Mel007 cells are studied, focusing on the effect of the plasma treatment dose on the expression of tumour suppressor protein TP73. Over-expression of TP73 causes cell growth arrest and/or apoptosis, and hence can potentially be targeted to enhance killing efficacy and selectivity of the plasma treatment. It is shown that the plasma treatment induces dose-dependent up-regulation of TP73 gene expression, resulting in significantly elevated levels of TP73 RNA and protein in plasma-treated melanoma cells. Silencing of TP73 expression by means of RNA interference inhibited the anticancer effects of the plasma, similar to the effect of caspase inhibitor z-VAD or ROS scavenger N-acetyl cysteine. These results confirm the role of TP73 protein in dose-dependent regulation of anticancer activity of atmospheric-pressure plasmas.

  17. Thermoradiotheraphy of cancer: an effective approach

    Directory of Open Access Journals (Sweden)

    Gerard C. van Rhoon

    2009-12-01

    Full Text Available Hyperthermia (HT means using controlled temperatures of 40-45°C for cancer treatment. HT is applied with differentmethods e.g. superficial-HT, locoregional deep-HT, interstitial-HT, intracavity-HT, and whole body-HT. HT can apply indifferent tumor sites such as breast cancer, melanoma, head and neck, cervix cancer, and glioblastoma. The Literature suggests that addition of HT to radiotherapy, chemotherapy, or both, will result better tumor response rate, local control, and survival rate; without increasing toxicity. HT can also improve palliative effects in patient. In recent years, due to substantial technical improvements made in achieving selected increaseof temperatures in superficial and deep-seated tumors,thermometry, and treatment planning; HT is becoming moreclinically accepted in Europe and the USA. HT, as an adjunctcancer treatment modality, is certainly a promising approach;however, it is not well known yet worldwide. Therefore, itseems there is need to know more about that. The purpose of this review is to provide an overview on the application of HT combined with conventional cancer treatment modalities,mainly radiotherapy. The article also introduces mechanism of HT, heating delivery modes, thermometry, and it summarizes results of randomized trials from Western research groups.

  18. Mechanistic Effects of Calcitriol in Cancer Biology

    Directory of Open Access Journals (Sweden)

    Lorenza Díaz

    2015-06-01

    Full Text Available Besides its classical biological effects on calcium and phosphorus homeostasis, calcitriol, the active vitamin D metabolite, has a broad variety of actions including anticancer effects that are mediated either transcriptionally and/or via non-genomic pathways. In the context of cancer, calcitriol regulates the cell cycle, induces apoptosis, promotes cell differentiation and acts as anti-inflammatory factor within the tumor microenvironment. In this review, we address the different mechanisms of action involved in the antineoplastic effects of calcitriol.

  19. Mechanisms of Enhanced Cell Killing at Low Doses: Implications for Radiation Risk

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Peter J. Johnston; Dr. George D. Wilson

    2003-10-15

    We have shown that cell lethality actually measured after exposure to low-doses of low-LET radiation, is markedly enhanced relative to the cell lethality previously expected by extrapolation of the high-dose cell-killing response. Net cancer risk is a balance between cell transformation and cell kill and such enhanced lethality may more than compensate for transformation at low radiation doses over a least the first 10 cGy of low-LET exposure. This would lead to a non-linear, threshold, dose-risk relationship. Therefore our data imply the possibility that the adverse effects of small radiation doses (<10 cGy) could be overestimated in specific cases. It is now important to research the mechanisms underlying the phenomenon of low-dose hypersensitivity to cell killing, in order to determine whether this can be generalized to safely allow an increase in radiation exposure limits. This would have major cost-reduction implications for the whole EM program.

  20. Cancer survivorship: A positive side-effect of more successful cancer treatment

    OpenAIRE

    Elizabeth Charlotte Moser; Françoise Meunier

    2014-01-01

    Over the past decades, early diagnosis, new drugs and more personalised multi-modality treatment have led to impressive increases in survival rates of patients with cancer. This success in treating cancer has resulted in a large and rapidly increasing number of cancer survivors, yet life after cancer is often compromised by a broad spectrum of late adverse treatment effects. Some encounter cardiovascular, second malignancies, cognitive or other morbidities which impair normal life in an impor...

  1. The Effect of Thermal Double Distilled Water on Gastric Cancer Cell Line and Its Effect in Peritoneal Lavage During Radical Gastrectomy

    Institute of Scientific and Technical Information of China (English)

    CHENJunqing; XUHuimian; 等

    2002-01-01

    Objective:To evaluate the effect andindications of radical gastrectomy combined with peritoneal lavage with thermal double distilled water(DDW)or DDW plus chlorthexidine acetate.Methods:On the bases of the study on the killing effect of 43℃ DDW on human gastric cancer cell line MGC-803 and its inhibiting effect on ascitic tumor of SY86B morse,500 cases of gastric cancer who underwent radical gastectomy from January 1986 to December 1995 were divided into three groups:group A(n=198) subject to radical gastrectomy and peritoneal lavage for 10min with 4000ml DDW at 43℃ ;group B(n=89)subject to radical gastrectomy and peritoneal lavage for 4min with 4000ml DDW plus 0.6g chlorthexidine acetate,and grup C(n=213) subject to radical gastrectomy and peritoneal lavage for 4 min with 4000ml normal saline at room temperature as control.Results Human gastric cancer cells MGC-803 could be completely killed by treatment of either 43℃ DDW for 10min or DDW plus 0.015ml/L chlorhexidine acetate for 4 min.Clinical trials proved group A and group B(called lavage group as a whole)had almost the same curative effects.The 1-year survival rate and 3-year survival rate were similar in different stages among the groups.The 5-year survival rate was 63.8% in the lavage group and 51.2% in the control group respectively.Most of the cases with good effect were at the mid-stage (Ⅱand Ⅲ stage).Conclusion Radical gastrectom combined with peritoneal peritoneal lavage before closing the abdomen has satisfying effect on patients with gastric cancer at stage Ⅱ and stage ⅢA.

  2. Prevention of cancer and the dose-effect relationship: the carcinogenic effects of ionizing radiations

    International Nuclear Information System (INIS)

    seldom occur. Promoting factors are agents that either perturb intercellular signalling or stimulate cell proliferation (e.g. hormones) or increase cell mortality: mechanical or chemical irritation (e.g. alcohol, bacteria, viruses) thereby inducing compensatory cell proliferation. Thus, gradually pre-cancerous cells become able to divide more rapidly with greater autonomy. This phase ends when a sub clone of cells has acquired the capacity of autonomous proliferation. The third phase is that of progression during which cells proliferate regularly without any stimulation. In one of the cells of one of the pre-cancerous lesions (e.g. polyps) a cell acquires the capacity of invading surrounding tissue or to metastasize. The whole carcinogenic process is very slow, extending over several decades, because the specific mutations seldom occur and the probability of an accumulation of several specific mutations in the same cell or cell lineage is very small. It can be accelerated by intense stimulation of cell proliferation or genetic instability. Ionizing radiations act firstly as a mutagen, however when the dose is high they also kill a significant proportion of cells and by a homeostatic mechanism they induce cell proliferation and clonal amplification. It has been claimed that even the smallest dose of radiation can induce a cancer. This concept is associated with the L.N.T. model and it is not based on scientific evidence. It has fuelled a fear of radiation which had detrimental consequences. Conversely the high efficacy of defense mechanisms against radio carcinogenesis, particularly when the tissue is not disorganized, can explain the lack of carcinogenic effect of contamination by small doses of radium or thorium which has been observed on radium dial painters or in patients injected with thorotrast. The study of second cancers in patients treated by radiotherapy could provide important information and should be actively pursued with two aims: reduce the incidence of

  3. Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

    Science.gov (United States)

    K. S., Uma Suganya; Govindaraju, K.; Ganesh Kumar, V.; Prabhu, D.; Arulvasu, C.; Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan

    2016-05-01

    Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G0/G1 to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

  4. Barriers to overcome for effective cancer control in Africa.

    Science.gov (United States)

    Harford, Joe B

    2015-08-01

    Cancer control in Africa is complicated due to large differences in cancer incidence between countries caused by differences in exposure to known risk factors. For example, substantial differences are seen when selected cancers in north Africa are compared with those in sub-Saharan Africa. In the future, population growth and demographic shifts are likely to have profound effects on the prevalence of cancer across the continent. Likewise, many factors outside of health care such as language differences, conflict, and poverty can affect cancer control efforts. Although cooperation in cancer control efforts is desirable, differences in cultural and geopolitical factors that characterise African countries and their populations, together with the sheer size of the continent, present unique challenges to effective cancer control. This Series paper discusses factors related to the size, diversity, and conditions within Africa that present barriers to optimal collaboration in cancer control efforts across the continent. PMID:26248846

  5. Deprive to kill: glutamine closes the gate to anticancer monocarboxylic drugs.

    Science.gov (United States)

    Cardaci, Simone; Ciriolo, Maria Rosa

    2012-12-01

    Killing properties of antitumor drugs can be enhanced by strategies targeting biochemical adaptations of cancer cells. Recently, we reported that depriving cancer cells of glutamine is a feasible approach to enhance antitumor effects of the alkylating analog of pyruvic acid, 3-bromopyruvate, which rely on the induction of autophagic cell death by metabolic-oxidative stress. 3-bromopyruvate chemopotentiation is the result of its increased intracellular uptake mediated by the monocarboxylate transporter 1, whose expression is post-transcriptionally increased upon glutamine withdrawal. Overall, our results identified the metabolic condition able to increase the selectivity of 3-bromopyruvate targets in neoplastic tissues, thereby providing a stage for its use in clinical settings for targeting malignancies and represent a proof of principle that modulation of glutamine availability can influence the delivery of monocarboxylic drugs into tumors. PMID:22932475

  6. How Ixtoc 1 was killed

    Energy Technology Data Exchange (ETDEWEB)

    1980-04-01

    More than nine months after it erupted 6/3/79, Petroleos Mexicanos' Ixtoc 1 blowout in Campeche Bay was killed with three cement plugs having a total length of 2885 ft. After drilling of relief wells, 200 sacks of cement were used to form the 685 ft. long bottom plug. After inserting an interval of mud, an additional 200 sacks of cement were pumped down to form a 550 ft. plug. The final up-hole plug was formed by 500 sacks of quick-setting cement, which formed a 1650 ft. long plug.

  7. Killing(-Yano) Tensors in String Theory

    CERN Document Server

    Chervonyi, Yuri

    2015-01-01

    We construct the Killing(-Yano) tensors for a large class of charged black holes in higher dimensions and study general properties of such tensors, in particular, their behavior under string dualities. Killing(-Yano) tensors encode the symmetries beyond isometries, which lead to insights into dynamics of particles and fields on a given geometry by providing a set of conserved quantities. By analyzing the eigenvalues of the Killing tensor, we provide a prescription for constructing several conserved quantities starting from a single object, and we demonstrate that Killing tensors in higher dimensions are always associated with ellipsoidal coordinates. We also determine the transformations of the Killing(-Yano) tensors under string dualities, and find the unique modification of the Killing-Yano equation consistent with these symmetries. These results are used to construct the explicit form of the Killing(-Yano) tensors for the Myers-Perry black hole in arbitrary number of dimensions and for its charged version.

  8. Effects of Prostate Cancer Screening and Treatment

    NARCIS (Netherlands)

    E.M. Wever (Elisabeth)

    2012-01-01

    textabstractProstate cancer is the second most frequently diagnosed cancer of men worldwide. The number of new cases worldwide was estimated at 899,000 and accounted for 13.6% of all cancers in men in 2008. With an estimated 258,000 deaths in 2008, prostate cancer is the sixth leading cause of death

  9. Effects of Recombinant Erythropoietin on Breast Cancer-Initiating Cells

    OpenAIRE

    Tiffany M. Phillips; Kwanghee Kim; Erina Vlashi; McBride, William H.; Frank Pajonk

    2007-01-01

    BACKGROUND: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs). In breast can...

  10. Effectiveness of pranayama on cancer-related fatigue in breast cancer patients undergoing radiation therapy: A randomized controlled trial

    OpenAIRE

    Jyothi Chakrabarty; M S Vidyasagar; Donald Fernandes; Ganapathi Joisa; Prabha Varghese; Sreemathi Mayya

    2015-01-01

    Context: Incidence of breast cancer is very high among women around the world. Breast cancer patients experience cancer-related fatigue at some points during the treatment for breast cancer. Since cancer-related fatigue is of multifactorial origin, there are no evidence-based treatment strategies for fatigue. This study tested the effectiveness of certain pranayama techniques in reducing cancer-related fatigue among breast cancer patients undergoing radiation therapy. Aims: The objective of t...

  11. Cancer stage, comorbidity, and socioeconomic differences in the effect of cancer on labour market participation

    DEFF Research Database (Denmark)

    Thielen, Karsten; Kolodziejczyk, Christophe; Andersen, Ingelise;

    2015-01-01

    Registry to follow 7372 women aged 30-60, who were in the labour force when diagnosed with breast cancer in 2000-06 and survived at least three years. Controls were 213,276 women without breast cancer. Inequalities in employment outlook were estimated as interaction effects in linear regression between...... educational attainment and disease on employment. RESULTS: There is significant interaction between education and breast cancer, but it is only marginally affected by including stage and comorbidity in the regression models. Education, breast cancer stage, and comorbidity all have strong effects on later...... employment, and a considerable amount of the educational effect is mediated by comorbidity and pre-cancer labour market participation and income. CONCLUSION: The result of the study is negative in the sense that the stronger effect of breast cancer on employment among low-educated compared to highly educated...

  12. Killing effect of pyrethroid aerosol compounds for mosquitoes, flies and cockroaches%油基拟除虫菊酯复配气雾剂实验室杀虫效果观察

    Institute of Scientific and Technical Information of China (English)

    谭伟龙; 艾乐乐; 钱万红; 陈超

    2012-01-01

    目的 筛选几种油基拟除虫菊酯复配气雾剂,在实验室观察其对淡色库蚊、家蝇和德国小蠊的杀灭效果.方法 根据GB/T 13917.2-2009,用圆筒法测定气雾杀虫剂对3种昆虫的半数击倒时间(KT50),根据GB/T13917.10-2009,测试模拟现场实验效果.结果 对淡色库蚊的杀灭实验中,1号和3号配方的KT50均<1 min,其他2种配方均<2min;对家蝇的杀灭实验中,3号配方的击倒时间最短,为0.90 min,其他3种配方均<2 min;对德国小蠊的杀灭实验中,KT50值均<1 min;3种试虫的24 h死亡率均为100%.模拟现场实验中,4种配方对3种试虫的1h击倒率和24 h死亡率均为100%.结论 4种复配杀虫剂配方均达到了快速杀灭蚊、蝇和蜚蠊的效果,可以进入下一步实验.%Objective To identify efficacy of pyrethroid aerosol insecticides in killing Culex pipiens pallens, Musca domestica and Blattella germanica. Methods KT50 is one of four kinds of aerosol insecticides on three types of insects were tested according to GB/T 13917.2 - 2009 in hermetic round canister. Killing efficacy in simulated fields was tested according to GB/T 13917.10-2009. Results The KT50 values of four kinds of aerosol insecticides were less than 2 minutes for Cx. Pipiens pallens and M. domestica, and less than 1 minute for B. germanica. The 24 h-mortality of insects used in the hermetic round canister was 100%. The one -hour killing efficacy of the four aerosol insecticides in simulated fields for Cx. Pipiens pallens, M. domestica and B. germanica was 100%. Conclusion The four aerosol insecticides all showed fast killing effects for Cx. Pipiens pallens, M. domestica and B. germanica.

  13. Cancer stage, comorbidity, and socioeconomic differences in the effect of cancer on labour market participation

    DEFF Research Database (Denmark)

    Thielen, Karsten; Kolodziejczyk, Christophe; Andersen, Ingelise;

    2015-01-01

    Registry to follow 7372 women aged 30-60, who were in the labour force when diagnosed with breast cancer in 2000-06 and survived at least three years. Controls were 213,276 women without breast cancer. Inequalities in employment outlook were estimated as interaction effects in linear regression between...... employment, and a considerable amount of the educational effect is mediated by comorbidity and pre-cancer labour market participation and income. CONCLUSION: The result of the study is negative in the sense that the stronger effect of breast cancer on employment among low-educated compared to highly educated...

  14. M-Cell Targeting of Whole Killed Bacteria Induces Protective Immunity against Gastrointestinal Pathogens▿

    OpenAIRE

    Chionh, Yok-Teng; Wee, Janet L. K.; Every, Alison L.; Ng, Garrett Z.; Sutton, Philip

    2009-01-01

    As the majority of human pathogens infect via a mucosal surface, delivery of killed vaccines by mucosal routes could potentially improve protection against many such organisms. Our ability to develop effective killed mucosal vaccines is inhibited by a lack of adjuvants that are safe and effective in humans. The Ulex europaeus agglutinin I (UEA-I) lectin specifically binds M cells lining the murine gastrointestinal tract. We explored the potential for M-cell-targeted vaccination of whole, kill...

  15. Modeling the Effects of Vorinostat In Vivo Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells.

    Science.gov (United States)

    Ke, Ruian; Lewin, Sharon R; Elliott, Julian H; Perelson, Alan S

    2015-10-01

    Recent efforts to cure human immunodeficiency virus type-1 (HIV-1) infection have focused on developing latency reversing agents as a first step to eradicate the latent reservoir. The histone deacetylase inhibitor, vorinostat, has been shown to activate HIV RNA transcription in CD4+ T-cells and alter host cell gene transcription in HIV-infected individuals on antiretroviral therapy. In order to understand how latently infected cells respond dynamically to vorinostat treatment and determine the impact of vorinostat on reservoir size in vivo, we have constructed viral dynamic models of latency that incorporate vorinostat treatment. We fitted these models to data collected from a recent clinical trial in which vorinostat was administered daily for 14 days to HIV-infected individuals on suppressive ART. The results show that HIV transcription is increased transiently during the first few hours or days of treatment and that there is a delay before a sustained increase of HIV transcription, whose duration varies among study participants and may depend on the long term impact of vorinostat on host gene expression. Parameter estimation suggests that in latently infected cells, HIV transcription induced by vorinostat occurs at lower levels than in productively infected cells. Furthermore, the estimated loss rate of transcriptionally induced cells remains close to baseline in most study participants, suggesting vorinostat treatment does not induce latently infected cell killing and thus reduce the latent reservoir in vivo.

  16. Effect of slag composition on the kinetics of formation of Al{sub 2}O{sub 3}-MgO inclusions in aluminium killed ferritic stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Okuyama, G.

    2000-02-01

    Kinetics of both slag/metal reactions and metal/inclusion reactions were investigated experimentally using 20kg vacuum induction furnace in order to clarify the mechanism of the formation of MgAl{sub 2}O{sub 4} spinel inclusions in aluminum killed ferritic stainless steel (SUS430). The results obtained are summarized as follows: (1) By reducing CaO/SiO{sub 2} and CaO/Al{sub 2}O{sub 3} ratio of top slag, MgO contents in Al{sub 2}O{sub 3} based inclusions decreased. (2) The two film theory was employed to analyze the rate determining step of slag/metal reaction (reduction of MgO in top slag). By this model, it was found that the rate determining step of the reaction was the mass transfer of Mg through the film in molten steel. The increase rate of Mg in molten steel is determined by the activities of soluble oxygen and MgO at the slag/metal interface, and hence by slag composition. (3) The unreacted core model was employed to analyze the rate determining step of metal/inclusions reaction. The analysis showed that the rate determining step of the reaction in the case of 20 kg vacuum induction furnace was the diffusion of Mg in molten steel. (author)

  17. Tumor cell-specific photothermal killing by SELEX-derived DNA aptamer-targeted gold nanorods

    Science.gov (United States)

    Chandrasekaran, Ramya; Lee, Alexander Sheng Wei; Yap, Lim Wei; Jans, David A.; Wagstaff, Kylie M.; Cheng, Wenlong

    2015-12-01

    Despite widespread availability of cytotoxic chemotherapeutic agents, the killing of tumour cells without affecting healthy surrounding tissue remains elusive, although recent developments in terms of plasmonic nanoparticles capable of photothermal killing have some promise. Here we describe novel DNA aptamer-tethered gold nanorods (GNRs) that act as efficient photothermal therapeutics against tumour cells, but not their isogenic normal cell counterparts. A modified Cell-SELEX process was developed to select a novel DNA aptamer (KW16-13) that specifically recognised and was internalised by cells of the MCF10CA1h human breast ductal carcinoma line but not by those of its isogenic normal counterpart (MCF10A). GNRs conjugated to KW16-13 were readily internalized by the MCF10CA1h tumour cells with minimal uptake by MCF10A normal cells. Upon near infrared (NIR) light irradiation, tumour cell death of >96%, could be effected, compared to 71-fold tumor cell death than GNRs-targeted with a previously described aptamer. This demonstrates the significant potential for aptamer functionalised-GNRs to be used effective and above all selective anti-cancer photothermal therapeutics.Despite widespread availability of cytotoxic chemotherapeutic agents, the killing of tumour cells without affecting healthy surrounding tissue remains elusive, although recent developments in terms of plasmonic nanoparticles capable of photothermal killing have some promise. Here we describe novel DNA aptamer-tethered gold nanorods (GNRs) that act as efficient photothermal therapeutics against tumour cells, but not their isogenic normal cell counterparts. A modified Cell-SELEX process was developed to select a novel DNA aptamer (KW16-13) that specifically recognised and was internalised by cells of the MCF10CA1h human breast ductal carcinoma line but not by those of its isogenic normal counterpart (MCF10A). GNRs conjugated to KW16-13 were readily internalized by the MCF10CA1h tumour cells with minimal

  18. 戊二醛癸甲溴铵溶液对HP-PRRSV体外杀灭效果测定%Killing Effect Determination of Glutaral and Deciquam Solution to High Pathogenic Porcinereproductive and Respiratory Syndrome Viruse(PRRSV)in Vitro

    Institute of Scientific and Technical Information of China (English)

    李云; 贾伟新

    2014-01-01

    In view of high pathogenic porcinereproductive and respiratory syndrome viruse(PRRSV), Key Lab-oratory of Animal Disease Control and Prevention of Ministry of Agriculture used glutaral and deciquam solution to test the killing effect in vitro. The result showed the concentration of glutaral and deciquam solution higher than or equal to 0.01%could completely kill the PRRSV in vitro. According to the result, the recommended con-centration of this solution for PRRSV is 0.01%, namely 1:10000 dilution. Higher concentration would be neces-sary according to different conditions.%针对高致病性蓝耳病病毒(PRRSV),农业部动物疫病防控重点开放实验室用戊二醛癸甲溴铵溶液对其进行了体外杀灭效果试验,结果显示大于或等于0.01%浓度的戊二醛癸甲溴铵溶液可体外完全杀灭PRRSV。根据结果建议该消毒剂对PRRSV临床使用浓度为≥0.01%,即1:10000稀释,但同时也要根据具体情况具体分析,适当提高使用浓度。

  19. Killing effects of garlic on the isolated encysted metacercaria of Paragonimus westermani%大蒜对离体卫氏并殖吸虫囊蚴杀灭作用的研究

    Institute of Scientific and Technical Information of China (English)

    倪李佳; 刘洁; 沈浩贤; 陆予云; 黄子然; 何宇巍; 吕威

    2012-01-01

    Objective The research is aimed to evaluate the killing effects of garlic on the isolated encysted metacercaria of Paragonimus westermani, and provide scientific basis and suggestions for Wei's paragonimiasis prevention. Methods Encysted metacercarias of Paragonimus westermani were collected from Sinopotamon pinheense by artificial digestion method. The encysted metacercarias were divided into various groups with 10 metacercarias per group, and were immersed into garJie juice (22 to 23^) for different periods of time. The effect of garlic on the worm activities was then evaluated under a microscope. Results Enhanced activities of metacercaria were observed in the first 1 to 8 minutes immersion with garlic. Metacercarias became less active between 9 to 20 minutes and some started dying when immersion time rose to 25 minutes with 6.67% rate of death. The death rate increased to 41.33% and 91.67% respectively when the time was between 30 to 100 and between 120 to 140 minutes. All metacercarias were killed at 180 to 210 minutes. Morphological alteration and activity of the encysted metacercarias were not changed in the control group. Conclusions Although garlic is low-grade killing effect to encysted metacercarias, it can not kill the metacercarias within a shot time. It is not advisable to kill encysted metacercarias by garlic for the purpose of preventing infection.%目的 研究大蒜对离体卫氏并殖吸虫囊蚴的杀灭作用,为预防卫氏并殖吸虫病提供科学依据和建议.方法 采用人工消化法从平和华溪蟹中获取卫氏并殖吸虫囊蚴,设30个时间段,每个时间段做3组平行实验,共90组,每组10个囊蚴,将囊蚴置于定量大蒜原汁中,在22~23℃下,分别作用不同时间,显微镜下观察囊蚴的活动情况.结果 大蒜原汁对卫氏并殖吸虫囊蚴作用1~8 min,囊蚴内后尾蚴活动增强;作用9~20 min,后尾蚴活动力降低.作用25 min,囊蚴开始死亡,死亡率为6 67%;作用30~100

  20. Cooperative Therapeutic Effects of Herpes Simplex Virus Thymidine Kinase Gene/Ganciclovir System and Chemotherapeutic Agents on Prostate Cancer in vitro

    Institute of Scientific and Technical Information of China (English)

    XING Yifei; XIAO Yajun; LU Gongcheng; ZENG Fuqing; ZHAO Jun; XIONG Ping; FENG Wei

    2006-01-01

    The killing effects of herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) approach by the addition of several commonly clinical chemotherapeutic agents on hormone refractory prostate cancer (HRPC) cells PC-3m were investigated. After transferring of the HSV-tk gene into PC-3m cells, mRNA and protein expression of HSV-tk was detected by reverse-transcript polymerase chain reaction (RT-PCR) and strept avidin-biotin complex (SABC) immunohistochemical method. The killing effect of GCV, cisplatin (CDDP), etoposide (VP-16), vincristine (VCR), methotrexate (MTX), 5-fluorouracil (5-Fu), and suramin on PC-3m cells was evaluated by morphological assessment analysis, trypan blue exclusion assay and MTT assay respectively. Additionally, the cooperative effect of HSV-tk/GCV system combined with the above agents on the target cancer cells was determined by MTT. Furthermore, apoptosis and necrosis induced by GCV plus 5-Fu or suramin was analyzed by flow cytometry (FCM). The results showed that that there was HSV-tk mRNA and protein expression in pDR2-tk plasmid transduced PC-3m cell. Combination of GCV with VP-16, VCR, 5-Fu or suramin led to an enhanced cellular killing effect, but with CDDP resulted in a reduced one and with MTX in an approximate one. FCM revealed that synergistic use of GCV and 5-fu or suramin resulted in a rather large proportion of apoptosis and necrosis with the apoptosis index being 36.38 % and 35.51%, and the proportion of necrosis being 33.05 % and 28.87 %, respectively. In conclusion, HSV-tk/CGV approach by addition of certain clinical available chemotherapeutic drugs brings on statistically significant enhanced cell killing over single-agent treatment.Our results highlight the potential for such new combination therapies for future treatments of HRPC.

  1. Adenovirus-mediated and tumor-specific transgene expression of the sodium-iodide symporter from the human telomerase reverse transcriptase promoter enhances killing of lung cancer cell line in vitro

    Institute of Scientific and Technical Information of China (English)

    SHI Yi-zhen; ZHANG Jun; LIU Zeng-li; DU Shou-ying; SHEN Yong-mei

    2010-01-01

    Background The sodium-iodide symporter (NIS) protein can mediate the active radioiodine uptake.The human telomerase reverse transcriptase (hTERT) promoter is known to be selectively reactivated in majority of tumors and hence could be used for tumor targeting.We constructed a recombinant adenovirus containing the human sodium iodide symporter (hNIS) gene directed by the hTERT promoter, characterized the ability of infected cells in uptaking iodide, and explored the therapeutic efficacy of 131I in a lung cancer cell line in vitro.Methods The hTERT promoter was amplified by PCR from DNA isolated from log-phase HepG2 cells, subcloned into lineralized FL*-hNIS/pcDNA3, and then the hTERT-hNIS sequence was subcloned into the shuttle plasmid pAdTrack.The recombinant adenovirus Ad-hTERT-hNIS was constructed by AdEasy system.A positive control adenovirusAd-CMV-hNIS and a negative control adenovirus Ad-CMV were created similarly.A549 cells were transduced with recombinant adenoviruses.125I uptake studies and sodium perchlorate suppression studies were used to confirm hNIS expression and function.Toxic effects of 131I on tumor cells were studied by in vitro clonogenic assay.Results We first successfully constructed an adenovirus mediated transgene expression system of the hNIS under the control of hTERT promoter.When infected with recombinant adenovirus constructs expressing hNIS directed by hTERTand CMV-promoters (Ad-hTERT-hNIS and Ad-CMV-hNIS, respectively), the lung cancer cell line A549 had increased ability to uptake radioiodide up to 23- and 30- fold compared to the control parental cells, respectively.The radioiodide uptake ability of both the Ad-CMV-hNIS and Ad-hTERT-hNIS transduced cell lines were repressed 11-fold by sodium perchlorate (NaCIO4).The subsequent in vitro clonogenic assay of the infected A549 cell line was further repressed to 23% (Ad-CMV-hNIS) and 30% (Ad-hTERT-hNIS) of the control group after receiving radioiodide for 7 hours (P <0.001).Conclusion

  2. Observation on Ultraviolet Irradiation on Multi-drug Resistant Acinetobacter Baumannii in the Killing Effect under Different Humidity%紫外线对多药耐药鲍曼不动杆菌杀灭效果观察

    Institute of Scientific and Technical Information of China (English)

    王云凤; 刘奕

    2012-01-01

    Objective To investigate the killing effect of ultraviolet irradiation on multi-drug resistant Acinetobacter bauman-nii. Methods In the "dry" environment, Acinetobacter bauraannii was inoculated on nutrient agar medium with multi-drug resistant, and placed in UV lamp 0.6 m,l m,2 m,irradiation at different times to observe the killing effect. Results In the "dry" environmental conditions, Acinetobacter baumannii was exposured to UV lamp 0. 6 m for 8 min, the ultraviolet light 1 m,2 m light for 120 min and 30 min,poured nutrient agar,35 °C 48 h culture sterile growth;direct inoculation of bacteria in nutrient agar medium , ultraviolet light irradiation 49 min 0.6m sterile growth; ultraviolet light 1 m,2 m 30 min and 120 min, there existed bacteri-a growth. Conclusion In the "dry" environment,the conventional method of ultraviolet disinfection can kill multi-drug resistant Acinetobacter baumannii; in the humid environment, conventional UV disinfection methods can not completely kill multi-drug resistant Acinetobacter baumannii, even if the extension exposure time can not achieve the desired sterilization; only shorten the distance of irradiation and extend the time before UV irradiation can completely kill the bacteria.%目的 了解紫外线照射对多药耐药鲍曼不动杆菌的杀灭效果.方法 将“干燥”环境下和接种于营养琼脂培养基上的多药耐药鲍曼不动杆菌,分别置于紫外线灯下0.6m、1 m、2m,照射不同时间,观察杀灭效果.结果 在“干燥”环境条件下多药耐药鲍曼不动杆菌于紫外线灯下0.6m照射8 min,于紫外线灯下1 m、2 m照射120 min和30 min后,倾注营养琼脂,35℃培养48 h均无菌生长;细菌直接接种于营养琼脂培养基上,紫外线灯下0.6m照射49 min无菌生长;紫外线灯下1 m、2m照射30 min和120 min均有菌生长.结论 “干燥”环境下,常规的紫外线消毒方法可杀灭多药耐药鲍曼不动杆菌;高湿环境下,常规紫外线

  3. Efficient Kill-Save Ratios Ease Up the Cognitive Demands on Counterintuitive Moral Utilitarianism.

    Science.gov (United States)

    Trémolière, Bastien; Bonnefon, Jean-François

    2014-04-10

    The dual-process model of moral judgment postulates that utilitarian responses to moral dilemmas (e.g., accepting to kill one to save five) are demanding of cognitive resources. Here we show that utilitarian responses can become effortless, even when they involve to kill someone, as long as the kill-save ratio is efficient (e.g., 1 is killed to save 500). In Experiment 1, participants responded to moral dilemmas featuring different kill-save ratios under high or low cognitive load. In Experiments 2 and 3, participants responded at their own pace or under time pressure. Efficient kill-save ratios promoted utilitarian responding and neutered the effect of load or time pressure. We discuss whether this effect is more easily explained by a parallel-activation model or by a default-interventionist model.

  4. Fish Kills in Ireland in 1990

    OpenAIRE

    Moriarty, C.

    1991-01-01

    The total of 52 fish kills in 1990 was a marked improvement over the previous year when 111 were reported. Although this result was no better than that for 1988, it represented a considerable achievement because 1988 experienced a wet summer with high water flows while 1990 was exceptionally dry. Because of the poor dilution of pollutants, low river flows are usually associated with an increase in the number of fish kills. All three traditional causes of fish kills, agriculture, industry a...

  5. Immune Killing Activity of Lymphocytes on Hela Cells Expressing Interleukin-12 In Vitro

    Institute of Scientific and Technical Information of China (English)

    Huiyan WANG; Suhua CHEN

    2008-01-01

    The killing effects of lymphocytes on Hela cells expressing intedeukin-12 (IL-12) in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression of IL-12 in Hela cells was detected quantitatively by ELISA; Changes in killing effects of lymphocytes on Hela cells expressing IL-12 were observed by MTT. It was found that Hela cells could express IL-12 between 24h and 72h after transfection. Killing activity of lymphocytes on Hela cells expressing IL-12 was significantly enhanced. It was concluded by cell transfection technique, Hela cells could express IL-12 and were more easily killed by lymphocytes.

  6. Effect of chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy on patients’ prognosis

    Institute of Scientific and Technical Information of China (English)

    Xin-Cheng Shu; Ping Gao; Xin-Jua Zuo

    2016-01-01

    Objective:To study the effect of chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy on patients' prognosis.Methods:A total of78 cases of patients with colon cancer who received radical surgery of colon cancer assisted by postoperative chemotherapy in our hospital from May 2012 to December 2014 were selected for treatment and randomly divided into two groups, combined treatment group received chemotherapy combined with cascade primed immune cell therapy, simple chemotherapy group received FOLFOX chemotherapy, and then serum tumor marker contents and angiogenesis molecule contents as well as red blood cell immune function indicators in peripheral blood were detected.Results:Serum tumor markers CCSA-2, CCSA-3, CCSA-4, PTN, NGAL and sMICA as well as angiogenesis molecules VEGF, FGF10, sICAM-1, sVCAM-1, Musashi1 and Dkk1 contents of combined treatment group were lower than those of conventional chemotherapy group; the proportion of CR1, CR3, CD58 and CD59 as well as the rosette formation rates of red blood cell C3b receptor and immune complex in peripheral blood of combined treatment group were significantly higher than those of conventional chemotherapy group.Conclusions:Chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy helps to kill tumor cells and inhibit angiogenesis while enhance red blood cell immune function, and it can improve the prognosis of radical surgery of colon cancer.

  7. The antioxidant, MnTE-2-PyP, prevents side-effects incurred by prostate cancer irradiation.

    Directory of Open Access Journals (Sweden)

    Rebecca E Oberley-Deegan

    Full Text Available Prostate cancer is the most commonly diagnosed cancer, with an estimated 240,000 new cases reported annually in the United States. Due to early detection and advances in therapies, more than 90% of patients will survive 10 years post diagnosis and treatment. Radiation is a treatment option often used to treat localized disease; however, while radiation is very effective at killing tumor cells, normal tissues are damaged as well. Potential side-effects due to prostate cancer-related radiation therapy include bowel inflammation, erectile dysfunction, urethral stricture, rectal bleeding and incontinence. Currently, radiation therapy for prostate cancer does not include the administration of therapeutic agents to reduce these side effects and protect normal tissues from radiation-induced damage. In the current study, we show that the small molecular weight antioxidant, MnTE-2-PyP, protects normal tissues from radiation-induced damage in the lower abdomen in rats. Specifically, MnTE-2-PyP protected skin, prostate, and testes from radiation-induced damage. MnTE-2-PyP also protected from erectile dysfunction, a persistent problem regardless of the type of radiation techniques used because the penile neurovascular bundles lay in the peripheral zones of the prostate, where most prostate cancers reside. Based on previous studies showing that MnTE-2-PyP, in combination with radiation, further reduces subcutaneous tumor growth, we believe that MnTE-2-PyP represents an excellent radioprotectant in combination radiotherapy for cancer in general and specifically for prostate cancer.

  8. A Sequential Model of Host Cell Killing and Phagocytosis by Entamoeba histolytica

    OpenAIRE

    Adam Sateriale; Huston, Christopher D.

    2011-01-01

    The protozoan parasite Entamoeba histolytica is responsible for invasive intestinal and extraintestinal amebiasis. The virulence of Entamoeba histolytica is strongly correlated with the parasite's capacity to effectively kill and phagocytose host cells. The process by which host cells are killed and phagocytosed follows a sequential model of adherence, cell killing, initiation of phagocytosis, and engulfment. This paper presents recent advances in the cytolytic and phagocytic processes of Ent...

  9. Rotating Killing horizons in generic $F(R)$ gravity theories

    CERN Document Server

    Bhattacharya, Sourav

    2016-01-01

    We discuss various properties of rotating Killing horizons in generic non-singular $F(R)$ theories of gravity in dimension four for spacetimes endowed with two commuting Killing vector fields. By constructing a suitable $(3+1)$-foliation, we show that similar to Einstein's gravity, we must have $T_{ab}k^ak^b=0$ on the Killing horizon, where $k^a$ is a null geodesic tangent to the horizon. For axisymmetric spacetimes, the effective gravitational coupling $\\sim\\,F'^{-1}(R)$ should usually depend upon the polar coordinate and hence need not necessarily be a constant on the Killing horizon. We prove that the surface gravity of such a Killing horizon must be a constant, irrespective of whether $F'(R)$ is a constant there or not. We next use these results to derive some simple corollaries. In particular, we point out that the no hair theorem for the real massive vector field need not necessarily hold for a generic $F(R)$, unless some additional condition is satisfied.

  10. Scientific projection paper for mutagenesis, transformation and cell killing

    International Nuclear Information System (INIS)

    Our knowledge about mutagenesis, transformation, and cell killing by ionizing radiation consists of large bodies of data, which are potentially useful in terms of application to human risk assessment and to the constructive use of radiation, as in cancer treatment. The three end-points discussed above are united by at least five significant concepts in radiation research strategy: (1) The inter-relationships among the important end-points, mutation, carcinogenesis, and cell killing. Research on one is meaningful only in the context of information about the other two. (2) The interaction of radiations with other agents in producing these end-points. (3) The mechanisms of action of other environmental mutagenic, carcinogenic, and cytotoxic agents. (4) The use of repair deficient human mutant cells. (5) The study of radiation damage mechanisms. There is no better way to extrapolate laboratory data to the clinical and public worlds than to understand the underlying biological mechanisms that produced the data

  11. Effects of an expressive writing intervention on cancer-related distress in Danish breast cancer survivors

    DEFF Research Database (Denmark)

    Jensen-Johansen, Mikael Birkelund; Christensen, Søren; Valdimarsdottir, Heiddis;

    2013-01-01

    Objective: To examine the effects of an expressive writing intervention (EWI) on cancer-related distress, depressive symptoms, and mood in women treated for early stage breast cancer. Methods: A nationwide sample of 507 Danish women who had recently completed treatment for primary breast cancer w...... of previous results with cancer patients, no main effects of EWI were found for cancer-related distress, depressive symptoms, and mood. Moderator analyses suggested that choice of writing topic and ability to process emotional experiences should be studied further.......Objective: To examine the effects of an expressive writing intervention (EWI) on cancer-related distress, depressive symptoms, and mood in women treated for early stage breast cancer. Methods: A nationwide sample of 507 Danish women who had recently completed treatment for primary breast cancer...... were randomly assigned to three 20-min home-based writing exercises, one week apart, focusing on either emotional disclosure (EWI group) or a non-emotional topic (control group). Cancer-related distress [Impact of Event Scale (IES)], depressive symptoms (Beck Depression Inventory—Short Form...

  12. Anti-cancer efficacy of nonthermal plasma dissolved in a liquid, liquid plasma in heterogeneous cancer cells

    OpenAIRE

    Ngoc Hoan Nguyen; Hyung Jun Park; Sang Sik Yang; Kyeong Sook Choi; Jong-Soo Lee

    2016-01-01

    The therapeutic potential of nonthermal plasma for cancer treatment has been reported recently. The heterogeneity of cancer cells need to be addressed to design effective anticancer treatments. Here, we show that treatment with nonthermal atmospheric-pressure plasma dissolved in a liquid (liquid plasma) induces oxidative stress in heterogeneous populations of cancer cells and ultimately kills these cells via apoptosis, regardless of genetic status, e.g., mutations in p53 and other DNA-damage-...

  13. Effect of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality

    Science.gov (United States)

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

    2016-01-01

    Abstract Background: Observational studies have suggested that vitamin B supplementation is associated with cancer risk, but this association remains controversial. A pooled data-based meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCTs) investigating the effects of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality. Methods: PubMed, EmBase, and the Cochrane Library databases were searched to identify trials to fit our analysis through August 2015. Relative risk (RR) was used to measure the effect of vitamin B supplementation on the risk of cancer incidence, death due to cancer, and total mortality using a random-effect model. Cumulative meta-analysis, sensitivity analysis, subgroup analysis, heterogeneity tests, and tests for publication bias were also conducted. Results: Eighteen RCTs reporting the data on 74,498 individuals were included in the meta-analysis. Sixteen of these trials included 4103 cases of cancer; in 6 trials, 731 cancer-related deaths occurred; and in 15 trials, 7046 deaths occurred. Vitamin B supplementation had little or no effect on the incidence of cancer (RR: 1.04; 95% confidence interval [CI]: 0.98–1.10; P = 0.216), death due to cancer (RR, 1.05; 95% CI: 0.90–1.22; P = 0.521), and total mortality (RR, 1.00; 95% CI: 0.94–1.06; P = 0.952). Upon performing a cumulative meta-analysis for cancer incidence, death due to cancer, and total mortality, the nonsignificance of the effect of vitamin B persisted. With respect to specific types of cancer, vitamin B supplementation significantly reduced the risk of skin melanoma (RR, 0.47; 95% CI: 0.23–0.94; P = 0.032). Conclusion: Vitamin B supplementation does not have an effect on cancer incidence, death due to cancer, or total mortality. It is associated with a lower risk of skin melanoma, but has no effect on other cancers. PMID:27495015

  14. Stages of Skin Cancer

    Science.gov (United States)

    ... cells than in normal cells. For skin cancer, laser light is shined onto the skin and the drug becomes active and kills the cancer cells. Photodynamic therapy causes little damage to healthy tissue. Biologic therapy ...

  15. Skin Cancer Treatment

    Science.gov (United States)

    ... cells than in normal cells. For skin cancer, laser light is shined onto the skin and the drug becomes active and kills the cancer cells. Photodynamic therapy causes little damage to healthy tissue. Biologic therapy ...

  16. Cancer survivorship: A positive side-effect of more successful cancer treatment.

    Science.gov (United States)

    Moser, Elizabeth Charlotte; Meunier, Françoise

    2014-06-01

    Over the past decades, early diagnosis, new drugs and more personalised multi-modality treatment have led to impressive increases in survival rates of patients with cancer. This success in treating cancer has resulted in a large and rapidly increasing number of cancer survivors, yet life after cancer is often compromised by a broad spectrum of late adverse treatment effects. Some encounter cardiovascular, second malignancies, cognitive or other morbidities which impair normal life in an important way. Some patients are confronted with societal discrimination due to slower performance, chronic fatigue or partial inability and these things can adversely affect employment, education, insurance or mortgage opportunities. In 2012, the European Organisation of Research and Treatment of Cancer (EORTC) Survivorship Task Force was created to focus research efforts on late morbidity of cancer treatment and its impact on society. On 30-31st January 2014, the 1st EORTC Cancer Survivorship Summit was organised to facilitate interaction between clinicians, researchers, social workers, patients, insurers, bankers and policy makers. This important event addressed the needs of cancer survivors, and new collaborations between academic groups, patient advocates, financial and political representatives were formed to guide future European research and health policies in this field. This special issue of the European Journal of Cancer is entirely dedicated to this Summit and addresses, respectively, second malignancies, cardiovascular disease, cognitive dysfunction, infertility/sexuality and psycho-social problems following cancer treatment. PMID:26217161

  17. Granzyme B-based cytolytic fusion protein targeting EpCAM specifically kills triple negative breast cancer cells in vitro and inhibits tumor growth in a subcutaneous mouse tumor model

    NARCIS (Netherlands)

    Amoury, Manal; Kolberg, Katharina; Anh-Tuan Pham, [Unknown; Hristodorov, Dmitrij; Mladenov, Radoslav; Di Fiore, Stefano; Helfrich, Wijnand; Kiessling, Fabian; Fischer, Rainer; Pardo, Alessa; Thepen, Theophilus; Hussain, Ahmad F.; Nachreiner, Thomas; Barth, Stefan

    2016-01-01

    Triple-negative breast cancer (TNBC) is associated with poor prognosis and high prevalence among young premenopausal women. Unlike in other breast cancer subtypes, no targeted therapy is currently available. Overexpression of epithelial cell adhesion molecule (EpCAM) in 60% of TNBC tumors correlates

  18. Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer

    Directory of Open Access Journals (Sweden)

    María Angeles Martín

    2016-01-01

    Full Text Available Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to interfere at the three stages of cancer. Cocoa has been demonstrated to counteract oxidative stress and to have a potential capacity to interact with multiple carcinogenic pathways involved in inflammation, proliferation and apoptosis of initiated and malignant cells. Therefore, restriction of oxidative stress and/or prevention or delayed progression of cancer stages by cocoa antioxidant compounds has gained interest as an effective approach in colorectal cancer prevention. In this review, we look over different in vitro and in vivo studies that have identified potential targets and mechanisms whereby cocoa and their flavonoids could interfere with colonic cancer. In addition, evidence from human studies is also illustrated.

  19. Humane killing of animals for disease control purposes.

    Science.gov (United States)

    Thornber, P M; Rubira, R J; Styles, D K

    2014-04-01

    Killing for disease control purposes is an emotional issue for everyone concerned. Large-scale euthanasia or depopulation of animals may be necessary for the emergency control or eradication of animal diseases, to remove animals from a compromised situation (e.g. following flood, storm, fire, drought or a feed contamination event), to effect welfare depopulation when there is an oversupply due to a dysfunctional or closed marketing channel, or to depopulate and dispose of animals with minimal handling to decrease the risk of a zoonotic disease infecting humans. The World Organisation for Animal Health (OIE) developed international standards to provide advice on humane killing for various species and situations. Some fundamental issues are defined, such as competency of animal handling and implementation of humane killing techniques. Some of these methods have been used for many years, but novel approaches for the mass killing of particular species are being explored. Novel vaccines and new diagnostic techniques that differentiate between vaccinated and infected animals will save many animals from being killed as part of biosecurity response measures. Unfortunately, the destruction of affected livestock will still be required to control diseases whilst vaccination programmes are activated or where effective vaccines are not available. This paper reviews the principles of humane destruction and depopulation and explores available techniques with their associated advantages and disadvantages. It also identifies some current issues that merit consideration, such as legislative conflicts (emergency disease legislation versus animal welfare legislation, occupational health and safety), media issues, opinions on the future approaches to killing for disease control, and animal welfare.

  20. Humane killing of animals for disease control purposes.

    Science.gov (United States)

    Thornber, P M; Rubira, R J; Styles, D K

    2014-04-01

    Killing for disease control purposes is an emotional issue for everyone concerned. Large-scale euthanasia or depopulation of animals may be necessary for the emergency control or eradication of animal diseases, to remove animals from a compromised situation (e.g. following flood, storm, fire, drought or a feed contamination event), to effect welfare depopulation when there is an oversupply due to a dysfunctional or closed marketing channel, or to depopulate and dispose of animals with minimal handling to decrease the risk of a zoonotic disease infecting humans. The World Organisation for Animal Health (OIE) developed international standards to provide advice on humane killing for various species and situations. Some fundamental issues are defined, such as competency of animal handling and implementation of humane killing techniques. Some of these methods have been used for many years, but novel approaches for the mass killing of particular species are being explored. Novel vaccines and new diagnostic techniques that differentiate between vaccinated and infected animals will save many animals from being killed as part of biosecurity response measures. Unfortunately, the destruction of affected livestock will still be required to control diseases whilst vaccination programmes are activated or where effective vaccines are not available. This paper reviews the principles of humane destruction and depopulation and explores available techniques with their associated advantages and disadvantages. It also identifies some current issues that merit consideration, such as legislative conflicts (emergency disease legislation versus animal welfare legislation, occupational health and safety), media issues, opinions on the future approaches to killing for disease control, and animal welfare. PMID:25000803

  1. Effectiveness of ultrasound for breast cancer screening

    International Nuclear Information System (INIS)

    To evaluate the effectiveness of ultrasound (US) for breast cancer screening, we conducted a retrospective survey of 856 breast cancer patients who were preoperatively examined by mammography (MMG) and US. Their average age was 54.7 years, with a range of 24 to 92 years. MMG revealed positive findings in 771 patients (90.1%), and negative findings in the remaining 85 patients (9.9%). Likewise, US revealed positive findings in 835 patients (97.5%), and negative findings in the remaining 21 patients (2.5%). Accordingly, the proportion of positive finding in US was significantly higher than that in MMG (chi-square test, p<0.0001). The incidence of negative findings with MMG was inversely related to age: 5.8% for patients in their 70s, 5.7% for those in their 60s, 8.3% for those in their 50s, 11.1% for those in their 40s, and 26.2% for those in their 30s or younger, because of the higher breast density in younger women (chi-square test, p<0.0001). The incidence of positive findings was 99.4% for tumors 2.1 to 3.0 cm in size, 96.3% for those measuring 1.6 to 2.0 cm, 94.3% for those measuring 1.1 to 1.5 cm, and 75.4% for those less than or equal to 1.0 cm (chi-square test, p<0.0001). Among the 85 patients with negative findings by MMG, 70(82.4%) were positive and 15 (17.6%) were negative by US. As findings of calcification by US, high echo spots plus a tumor lesion were observed in 59 patients (71.1%), high echo spots only were noted in 22 patients (26.5%), and high echo spots were not seen in 2 patients (2.4%). In conclusion, parallel use of MMG and US is recommended for breast cancer screening, especially for women in their 50s or younger, to reduce the incidence of misdiagnosis. (author)

  2. A multidimensional cancer rehabilitation program for cancer survivors - Effectiveness on health-related quality of life

    NARCIS (Netherlands)

    van Weert, E; Hoekstra-Weebers, J; Grol, B; Otter, R; Arendzen, HJ; Postema, K; Sanderman, R; van der Schans, C

    2005-01-01

    Objective: A multidimensional rehabilitation program for cancer survivors was developed to overcome cancer-related problems and to improve quality of life. The two purposes of the study were to describe the effectiveness of the program and to obtain information about patient preferences for multi or

  3. Effects of smoking on oral cancer transcriptome

    OpenAIRE

    Zain, R. B.; Karen-Ng, L. P.; Cheong, S C; Anwar, A.; Mustaffa, W. M. W.; Prepagaran, N.; Zaini, Z.; Merican, A. F.; Abraham, M. T.; Tay, K. K.; Rahman, Z. A. A.; Jallaludin, A.

    2011-01-01

    Introduction: Oral cancer is a debilitating disease and the survival rates for these patients have not improved over the past decades. Tobacco smoking is one of the most common risk factor associated with oral cancer. Objectives: To explore and identify differential genes expression associated with tobacco smoking. Methodology: Next generation sequencing using the Illumina Genome Analyzer was done to sequence five fresh frozen oral cancer tissue samples from smoking patients, two of which wer...

  4. Natural Product Shows Effectiveness in Combating Colorectal Cancer | Poster

    Science.gov (United States)

    An herbal extract used for centuries to prevent heart disease has now been shown to be effective against colorectal cancer when tested in laboratory cell cultures. Scientists from NCI at Frederick found that the natural extract cryptotanshinone (CPT) stops the uncontrolled cell growth characteristic of cancer by interfering with a protein that has been implicated in several cancers, including those of the colon and rectum. The results appear in the journal Molecular and Cellular Biochemistry.

  5. Radiosensitizing effect of gold nanoparticles in carbon ion irradiation of human cervical cancer cells

    Science.gov (United States)

    Kaur, Harminder; Avasthi, D. K.; Pujari, Geetanjali; Sarma, Asitikantha

    2013-07-01

    Noble metal nanoparticles have received considerable attention in biotechnology for their role in bio sensing due to surface plasmon resonance, medical diagnostics due to better imaging contrast and therapy. The radiosensitization effect of gold nanoparticles (AuNP) has been gaining popularity in radiation therapy of cancer cells. The better depth dose profile of energetic ion beam proves its superiority over gamma radiation for fighting against cancer. In the present work, the glucose capped gold nanoparticles (Glu-AuNP) were synthesised and internalized in the HeLa cells. Transmission electron microscopic analysis of ultrathin sections of Glu-AuNP treated HeLa cells confirmed the internalization of Glu-AuNPs. Control HeLa cells and Glu-AuNp treated HeLa cells were irradiated at different doses of 62 MeV 12C ion beam (LET - 290keV/μm) at BIO beam line of using 15UD Pelletron accelerator at Inter University Accelerator Centre, New Delhi, India. The survival fraction was assessed by colony forming assay which revealed that the dose of carbon ion for 90% cell killing in Glu-AuNP treated HeLa cells and control HeLa cells are 2.3 and 3.2 Gy respectively. This observation shows ˜ 28% reduction of 12C6+ ion dose for Glu-AuNP treated HeLa cells as compared to control HeLa cells.

  6. Lentiviral vectors in cancer immunotherapy.

    Science.gov (United States)

    Oldham, Robyn Aa; Berinstein, Elliot M; Medin, Jeffrey A

    2015-01-01

    Basic science advances in cancer immunotherapy have resulted in various treatments that have recently shown success in the clinic. Many of these therapies require the insertion of genes into cells to directly kill them or to redirect the host's cells to induce potent immune responses. Other analogous therapies work by modifying effector cells for improved targeting and enhanced killing of tumor cells. Initial studies done using γ-retroviruses were promising, but safety concerns centered on the potential for insertional mutagenesis have highlighted the desire to develop other options for gene delivery. Lentiviral vectors (LVs) have been identified as potentially more effective and safer alternative delivery vehicles. LVs are now in use in clinical trials for many different types of inherited and acquired disorders, including cancer. This review will discuss current knowledge of LVs and the applications of this viral vector-based delivery vehicle to cancer immunotherapy.

  7. The effect of anxiety on breast cancer patients

    Directory of Open Access Journals (Sweden)

    Shadiya Mohamed Saleh Baqutayan

    2012-01-01

    Full Text Available Cancer is a disease wherein abnormal cells divide without control and are able to attack other tissues. Most of the patients and their families face some degree of depression, anxiety, and fear when cancer becomes a part of their lives. They feel helpless and eager to find ways on how to get rid of it. The study focuses on anxiety among breast cancer patients. It aims at investigating cancer, its symptoms, and effects the disease has on the anxiety level of patients.

  8. Hepatic late adverse effects after antineoplastic treatment for childhood cancer

    NARCIS (Netherlands)

    R.L. Mulder; E.C. van Dalen; M. van den Hof; D. Bresters; B.G.P. Koot; S.M. Castellino; Y. Loke; E. Leclercq; P.N. Post; H.N. Caron; A. Postma; L.C.M. Kremer

    2011-01-01

    Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. Howev

  9. The effect of lifestyle factors on gynaecological cancer.

    OpenAIRE

    Rieck, Gudrun; Fiander, Alison

    2006-01-01

    KEYWORDS CLASSIFICATION: adverse effects;Alcohol Drinking;complications;Contraceptives,Oral,Hormonal;Diet;etiology;Estrogen Replacement Therapy;Evaluation;Exercise;Female;Genital Neoplasms,Female;Humans;Life Style;lifestyle modulation of cancer & cancer biomarkers;Obesity;prevention & control;Papillomaviridae;Papillomavirus Infections;Reproductive History;Risk Factors;Smoking;Wales.

  10. Students with Cancer: Presenting Issues and Effective Solutions

    Science.gov (United States)

    Root, Melissa M.; Bray, Melissa A.; Maykel, Cheryl; Cross, Karen; Shankar, Nilani L.; Theodore, Lea A.

    2016-01-01

    Practitioners working with children diagnosed with cancer in the school environment must consider several facets in order to effectively work with the child and family. The remission rate for children with cancer is relatively high, so one must consider whether the child is anticipating treatment, actively in treatment, or posttreatment when one…

  11. Sexual dysfunction and infertility as late effects of cancer treatment.

    Science.gov (United States)

    Schover, Leslie R; van der Kaaij, Marleen; van Dorst, Eleonora; Creutzberg, Carien; Huyghe, Eric; Kiserud, Cecilie E

    2014-06-01

    Sexual dysfunction is a common consequence of cancer treatment, affecting at least half of men and women treated for pelvic malignancies and over a quarter of people with other types of cancer. Problems are usually linked to damage to nerves, blood vessels, and hormones that underlie normal sexual function. Sexual dysfunction also may be associated with depression, anxiety, relationship conflict, and loss of self-esteem. Innovations in cancer treatment such as robotic surgery or more targeted radiation therapy have not had the anticipated result of reducing sexual dysfunction. Some new and effective cancer treatments, including aromatase inhibitors for breast cancer or chemoradiation for anal cancer also have very severe sexual morbidity. Cancer-related infertility is an issue for younger patients, who comprise a much smaller percentage of total cancer survivors. However, the long-term emotional impact of being unable to have a child after cancer can be extremely distressing. Advances in knowledge about how cancer treatments may damage fertility, as well as newer techniques to preserve fertility, offer hope to patients who have not completed their childbearing at cancer diagnosis. Unfortunately, surveys in industrialised nations confirm that many cancer patients are still not informed about potential changes to their sexual function or fertility, and all modalities of fertility preservation remain underutilised. After cancer treatment, many patients continue to have unmet needs for information about restoring sexual function or becoming a parent. Although more research is needed on optimal clinical practice, current studies suggest a multidisciplinary approach, including both medical and psychosocial treatment options. PMID:26217165

  12. A cancer-favoring oncolytic vaccinia virus shows enhanced suppression of stem-cell like colon cancer

    Science.gov (United States)

    Yoo, So Young; Bang, Seo Young; Jeong, Su-Nam; Kang, Dae Hwan; Heo, Jeong

    2016-01-01

    Stem cell-like colon cancer cells (SCCs) pose a major challenge in colon cancer treatment because of their resistance to chemotherapy and radiotherapy. Oncolytic virus-based therapy has shown promising results in uncured cancer patients; however, its effects on SCCs are not well studied yet. Here, we engineered a cancer-favoring oncolytic vaccinia virus (CVV) as a potent biotherapeutic and investigated its therapeutic efficacy in terms of killing SCCs. CVV is an evolved Wyeth strain vaccinia virus (EVV) lacking the viral thymidine kinase. SCC models were established using human or mouse colon cancer spheres, which continuously expressed stemness markers. The cancer-favoring characteristics and different cytotoxic pathways for killing cancer cells successfully overrode general drug resistance, thereby killing colon cancer cells regardless of the presence of SCCs. Subcutaneously injected HT29 spheres showed lower growth in CVV-treated models than in 5-Fu-treated models. Intraperitoneally injected CT26 spheres induced tumor masses in the abdominal region. CVV-treated groups showed higher survival rates and smaller tumor mass formation, compared to 5-Fu-treated groups. Interestingly, the combined treatment of CVV with 5-Fu showed improved survival rates and complete suppression of tumor mass. The CVV developed in this study, thus, effectively suppresses SCCs, which can be synergistically enhanced by simultaneous treatment with the anticancer drug 5-Fu. Our novel CVV is highly advantageous as a next-generation therapeutic for treating colon cancer. PMID:26918725

  13. 树突状细胞的诱导培养及对胃癌细胞株MKN45的体外杀伤效应的初步研究%Preliminary studying on dendritic cell culture and its killing effect on gastric carcinoma cell line MKN 45

    Institute of Scientific and Technical Information of China (English)

    孙梯业; 颜伟; 孙冬丽; 刘全达; 段伟宏; 周宁新

    2010-01-01

    目的 探讨树突状细胞(DC)体外培养的方法及CpG ODN1826刺激DC对胃癌细胞MKN45的杀伤效应.方法 分离正常人外周血DC,培养至第5天,实验分为4组,A组[粒细胞-巨噬细胞集落刺激因子(GM-CSF)+白细胞介素-4(IL-4)]、B组[GM-CSF+IL-4+肿瘤坏死因子-α(TNF-α)]、C组(nonCpG ODN)和D组(CpG ODN 1826).自外周血单核细胞(PBMC)诱导分离DC,流式细胞仪检测DC表面标志,MTT法测定其刺激对同种异体淋巴细胞增殖的影响及对胃癌细胞的杀伤效应.结果 体外培养至第10天,D组和B组均出现大量典型的DC形态.倒置显微镜下见细胞呈树突状、伪足状突起.流式细胞仪检测,D组显著高表达共刺激分子(CD40、CD1a、CD80、CD86)和MHC-Ⅱ类分子,均分别高于其他各组(P<0.05).在体外能强烈刺激同种异体混合淋巴细胞的增殖,显著增强DC杀伤胃癌细胞MKN45的活性.结论 该培养方法可获得较高纯度典型的DC,同时CpG ODN可显著诱导人外周血DC分化成熟,增强DC对胃癌细胞MKN45的杀伤作用.%Objective To explore the cultivated methods of dendritic cells (DC) and the killing effect of DC stimulated by CpG ODN1826 on gastritic cancer cells MKN45 in vitro. Methods DC was induced from peripheral blood monocytes stimulated by A group ( GM- CSF + IL-4 ), B group ( GM- CSF + IL-4 + TNF- α), C group(nonCpG ODN) and D group( CpG ODN 1826). The surface markers of DC was analyzed via flow cytometry, and the abilities to stimulate proliferation of allogenic lymphocyte by DC and antitumor experiment were detected by MTT assay. Results On day 10, a majority of cells showed typical morphology of DC in D group and B group with visible branching-like and pseudopod-like structures under microscope. The results of flow cytometry showed that there are significantly high expressed co-stimulated molecules such as CD40, CD1a,CD80, CD86 and MHC- Ⅱ in D group compared to other experimental groups ( P < 0.05 ), which

  14. Patterns and Composition of Road-Killed Wildlife in Northwest Argentina

    Science.gov (United States)

    Cuyckens, Griet An Erica; Mochi, Lucía Sol; Vallejos, María; Perovic, Pablo Gastón; Biganzoli, Fernando

    2016-11-01

    Roads have important effects on wildlife, such as natural habitat fragmentation and degradation and direct killing of fauna, which leads to reductions in wildlife population size. We focused on a principal road in Northwest Argentina to test for the effect of seasonality and landscape features on the composition of road-killed wildlife. We conducted regularly scheduled road trips during the dry and wet seasons. We recorded the presence or absence of a vegetation curtain or hedge along the road. We measured land use by remote sensing in a 500 m buffer along the road. We compared the abundance of animals killed between seasons (dry and wet) for different taxonomic groups (mammals, birds and reptiles) and for different origins (domestic and native). We built linear mixed models to test the effect of landscape features on the abundance of killed animals. Two hundred and ninety-three individuals were killed, belonging to 35 species; 75.8 % were native and 24.2 % domestic species. The majority of animals killed were mid-sized mammals. More animals were killed during the dry season. The most important factors to explain the wildlife road-killing were the season and the proportion of agricultural landscape. The composition of the killed animals changed with the season. The proportion of agricultural landscape incremented the number of killed birds and mammals during both seasons, without affecting reptiles. The ratio of wild to domestic animals killed was dependent on the season. This study sets a precedent as the first in road ecology in Northwest Argentina and should be taken into account for road planning and regulation.

  15. Growth inhibitory effects of Phyllanthus niruri extracts in combination with cisplatin on cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Raimundo Fernandes de Araújo Júnior; Luiz Alberto Lira Soares; Cínthia Raquel da Costa Porto; Ranniere Gurgel Furtado de Aquino; Hugo Gon(c)alo Guedes; Pedro Ros Petrovick; Tatiane Pereira de Souza

    2012-01-01

    AIM:To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cisplatin on two cancer cell lines.METHODS:Colorectal carcinoma (HT29) and human hepatocellular carcinoma (HepG2) cells were treated with spray-dried extracts of Phy//anthus niruri (SDEPN) either alone or in combination with cisplatin at different concentrations (0.5 mg/mL and 1 mg/mL) for 4 h and 24 h.To verify and quantify cancer cells treated with these products as well as identify the cell cycle stage and cell viability,we stained the cells with propidium iodide and assessed them by flow cytometry.The percentage of cells in different cell cycle phases was quantified and data were expressed as histograms.Significant differences between groups were determined using analysis of variance and Bonferroni's test,as indicated.A value of P < 0.05 was considered to be statistically significant.RESULTS:SDEPN had significantly different cytotoxic effects on HT29 (2.81 ± 0.11 vs 3.51 ± 1.13,P > 0.05) and HepG2 (5.07 ± 0.3 vs 15.9 ± 1.04,P <0.001) cells when compared to control cells for 4 h.SDEPN also had significantly different cytotoxic effects on HT29 (1.91 ± 0.57 vs 4.53 ± 1.22,P > 0.05) and HepG2 (14.56 ± 1.6 vs 35.67 ± 3.94,P < 0.001) cells when compared to control cells for 24 h.Both cell lines were killed by cisplatin in a dose-dependent manner compared to control cells (HepG2 cells for 4 h:10.78 ± 1.58 vs 53.89 ± 1.53,P < 0.001; 24 h:8.9 ± 1.43 vs 62.78 ± 1.87,P < 0.001 and HT29 cells for 4 h:9.52 ± 0.913 vs 49.86 ± 2.89,P < 0.001; 24 h:11.78 ± 1.05 vs 53.34 ± 2.65,P < 0.001).In HT29 cells,pretreatment with SDEPN and subsequent treatment with cisplatin resulted in a greater number of cells being killed (12.78 ± 1.01 vs 93.76 ± 1.6,P < 0.001).HepG2 cells showed significant cell killing with treatment with SDEPN when combined with cisplatin (12.87±2.78 vs 78.8 ± 3.02,P < 0.001).CONCLUSION:SDEPN is selectively toxic

  16. Effect of patient variation on standard- and hypo-fractionated radiotherapy of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, W; Li, J; Ma, C-M [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111 (United States)

    2005-04-07

    Recent publications suggested that the {alpha}/{beta} ratio in the well-known linear quadratic (LQ) model could be as low as 1.5 Gy for prostate cancer, indicating that prostate cancer control might be very sensitive to changes in the dose fractionation scheme. This also suggests that the standard-fractionation scheme based on large {alpha}/{beta} ratios may not be optimal for the radio-therapeutic management of prostate cancer. Hypo-fractionated radiotherapy for prostate cancer has received more attention recently as an alternative treatment strategy, which may lead to reduced treatment time and cost. However, hypo-fractionated radiotherapy may be more sensitive to patient variation in terms of disease control than standard-fractionated radiotherapy. The variation of LQ parameters {alpha} and {beta} for a patient population may compromise the outcome of the treatment. This effect can be studied by the introduction of the {sigma}{sub {alpha}} and {sigma}{sub {beta}} parameters, which are the standard deviations of Gaussian distributions around {alpha}{sub 0} and {beta}{sub 0}. The purpose of this study is to examine the effect of patient variation in {alpha} and {beta} on tumour control probability for standard- and hypo-fractionated radiotherapy of prostate cancer. The tumour control probability based on the LQ model is calculated using parameters {alpha}, {beta}, {sigma}{sub {alpha}} and {sigma}{sub {beta}}. Our results show that {sigma}{sub {alpha}} is an important parameter for radiotherapy fractionation, independent of the {alpha}/{beta} ratio. A large {sigma}{sub {alpha}} will result in a significant increase in the radiation dose required to achieve the same 95% TCP. Compared with the standard-fractionated scheme, {sigma}{sub {alpha}} has a smaller effect on hypo-fractionated treatment at lower {alpha}/{beta} ratios. On the other hand, for lower {alpha}/{beta} ratios, the {beta} term also plays a more important role in cell-killing and therefore the patient

  17. The killing effect of Ascaris peptide yeast fermentation products on Leishmania donovani%蛔虫抗菌肽酵母发酵产物对杜氏利什曼原虫杀伤作用的研究

    Institute of Scientific and Technical Information of China (English)

    仲维霞; 屈金辉; 王洪法; 赵桂华; 崔勇

    2011-01-01

    目的 研究蛔虫抗菌肽酵母发酵产物对杜氏利什曼原虫的抑杀作用,探讨此抗菌肽可作为治疗黑热病的药物的可能性.方法 培养利什曼原虫至适当浓度,接种于96孔组织培养板中,设实验组和对照组,实验组分别加入10μl浓度为30、60、90、120、150、180μg∥ml的蛔虫抗菌肽酵母发酵产物浓缩上清液,每个浓度重复9孔,对照组加相应体积的对照表达产物,分别在连续培养24、48和72 h后,每孔加入20μl四甲基偶氮唑盐(5 mg∥ml),继续培养4 h,每孔加入100μlformanzan溶解液,孵育4 h左右,在570 am测定吸光度,根据吸光度数值计算杀伤率.结果 实验组按浓度由低到高(30~180μg//ml)对应的杀伤率在培养24 h后为20.12%、41.39%、64.89%、65.14%、66.49%和66.49%,培养48 h后为40.12%、67.34%、75.1l%、82.03%、82.75%和82.75%;培养72 h后为45.89%、65.57%、78.49%、82.58%、85.38%和85.38%.蛔虫抗菌肽发酵产物浓度为150μg/ml时,杀伤作用最大,杀伤率为85.38%,IC50为50μg/ml.结论 蛔虫抗菌肽对利什曼原虫有很强的杀伤作用.%Objective To study the killing effect of yeast fermentation product of Ascaris antibacterial peptide on Leishmania donovani and to investigate the possibility of antibacterial peptide as drug for kala-azar.Methods Leishmania was cultured to appropriate concentration,and was seeded in 96-well tissue culture plate.Experimental test and the negative control hole were designed.Then 10 μl supernatant of induced bacteria expression product was added into experimental hole with concentration of 30,60,90,120,150 and 180μg/ml.All levels were repeated nine holes.Then 20 μl methyl thiazolyl tetrazolium(MTT,5 mg/ml)was added into each hole and culturing for 4 h after culturing for 24,48 and 72 h,and another 100μl of Formanzan was pulsed,absorbance was read at 570 nm after another 4 h cultured.The killing effect is calculate from A570.Results At concentrations of the experimental

  18. Ultraviolet radiation: effects on risks of prostate cancer and other internal cancers

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Samuel J. [Human Genomics Research Group, Institute of Science and Technology in Medicine and Department of Urology, Keele University School of Medicine, University Hospital of North Staffordshire, Hartshill Campus, Stoke-on-Trent, ST4 7PA Staffordshire (United Kingdom); Fryer, Anthony A. [Human Genomics Research Group, Institute of Science and Technology in Medicine and Department of Urology, Keele University School of Medicine, University Hospital of North Staffordshire, Hartshill Campus, Stoke-on-Trent, ST4 7PA Staffordshire (United Kingdom); Strange, Richard C. [Human Genomics Research Group, Institute of Science and Technology in Medicine and Department of Urology, Keele University School of Medicine, University Hospital of North Staffordshire, Hartshill Campus, Stoke-on-Trent, ST4 7PA Staffordshire (United Kingdom)]. E-mail: paa00@keele.ac.uk

    2005-04-01

    Governmental and research agencies worldwide have strongly advocated sun avoidance strategies in an attempt to counter marked increases in skin cancer incidence. Concurrently, there are reports describing widespread Vitamin D{sub 3} deficiency. Because 1,25-dihydroxyvitamin D{sub 3}, through interaction with the Vitamin D receptor, exerts pleiotrophic effects, such deficiency might be expected to have clinical consequences. Indeed, various reports indicate that exposure to ultraviolet radiation (UVR) exerts a protective effect on development of some common diseases including internal cancers and multiple sclerosis. We describe studies indicating that modest exposure reduces risk of prostate cancer. The effect of UVR is mediated by skin type; at lower levels of exposure a relative inability to effect skin pigmentation is protective presumably because it allows more efficient Vitamin D{sub 3} synthesis. Polymorphic variants in genes associated with pigmentation including melanocyte stimulating hormone receptor and tyrosinase are also associated with prostate cancer risk. Overall, though preliminary and requiring cautious interpretation, these data indicate that moderate UVR exposure together with characteristics linked with less effective tanning confer reduced prostate cancer risk. Clearly, it is important to define safe levels of UVR that do not result in increased risk of skin cancers such as malignant melanoma.

  19. Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation

    OpenAIRE

    Averbeck, Nicole B.; Topsch, Jana; Scholz, Michael; Kraft-Weyrather, Wilma; Durante, Marco; Taucher-Scholz, Gisela

    2016-01-01

    Radiotherapy of solid tumors with charged particles holds several advantages in comparison to photon therapy; among them conformal dose distribution in the tumor, improved sparing of tumor-surrounding healthy tissue, and an increased relative biological effectiveness (RBE) in the tumor target volume in the case of ions heavier than protons. A crucial factor of the biological effects is DNA damage, of which DNA double-strand breaks (DSBs) are the most deleterious. The reparability of these les...

  20. Sulfonated aluminum phthalocyanines for two-photon photodynamic cancer therapy: the effect of the excitation wavelength

    International Nuclear Information System (INIS)

    Sulfonated aluminum phthalocyanine (AlPcS) is a well-studied photosensitizer which has been widely used in research and in clinical applications of the photodynamic therapy of cancers. Conventionally, one-photon excitation was used, but it was unknown whether two-photon excitation of AlPcS was equally effective. In this study, the two-photon absorption cross sections of AlPcS at near infrared wavelengths were deduced from femtosecond (fs) laser-induced fluorescence. We found that the two-photon absorption cross section of AlPcS was strongly dependent on the excitation wavelength. It was about 19 GM when excited at 800 nm, but grew to 855 GM when excited at 750 nm. The 750 nm fs-laser-induced fluorescence images of AlPcS in human nasopharyngeal carcinoma cells were clearly visible while the corresponding images were very dim when excited at 800 nm. Singlet oxygen production was 13 times higher when excited at 750 nm relative to 800 nm. Our subsequent in vitro experiments showed that 750 nm two-photon excitation with an unfocused fs laser beam damaged cancer cells in a light-dose-dependent manner typical of photodynamic therapy (PDT). The killing at 750 nm was about 9–10 times more efficient than at 800 nm. These results demonstrated for the first time that AlPcS has good potential for two-photon PDT of cancers. (paper)

  1. Arthritis Possible Side Effect of Certain Cancer Drugs: Study

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159602.html Arthritis Possible Side Effect of Certain Cancer Drugs: Study ... increase risk for joint and tissue disease, including arthritis, new research suggests. "We keep having referrals coming ...

  2. Dose-dependent ATP depletion and cancer cell death following calcium electroporation, relative effect of calcium concentration and electric field strength.

    Directory of Open Access Journals (Sweden)

    Emilie Louise Hansen

    Full Text Available Electroporation, a method for increasing the permeability of membranes to ions and small molecules, is used in the clinic with chemotherapeutic drugs for cancer treatment (electrochemotherapy. Electroporation with calcium causes ATP (adenosine triphosphate depletion and cancer cell death and could be a novel cancer treatment. This study aims at understanding the relationship between applied electric field, calcium concentration, ATP depletion and efficacy.In three human cell lines--H69 (small-cell lung cancer, SW780 (bladder cancer, and U937 (leukaemia, viability was determined after treatment with 1, 3, or 5 mM calcium and eight 99 μs pulses with 0.8, 1.0, 1.2, 1.4 or 1.6 kV/cm. Fitting analysis was applied to quantify the cell-killing efficacy in presence of calcium. Post-treatment intracellular ATP was measured in H69 and SW780 cells. Post-treatment intracellular ATP was observed with fluorescence confocal microscopy of quinacrine-labelled U937 cells.Both H69 and SW780 cells showed dose-dependent (calcium concentration and electric field decrease in intracellular ATP (p<0.05 and reduced viability. The 50% effective cell kill was found at 3.71 kV/cm (H69 and 3.28 kV/cm (SW780, reduced to 1.40 and 1.15 kV/cm (respectively with 1 mM calcium (lower EC50 for higher calcium concentrations. Quinacrine fluorescence intensity of calcium-electroporated U937 cells was one third lower than in controls (p<0.0001.Calcium electroporation dose-dependently reduced cell survival and intracellular ATP. Increasing extracellular calcium allows the use of a lower electric field.This study supports the use of calcium electroporation for treatment of cancer and possibly lowering the applied electric field in future trials.

  3. ABT-737 synergizes with Bortezomib to kill melanoma cells

    Directory of Open Access Journals (Sweden)

    Steven N. Reuland

    2012-02-01

    The BH3 mimetic ABT-737 is a potent inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-XL, and Bcl-w. The Bcl-2 family modulates sensitivity to anticancer drugs in many cancers, including melanomas. In this study, we examined whether ABT-737 is effective in killing melanoma cells either alone or in combination with a proteasome inhibitor already in clinical use (Bortezomib in vitro and in vivo, and further evaluated the mechanisms of action. Results showed that ABT-737 alone induced modest cytotoxicity in melanoma cells, but only at higher doses. Knock-down of the anti-apoptotic proteins Bcl-2, Bcl-XL, or Mcl-1 with siRNAs demonstrated that Mcl-1 is the critical mediator of melanoma's resistance to ABT-737 treatment. However, ABT-737 displayed strong synergistic lethality when combined with Bortezomib. Immunoblot analyses demonstrated that Bortezomib increased expression of Noxa, a pro-apoptotic Bcl-2 member that antagonizes Mcl-1. Additionally, siRNA-mediated inhibition of Noxa expression protected melanoma cells from cytotoxicity induced by the combination treatment. These results demonstrate that Bortezomib synergizes with ABT-737 by neutralizing Mcl-1's function via increased levels of Noxa. In a xenograft mouse model, although drug doses were limited due to toxicity, ABT-737 or Bortezomib slowed melanoma tumor growth compared to the control, and the drug combination significantly decreased growth compared to either drug alone. These data imply that less toxic drugs fulfilling a function similar to Bortezomib to neutralize Mcl-1 are promising candidates for combination with ABT-737 for treating melanomas.

  4. The Geometry of D=11 Killing Spinors

    CERN Document Server

    Gauntlett, J P; Gauntlett, Jerome P.; Pakis, Stathis

    2003-01-01

    We propose a way to classify all supersymmetric configurations of D=11 supergravity using the G-structures defined by the Killing spinors. We show that the most general bosonic geometries admitting a Killing spinor have at least an SU(5) or an (Spin(7)\\ltimes R^8)x R structure, depending on whether the Killing vector constructed from the Killing spinor is timelike or null, respectively. In the former case we determine what kind of SU(5) structure is present and show that almost all of the form of the geometry is determined by the structure. We also deduce what further conditions must be imposed in order that the equations of motion are satisfied. We illustrate the formalism with some known solutions and also present some new solutions including a rotating generalisation of the resolved membrane solutions and generalisations of the recently constructed D=11 Godel solution.

  5. Killing superalgebras for Lorentzian four-manifolds

    CERN Document Server

    de Medeiros, Paul; Santi, Andrea

    2016-01-01

    We determine the Killing superalgebras underpinning field theories with rigid unextended supersymmetry on Lorentzian four-manifolds by re-interpreting them as filtered deformations of $\\mathbb{Z}$-graded subalgebras with maximum odd dimension of the $N{=}1$ Poincar\\'e superalgebra in four dimensions. Part of this calculation involves computing a Spencer cohomology group which, by analogy with a similar result in eleven dimensions, prescribes a notion of Killing spinor, which we identify with the defining condition for bosonic supersymmetric backgrounds of minimal off-shell supergravity in four dimensions. We prove that such Killing spinors always generate a Lie superalgebra, and that this Lie superalgebra is a filtered deformation of a subalgebra of the $N{=}1$ Poincar\\'e superalgebra in four dimensions. Demanding the flatness of the connection defining the Killing spinors, we obtain equations satisfied by the maximally supersymmetric backgrounds. We solve these equations, arriving at the classification of ma...

  6. Homefucking is Killing Prostitution / Taavi Eelmaa

    Index Scriptorium Estoniae

    Eelmaa, Taavi, 1971-

    2008-01-01

    Mis jääb vaatajale teatrietendusest meelde? Ilmus Kris Moori raamat "Homefucking is Killing Prostitution". Raamat sisaldab tekste ja Erki Lauri fotosid Von Krahli Teatri samanimelisest etendusest, mida kordagi ei mängitud

  7. The use of Zymosan A and bacteria anchored to tumor cells for effective cancer immunotherapy: B16-F10 murine melanoma model.

    Science.gov (United States)

    Waldmannová, Eva; Caisová, Veronika; Fáberová, Julie; Sváčková, Petra; Kovářová, Markéta; Sváčková, Denisa; Kumžáková, Zuzana; Jačková, Adéla; Vácová, Nikol; Nedbalová, Pavla; Horká, Marie; Kopecký, Jan; Ženka, Jan

    2016-10-01

    The idea of using killed microorganisms or their parts for a stimulation of immunity in the cancer immunotherapy is very old, but the question of interactions and binding of these preparations to tumor cells has not been addressed so far. The attachment of Zymosan A and both Gram-positive and Gram-negative bacteria to tumor cells was tested in in vivo experiments. This binding was accomplished by charge interactions, anchoring based on hydrophobic chains and covalent bonds and proved to be crucial for a strong immunotherapeutic effect. The establishment of conditions for simultaneous stimulation of both Toll-like and phagocytic receptors led to very strong synergy. It resulted in tumor shrinkage and its temporary or permanent elimination. The role of neutrophils in cancer immunotherapy was demonstrated and the mechanism of their action (frustrated phagocytosis) was proposed. Finally, therapeutic approaches applicable for safe human cancer immunotherapy are discussed. Heat killed Mycobacterium tuberculosis covalently attached to tumor cells seems to be promising tool for this therapy.

  8. Adoptive cell transfer: a clinical path to effective cancer immunotherapy

    OpenAIRE

    Rosenberg, Steven A.; Restifo, Nicholas P; Yang, James C.; Morgan, Richard A.; Dudley, Mark E.

    2008-01-01

    Adoptive cell therapy (ACT) using autologous tumour-infiltrating lymphocytes has emerged as the most effective treatment for patients with metastatic melanoma and can mediate objective cancer regression in approximately 50% of patients. The use of donor lymphocytes for ACT is an effective treatment for immunosuppressed patients who develop post-transplant lymphomas. The ability to genetically engineer human lymphocytes and use them to mediate cancer regression in patients, which has recently ...

  9. Measurement of bacterial ingestion and killing by macrophages.

    Science.gov (United States)

    Campbell, P A; Canono, B P; Drevets, D A

    2001-05-01

    This unit presents fairly simple assays for measuring the binding of bacteria to macrophages, internalization of bacteria (also called ingestion or phagocytosis), and bacterial killing by macrophages. The first basic protocol describes how to measure the ability of macrophages to ingest bacteria. Because it is critical to remove residual extracellular organisms, the protocol presents two alternative steps to accomplish this: a washing procedure and a more stringent method in which cells are sedimented through sucrose. In addition, it is important to distinguish those bacteria truly ingested by a macrophage from those that are bound to, but not internalized by, the cell. A simple but effective way to do this is described in an alternate protocol. The unit also presents two ways to measure the ability of a macrophage to kill bacteria it has internalized. The first is a straightforward assay in which bacterial colonies are enumerated before and after a killing period; a subsequent colony count will indicate whether the bacteria grew within or were killed by the macrophage. The second protocol describes a way to measure bacterial viability based on bacterial metabolism, in which the ability of bacterial dehydrogenases to mediate the reduction of a tetrazolium salt to purple formazan is monitored by measuring absorbance spectrophotometrically.

  10. Teleparallel Killing Vectors of the Einstein Universe

    OpenAIRE

    M. Sharif; Amir, M. Jamil

    2007-01-01

    In this short paper we establish the definition of the Lie derivative of a second rank tensor in the context of teleparallel theory of gravity and also extend it for a general tensor of rank $p+q$. This definition is then used to find Killing vectors of the Einstein universe. It turns out that Killing vectors of the Einstein universe in the teleparallel theory are the same as in General Relativity.

  11. Killing transform on regular Dirichlet subspaces

    OpenAIRE

    Li, Liping; Ying, Jiangang

    2015-01-01

    In this paper, we shall consider the killing transform induced by a multiplicative functional on regular Dirichlet subspaces of a fixed Dirichlet form. Roughly speaking, a regular Dirichlet subspace is a closed subspace with Dirichlet and regular properties of fixed Dirichlet space. By using the killing transforms, our main results indicate that the big jump part of fixed Dirichlet form is not essential for discussing its regular Dirichlet subspaces. This fact is very similar to the status of...

  12. The effect of kleptoparasitic bald eagles and gyrfalcons on the kill rate of peregrine falcons hunting dunlins wintering in British Columbia

    NARCIS (Netherlands)

    Dekker, T.J.; Out, M.; Tabak, M.; Ydenberg, R.C.

    2012-01-01

    Kleptoparasitism in birds has been the subject of much research, and the Bald Eagle (Haliaeetus leucocephalus) is a known kleptoparasite. It has been reported to pirate ducks captured by Peregrine Falcons (Falco peregrinus), but ours is the first study to examine the effect of kleptoparasitic Bald E

  13. Effect of preoperative S-1 combined with regional transcatheter arterial chemoembolization on malignant degree of locally advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ru-Juan Xu

    2016-01-01

    Objective:To study the effect of preoperative S-1 combined with regional transcatheter arterial chemoembolization on malignant degree of locally advanced gastric cancer. Methods:A total of 134 patients who were diagnosed with advanced gastric cancer in our hospital from May 2012 to December 2014 were selected for study, received surgical resection after chemotherapy, and were divided into intravenous chemotherapy group and combined treatment group according to different chemotherapy regimens. After chemotherapy and before operation, serum tumor marker levels were detected;after operation, recurrence and metastasis-related molecule levels in tumor tissue were detected. Results:After chemotherapy and before operation, serum CEA, CA199, CA72-4, TSGF, ESM-1 and DKK-1 levels of combined treatment group were significantly lower than those of intravenous chemotherapy group;TET1, TET2, LATS1 and RUNX3 levels in tumor tissue of combined treatment group were higher than those of intravenous chemotherapy group while Sipa1, GOLPH3, AEP, MT2-MMP, OPN, Galectin-1, Galectin-3 and Galectin-9 levels were lower than those of intravenous chemotherapy group. Conclusions:Compared with systemic intravenous chemotherapy, preoperative S-1 combined with regional transcatheter arterial chemoembolization can more effectively kill gastric cancer cells and prevent tumor recurrence and metastasis at molecular level.

  14. Design of targeted B cell killing agents.

    Directory of Open Access Journals (Sweden)

    Alexey V Stepanov

    Full Text Available B cells play an important role in the pathogenesis of both systemic and organ-specific autoimmune diseases. Autoreactive B cells not only produce autoantibodies, but also are capable to efficiently present specific autoantigens to T cells. Furthermore, B cells can secrete proinflammatory cytokines and amplify the vicious process of self-destruction. B cell-directed therapy is a potentially important approach for treatment of various autoimmune diseases. The depletion of B cells by anti-CD20/19 monoclonal antibody Retuximab® used in autoimmune diseases therapy leads to systemic side effects and should be significantly improved. In this study we designed a repertoire of genetically engineered B cell killers that specifically affected one kind of cells carrying a respective B cell receptor. We constructed immunotoxins (ITs, fused with c-myc epitope as a model targeting sequence, based on barnase, Pseudomonas toxin, Shiga-like toxin E.coli and Fc domain of human antibody IgGγ1. C-MYC hybridoma cell line producing anti-c-myc IgG was chosen as a model for targeted cell depletion. C-myc sequence fused with toxins provided addressed delivery of the toxic agent to the target cells. We demonstrated functional activity of designed ITs in vitro and showed recognition of the fusion molecules by antibodies produced by targeted hybridoma. To study specificity of the proposed B cells killing molecules, we tested a set of created ITs ex vivo, using C-MYC and irrelevant hybridoma cell lines. Pseudomonas-containing IT showed one of the highest cytotoxic effects on the model cells, however, possessed promiscuous specificity. Shiga-like toxin construct demonstrated mild both cytotoxicity and specificity. Barnase and Fc-containing ITs revealed excellent balance between their legibility and toxic properties. Moreover, barnase and Fc molecules fused with c-myc epitope were able to selectively deplete c-myc-specific B cells and decrease production of anti

  15. Green tea’s effects in the breast cancer risk

    Directory of Open Access Journals (Sweden)

    Carlos Pardos-Sevilla

    2014-04-01

    Full Text Available Phytochemicals like catechins from green tea might modify the epigenome and transcirptome of tumoral cells. The objective of the present review is to retrospectively evaluate literature examining the mechanisms throughout the green tea could exert a protective effect on breast cancer risk. In this work, more than 100 articles published during the last 15 years that relate tea consumption and breast cancer prevalence and development have been analysed. Green tea polyphenols can reduce risk of breast cancer throughout the inhibition of estrogenic and chemotoxic activity in liver, stimulation of metabolic pathway of glutathione conjugation, improvement of the metabolic syndrome, as well as control of immune system regulation, oxidative stress and DNA methylation. Although in vitro and animal studies show the potential ability of green tea polyphenols to act against breast cancer, the lack of experiments in humans, are the major factors in limiting us to conduct dietary recommendations based on scientific evidence for the management of patients with breast cancer.

  16. Chemopreventive effect of apple and berry fruits against colon cancer.

    Science.gov (United States)

    Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko; Octorina Dewi, Dyah Ekashanti; Narayanan, Aqilah Leela T; Balaji, Arunpandian; Subramanian, Aruna Priyadarshini; Yusof, Mustafa

    2014-12-01

    Colon cancer arises due to the conversion of precancerous polyps (benign) found in the inner lining of the colon. Prevention is better than cure, and this is very true with respect to colon cancer. Various epidemiologic studies have linked colorectal cancer with food intake. Apple and berry juices are widely consumed among various ethnicities because of their nutritious values. In this review article, chemopreventive effects of these fruit juices against colon cancer are discussed. Studies dealing with bioavailability, in vitro and in vivo effects of apple and berry juices are emphasized in this article. A thorough literature survey indicated that various phenolic phytochemicals present in these fruit juices have the innate potential to inhibit colon cancer cell lines. This review proposes the need for more preclinical evidence for the effects of fruit juices against different colon cancer cells, and also strives to facilitate clinical studies using these juices in humans in large trials. The conclusion of the review is that these apple and berry juices will be possible candidates in the campaign against colon cancer.

  17. Effects of Recombinant Erythropoietin on Breast Cancer-Initiating Cells

    Directory of Open Access Journals (Sweden)

    Tiffany M. Phillips

    2007-12-01

    Full Text Available BACKGROUND: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs. In breast cancer, CICs can be identified by phenotypic markers and their fate is controlled by the Notch pathway. METHODS: In this study, we investigated the effect of erythropoietin on CICs in breast cancer cell lines. Levels of erythropoietin receptor (EpoR, CD24, CD44, Jagged-1 expression, activation of Notch-1 were assessed by flow cytometry. Self-renewing capacity of CICs was investigated in sphere formation assays. RESULTS: EpoR expression was found on the surface of CICs. Recombinant human Epo (rhEpo increased the numbers of CICs and self-renewing capacity in a Notch-dependent fashion by induction of Jagged-1. Inhibitors of the Notch pathway and P13-kinase blocked both effects. CONCLUSIONS: Erythropoietin functionally affects CICs directly. Our observation may explain the negative impact of recombinant Epo on local control and survival of cancer patients with EpoR-positive tumors.

  18. Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation.

    Science.gov (United States)

    Averbeck, Nicole B; Topsch, Jana; Scholz, Michael; Kraft-Weyrather, Wilma; Durante, Marco; Taucher-Scholz, Gisela

    2016-01-01

    Radiotherapy of solid tumors with charged particles holds several advantages in comparison to photon therapy; among them conformal dose distribution in the tumor, improved sparing of tumor-surrounding healthy tissue, and an increased relative biological effectiveness (RBE) in the tumor target volume in the case of ions heavier than protons. A crucial factor of the biological effects is DNA damage, of which DNA double-strand breaks (DSBs) are the most deleterious. The reparability of these lesions determines the cell survival after irradiation and thus the RBE. Interestingly, using phosphorylated H2AX as a DSB marker, our data in human fibroblasts revealed that after therapy-relevant spread-out Bragg peak irradiation with carbon ions DSBs are very efficiently rejoined, despite an increased RBE for cell survival. This suggests that misrepair plays an important role in the increased RBE of heavy-ion radiation. Possible sources of erroneous repair will be discussed. PMID:26904506

  19. Efficient rejoining of DNA double-strand breaks despite increased cell-killing effectiveness following spread-out Bragg peak carbon-ion irradiation

    Directory of Open Access Journals (Sweden)

    Nicole Bernadette Averbeck

    2016-02-01

    Full Text Available Radiotherapy of solid tumors with charged particles holds several advantages in comparison to photon therapy; among them conformal dose distribution in the tumor, improved sparing of tumor-surrounding healthy tissue, and an increased relative biological effectiveness (RBE in the tumor target-volume in the case of ions heavier than protons. A crucial factor of the biological effects is DNA damage, of which DNA double strand breaks (DSBs are the most deleterious. The reparability of these lesions determines the cell survival after irradiation and thus the RBE. Interestingly, using phosphorylated H2AX as a DSB marker, our data in human fibroblasts revealed that after therapy-relevant spread-out Bragg Peak irradiation with carbon ions DSBs are very efficiently rejoined, despite an increased RBE for cell survival. This suggests that misrepair plays an important role in the increased RBE of heavy-ion radiation. Possible sources of erroneous repair will be discussed.

  20. Effects of haulm killing and gibberellic acid on seed potato (Solanum tuberosum L.) and techniques for micro- and minituber production in northern latitudes

    OpenAIRE

    Virtanen, E.

    2014-01-01

    Abstract Seed potato is the starting point in the potato (Solanum tuberosum L.) production chain. In order to secure potato production in a variety of production conditions, plant diseases must be controlled and the yield characteristics of the used cultivars ensured. In addition, production must be cost-effective. Characteristics particular to northern production conditions include long periods of daylight and a short growing season as well as a several months long seed potato storage pe...

  1. Effectiveness of multidimensional cancer survivor rehabilitation and cost-effectiveness of cancer rehabilitation in general: a systematic review

    NARCIS (Netherlands)

    Mewes, J.C.; Steuten, L.M.G.; IJzerman, M.J.; Harten, van W.H.

    2012-01-01

    Introduction. Many cancer survivors suffer from a combination of disease- and treatment-related morbidities and complaints after primary treatment. There is a growing evidence base for the effectiveness of monodimensional rehabilitation interventions; in practice, however, patients often participate

  2. The Study on Anti-cancer Effects of Distilling Fresh-ginseng Herbal acupuncture against implanted Sarcoma-180 in vivo and A549 human epithelial lung cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Hae-Young Jang

    2004-12-01

    no significant difference in interferon-γ. Conclusion : According to the results, fresh ginseng herbal-acupuncture took a little effects in cancer. In using distilled fresh ginseng herbal acupuncture has effect on Cox-2 decrease. However, the difference in concentration of fresh ginseng showed no effect on killing cancer cell. It is assumed that inaccurate concentration of herbal acupuncture and fresh ginseng component could be the reason for this result. Therefore, future consideration will be studies on herbal acupuncture concentration.

  3. Cu-Au alloy nanostructures coated with aptamers: a simple, stable and highly effective platform for in vivo cancer theranostics

    Science.gov (United States)

    Ye, Xiaosheng; Shi, Hui; He, Xiaoxiao; Yu, Yanru; He, Dinggeng; Tang, Jinlu; Lei, Yanli; Wang, Kemin

    2016-01-01

    As a star material in cancer theranostics, photoresponsive gold (Au) nanostructures may still have drawbacks, such as low thermal conductivity, irradiation-induced melting effect and high cost. To solve the problem, copper (Cu) with a much higher thermal conductivity and lower cost was introduced to generate a novel Cu-Au alloy nanostructure produced by a simple, gentle and one-pot synthetic method. Having the good qualities of both Cu and Au, the irregularly-shaped Cu-Au alloy nanostructures showed several advantages over traditional Au nanorods, including a broad and intense near-infrared (NIR) absorption band from 400 to 1100 nm, an excellent heating performance under laser irradiation at different wavelengths and even a notable photostability against melting. Then, via a simple conjugation of fluorophore-labeled aptamers on the Cu-Au alloy nanostructures, active targeting and signal output were simultaneously introduced, thus constructing a theranostic platform based on fluorophore-labeled, aptamer-coated Cu-Au alloy nanostructures. By using human leukemia CCRF-CEM cancer and Cy5-labeled aptamer Sgc8c (Cy5-Sgc8c) as the model, a selective fluorescence imaging and NIR photothermal therapy was successfully realized for both in vitro cancer cells and in vivo tumor tissues. It was revealed that Cy5-Sgc8c-coated Cu-Au alloy nanostructures were not only capable of robust target recognition and stable signal output for molecular imaging in complex biological systems, but also killed target cancer cells in mice with only five minutes of 980 nm irradiation. The platform was found to be simple, stable, biocompatible and highly effective, and shows great potential as a versatile tool for cancer theranostics.As a star material in cancer theranostics, photoresponsive gold (Au) nanostructures may still have drawbacks, such as low thermal conductivity, irradiation-induced melting effect and high cost. To solve the problem, copper (Cu) with a much higher thermal conductivity

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

    Directory of Open Access Journals (Sweden)

    Hye-Yeon Han

    2014-01-01

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

  5. Yoga-Based Rehabilitation Program in Reducing Physical and Emotional Side Effects in Patients With Cancer

    Science.gov (United States)

    2015-12-09

    Alopecia; Anxiety; Breast Carcinoma; Cognitive Side Effects of Cancer Therapy; Colorectal Carcinoma; Depression; Fatigue; Lung Carcinoma; Nausea and Vomiting; Pain; Psychological Impact of Cancer; Sleep Disorder; Weight Change

  6. 大蒜汁对旋毛虫幼虫杀灭效果研究%Kill effect of different concentrations of garlic juice on Trichinella spiralis muscle larva

    Institute of Scientific and Technical Information of China (English)

    罗卉; 张云; 肖明洋; 饶永庚; 张莉

    2014-01-01

    Objective By comparing the different concentrations of garlic juice soak meat containing trichinella spiralis muscle larva influence on mice's appeal, to assess the garlic juice on the killing effect of trichinella spiralis larvae. Methods Kunming mice were divided into 5 groups, only 30 fed by different concentrations of garlic juice concentration (100.00%, 50.00%, 25.00%, 12.50% respectively) and normal saline containing trichinella spiralis muscle larva soak for half an hour of meat, feeding profile control after 30 d kill mice, observation and counting muscle larvae. Results The mice fed by 100%, 50.00%, 25.00%, 12.50% concentration of garlic juice, and normal saline containing trichinella spiralis muscle larva soak for half an hour after meat, detection of trichinella spiralis muscle in muscle larvae number is 0, 10, 60, 140 and 235. Conclusion The infectivity of Trichinella spiralis muscle larvae was decreased after the treatment of certain concentrations with garlic juice.%目的:通过比较经不同浓度大蒜汁浸泡含旋毛虫肌幼虫的肉块对小鼠感染力的影响,来评估大蒜汁对旋毛虫幼虫的杀灭效果。方法30只昆明小鼠分为5组,喂食经不同浓度的大蒜汁(浓度分别为100.00%、50.00%、25.00%、12.50%)和生理盐水浸泡半小时含有旋毛虫肌幼虫的肉,饲喂30d后剖杀小鼠,观察和计数肌幼虫数。结果小鼠饲喂经100.00%、50.00%、25.00%、12.50%浓度大蒜汁和生理盐水浸泡半小时含有旋毛虫肌幼虫的肉后,在单位肌肉中检出旋毛虫肌幼虫数为0条、10条、60条、140条和235条。结论含旋毛虫肌幼虫的肉经一定浓度的大蒜汁浸泡后其旋毛虫肌幼虫的感染力会降低。

  7. Beyond the visible: Managing heart disease and cancer with nuclear science

    International Nuclear Information System (INIS)

    Heart disease and cancer are the world's number one and two killers. According to the World Health Organization (WHO), heart disease kills 17 million people a year - almost one third of all deaths worldwide - and cancer causes 7 million deaths every year. Early and accurate diagnosis is vital for effective treatment of both heart disease and cancer. Nuclear medicine techniques are helping to provide the vital information that doctors need to make decisions about treatment and disease management for patients

  8. Guidance on the assessment criteria for studies evaluating the effectiveness of stunning interventions regarding animal protection at the time of killing

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Animal Health and Welfare (AHAW

    2013-12-01

    Full Text Available This guidance defines the assessment process and the criteria that will be applied by the Animal Health and Welfare Panel to studies on known new or modified legal stunning interventions to determine their suitability for further assessment. The criteria that need to be fulfilled are eligibility criteria, reporting quality criteria and methodological quality criteria. The eligibility criteria are based upon the legislation and previously published scientific data. They focus on the intervention and the outcomes of interest, i.e. immediate onset of unconsciousness and insensibility or absence of avoidable pain, distress and suffering until the loss of consciousness and sensibility, and duration of the unconsciousness and insensibility (until death. If a study fulfils the eligibility criteria, it will be assessed regarding a set of reporting quality criteria that are based on the REFLECT and the STROBE statements. As a final step in this first assessment phase, the methodological quality of the submitted study will be assessed. If the criteria regarding eligibility, reporting quality and methodological quality are fulfilled, a full assessment of the animal welfare implications of the proposed alternative stunning intervention, including both pre-stunning and stunning phases, and an evaluation of the quality, strength and external validity of the evidence presented would be carried out at the next level of the assessment. In the case that the criteria regarding eligibility and reporting quality and methodological quality are not fulfilled, the assessment report of the panel will highlight the shortcomings and indicate where improvements are required before the study can be assessed further. In addition to the assessment criteria, the guidance also specifies general aspects applicable to studies on stunning interventions that should be considered when studying the effectiveness of stunning interventions.

  9. VP22-CD基因工程化载体对胶质瘤细胞体外杀伤作用的研究%Effect of VP22-CD genetically engineered vectors on killing glioma cells in vitro

    Institute of Scientific and Technical Information of China (English)

    米蕊芳; 金贵善; 张俊文; 周益强; 徐恒周; 程森; 刘福生

    2016-01-01

    目的 构建CD以及VP22-CD基因工程化载体,并探讨其在体外对胶质瘤细胞的杀伤作用.方法 利用聚合酶链式反应(PCR)得到CD以及VP22基因片段;利用In-fusion基因克隆方法将得到的基因片段插入到pEGFP-N1载体中,构建CD以及VP22-CD基因工程化载体;利用脂质体转染的方法将构建的基因工程化载体转染到胶质瘤细胞C6及U87细胞中,并通过体外光镜及荧光显微镜观察转染率;利用MTT比色法评价加入前药5-氟胞嘧啶后对转染后胶质瘤细胞的杀伤率.结果 (1)将CD基因或VP22-CD融合基因插入到pEGFP-CD载体中,构建得到pEGFP-CD以及pEGFP-VP22-CD载体.(2)pEGFP-CD及pEGFP-VP22-CD载体可转染入C6或U87胶质瘤细胞,转染率分别为2.5%和3.7%以及2.0%和4.1%.(3)在C6或U87细胞中转染pEGFP-CD或pEGFP-VP22-CD载体并加入前药5-氟胞嘧啶后,细胞的存活率分别为(30.36±0.63)%和(11.75±1.01)%以及(28.78±3.62)%和(18.26±2.27)%,与转染pEGFP-N1组相比差异均有统计学意义(均P<0.05).(4)在C6或U87细胞中加入前药5-氟胞嘧啶后,转染pEGFP-VP22-CD组与转染pEGFP-CD组相比差异均有统计学意义(均P<0.05).结论 CD/5-FC系统在体外对恶性胶质瘤细胞具有显著的杀伤作用和旁观者效应;并且穿梭蛋白VP22可进一步促进系统对细胞的杀伤作用.%Objectives To construct CD and VP22-CD genetically engineered vectors and to investigate their killing effects on glioma cells in vitro.Methods CD and VP22 gene segments were obtain using polymerase chain reaction (PCR).The obtained gene fragments were inserted into pEGFP-N1 vectors using in-fusion gene cloning method.CD and VP22-CD gene engineering vectors were constructed.The constructed gene engineering vectors were transfected into the glioma cells C6 and U87 cells using the liposome transfection method,and the transfection efficiency was observed through in vitro light microscope and fluorescence microscope.The kill

  10. Effects of Partial Substitution of Fish Meal by Soybean Meal with or without Heat-Killed Lactobacillus plantarum (LP20 on Growth Performance, Digestibility, and Immune Response of Amberjack, Seriola dumerili Juveniles

    Directory of Open Access Journals (Sweden)

    Mahmoud A. O. Dawood

    2015-01-01

    Full Text Available A 56-day feeding trial was conducted to evaluate the effects of supplemented diets with heat-killed Lactobacillus plantarum (HK-LP with graded levels of soybean meal (SBM on growth, digestibility, blood parameters, and immune response of Seriola dumerili (initial weight, 25.05 ± 0.1 g. Seven isonitrogenous and isolipidic practical diets were formulated to contain 0%, 15%, 30%, and 45% SBM, and each SBM level was supplemented with HK-LP at 0.0 and 0.1%. Fish fed diet which contains 30% SBM with HK-LP grew significantly faster than the other groups with notable feed intake and protein retention. Further, protein gain, whole body protein content, protease activity, protein, and lipid digestibility were significantly increased for all fish groups except for fish fed diet which contains 45% SBM with or without HK-LP. Interestingly, lysozyme activity was significantly enhanced in fish fed diets that contain 15% and 30% SBM with HK-LP. Hematocrit, peroxidase, and bactericidal activities revealed a significant increase in 30% SBM with HK-LP group. In addition, fish fed diets which contain 0% and 30% SBM with HK-LP showed higher tolerance against low-salinity stress compared with other groups. In conclusion, the addition of HK-LP to amberjack diets appeared to improve SBM utilization, immune response, and stress resistance.

  11. Effects of partial substitution of fish meal by soybean meal with or without heat-killed Lactobacillus plantarum (LP20) on growth performance, digestibility, and immune response of amberjack, Seriola dumerili juveniles.

    Science.gov (United States)

    Dawood, Mahmoud A O; Koshio, Shunsuke; Ishikawa, Manabu; Yokoyama, Saichiro

    2015-01-01

    A 56-day feeding trial was conducted to evaluate the effects of supplemented diets with heat-killed Lactobacillus plantarum (HK-LP) with graded levels of soybean meal (SBM) on growth, digestibility, blood parameters, and immune response of Seriola dumerili (initial weight, 25.05 ± 0.1 g). Seven isonitrogenous and isolipidic practical diets were formulated to contain 0%, 15%, 30%, and 45% SBM, and each SBM level was supplemented with HK-LP at 0.0 and 0.1%. Fish fed diet which contains 30% SBM with HK-LP grew significantly faster than the other groups with notable feed intake and protein retention. Further, protein gain, whole body protein content, protease activity, protein, and lipid digestibility were significantly increased for all fish groups except for fish fed diet which contains 45% SBM with or without HK-LP. Interestingly, lysozyme activity was significantly enhanced in fish fed diets that contain 15% and 30% SBM with HK-LP. Hematocrit, peroxidase, and bactericidal activities revealed a significant increase in 30% SBM with HK-LP group. In addition, fish fed diets which contain 0% and 30% SBM with HK-LP showed higher tolerance against low-salinity stress compared with other groups. In conclusion, the addition of HK-LP to amberjack diets appeared to improve SBM utilization, immune response, and stress resistance. PMID:25705667

  12. Pan-Bcl-2 inhibitor AT-101 enhances tumor cell killing by EGFR targeted T cells.

    Directory of Open Access Journals (Sweden)

    Archana Thakur

    Full Text Available Pancreatic cancer is a deadly disease and has the worst prognosis among almost all cancers and is in dire need of new and improved therapeutic strategies. Conditioning of tumor cells with chemotherapeutic drug has been shown to enhance the anti-tumor effects of cancer vaccines and adoptive cell therapy. In this study, we investigated the immunomodulatory effects of pan-Bcl-2 inhibitor AT-101 on pancreatic cancer (PC cell cytotoxicity by activated T cells (ATC. The effects of AT-101 on cytotoxicity, early apoptosis, and Granzyme B (GrzB and IFN-γ signaling pathways were evaluated during EGFR bispecific antibody armed ATC (aATC-mediated killing of L3.6pl and MiaPaCa-2 PC cells pre-sensitized with AT-101. We found that pretreatment of tumor cells with AT-101 enhanced susceptibility of L3.6pl and MiaPaCa-2 tumor cells to ATC and aATC-mediated cytotoxicity, which was in part mediated via enhanced release of cytolytic granule GrzB from ATC and aATC. AT-101-sensitized L3.6pl cells showed up-regulation of IFN-γ-mediated induction in the phosphorylation of Ser(727-Stat1 (pS(727-Stat1, and IFN-γ induced dephosphorylation of phospho-Tyr(705-Stat3 (pY(705-Stat3. Priming (conditioning of PC cells with AT-101 can significantly enhance the anti-tumor activity of EGFRBi armed ATC through increased IFN-γ induced activation of pS(727-Stat1 and inhibition of pY(705-Stat3 phosphorylation, and resulting in increased ratio of pro-apoptotic to anti-apoptotic proteins. Our results verify enhanced cytotoxicity after a novel chemotherapy conditioning strategy against PC that warrants further in vivo and clinical investigations.

  13. Recombinant Newcastle Disease Virus Anhinga Strain and TRAIL Protein Cooperate to Kill Cancer Cells in Culture%重组新城疫病毒Anhinga株与TRAIL蛋白协同杀伤肿瘤细胞

    Institute of Scientific and Technical Information of China (English)

    郝景波; 王文飞; 吴云舟; 刘铭瑶; 高振秋; 张巧; 颜世君; 李德山

    2011-01-01

    将新城疫病毒(Newscastle disease virus,NDV)Anhinga株的全长基因组cDNA克隆质粒、pTM1-L、pTM1-P、pTM1-NP表达质粒共转染稳定表达T7 RNA聚合酶的BSRT7/5细胞,得到拯救NDV病毒.通过PCR、酶切法、测序证明拯救病毒中存在引入的分子标签.通过血凝实验、蚀斑测定证明成功拯救病毒.并研究了该重组病毒对4种不同人肿瘤细胞的体外杀伤效果.首次证明重组Anhinga株对SMMC-7721细胞、A549细胞、HepG2细胞和SH-SY5Y细胞均有杀伤作用.该重组病毒主要诱导SMMC-7721细胞和A549细胞凋亡,诱导HepG2细胞和SH-SY5Y细胞坏死.TNF家族成员TRAIL蛋白可以显著增强NDV杀伤肿瘤细胞的效果.本实验为进一步研究重组NDV用于肿瘤治疗奠定基础.%The plasmid containing the full -length cDNA from Newcastle disease virus (NDV) Anhinga strain was cotransfected with helper plasmids encoding viral nucleoprotein, phosphoprotein and large polymerase protein into BSR T7/5 cells stably expressing the T7 RNA polymerase. The recombinant virus was rescued and amplified by inoculation of the supernatant from the transfected cells into the allantoic cavity of specific-pathogen free chicken embryos. By reverse transcriptase-PCR ( RT-PCR), restriction digestion and sequencing confirmation, the success of the rescue process was confirmed by identification of the unique molecular tag of the rescued virus. We also measured virus hemagglutination ( HA ) titer through the hemagglutination test ( HA test), and determined viral titers by plaque - formation units.Thus, we conclude that the virus was rescued successfully from the cDNA. We evaluated the cancer therapeutic potential of the rescued NDV in tumor cells, SH-SY5Y, A549, SMMC-7721 and HepG2 cells. Our data showed that the recombinant NDV could induce apoptosis in A549 and SMMC-7721 cells,and induce necrosis in SH-SY5Y and HepG-2 cells. The inhibitory effects of the recombinant virus on growth of the tumor cells

  14. Effect of Psychosocial Factors on Cancer Risk and Survival

    OpenAIRE

    ,

    2014-01-01

    Psychosocial factors such as personality traits and depression may alter immune and endocrine function, with possible effects on cancer incidence and survival. Although these factors have been extensively studied as risk and prognostic factors for cancer, the associations remain unclear. The author used data from prospective cohort studies in population-based and clinical databases to investigate these relations. The findings do not support the hypotheses that personality traits and depressio...

  15. Piperlongumine selectively kills glioblastoma multiforme cells via reactive oxygen species accumulation dependent JNK and p38 activation.

    Science.gov (United States)

    Liu, Ju Mei; Pan, Feng; Li, Li; Liu, Qian Rong; Chen, Yong; Xiong, Xin Xin; Cheng, Kejun; Yu, Shang Bin; Shi, Zhi; Yu, Albert Cheung-Hoi; Chen, Xiao Qian

    2013-07-19

    Piperlongumine (PL), a natural alkaloid isolated from the long pepper, may have anti-cancer properties. It selectively targets and kills cancer cells but leaves normal cells intact. Here, we reported that PL selectively killed glioblastoma multiforme (GBM) cells via accumulating reactive oxygen species (ROS) to activate JNK and p38. PL at 20μM could induce severe cell death in three GBM cell lines (LN229, U87 and 8MG) but not astrocytes in cultures. PL elevated ROS prominently and reduced glutathione levels in LN229 and U87 cells. Antioxidant N-acetyl-L-cysteine (NAC) completely reversed PL-induced ROS accumulation and prevented cell death in LN229 and U87 cells. In LN229 and U87 cells, PL-treatment activated JNK and p38 but not Erk and Akt, in a dosage-dependent manner. These activations could be blocked by NAC pre-treatment. JNK and p38 specific inhibitors, SB203580 and SP600125 respectively, significantly blocked the cytotoxic effects of PL in LN229 and U87 cells. Our data first suggests that PL may have therapeutic potential for one of the most malignant and refractory tumors GBM. PMID:23796709

  16. Identification and Structural Analysis of an l-Asparaginase Enzyme from Guinea Pig with Putative Tumor Cell Killing Properties*

    Science.gov (United States)

    Schalk, Amanda M.; Nguyen, Hien-Anh; Rigouin, Coraline; Lavie, Arnon

    2014-01-01

    The initial observation that guinea pig serum kills lymphoma cells marks the serendipitous discovery of a new class of anti-cancer agents. The serum cell killing factor was shown to be an enzyme with l-asparaginase (ASNase) activity. As a direct result of this observation, several bacterial l-asparaginases were developed and are currently approved by the Food and Drug Administration for the treatment of the subset of hematological malignancies that are dependent on the extracellular pool of the amino acid asparagine. As drugs, these enzymes act to hydrolyze asparagine to aspartate, thereby starving the cancer cells of this amino acid. Prior to the work presented here, the precise identity of this guinea pig enzyme has not been reported in the peer-reviewed literature. We discovered that the guinea pig enzyme annotated as H0W0T5_CAVPO, which we refer to as gpASNase1, has the required low Km property consistent with that possessed by the cell-killing guinea pig serum enzyme. Elucidation of the ligand-free and aspartate complex gpASNase1 crystal structures allows a direct comparison with the bacterial enzymes and serves to explain the lack of l-glutaminase activity in the guinea pig enzyme. The structures were also used to generate a homology model for the human homolog hASNase1 and to help explain its vastly different kinetic properties compared with gpASNase1, despite a 70% sequence identity. Given that the bacterial enzymes frequently present immunogenic and other toxic side effects, this work suggests that gpASNase1 could be a promising alternative to these bacterial enzymes. PMID:25320094

  17. Effect of S-1 combined with cisplatin intraperitoneal circulatory hyperthermia perfusion treatment on malignant molecule expression in gastric cancer patients with ascites as well as side effect assessment

    Institute of Scientific and Technical Information of China (English)

    Shuo Jian

    2016-01-01

    Objective:To study the effect of S-1 combined with cisplatin intraperitoneal circulatory hyperthermia perfusion on malignant molecule expression in gastric cancer patients with ascites as well as the related side effect.Methods: Gastric cancer patients with ascites who were treated in our hospital from February 2012 to July 2015 were selected as research subjects and randomly divided into perfusion chemotherapy group and routine chemotherapy group, and then overall chemotherapy conditions, ascites FGF molecule content, peripheral blood immune function indexes and the degree of side effect were compared between two groups. Results:Average treatment cycles of perfusion chemotherapy group were more than those of routine chemotherapy group, and ascites drainage volume within two cycles of chemotherapy was significantly less than that of routine chemotherapy group; after two cycles of chemotherapy, bFGF, FGF-2, FGF19 and FGFR4 content in ascites of perfusion chemotherapy group were significantly lower than those of routine chemotherapy group, CD3+CD4+, CD3+CD56+ and CD3-CD56+ cell content in peripheral blood were higher than those of routine chemotherapy group, and CD3+CD8+ cell content was lower than that of routine chemotherapy group; during chemotherapy, the number of cases with decreased numeration of leukocyte, abnormal liver function, abnormal kidney function and diarrhea of perfusion chemotherapy group were significantly lower than those of routine chemotherapy group.Conclusions: S-1 combined with cisplatin intraperitoneal circulatory hyperthermia perfusion chemotherapy can more effectively improve treatment compliance, suppress ascites, kill gastric cancer cells and improve immune function. It has fewer side effect and is the ideal way to treat gastric cancer with ascites.

  18. Killing superalgebras for Lorentzian four-manifolds

    Science.gov (United States)

    de Medeiros, Paul; Figueroa-O'Farrill, José; Santi, Andrea

    2016-06-01

    We determine the Killing superalgebras underpinning field theories with rigid unextended supersymmetry on Lorentzian four-manifolds by re-interpreting them as filtered deformations of mathbb{Z} -graded subalgebras with maximum odd dimension of the N = 1 Poincaré superalgebra in four dimensions. Part of this calculation involves computing a Spencer cohomology group which, by analogy with a similar result in eleven dimensions, prescribes a notion of Killing spinor, which we identify with the defining condition for bosonic supersymmetric backgrounds of minimal off-shell supergravity in four dimensions. We prove that such Killing spinors always generate a Lie superalgebra, and that this Lie superalgebra is a filtered deformation of a subalgebra of the N = 1 Poincaré superalgebra in four dimensions. Demanding the flatness of the connection defining the Killing spinors, we obtain equations satisfied by the maximally supersymmetric backgrounds. We solve these equations, arriving at the classification of maximally supersymmetric backgrounds whose associated Killing superalgebras are precisely the filtered deformations we classify in this paper.

  19. Photokilling of T-24 human bladder cancer cells with titanium dioxide.

    OpenAIRE

    Kubota, Y; Shuin, T; Kawasaki, C.; Hosaka, M; Kitamura, H.; Cai, R.; Sakai, H.; Hashimoto, K; Fujishima, A

    1994-01-01

    A photoexcited titanium dioxide surface has a strong ability to decompose water into hydrogen and oxygen. We have studied this effect in order to use it to kill cancer cells in vitro and in vivo. A distinct cell killing effect was observed on cultured T-24 human bladder cancer cells treated with titanium dioxide particles and 300-400 nm UV light irradiation. Titanium dioxide plus UV light also dramatically suppressed the tumour growth of T-24 cells that were implanted in nude mice. Cells cult...

  20. The killing of African trypanosomes by ethidium bromide.

    Directory of Open Access Journals (Sweden)

    Arnab Roy Chowdhury

    Full Text Available Introduced in the 1950s, ethidium bromide (EB is still used as an anti-trypanosomal drug for African cattle although its mechanism of killing has been unclear and controversial. EB has long been known to cause loss of the mitochondrial genome, named kinetoplast DNA (kDNA, a giant network of interlocked minicircles and maxicircles. However, the existence of viable parasites lacking kDNA (dyskinetoplastic led many to think that kDNA loss could not be the mechanism of killing. When recent studies indicated that kDNA is indeed essential in bloodstream trypanosomes and that dyskinetoplastic cells survive only if they have a compensating mutation in the nuclear genome, we investigated the effect of EB on kDNA and its replication. We here report some remarkable effects of EB. Using EM and other techniques, we found that binding of EB to network minicircles is low, probably because of their association with proteins that prevent helix unwinding. In contrast, covalently-closed minicircles that had been released from the network for replication bind EB extensively, causing them, after isolation, to become highly supertwisted and to develop regions of left-handed Z-DNA (without EB, these circles are fully relaxed. In vivo, EB causes helix distortion of free minicircles, preventing replication initiation and resulting in kDNA loss and cell death. Unexpectedly, EB also kills dyskinetoplastic trypanosomes, lacking kDNA, by inhibiting nuclear replication. Since the effect on kDNA occurs at a >10-fold lower EB concentration than that on nuclear DNA, we conclude that minicircle replication initiation is likely EB's most vulnerable target, but the effect on nuclear replication may also contribute to cell killing.

  1. α,β-Unsaturated Carbonyl System of Chalcone-Based Derivatives is Responsible for Broad Inhibition of Proteasomal Activity and Preferential Killing of Human Papilloma Virus (HPV)-Positive Cervical Cancer Cells

    OpenAIRE

    Bazzaro, Martina; Anchoori, Ravi K.; Mudiam, Mohana Krishna R; Issaenko, Olga; Kumar, Srinivas; Karanam, Balasubramanyam; Lin, Zhenhua; Vogel, Rachel Isaksson; Gavioli, Riccardo; Destro, Federica; Ferretti, Valeria; Roden, Richard BS; Khan, Saeed R.

    2010-01-01

    Proteasome inhibitors have potential for the treatment of cervical cancer. We describe the synthesis and biological characterization of a new series of 1,3-diphenylpropen-1-one (chalcone)-based derivatives lacking the boronic acid moieties of the previously reported chalcone-based proteasome inhibitor 3,5-bis-(4-boronic acid-benzylidene)-1-methyl-piperidin- 4-one and bearing a variety of amino acid substitutions on the amino-group of the 4-piperidone. Our lead compound 2 (RA-1) inhibits prote...

  2. 75 FR 62469 - Drawbridge Operation Regulations; Newtown Creek, Dutch Kills, English Kills, and Their...

    Science.gov (United States)

    2010-10-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulations; Newtown Creek, Dutch Kills, English Kills, and Their Tributaries, NY, Maintenance AGENCY: Coast Guard, DHS. ACTION: Notice of...

  3. 75 FR 30299 - Drawbridge Operation Regulations; Newtown Creek, Dutch Kills, English Kills, and Their...

    Science.gov (United States)

    2010-06-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulations; Newtown Creek, Dutch Kills, English Kills, and Their Tributaries, NY, Maintenance AGENCY: Coast Guard, DHS. ACTION: Notice of...

  4. Effects of vascularization on cancer nanochemotherapy outcomes

    Science.gov (United States)

    Paiva, L. R.; Ferreira, S. C.; Martins, M. L.

    2016-08-01

    Cancer therapy requires anticancer agents capable of efficient and uniform systemic delivery. One promising route to their development is nanotechnology. Here, a previous model for cancer chemotherapy based on a nanosized drug carrier (Paiva et al., 2011) is extended by including tissue vasculature and a three-dimensional growth. We study through computer simulations the therapy against tumors demanding either large or small nutrient supplies growing under different levels of tissue vascularization. Our results indicate that highly vascularized tumors demand more aggressive therapies (larger injected doses administrated at short intervals) than poorly vascularized ones. Furthermore, nanoparticle endocytic rate by tumor cells, not its selectivity, is the major factor that determines the therapeutic success. Finally, our finds indicate that therapies combining cytotoxic agents with antiangiogenic drugs that reduce the abnormal tumor vasculature, instead of angiogenic drugs that normalize it, can lead to successful treatments using feasible endocytic rates and administration intervals.

  5. 9 CFR 113.206 - Wart Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Wart Vaccine, Killed Virus. 113.206... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart Vaccine, Killed Virus. Wart Vaccine, Killed Virus, shall be...

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

    Science.gov (United States)

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

    2010-08-01

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

  7. Strong synergy of heat and modulated electromagnetic field in tumor cell killing

    Energy Technology Data Exchange (ETDEWEB)

    Andocs, Gabor [Frederic Joliot Curie National Research Inst. for Radiobiology and Radiohygiene, Budapest (Hungary)]|[St. Istvan Univ., Budapest (Hungary). Dept. of Pharmacology and Toxicology; Renner, Helmut [Klinikum Nuernberg (Germany). Clinic of Radiooncology; Balogh, Lajos [Frederic Joliot Curie National Research Inst. for Radiobiology and Radiohygiene, Budapest (Hungary); Fonyad, Laszlo [Semmelweis Univ., Budapest (Hungary). 1. Dept. of of Pathology and Experimental Cancer Research; Jakab, Csaba [St. Istvan Univ., Budapest (Hungary). Dept. of Pathology; Szasz, Andras [St. Istvan Univ., Goedoelloe (Hungary). Biotechnics Dept.

    2009-02-15

    Hyperthermia is an emerging complementary method in radiooncology. Despite many positive studies and comprehensive reviews, the method is not widely accepted as a combination to radiotherapy. Modulated electrohyperthermia (mEHT; capacitive, electric field modulated, 13.56 MHz) has been used in clinical practice for almost 2 decades in Germany, Austria and Hungary. This in vivo study in nude mice xenograft tumors compares mEHT with 'classic' radiative hyperthermia (radHT). Nude mice were xenografted with HT29 human colorectal carcinoma cells. 28 mice in four groups with seven animals each and two tumors per animal (totally 56 tumors) were included in the present study: group 1 as untreated control; group 2 treated with radHT at 42 C; group 3 treated with mEHT at identical 42 C; group 4 treated with mEHT at 38 C (by intensively cooling down the tumor). 24 h after treatment, animals were sacrificed and the tumor cross sections studied by precise morphological methods for the respective relative amount of 'dead' tumor cells. The effect of mEHT established a double effect as a synergy between the purely thermal (temperature-dependent) and nonthermal (not directly temperature-dependent) effects. The solely thermal enhancement ratio (TER) of cell killing was shown to be 2.9. The field enhancement ratio (FER) at a constant temperature of 42 C was measured as 3.2. Their complex application significantly increased the therapeutic enhancement to 9.4. mEHT had a remarkable cancer cell-killing effect in a nude mice xenograft model. (orig.)

  8. Photoexcited quantum dots for killing multidrug-resistant bacteria

    Science.gov (United States)

    Courtney, Colleen M.; Goodman, Samuel M.; McDaniel, Jessica A.; Madinger, Nancy E.; Chatterjee, Anushree; Nagpal, Prashant

    2016-05-01

    Multidrug-resistant bacterial infections are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics. Metal nanoparticles can induce cell death, yet the toxicity effect is typically nonspecific. Here, we show that photoexcited quantum dots (QDs) can kill a wide range of multidrug-resistant bacterial clinical isolates, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Escherichia coli, and extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Salmonella typhimurium. The killing effect is independent of material and controlled by the redox potentials of the photogenerated charge carriers, which selectively alter the cellular redox state. We also show that the QDs can be tailored to kill 92% of bacterial cells in a monoculture, and in a co-culture of E. coli and HEK 293T cells, while leaving the mammalian cells intact, or to increase bacterial proliferation. Photoexcited QDs could be used in the study of the effect of redox states on living systems, and lead to clinical phototherapy for the treatment of infections.

  9. Synergistic effect of chimeric antigen receptors and cytokine-induced killer cells: An innovative combination for cancer therapy

    Directory of Open Access Journals (Sweden)

    Binh Thanh Vu

    2016-06-01

    Full Text Available In recent years, the combination of gene and immunotherapy for cancer treatment has been regarded as innovative and promising; together, both therapies can help overcome limitations associated with conventional treatments. In order to augment anti-cancer efficacy and to maintain the specificity of antibody therapy, chimeric antigen receptor (CAR-modified T cells, directed toward tumor-specific antigens, have emerged as a novel and promising therapeutic platform. CARs consist of a B cell receptor (BCR-derived extracellular domain and T cell receptor (TCR-associated signaling elements. Cytokine-induced killer (CIK cells are the effector immune cells that can be activated ex vivo and possess both the anti-tumor potency of T lymphocytes and the non-major histocompatibility complex-restricted elimination of natural killer cells. With their pre-eminent ability for robust proliferation, CIK cells may overcome the main limitations of adoptive immunotherapy strategies. CIK cells have strong tumor cell killing capacity; they are effective against a wide variety of malignant tumors and have been shown to be safe in cancer patients. This review summarizes the characteristics of CARs which make them attractive for in cancer treatment strategies. In addition, the role of CIK cells and the advantages of combining CIK cells with CAR-based therapy will be discussed. Scientific evidence to support their combined therapeutic application will be highlighted, with a focus on how their innovative combination may be translated into cancer clinical trials. [Biomed Res Ther 2016; 3(6.000: 653-665

  10. Did the greenhouse effect kill the dinosaurs

    Science.gov (United States)

    Okeefe, John D.; Ahrens, Thomas J.

    1988-01-01

    According to a study at the California Institute of Technology, the carbon dioxide (CO2) released by a meteor or comet striking the earth 65 million years ago could have doomed many species of animals and plants by dramatically raising temperatures worldwide. The results of this study will be presented at the 19th Lunar and Planetary Science Conference in Houston, Texas.

  11. Effectiveness of irradiation in killing pathogens

    International Nuclear Information System (INIS)

    United States Environmental Protection Agency regulations include gamma ray irradiation of sludge as an approved Process to Further Reduce Pathogens (PFRP) prior to land application. Research at Sandia National Laboratories on pathogen inactivation in sludge by gamma irradiation has demonstrated that the 1 Mrad PFRP dose is capable, by itself, of eliminating bacterial, fungal, and parasitic pathogens from sludge. Gamma irradiation of sludge in conjunction with the required Processes to Significantly Reduce Pathogens (PSRP) should also eliminate the viral hazard from wastewater sludges

  12. Combination Effect of Nimotuzumab with Radiation in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hye Kyung; Kim, Mi Sook; Jeong, Jae Hoon [Korea Institute of Radiologicaland Medical Sciences, Seoul (Korea, Republic of)

    2010-11-15

    To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.

  13. On the algebraic structure of Killing superalgebras

    CERN Document Server

    Figueroa-O'Farrill, José

    2016-01-01

    We study the algebraic structure of the Killing superalgebra of a supersymmetric $11$-dimensional supergravity background and show that it is isomorphic to a filtered deformation of a $\\mathbb Z$-graded subalgebra of the Poincar\\'e superalgebra. We then re-interpret the classification problem for backgrounds which preserve more than half of the supersymmetry as the classification problem of certain admissible filtered subdeformations of the Poincar\\'e superalgebra. In particular we relate the bosonic field equations of $11$-dimensional supergravity to the Jacobi identity of the Killing superalgebra and show in this way that preserving more than half the supersymmetry implies the bosonic field equations.

  14. Killing spinors of some supergravity solutions

    CERN Document Server

    Arean, D

    2006-01-01

    We compute explicitly the Killing spinors of some ten dimensional supergravity solutions. We begin with a 10d metric of the form $\\RR^{1,3}\\times{\\cal Y}_6$, where ${\\cal Y}_6$ is either the singular conifold or any of its resolutions. Then, we move on to the Klebanov-Witten and Klebanov-Tseytlin backgrounds, both constructed over the singular conifold; and we also study the Klebanov-Strassler solution, built over the deformed conifold. Finally, we determine the form of the Killing spinors for the non-commutative deformation of the Maldacena-N\\'u\\~nez geometry.

  15. 鸡新城疫二价油乳剂灭活苗的研制及免疫效果%Preparation of a divalent oil emulsion killed vaccine against Ne wcastle disease and its immunogenic effects

    Institute of Scientific and Technical Information of China (English)

    张晓根; 何雷堂

    2001-01-01

    Chick blastocysts were vaccinated with ND Lasota atte nuated strain and NDV local isolated strain (F gene type Ⅶ)-HD1,respecti vely,followed by collection of allantoic fluid,preparation of viral antigen flui d,proportionate mixing after being killed with formalin,and emulsion into a oil -coated water-type emulsion vaccine with a white oil adjuvant.All technical pa rameters determined of the divalent vaccine showed that it was safe without side effects.Immunological protection happened with 100% challenging protection 3 we eks after vaccination.Examination of immunological antibodies 2 weeks after vacc ination indicated that the antibody titer for NDHI reached 81og2.Application of this vaccine on some breeding chicken farms and laying hen farms has produced sa tisfactory results,effectively keeping Newcastle disease in check.%用NDLasota弱毒株、NDV地方分离株(F基因Ⅶ型)—HD1,分别接种鸡胚,收集尿囊液,制备病毒抗原液,福尔马林灭活后按一定比例混合,与白油佐剂乳化成油包水型乳剂疫苗,并对二价苗各项技术指标进行了测定,证明本疫苗安全、无副作用,接种后3周产生免疫保护,攻毒保护率为100%,接种2周后通过免疫抗体检测,NDHI抗体效价达8log2.疫苗在鸡场应用,获得了满意效果,有效的控制了ND的发生与流行.

  16. Do Mouthwashes Really Kill Bacteria?

    Science.gov (United States)

    Corner, Thomas R.

    1984-01-01

    Errors in determining the effectiveness of mouthwashes, disinfectants, and other household products as antibacterial agents may result from using broth cultures and/or irregularly shaped bits of filter paper. Presents procedures for a better technique and, for advanced students, two additional procedures for introducing quantitative analysis into…

  17. Platelets kill intraerythrocytic malarial parasites and mediate survival to infection.

    Science.gov (United States)

    McMorran, Brendan J; Marshall, Vikki M; de Graaf, Carolyn; Drysdale, Karen E; Shabbar, Meriam; Smyth, Gordon K; Corbin, Jason E; Alexander, Warren S; Foote, Simon J

    2009-02-01

    Platelets play a critical role in the pathogenesis of malarial infections by encouraging the sequestration of infected red blood cells within the cerebral vasculature. But platelets also have well-established roles in innate protection against microbial infections. We found that purified human platelets killed Plasmodium falciparum parasites cultured in red blood cells. Inhibition of platelet function by aspirin and other platelet inhibitors abrogated the lethal effect human platelets exert on P. falciparum parasites. Likewise, platelet-deficient and aspirin-treated mice were more susceptible to death during erythrocytic infection with Plasmodium chabaudi. Both mouse and human platelets bind malarial-infected red cells and kill the parasite within. These results indicate a protective function for platelets in the early stages of erythrocytic infection distinct from their role in cerebral malaria.

  18. 硝唑尼特体外抑杀阴道毛滴虫效果观察%Inhibiting and killing effect of nitazoxanide on Trichomonas vaginalis in vitro

    Institute of Scientific and Technical Information of China (English)

    丁鹤; 刘畅; 刘鑫; 曲晗; 宫鹏涛; 李建华; 杨举; 张西臣

    2011-01-01

    Objective To observed the inhibiting and killing effect of the Nitazoxanide on Trichomonas vaginalis in vitro.Methods Different concentrations at 2, 1, 0.5, 0.25, 0.125, 0.062 5 and 0.031 25 mg/ml)and different times at 12 h and 24 h were selected to act on the two kinds of trophozoites (T.vaginalis infected with T.vaginalis virus (TVV) and T.vaginalis without TVV ).Meanwhile Metronidazole as the drug control.Results With the concentrations and action time increased, the inhibition rates of Nitazoxanide on T.vaginalis were raised.Using microscope we observed the activity of the trophozoites has decreased and some precipitation of death trophozoites at the bottom of medium.The trophozoites looked disintegration with appearance of vacuoles in cytoplasm, exfoliation of flagella, distorted with nucleus and membrance rupture.The statistical analysis revealed that the inhibition rate of Nitazoxanide on the two kinds of trophozoites had no distinction(x2 =0.12, P>0.05).However, there was a significant difference between Metronidazole and Nitazoxanide acted on T.vaginalis without TVV (x2 = 4.43, P<0.01).The inhibition rate of the Metronidazole and Nitazoxanide(1 mg/ml)was 81.06% and 100% at 24 h, respectively.Conclusion It was concluded that the Nitazoxanide has a good inhibiting and killing effect on T.vaginalis.In addition , the effectiveness of inhibition of Nitazoxanide on T.vaginalis without TVV may be superiorer than Metronidazole in vitro test.%目的 观察硝唑尼特体外抑杀阴道毛滴虫效果.方法 分别以2、1、0.5、0.25、0.125、0.062 5和0.031 25mg/ml,硝唑尼特作用于阴道毛滴虫携病毒株与无病毒株12和24 h,观察体外抑杀效果.实验以甲硝唑作为药物对照.结果 随着药物浓度的增加和作用时间的延长,硝唑尼特对两种虫株的抑制率均增高,显微镜下可见滋养体活力下降,培养基底部有死亡虫体沉淀,染色后可见滋养体细胞质内有空泡,

  19. Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms.

    Directory of Open Access Journals (Sweden)

    Andrea M Binnebose

    Full Text Available Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a therapeutic approach that shows promise in the treatment of onchocerciasis and lymphatic filariasis. Here we demonstrate the use of a biodegradable polyanhydride nanoparticle-based platform for the co-delivery of the antibiotic doxycycline with the antiparasitic drug, ivermectin, to reduce microfilarial burden and rapidly kill adult worms. When doxycycline and ivermectin were co-delivered within polyanhydride nanoparticles, effective killing of adult female Brugia malayi filarial worms was achieved with approximately 4,000-fold reduction in the amount of drug used. Additionally the time to death of the macrofilaria was also significantly reduced (five-fold when the anti-filarial drug cocktail was delivered within polyanhydride nanoparticles. We hypothesize that the mechanism behind this dramatically enhanced killing of the macrofilaria is the ability of the polyanhydride nanoparticles to behave as a Trojan horse and penetrate the cuticle, bypassing excretory pumps of B. malayi, and effectively deliver drug directly to both the worm and Wolbachia at high enough microenvironmental concentrations to cause death. These provocative findings may have significant consequences for the reduction in the amount of drug and the length of treatment required for filarial infections in terms of patient compliance and reduced cost of treatment.

  20. Cancer and non-cancer effects in Japanese atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Little, M P [Department of Epidemiology and Public Health, Imperial College, London W2 1PG (United Kingdom)], E-mail: mark.little@imperial.ac.uk

    2009-06-01

    The survivors of the atomic bombings in Hiroshima and Nagasaki are a general population of all ages and sexes and, because of the wide and well characterised range of doses received, have been used by many scientific committees (International Commission on Radiological Protection (ICRP), United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), Biological Effects of Ionizing Radiations (BEIR)) as the basis of population cancer risk estimates following radiation exposure. Leukaemia was the first cancer to be associated with atomic bomb radiation exposure, with preliminary indications of an excess among the survivors within the first five years after the bombings. An excess of solid cancers became apparent approximately ten years after radiation exposure. With increasing follow-up, excess risks of most cancer types have been observed, the major exceptions being chronic lymphocytic leukaemia, and pancreatic, prostate and uterine cancer. For most solid cancer sites a linear dose response is observed, although in the latest follow-up of the mortality data there is evidence (p = 0.10) for an upward curvature in the dose response for all solid cancers. The only cancer sites which exhibit (upward) curvature in the dose response are leukaemia, and non-melanoma skin and bone cancer. For leukaemia the dose response is very markedly upward curving, indeed largely describable as a pure quadratic dose response, particularly in the low dose (0-2 Sv) range. Even 55 years after the bombings over 40% of the Life Span Study cohort remain alive, so continued follow-up of this group is vital for completing our understanding of long-term radiation effects in people. In general, the relative risks per unit dose among the Japanese atomic bomb survivors are greater than those among comparable subsets in studies of medically exposed individuals. Cell sterilisation largely accounts for the discrepancy in relative risks between these two populations, although other

  1. A Gompertzian model with random effects to cervical cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Mazlan, Mazma Syahidatul Ayuni; Rosli, Norhayati [Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, 26300 Gambang, Pahang (Malaysia)

    2015-05-15

    In this paper, a Gompertzian model with random effects is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via maximum likehood estimation. We apply 4-stage Runge-Kutta (SRK4) for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of the cervical cancer growth. Low values of root mean-square error (RMSE) of Gompertzian model with random effect indicate good fits.

  2. Synergistic Effects of PPARγ Ligands and Retinoids in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2008-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are members of the nuclear receptor superfamily. The activation of PPARs by their specific ligands is regarded as one of the promising strategies to inhibit cancer cell growth. However, recent clinical trials targeting several common cancers showed no beneficial effect when PPAR ligands are used as a monotherapy. Retinoid X receptors (RXRs, which play a critical role in normal cell proliferation as a master regulator for nuclear receptors, preferentially form heterodimers with PPARs. A malfunction of RXRα due to phosphorylation by the Ras/MAPK signaling pathway is associated with the development of certain types of human malignancies. The activation of PPARγ/RXR heterodimer by their respective ligands synergistically inhibits cell growth, while inducing apoptosis in human colon cancer cells when the phosphorylation of RXRα was inhibited. We herein review the synergistic antitumor effects produced by the combination of the PPAR, especially PPARγ, ligands plus other agents, especially retinoids, in a variety of human cancers. We also focus on the phosphorylation of RXRα because the inhibition of RXRα phosphorylation and the restoration of its physiological function may activate PPAR/RXR heterodimer and, therefore, be a potentially effective and critical strategy for the inhibition of cancer cell growth.

  3. Distinct roles of Ape1 protein, an enzyme involved in DNA repair, in high or low linear energy transfer ionizing radiation-induced cell killing.

    Science.gov (United States)

    Wang, Hongyan; Wang, Xiang; Chen, Guangnan; Zhang, Xiangming; Tang, Xiaobing; Park, Dongkyoo; Cucinotta, Francis A; Yu, David S; Deng, Xingming; Dynan, William S; Doetsch, Paul W; Wang, Ya

    2014-10-31

    High linear energy transfer (LET) radiation from space heavy charged particles or a heavier ion radiotherapy machine kills more cells than low LET radiation, mainly because high LET radiation-induced DNA damage is more difficult to repair. Relative biological effectiveness (RBE) is the ratio of the effects generated by high LET radiation to low LET radiation. Previously, our group and others demonstrated that the cell-killing RBE is involved in the interference of high LET radiation with non-homologous end joining but not homologous recombination repair. This effect is attributable, in part, to the small DNA fragments (≤40 bp) directly produced by high LET radiation, the size of which prevents Ku protein from efficiently binding to the two ends of one fragment at the same time, thereby reducing non-homologous end joining efficiency. Here we demonstrate that Ape1, an enzyme required for processing apurinic/apyrimidinic (known as abasic) sites, is also involved in the generation of small DNA fragments during the repair of high LET radiation-induced base damage, which contributes to the higher RBE of high LET radiation-induced cell killing. This discovery opens a new direction to develop approaches for either protecting astronauts from exposure to space radiation or benefiting cancer patients by sensitizing tumor cells to high LET radiotherapy. PMID:25210033

  4. Antitumor effect of recombinant human endostatin combined with cisplatin on rats with transplanted Lewis lung cancer

    Institute of Scientific and Technical Information of China (English)

    Zhan-Wu Yu; Ying-Hua Ju; Cheng-Liang Yang; Han-Bing Yu; Quan Luo; Ye-Gang Ma; Yong-Yu Liu

    2015-01-01

    smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor.Conclusions:Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.

  5. Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    Min-Hua Zheng; Bao-Ming Yu; Bo Feng; Jian-Wen Li; Ai-Guo Lu; Ming-Liang Wang; Wei-Guo Hu; Ji-Yuan Sun; Yan-Yan Hu; Jun-Jun Ma

    2005-01-01

    AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT.METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7th d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay.RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F= 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (χ2 = 25.67, P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups.CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer.The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.

  6. Neurobiological effects of melatonin as related to cancer.

    Science.gov (United States)

    Hoang, Ba X; Shaw, David G; Pham, Phuong T; Levine, Stephen A

    2007-12-01

    Melatonin is a neurohormone naturally found in humans. Melatonin plays a role in maintaining sleep-wake rhythms; supplementation may help to regulate sleep disturbance that occur with jet lag, rotating shift-work and depression. Preliminary study of melatonin has shown potential for use in the treatment of epilepsy, tinnitus, migraine and neurodegenerative diseases. The latest publication in the Journal of Pineal Research by Edward Mills and colleagues has shown a compelling role of melatonin for the treatment of cancer. Melatonin's consistent relationship with cancer has been shown in many studies assessing links between shift work and cancer rates. High levels of melatonin have been linked to slower cancer progression. How melatonin affects cancer remains largely unclear. Although previous studies suggest different possible mechanisms, many of them are far distant from the primary physiological role of melatonin as a neurohormone. Conflicting studies are found on the role of melatonin in neurodegenerative diseases and cancer. In this article, we try to build and substantiate a neurobiological concept for the anticancer effects of melatonin. PMID:18090123

  7. Influence of low-dose naloxone on the pain-killing effect of opium receptor agonist%小剂量纳络酮对阿片受体激动剂镇痛效应的影响

    Institute of Scientific and Technical Information of China (English)

    何珂; 何毅; 刘毅; 么继钢; 卓九五; 刘旭; 戴体俊

    2009-01-01

    目的:观察小剂量纳络酮(naloxone,N)对阿片受体(部分)激动剂镇痛效应的影响.方法:将小鼠分为芬太尼(fenta-nyl,F)、瑞芬太尼(remifentanil,R)及布托啡诺(butorphanol,B)3大组,每组再分为4小组:即F+NS组、F+N(100,10,1 ng)组,R+NS组、R+N(100,10,1 ng)组以及B+NS组、B+N(100,10,1 ng)组.用热板实验和扭体实验观察纳络酮对以上药物镇痛小鼠热板实验痛阈(pain threshold in hot-plate test,HPPT)和扭体次数的影响.结果:分别与F+NS组、R+NS组或B+NS组比较,F+N(10 ng)组、R+N(100,10,1 ng)组的HPPT增高(P0.05);F+N(100,10 ng)组、R+N(100,10,1 ng)组、B+N(10 ng)组小鼠扭体次数均减少(P0. 05);The stretching numbers of mice of F+N(100,10 ng) group, R+N (100,10,1 ng) group, B+N (10 ng) group decreased (F<0. 05 or P<0. 01). CONCLUSION Low-dose naloxone can increase the pain-killing effect of opium recep-tor (partial) agonist.

  8. Effects of disrupting the polyketide synthase gene WdPKS1 in Wangiella [Exophiala] dermatitidis on melanin production and resistance to killing by antifungal compounds, enzymatic degradation, and extremes in temperature

    Directory of Open Access Journals (Sweden)

    Mandal Piyali

    2006-06-01

    Full Text Available Abstract Background Wangiella dermatitidis is a human pathogenic fungus that is an etiologic agent of phaeohyphomycosis. W. dermatitidis produces a black pigment that has been identified as a dihydroxynaphthalene melanin and the production of this pigment is associated with its virulence. Cell wall pigmentation in W. dermatitidis depends on the WdPKS1 gene, which encodes a polyketide synthase required for generating the key precursor for dihydroxynaphthalene melanin biosynthesis. Results We analyzed the effects of disrupting WdPKS1 on dihydroxynaphthalene melanin production and resistance to antifungal compounds. Transmission electron microscopy revealed that wdpks1Δ-1 yeast had thinner cell walls that lacked an electron-opaque layer compared to wild-type cells. However, digestion of the wdpks1Δ-1 yeast revealed small black particles that were consistent with a melanin-like compound, because they were acid-resistant, reacted with melanin-binding antibody, and demonstrated a free radical signature by electron spin resonance analysis. Despite lacking the WdPKS1 gene, the mutant yeast were capable of catalyzing the formation of melanin from L-3,4-dihyroxyphenylalanine. The wdpks1Δ-1 cells were significantly more susceptible to killing by voriconazole, amphotericin B, NP-1 [a microbicidal peptide], heat and cold, and lysing enzymes than the heavily melanized parental or complemented strains. Conclusion In summary, W. dermatitidis makes WdPKS-dependent and -independent melanins, and the WdPKS1-dependent deposition of melanin in the cell wall confers protection against antifungal agents and environmental stresses. The biological role of the WdPKS-independent melanin remains unclear.

  9. Gas Well Blowout Kills 243 People

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ At least 243 people have been killed and scores of others poisoned in a devastating blowout at a natural gas field in Southwest China's Chongqing municipality on December 24. The accident happened at the Chuandongbei gas field in Kaixian county of Chongqing municipality.

  10. Killing Hitler: A Writer's Journey and Angst.

    Science.gov (United States)

    Thaler, Paul

    2002-01-01

    Describes the author's experiences in preparing a talk that "evokes the specter" of Adolf Hitler and in writing an historical account of a British plot to kill Hitler. Address the question of why the British allowed him to live that final year of the war. Muses on why scholars write, and the impact of violence and terrorism. (SG)

  11. The evolution of reduced microbial killing.

    Science.gov (United States)

    Vriezen, Jan A C; Valliere, Michael; Riley, Margaret A

    2009-01-01

    Bacteria engage in a never-ending arms race in which they compete for limited resources and niche space. The outcome of this intense interaction is the evolution of a powerful arsenal of biological weapons. Perhaps the most studied of these are colicins, plasmid-based toxins produced by and active against Escherichia coli. The present study was designed to explore the molecular responses of a colicin-producing strain during serial transfer evolution. What evolutionary changes occur when colicins are produced with no target present? Can killing ability be maintained in the absence of a target? To address these, and other, questions, colicinogenic strains and a noncolicinogenic ancestor were evolved for 253 generations. Samples were taken throughout the experiment and tested for killing ability. By the 38th transfer, a decreased killing ability and an increase in fitness were observed in the colicin-producing strains. Surprisingly, DNA sequence determination of the colicin plasmids revealed no changes in plasmid sequences. However, a set of chromosomally encoded loci experienced changes in gene expression that were positively associated with the reduction in killing. The most significant expression changes were observed in DNA repair genes (which were downregulated in the evolved strains), Mg ion uptake genes (which were upregulated), and late prophage genes (which were upregulated). These results indicate a fine-tuned response to the evolutionary pressures of colicin production, with far more genes involved than had been anticipated. PMID:20333208

  12. Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP.

    Science.gov (United States)

    Chen, Yong; Liu, Ju Mei; Xiong, Xin Xin; Qiu, Xin Yao; Pan, Feng; Liu, Di; Lan, Shu Jue; Jin, Si; Yu, Shang Bin; Chen, Xiao Qian

    2015-03-20

    Hepatocellular carcinomas (HCC) are highly malignant and aggressive tumors lack of effective therapeutic drugs. Piperlongumine (PL), a natural product isolated from longer pepper plants, is recently identified as a potent cytotoxic compound highly selective to cancer cells. Here, we reported that PL specifically suppressed HCC cell migration/invasion via endoplasmic reticulum (ER)-MAPKs-CHOP signaling pathway. PL selectively killed HCC cells but not normal hepatocytes with an IC50 of 10-20 µM while PL at much lower concentrations only suppressed HCC cell migration/invasion. PL selectively elevated reactive oxygen species (ROS) in HCC cells, which activated or up-regulated downstream PERK/Ire 1α/Grp78, p38/JNK/Erk and CHOP subsequently. Administration of antioxidants completely abolished PL's effects on cell death and migration/invasion. However, pharmacological inhibition of ER stress-responses or MAPKs signaling pathways with corresponding specific inhibitors only reversed PL's effect on cell migration/invasion but not on cell death. Consistently, knocking-down of CHOP by RNA interference only reversed PL-suppressed HCC cell migration. Finally, PL significantly suppressed HCC development and activated the ER-MAPKs-CHOP signaling pathway in HCC xenografts in vivo. Taken together, PL selectively killed HCC cells and preferentially inhibited HCC cell migration/invasion via ROS-ER-MAPKs-CHOP axis, suggesting a novel therapeutic strategy for the highly malignant and aggressive HCC clinically. PMID:25788268

  13. The Effect of National Cancer Screening on Disparity Reduction in Cancer Stage at Diagnosis by Income Level.

    Directory of Open Access Journals (Sweden)

    Hye-Min Jung

    Full Text Available Early detection of cancer is an effective and efficient cancer management strategy. In South Korea, the National Health Insurance administers the National Cancer Screening Program to its beneficiaries. We examined the impact of the National Cancer Screening Program on socioeconomic disparities in cancer stage at diagnosis.Cancer patients registered in the Korean Central Cancer Registry from January 1, 2010 to December 31, 2010 with a diagnosis of gastric cancer (n = 22,470, colon cancer (n = 16,323, breast cancer (n = 10,076, or uterine cervical cancer (n = 2,447 were included. Income level was divided into three groups according to their monthly contribution of National Health Insurance. We employed absolute (age-standardized prevalence rate, slope index of inequality and relative (relative index of inequality measures to separately examine social disparities among participants and non-participants of the National Cancer Screening Program in terms of the early-stage rate.Age-standardized prevalence rates of early-stage by income group were always higher in participants than in non-participants. Furthermore, the age-standardized prevalence rate of early-stage in the low income group of the participants was also higher than that of the high income group of the non-participants. The sizes of disparities (both slope index of inequality and relative index of inequality are smaller in participants compared to non-participants.National Cancer Screening Program participation reduced income disparity in cancer stage at diagnosis. Population-based cancer screening programs can be used as an effective measure to reduce income disparity in cancer care.

  14. Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4 exhibits growth inhibitory effects in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Shayan eSarkar

    2015-10-01

    Full Text Available The gene Par-4 (Prostate Apoptosis Response 4 was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4 selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5′ AMV and apoplast signal peptide (aTP in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. Transgene integration was confirmed by genomic DNA PCR, Southern and Northern blotting, Real-time PCR and Nuclear run-on assays. Results of Western blot analysis and ELISA confirmed expression of recombinant SAC-Par-4-GFP protein and it was as high as 0.15% of total soluble protein. In addition, we found that targeting of plant recombinant SAC-Par-4-GFP to the apoplast and endoplasmic reticulum (ER was essential for the stability of plant recombinant protein in comparison to the bacterial derived SAC-Par-4. Deglycosylation analysis demonstrated that ER-targeted SAC-Par-4-GFP-SEKDEL undergoes O-linked glycosylation unlike apoplast-targeted SAC-Par-4-GFP. Furthermore, various in vitro studies like mammalian cells proliferation assay (MTT, apoptosis induction assays, and NF-κB suppression suggested the cytotoxic and apoptotic properties of plant-derived SAC-Par-4-GFP against multiple prostate cancer cell lines. Additionally, pre-treatment of MAT-LyLu prostate cancer cells with purified SAC-Par-4-GFP significantly delayed the onset of tumor in a syngeneic rat prostate cancer model. Taken altogether, we proclaim that plant made SAC-Par-4 may become a useful alternate therapy for effectively alleviating cancer in the new era.

  15. Sol-gel synthesis of magnetic TiO2 microspheres and characterization of their in vitro heating ability for hyperthermia treatment of cancer

    OpenAIRE

    Liu, Gengci; Kawashita, Masakazu; Li, Zhixia; Miyazaki, Toshiki; Kanetaka, Hiroyasu

    2015-01-01

    Common cancer treatments are invasive and lack specificity, leading to unwanted side effects. Because hyperthermia can kill cancer cells and damage proteins and structures within cells, it has been considered a novel, minimally invasive cancer treatment. However, many hyperthermia treatments cannot heat deep-seated tumors effectively and locally. Heat-generating magnetic microspheres can help address this challenge. However, current research has not produced microspheres that can be sufficien...

  16. Conserved features of cancer cells define their sensitivity of HAMLET-induced death; c-Myc and glycolysis

    OpenAIRE

    Storm, Petter; Puthia, Manoj Kumar; Aits, Sonja; Urbano, Alexander; Northen, Trent; Powers, Scott; Bowen, Ben; Chao, Yinxia; Reindl, Wolfgang; Lee, Do Yup; Sullivan, Nancy Liu; Zhang, Jianping; Trulsson, Maria; Yang, Henry; Watson, James

    2011-01-01

    HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small hairpin RNA inhibition, proteomic ...

  17. Defects in the oxidative killing of microorganisms by phagocytic leukocytes.

    Science.gov (United States)

    Roos, D; Weening, R S

    One of the most important mechanisms of phagocytic killing of ingested microorganisms by leukocytes is the generation of toxic oxygen products. During phagocytosis, neutrophils, as well as monocytes and macrophages, display a strongly increased cell respiration. Quantitatively the most important product of this reaction is hydrogen peroxide. Superoxide is also generated in large amounts, probably as an intermediate in the formation of hydrogen peroxide. Indications exist that singlet oxygen and hydroxyl radicals are also formed in this process. Some of these oxygen products have microbicidal properties by themselves. The effect of hydrogen peroxide is greatly enhanced by the enzyme myeloperoxidase. Several dysfunctions of this sytem are known. In chronic granulomatous disease the enzyme system that produces superoxide is not operative. Thus, no superoxide or hydrogen peroxide is generated, leading to a severely decreased bacterial killing capacity. The exact molecular defects in the X-linked and the autosomal form are as yet undefined. Two variants are also known: lipochrome histiocytosis, with different clinical and histological manifestations, and a 'triggering defect' where only strongly opsonized particles trigger the respiratory burst. Myeloperoxidase deficiency leads to slightly decreased killing capacity, especially for yeasts. In glucose-6-phosphate dehydrogenase deficiency no oxygen radicals or hydrogen peroxide are produced because no equivalents for oxygen reduction can be generated in the hexose-monophosphate shunt. Deficiencies in the glutathione redox system also result in impaired phagocyte function, probably because the cells have to be protected against their own toxic oxygen products. PMID:225141

  18. Contagion in Mass Killings and School Shootings.

    Directory of Open Access Journals (Sweden)

    Sherry Towers

    Full Text Available Several past studies have found that media reports of suicides and homicides appear to subsequently increase the incidence of similar events in the community, apparently due to the coverage planting the seeds of ideation in at-risk individuals to commit similar acts.Here we explore whether or not contagion is evident in more high-profile incidents, such as school shootings and mass killings (incidents with four or more people killed. We fit a contagion model to recent data sets related to such incidents in the US, with terms that take into account the fact that a school shooting or mass murder may temporarily increase the probability of a similar event in the immediate future, by assuming an exponential decay in contagiousness after an event.We find significant evidence that mass killings involving firearms are incented by similar events in the immediate past. On average, this temporary increase in probability lasts 13 days, and each incident incites at least 0.30 new incidents (p = 0.0015. We also find significant evidence of contagion in school shootings, for which an incident is contagious for an average of 13 days, and incites an average of at least 0.22 new incidents (p = 0.0001. All p-values are assessed based on a likelihood ratio test comparing the likelihood of a contagion model to that of a null model with no contagion. On average, mass killings involving firearms occur approximately every two weeks in the US, while school shootings occur on average monthly. We find that state prevalence of firearm ownership is significantly associated with the state incidence of mass killings with firearms, school shootings, and mass shootings.

  19. Contagion in Mass Killings and School Shootings

    Science.gov (United States)

    Towers, Sherry; Gomez-Lievano, Andres; Khan, Maryam; Mubayi, Anuj; Castillo-Chavez, Carlos

    2015-01-01

    Background Several past studies have found that media reports of suicides and homicides appear to subsequently increase the incidence of similar events in the community, apparently due to the coverage planting the seeds of ideation in at-risk individuals to commit similar acts. Methods Here we explore whether or not contagion is evident in more high-profile incidents, such as school shootings and mass killings (incidents with four or more people killed). We fit a contagion model to recent data sets related to such incidents in the US, with terms that take into account the fact that a school shooting or mass murder may temporarily increase the probability of a similar event in the immediate future, by assuming an exponential decay in contagiousness after an event. Conclusions We find significant evidence that mass killings involving firearms are incented by similar events in the immediate past. On average, this temporary increase in probability lasts 13 days, and each incident incites at least 0.30 new incidents (p = 0.0015). We also find significant evidence of contagion in school shootings, for which an incident is contagious for an average of 13 days, and incites an average of at least 0.22 new incidents (p = 0.0001). All p-values are assessed based on a likelihood ratio test comparing the likelihood of a contagion model to that of a null model with no contagion. On average, mass killings involving firearms occur approximately every two weeks in the US, while school shootings occur on average monthly. We find that state prevalence of firearm ownership is significantly associated with the state incidence of mass killings with firearms, school shootings, and mass shootings. PMID:26135941

  20. Glycan elongation beyond the mucin associated Tn antigen protects tumor cells from immune-mediated killing.

    Directory of Open Access Journals (Sweden)

    Caroline B Madsen

    Full Text Available Membrane bound mucins are up-regulated and aberrantly glycosylated during malignant transformation in many cancer cells. This results in a negatively charged glycoprotein coat which may protect cancer cells from immune surveillance. However, only limited data have so far demonstrated the critical steps in glycan elongation that make aberrantly glycosylated mucins affect the interaction between cancer cells and cytotoxic effector cells of the immune system. Tn (GalNAc-Ser/Thr, STn (NeuAcα2-6GalNAc-Ser/Thr, T (Galβ1-3GalNAc-Ser/Thr, and ST (NeuAcα2-6Galβ1-3GalNAc-Ser/Thr antigens are recognized as cancer associated truncated glycans, and are expressed in many adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the role of the cancer associated glycan truncations in immune-mediated killing we created glyco-engineered breast- and pancreatic cancer cells expressing only the shortest possible mucin-like glycans (Tn and STn. Glyco-engineering was performed by zinc finger nuclease (ZFN knockout (KO of the Core 1 enzyme chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc residue in O-linked glycans. We find that COSMC KO in the breast and pancreatic cancer cell lines T47D and Capan-1 increases sensitivity to both NK cell mediated antibody-dependent cellular-cytotoxicity (ADCC and cytotoxic T lymphocyte (CTL-mediated killing. In addition, we investigated the association between total cell surface expression of MUC1/MUC16 and NK or CTL mediated killing, and observed an inverse correlation between MUC16/MUC1 expression and the sensitivity to ADCC and CTL-mediated killing. Together, these data suggest that up-regulation of membrane bound mucins protects cells from immune mediated killing, and that particular glycosylation steps, as demonstrated for glycan elongation beyond Tn and STn, can be important for fine tuning of the immune escape mechanisms in cancer cells.

  1. Targeting Warburg Effect in Cancers with PEGylated Glucose.

    Science.gov (United States)

    Narayanan, Karthikeyan; Erathodiyil, Nandanan; Gopalan, Began; Chong, Shiya; Wan, Andrew C A; Ying, Jackie Y

    2016-03-01

    In highly proliferative cancer cells, energy is predominantly produced by a high rate of glycolysis, followed by lactic acid fermentation, despite the availability of oxygen - an observation known as the Warburg effect. As a consequence, cells employing this glycolytic pathway require high uptake of glucose and increased metabolic rates to maintain their proliferation. It has been hypothesized that by blocking glucose uptake using modified glucose molecules, apoptosis in the cancer cells can be induced. In this study, it has been showed that several poly(ethylene glycol) (PEG)-modified glucose compounds could reduce cell proliferation in various cancer cell lines by a phenomenon that blocked the availability of the glucose transporters and reduced AKT1 (serine/threonine-specific protein kinase) activation. Xenograft cancer models that are intravenously administered with glucose-conjugated branched PEG (GBrP) daily for 14 d show little tumor development, as compared to the control group without GBrP treatment. The toxicological effects and the pharmacokinetics of the PEGylated glucose are studied in rodents. The PEGylated glucose exerts no systemic toxicity at 40 mg kg(-1) dosage. However, doses above 80 mg kg(-1) show dose-dependent toxicity in all the organs analyzed. The present results suggest PEGylated glucose as a promising "metabolic therapy" approach for the treatment of cancer. PMID:26792539

  2. Late effects of breast cancer treatment and potentials for rehabilitation

    International Nuclear Information System (INIS)

    Background. Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million. Material and methods. The literature was reviewed with focus on data from the Nordic countries. Results. Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30-50% of patients after three to five years, lymphedema in 15-25% of patients, and restrictions of arm and shoulder movement in 35%. Physiotherapy is the standard treatment for the latter while no pain intervention trials have been published. Chemotherapy may cause infertility and premature menopause, resulting in vasomotor symptoms, sexual dysfunction, and osteoporosis, which are similar to the side effects of endocrine treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms include fear of recurrence, sleep disturbances, cognitive problems, fatigue, and sexual problems. Discussion. To improve rehabilitation, specific goals have to be formulated into national guidelines and high priority directed towards research into developing and testing new interventions for alleviating symptoms and side effects experienced by breast cancer survivors

  3. Late effects of breast cancer treatment and potentials for rehabilitation

    Energy Technology Data Exchange (ETDEWEB)

    Ewertz, Marianne (Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark)); Bonde Jensen, Anders (Inst. of Clinical Research, Univ. of Southern Denmark (Denmark))

    2011-02-15

    Background. Breast cancer is the most frequent malignant disease among women world wide. Survival has been improving leading to an increasing number of breast cancer survivors, in the US estimated to about 2.6 million. Material and methods. The literature was reviewed with focus on data from the Nordic countries. Results. Local therapies such as breast cancer surgery and radiotherapy may cause persistent pain in the breast area, arm, and shoulder reported by 30-50% of patients after three to five years, lymphedema in 15-25% of patients, and restrictions of arm and shoulder movement in 35%. Physiotherapy is the standard treatment for the latter while no pain intervention trials have been published. Chemotherapy may cause infertility and premature menopause, resulting in vasomotor symptoms, sexual dysfunction, and osteoporosis, which are similar to the side effects of endocrine treatment in postmenopausal women. Awareness of cardiotoxicity is needed since anthracyclines, trastuzumab, and radiotherapy can damage the heart. Breast cancer survivors have an increased risk of a major depression and far from all receive adequate anti-depressive treatment. Other psychological symptoms include fear of recurrence, sleep disturbances, cognitive problems, fatigue, and sexual problems. Discussion. To improve rehabilitation, specific goals have to be formulated into national guidelines and high priority directed towards research into developing and testing new interventions for alleviating symptoms and side effects experienced by breast cancer survivors

  4. Effect of acute exercise on prostate cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Helene Rundqvist

    Full Text Available Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among the candidates are modifications of endogenous hormone levels. Long-term exercise is known to reduce serum levels of growth stimulating hormones. In contrast, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as GH and IGF-1. It can be speculated that the elevation of serum growth factors may be detrimental to prostate cancer progression into malignancy. The incentive of the current study is to evaluate the effect of acute exercise serum on prostate cancer cell growth. We designed an exercise intervention where 10 male individuals performed 60 minutes of bicycle exercise at increasing intensity. Serum samples were obtained before (rest serum and after completed exercise (exercise serum. The established prostate cancer cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre-incubation before subcutaneous injection into SCID mice caused a delay in tumor formation. Serum analyses indicated two possible candidates for the effect; increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the fear of possible detrimental effects of acute exercise serum on tumor cell growth, we show that even the short-term effects seem to add to the overall beneficial influence of exercise on neoplasia.

  5. Principles of using Cold Atmospheric Plasma Stimulated Media for Cancer Treatment

    OpenAIRE

    Dayun Yan; Annie Talbot; Niki Nourmohammadi; Xiaoqian Cheng; Jerome Canady; Jonathan Sherman; Michael Keidar

    2015-01-01

    To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demons...

  6. Second primary cancer after treatment for cervical cancer. Late effects after radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Storm, H.H.

    1988-02-15

    Using data from the population-based Danish Cancer Registry, the relative risk (RR) of second primary cancer was assessed among 24,970 women with invasive cervical cancer (1943-1982) and 19,470 women with carcinoma in situ of the cervix. The analysis was stratified according to treatment with (+) and without (-) radiation. For all second primaries combined, a RR+ = 1.1 (95% confidence interval (CI) = 1.06-1.18) and a RR- = 1.3 (95% CI = 1.13-1.40) was observed after invasive cervical cancers and a RR+ = 3.5 (95% CI = 1.4-7.2) and RR- = 1.1 (95% CI = 0.7-1.6) following in situ cancer. The small overall excess of second primary cancer is accounted for by an increase of some cancers such as lung, bladder, and a concurrent decrease in others such as breast. Although not statistically different from nonirradiated, the RR increased with time since treatment among irradiated invasive cervical cancer patients in organs close to and at intermediate distance from the cervix, reaching a maximum after 30 or more years of follow-up (RR = 1.9; 95% CI = 1.4-2.5). Altogether, for these sites an excess of 64 cases per 10,000 women per year were attributable to radiation among survivors of 30+ years. The highest risks among long-term survivors were observed for the following: other genital organs (RR = 5.8; 95% CI = 1.8-13.0) bladder (RR = 5.5; 95% CI = 2.8-9.5), connective tissue (RR = 3.3; 95% CI = 0.4-12.0), stomach (RR = 2.5; 95% CI = 1.1-4.7) and rectum (RR = 2.4; 95% CI = 1.1-4.6). A significant deficit of risk for breast cancer (RR = 0.7, 95% CI = 0.6-0.8) was observed for 10+ years, may be attributable to the effect of ovarian ablation by radiotherapy.

  7. Inefficacy of vancomycin and teicoplanin in eradicating and killing Staphylococcus epidermidis biofilms in vitro.

    Science.gov (United States)

    Claessens, J; Roriz, M; Merckx, R; Baatsen, P; Van Mellaert, L; Van Eldere, J

    2015-04-01

    Biofilm-associated bacteria display a decreased susceptibility towards antibiotics. Routine assessment of antibiotic susceptibility of planktonic bacteria therefore offers an insufficient prediction of the biofilm response. In this study, in vitro biofilms of eight clinical Staphylococcus epidermidis strains were subjected to treatment with vancomycin, teicoplanin, oxacillin, rifampicin and gentamicin. In addition, the biofilms were subjected to combinations of an antibiotic with rifampicin. The effects on the biofilms were assessed by crystal violet staining to determine the total biofilm biomass, staining with XTT to determine bacterial cell viability, and microscopy. Combining these methods showed that treatment of S. epidermidis biofilms with glycopeptides increased the total biofilm biomass and that these antibiotics were not effective in killing bacteria embedded in biofilms. The decreased killing efficacy was more pronounced in biofilms produced by strains that were classified as 'strong' biofilm producers. Rifampicin, oxacillin and gentamicin effectively killed biofilm-associated bacteria of all tested strains. Combining antibiotics with rifampicin increased the killing efficacy without influencing the total biofilm biomass. When vancomycin or teicoplanin were combined with rifampicin, the increase in biofilm biomass was neutralised and also the killing efficacy was influenced in a positive way. We conclude that the combined methodology used in this study showed that glycopeptides were not effective in eradicating S. epidermidis biofilms but that combination with rifampicin improved the killing efficacy in vitro.

  8. Cost-effectiveness of colorectal cancer screening - An overview

    NARCIS (Netherlands)

    I. Lansdorp-Vogelaar (Iris); A.B. Knudsen (Amy); H. Brenner (Hermann)

    2010-01-01

    textabstractThere are several modalities available for a colorectal cancer (CRC) screening program. When determining which CRC screening program to implement, the costs of such programs should be considered in comparison to the health benefits they are expected to provide. Cost-effectiveness analysi

  9. Hepatic late adverse effects after antineoplastic treatment for childhood cancer

    NARCIS (Netherlands)

    Mulder, Renee L.; van Dalen, Elvira C.; Van den Hof, Malon; Bresters, Dorine; Koot, Bart G. P.; Castellino, Sharon M.; Loke, Yoon; Leclercq, Edith; Post, Piet N.; Caron, Huib N.; Postma, Aleida; Kremer, Leontien C. M.

    2011-01-01

    Background Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood ca

  10. Effect of cimetidine on survival after gastric cancer

    DEFF Research Database (Denmark)

    Tønnesen, H; Knigge, U; Bülow, Steffen;

    1988-01-01

    The effect of cimetidine on survival was investigated in 181 patients with gastric cancer. Immediately after operation or the decision not to operate, the patients were randomised in double-blind fashion to placebo or cimetidine 400 mg twice daily for two years or until death, with review every...

  11. The Effect of Cancer on Suicide among Elderly Holocaust Survivors

    Science.gov (United States)

    Nakash, Ora; Liphshitz, Irena; Keinan-Boker, Lital; Levav, Itzhak

    2013-01-01

    Jewish-Israelis of European origin with cancer have higher suicide rates relative to their counterparts in the general population. We investigated whether this effect results from the high proportion of Holocaust survivors among them, due to vulnerabilities arising from the earlier traumas they sustained. The study was based on all Jewish-European…

  12. The effects and costs of breast cancer screening

    NARCIS (Netherlands)

    H.J. de Koning (Harry)

    1993-01-01

    textabstractIn 1986, the Dutch Ministry of Welfare, Health and Cultural Affairs asked a research group to investigate the expected effect of breast cancer screening on mortality and possibly morbidity, if implemented in the Netherlands. The research group consisted of members from 3 centres, the Dep

  13. Differential effects of bisphosphonates on breast cancer cell lines

    NARCIS (Netherlands)

    Verdijk, R.; Franke, H.R.; Wolbers, F.; Vermes, I.

    2007-01-01

    Bisphosphonates may induce direct anti-tumor effects in breast cancers cells in virtro. In this study, six bisphosphonates were administered to three breast caner cell lines. Cell proliferation was measured by quantification of th expressio of Cyclin D1 mRNA. Apoptosis was determined by flow cytome

  14. Cancer-related fatigue : Predictors and effects of rehabilitation

    NARCIS (Netherlands)

    van Weert, Ellen; Hoekstra-Weebers, Josette; Otter, Renee; Postema, Klaas; Sanderman, Robbert; van der Schans, Cees

    2006-01-01

    Background. The aims of the study were to examine the effects of a multidimensional rehabilitation program on cancer-related fatigue, to examine concurrent predictors of fatigue, and to investigate whether change in fatigue over time was associated with change in predictors. Methods. Sample: 72 canc

  15. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    XU Tian-min; CUI Man-hua; XIN Ying; GU Li-ping; JIANG Xin; SU Man-man; WANG Ding-ding; WANG Wen-jia

    2008-01-01

    Background Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism.Methods The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells.Results In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3.Conclusions Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.

  16. The Effect of Cancer Warning Statements on Alcohol Consumption Intentions

    Science.gov (United States)

    Pettigrew, Simone; Jongenelis, Michelle I.; Glance, David; Chikritzhs, Tanya; Pratt, Iain S.; Slevin, Terry; Liang, Wenbin; Wakefield, Melanie

    2016-01-01

    In response to increasing calls to introduce warning labels on alcoholic beverages, this study investigated the potential effectiveness of alcohol warning statements designed to increase awareness of the alcohol-cancer link. A national online survey was administered to a diverse sample of Australian adult drinkers (n = 1,680). Along with…

  17. Effect of methoxychlor on Ca2+ handling and viability in OC2 human oral cancer cells.

    Science.gov (United States)

    Tseng, Li-Ling; Shu, Su-Shung; Kuo, Chun-Chi; Chou, Chiang-Ting; Hsieh, Yao-Dung; Chu, Sau-Tung; Chi, Chao-Chuan; Liang, Wei-Zhe; Ho, Chin-Man; Jan, Chung-Ren

    2011-05-01

    The effect of the insecticide methoxychlor on the physiology of oral cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) in human oral cancer cells (OC2) by using the Ca(2+)-sensitive fluorescent dye fura-2. Methoxychlor at 5-20 μM increased [Ca(2+)](i) in a concentration-dependent manner. The signal was reduced by 70% by removing extracellular Ca(2+). Methoxychlor-induced Ca(2+) entry was not affected by nifedipine, econazole, SK&F96365 and protein kinase C modulators but was inhibited by the phospholipase A2 inhibitor aristolochic acid. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished methoxychlor-induced [Ca(2+)](i) rise. Incubation with methoxychlor also inhibited thapsigargin- or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C with U73122 did not alter methoxychlor-induced [Ca(2+)](i) rise. At 5-20 μM, methoxychlor killed cells in a concentration-dependent manner. The cytotoxic effect of methoxychlor was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM). Annexin V-FITC data suggest that methoxychlor (10 and 20 μM) evoked apoptosis in a concentration-dependent manner. Together, in human OC2, methoxychlor induced a [Ca(2+)](i) rise probably by inducing phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via phospholipase A(2)-sensitive channels. Methoxychlor induced cell death that may involve apoptosis.

  18. Dirac operators and Killing spinors with torsion; Dirac-Operatoren und Killing-Spinoren mit Torsion

    Energy Technology Data Exchange (ETDEWEB)

    Becker-Bender, Julia

    2012-12-17

    On a Riemannian spin manifold with parallel skew torsion, we use the twistor operator to obtain an eigenvalue estimate for the Dirac operator with torsion. We consider the equality case in dimensions four and six. In odd dimensions we describe Sasaki manifolds on which equality in the estimate is realized by Killing spinors with torsion. In dimension five we characterize all Killing spinors with torsion and obtain certain naturally reductive spaces as exceptional cases.

  19. Gompertzian stochastic model with delay effect to cervical cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti [Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, 26300 Gambang, Pahang (Malaysia); Bahar, Arifah [Department of Mathematical Sciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor and UTM Centre for Industrial and Applied Mathematics (UTM-CIAM), Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia)

    2015-02-03

    In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

  20. Long-term effects of ionizing radiation

    International Nuclear Information System (INIS)

    This paper approaches the long-term effects of ionizing radiation considering the common thought that killing of cells is the basis for deterministic effects and that the subtle changes in genetic information are important in the development of radiation-induced cancer, or genetic effects if these changes are induced in germ cells

  1. Effects of screening for psychological distress on patient outcomes in cancer : A systematic review

    NARCIS (Netherlands)

    Meijer, Anna; Roseman, Michelle; Delisle, Vanessa C.; Milette, Katherine; Levis, Brooke; Syamchandra, Achyuth; Stefanek, Michael E.; Stewart, Donna E.; de Jonge, Peter; Coyne, James C.; Thombs, Brett D.

    2013-01-01

    Objective: Several practice guidelines recommend routine screening for psychological distress in cancer care. The objective was to evaluate the effect of screening cancer patients for psychological distress by assessing the (1) effectiveness of interventions to reduce distress among patients identif

  2. Effect of Protein Hydrolysates on Pancreatic Cancer Cells

    DEFF Research Database (Denmark)

    Ossum, Carlo G.; Andersen, Lisa Lystbæk; Nielsen, Henrik Hauch;

    Effect of Fish Protein Hydrolysates on Pancreatic Cancer Cells Carlo G. Ossum1, Lisa Lystbæk Andersen2, Henrik Hauch Nielsen2, Else K. Hoffmann1, and Flemming Jessen2 1University of Copenhagen, Department of Biology, Denmark, 2Technical University of Denmark (DTU), National Food Institute, Denmark...... activities affecting cell proliferation and ability to modulate caspase activity in pancreatic cancer cells COLO357 and BxPC-3 in vitro. A number of the hydrolysates showed caspase promoting activity; in particular products containing muscle tissue, i.e. belly flap, were able to stimulate caspase activity...... hydrolysates obtained by enzymatic hydrolysis on cancer cell proliferation. Skin and belly flap muscle from trout were hydrolysed with the unspecific proteases Alcalase, Neutrase, or UE1 (all from Novozymes, Bagsværd, Denmark) to a hydrolysis degree of 1-15%. The hydrolysates were tested for biological...

  3. Metabolic changes in cancer: beyond the Warburg effect

    Institute of Scientific and Technical Information of China (English)

    Weihua Wu; Shimin Zhao

    2013-01-01

    Altered metabolism is one of the hallmarks of cancer cells.The best-known metabolic abnormality in cancer cells is the Warburg effect,which demonstrates an increased glycolysis even in the presence of oxygen.However,tumor-related metabolic abnormalities are not limited to altered balance between glucose fermentation and oxidative phosphorylation.Key tumor genes such as p53 and c-myc are found to be master regulators of metabolism.Metabolic enzymes such as succinate dehydrogenase,fumarate hydratase,pyruvate kinase,and isocitrate dehydrogenase mutations or expressing level alterations are all linked to tumorigenesis.In this review,we introduce some of the cancer-associated metabolic disorders and current understanding of their molecular tumorigenic mechanisms.

  4. Anti cancer effects of curcumin: cycle of life and death

    Directory of Open Access Journals (Sweden)

    Das Tanya

    2008-10-01

    Full Text Available Abstract Increasing knowledge on the cell cycle deregulations in cancers has promoted the introduction of phytochemicals, which can either modulate signaling pathways leading to cell cycle regulation or directly alter cell cycle regulatory molecules, in cancer therapy. Most human malignancies are driven by chromosomal translocations or other genetic alterations that directly affect the function of critical cell cycle proteins such as cyclins as well as tumor suppressors, e.g., p53. In this respect, cell cycle regulation and its modulation by curcumin are gaining widespread attention in recent years. Extensive research has addressed the chemotherapeutic potential of curcumin (diferuloylmethane, a relatively non-toxic plant derived polyphenol. The mechanisms implicated are diverse and appear to involve a combination of cell signaling pathways at multiple levels. In the present review we discuss how alterations in the cell cycle control contribute to the malignant transformation and provide an overview of how curcumin targets cell cycle regulatory molecules to assert anti-proliferative and/or apoptotic effects in cancer cells. The purpose of the current article is to present an appraisal of the current level of knowledge regarding the potential of curcumin as an agent for the chemoprevention of cancer via an understanding of its mechanism of action at the level of cell cycle regulation. Taken together, this review seeks to summarize the unique properties of curcumin that may be exploited for successful clinical cancer prevention.

  5. Salivary Gland Cancer

    Science.gov (United States)

    ... contains antibodies that can kill germs. Salivary gland cancer is a type of head and neck cancer. It is rare. It may not cause any ... pain in your face Doctors diagnose salivary gland cancer using a physical exam, imaging tests, and a ...

  6. Evaluating Shielding Effectiveness for Reducing Space Radiation Cancer Risks

    Science.gov (United States)

    Cucinotta, Francis A.; Kim, Myung-Hee Y.; Ren, Lei

    2007-01-01

    We discuss calculations of probability distribution functions (PDF) representing uncertainties in projecting fatal cancer risk from galactic cosmic rays (GCR) and solar particle events (SPE). The PDF s are used in significance tests of the effectiveness of potential radiation shielding approaches. Uncertainties in risk coefficients determined from epidemiology data, dose and dose-rate reduction factors, quality factors, and physics models of radiation environments are considered in models of cancer risk PDF s. Competing mortality risks and functional correlations in radiation quality factor uncertainties are treated in the calculations. We show that the cancer risk uncertainty, defined as the ratio of the 95% confidence level (CL) to the point estimate is about 4-fold for lunar and Mars mission risk projections. For short-stay lunar missions (risk, however one that is mitigated effectively by shielding, especially for carbon composites structures with high hydrogen content. In contrast, for long duration lunar (>180 d) or Mars missions, GCR risks may exceed radiation risk limits, with 95% CL s exceeding 10% fatal risk for males and females on a Mars mission. For reducing GCR cancer risks, shielding materials are marginally effective because of the penetrating nature of GCR and secondary radiation produced in tissue by relativistic particles. At the present time, polyethylene or carbon composite shielding can not be shown to significantly reduce risk compared to aluminum shielding based on a significance test that accounts for radiobiology uncertainties in GCR risk projection.

  7. Upregulation of NAD(PH:Quinone Oxidoreductase By Radiation Potentiates the Effect of Bioreductive β-Lapachone on Cancer Cells

    Directory of Open Access Journals (Sweden)

    Eun K. Choi

    2007-08-01

    Full Text Available We found that (β-Lapachone ((β-Lap, a novel bioreductive drug, caused rapid apoptosis, clonogenic cell death in A549 human lung epithelial cancer cells in vitro in a dose-dependent manner. The clonogenic cell death caused by (β-Lap could be significantly inhibited by dicoumarol, an inhibitor of NAD(PH:quinone oxidoreductase (NO01, also by siRNA for NO01, demonstrating that N001-induced bioreduction of (β-Lap is an essential step in (β-Lap-induced cell death. Irradiation of A549 cells with 4 Gy caused a long-lasting upregulation of N001, thereby increasing N001mediated (β-Lap-induced cell deaths. Although the direct cause of (β-Lap-induced apoptosis is not yet clear, (β-Lap treatment reduced the expression of p53, NF-κB, whereas it increased cytochrome C release, caspase-3 activity, δ2AX foci formation. Importantly, (β-Lap treatment immediately after irradiation enhanced radiation-induced cell death, indicating that (β-Lap sensitizes cancer cells to radiation, in addition to directly killing some of the cells. The growth of A549 tumors induced in immunocompromised mice could be markedly suppressed by local radiation therapy when followed by (β-Lap treatment. This is the first study to demonstrate that combined radiotherapy, (β-Lap treatment can have a significant effect on human tumor xenografts.

  8. Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.

    Science.gov (United States)

    Wei, Wei-Jun; Shen, Chen-Tian; Song, Hong-Jun; Qiu, Zhong-Ling; Luo, Quan-Yong

    2016-09-01

    Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad β-blocker propranolol and β2-specific antagonist ICI118551, but not β1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate‑buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial. PMID:27432558

  9. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  10. Anti-Cancer Effects of Xanthones from Pericarps of Mangosteen

    Directory of Open Access Journals (Sweden)

    Yoshinori Nozawa

    2008-03-01

    Full Text Available Mangosteen, Garcinia mangostana Linn, is a tree found in South East Asia, and its pericarps have been used as traditional medicine. Phytochemical studies have shown that they contain a variety of secondary metabolites, such as oxygenated and prenylated xanthones. Recent studies revealed that these xanthones exhibited a variety of biological activities containing anti-inflammatory, anti-bacterial, and anti-cancer effects. We previously investigated the anti-proliferative effects of four prenylated xanthones from the pericarps; α-mangostin, β-mangostin, γ-mangostin, and methoxy-β-mangostin in various human cancer cells. These xanthones are different in the number of hydroxyl and methoxy groups. Except for methoxy-β-mangostin, the other three xanthones strongly inhibited cell growth at low concentrations from 5 to 20 μM in human colon cancer DLD-1 cells. Our recent study focused on the mechanism of α-mangostin-induced growth inhibition in DLD-1 cells. It was shown that the anti-proliferative effects of the xanthones were associated with cell-cycle arrest by affecting the expression of cyclins, cdc2, and p27; G1 arrest by α- mangostin and β-mangostin, and S arrest by γ-mangostin. α-Mangostin found to induce apoptosis through the activation of intrinsic pathway following the down-regulation of signaling cascades involving MAP kinases and the serine/threonine kinase Akt. Synergistic effects by the combined treatment of α-mangostin and anti-cancer drug 5-FU was to be noted. α-Mangostin was found to have a cancer preventive effect in rat carcinogenesis bioassay and the extract from pericarps, which contains mainly α-mangostin and γ- mangostin, exhibited an enhancement of NK cell activity in a mouse model. These findings could provide a relevant basis for the development of xanthones as an agent for cancer prevention and the combination therapy with

  11. Physical Activity and Gastrointestinal Cancers: Primary and Tertiary Preventive Effects and Possible Biological Mechanisms

    Directory of Open Access Journals (Sweden)

    Karen Steindorf

    2015-07-01

    Full Text Available Gastrointestinal cancers account for 37% of all cancer deaths worldwide, underlining the need to further investigate modifiable factors for gastrointestinal cancer risk and prognosis. This review summarizes the corresponding evidence for physical activity (PA, including, briefly, possible biological mechanisms. Despite high public health relevance, there is still a scarcity of studies, especially for tertiary prevention. Besides the convincing evidence of beneficial effects of PA on colon cancer risk, clear risk reduction for gastroesophageal cancer was identified, as well as weak indications for pancreatic cancer. Inverse associations were observed for liver cancer, yet based on few studies. Only for rectal cancer, PA appeared to be not associated with cancer risk. With regard to cancer-specific mortality of the general population, published data were rare but indicated suggestive evidence of protective effects for colon and liver cancer, and to a lesser extent for rectal and gastroesophageal cancer. Studies in cancer patients on cancer-specific and total mortality were published for colorectal cancer only, providing good evidence of inverse associations with post-diagnosis PA. Overall, evidence of associations of PA with gastrointestinal cancer risk and progression is promising but still limited. However, the already available knowledge further underlines the importance of PA to combat cancer.

  12. 77 FR 72858 - Toxicological Review of Inorganic Arsenic (Cancer and Noncancer Effects): In Support of Summary...

    Science.gov (United States)

    2012-12-06

    ... AGENCY Toxicological Review of Inorganic Arsenic (Cancer and Noncancer Effects): In Support of Summary... toxicological review of inorganic arsenic (cancer and noncancer effects) in support of the IRIS program. SUMMARY... toxicological review of chronic exposure to iAs (cancer and noncancer effects), which EPA intends to post in...

  13. Charge properties and bacterial contact-killing of hyperbranched polyurea-polyethyleneimine coatings with various degrees of alkylation

    NARCIS (Netherlands)

    Roest, Steven; van der Mei, Henny C.; Loontjens, Ton J. A.; Busscher, Henk J.

    2015-01-01

    Coatings of immobilized-quaternary-ammonium-ions (QUAT) uniquely kill adhering bacteria upon contact. QUAT-coatings require a minimal cationic-charge surface density for effective contact-killing of adhering bacteria of around 10(14) cm(-2). Quaternization of nitrogen is generally achieved through a

  14. Aromatase Inhibitors and Other Compounds for Lowering Breast Cancer Risk

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  15. The effect of breast cancer on personal income three years after diagnosis by cancer stage and education

    DEFF Research Database (Denmark)

    Andersen, Ingelise; Kolodziejczyk, Christophe; Thielen, Karsten;

    2015-01-01

    Background: The purpose of this study was to investigate whether there is an association between stage of incident breast cancer (BC) and personal income three years after diagnosis. The analysis further considered whether the association differed among educational groups. Methods: The study was...... based on information from Danish nationwide registers. A total of 7,372 women aged 30¿60 years diagnosed with BC, 48% with metastasis, were compared to 213,276 controls. Generalised linear models were used to estimate the effect of a cancer diagnosis on personal gross income three years after diagnosis......, stratified by education and stage of cancer. The models were adjusted for income two years prior to cancer diagnosis and demographic, geographic and co-morbidity covariates. Results: Adjusting for income two years prior to cancer diagnosis and other baseline covariates (see above), cancer had a minor effect...

  16. Coping with Cosmetic Effects of Cancer Treatment

    Science.gov (United States)

    ... coping with the most common cosmetic side effects. Hair Loss Hair thinning or hair loss is often ... a mild soap or shampoo. Avoid those with dyes, perfumes, or alcohol. Especially avoid acne soaps and ...

  17. Evaluating shielding effectiveness for reducing space radiation cancer risks

    International Nuclear Information System (INIS)

    We discuss calculations of probability distribution functions (PDF) representing uncertainties in projecting fatal cancer risk from galactic cosmic rays (GCR) and solar particle events (SPE). The PDFs are used in significance tests for evaluating the effectiveness of potential radiation shielding approaches. Uncertainties in risk coefficients determined from epidemiology data, dose and dose-rate reduction factors, quality factors, and physics models of radiation environments are considered in models of cancer risk PDFs. Competing mortality risks and functional correlations in radiation quality factor uncertainties are included in the calculations. We show that the cancer risk uncertainty, defined as the ratio of the upper value of 95% confidence interval (CI) to the point estimate is about 4-fold for lunar and Mars mission risk projections. For short-stay lunar missions (180d) or Mars missions, GCR risks may exceed radiation risk limits that are based on acceptable levels of risk. For example, the upper 95% CI exceeding 10% fatal risk for males and females on a Mars mission. For reducing GCR cancer risks, shielding materials are marginally effective because of the penetrating nature of GCR and secondary radiation produced in tissue by relativistic particles. At the present time, polyethylene or carbon composite shielding cannot be shown to significantly reduce risk compared to aluminum shielding based on a significance test that accounts for radiobiology uncertainties in GCR risk projection

  18. Combined therapeutic effect and molecular mechanisms of metformin and cisplatin in human lung cancer xenografts in nude mice

    Directory of Open Access Journals (Sweden)

    Yu-Qin Chen

    2015-01-01

    Full Text Available Objective: This work was aimed at studying the inhibitory activity of metformin combined with the commonly used chemotherapy drug cisplatin in human lung cancer xenografts in nude mice. We also examined the combined effects of these drugs on the molecular expression of survivin, matrix metalloproteinase-2 (MMP-2, vascular endothelial growth factor-C (VEGF-C, and vascular endothelial growth factorreceptor-3 (VEGFR-3 to determine the mechanism of action and to explore the potential applications of the new effective drug therapy in lung cancer. Materials and Methods: The nude mice model of lung cancer xenografts was established, and mice were randomly divided into the metformin group, the cisplatin group, the metformin + cisplatin group, and the control group. The animals were killed 42 days after drug administration, and the tumor tissues were then sampled to detect the messenger ribonucleic acid (mRNA and protein expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR. Results: The protein and mRNA expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 in the cisplatin group and the combined treatment group were lower than that in the control group (P < 0.05. In the metformin group, the expression of MMP-2 protein and mRNA was lower than that in the control group (P < 0.05. The protein and mRNA expression levels of survivin, MMP-2, VEGF-C, and VEGFR-3 in the combined treatment group were lower than that in the cisplatin group and the metformin group (P < 0.05. Conclusions: Metformin inhibited the expression of MMP-2, cisplatin and the combined treatment inhibited the expression of survivin, MMP-2, VEGF-C, and VEGFR-3, and the combined treatment of metformin with cisplatin resulted in enhanced anti-tumor efficacy.

  19. The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Zheng Wei Lee

    Full Text Available The slow-releasing hydrogen sulfide (H₂S donor, GYY4137, caused concentration-dependent killing of seven different human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11 and U2OS but did not affect survival of normal human lung fibroblasts (IMR90, WI-38 as determined by trypan blue exclusion. Sodium hydrosulfide (NaHS was less potent and not active in all cell lines. A structural analogue of GYY4137 (ZYJ1122 lacking sulfur and thence not able to release H₂S was inactive. Similar results were obtained using a clonogenic assay. Incubation of GYY4137 (400 µM in culture medium led to the generation of low (<20 µM concentrations of H₂S sustained over 7 days. In contrast, incubation of NaHS (400 µM in the same way led to much higher (up to 400 µM concentrations of H₂S which persisted for only 1 hour. Mechanistic studies revealed that GYY4137 (400 µM incubated for 5 days with MCF-7 but not IMR90 cells caused the generation of cleaved PARP and cleaved caspase 9, indicative of a pro-apoptotic effect. GYY4137 (but not ZYJ1122 also caused partial G₂/M arrest of these cells. Mice xenograft studies using HL-60 and MV4-11 cells showed that GYY4137 (100-300 mg/kg/day for 14 days significantly reduced tumor growth. We conclude that GYY4137 exhibits anti-cancer activity by releasing H₂S over a period of days. We also propose that a combination of apoptosis and cell cycle arrest contributes to this effect and that H₂S donors should be investigated further as potential anti-cancer agents.

  20. Opioid receptor activation triggering downregulation of cAMP improves effectiveness of anti-cancer drugs in treatment of glioblastoma

    Science.gov (United States)

    Friesen, Claudia; Hormann, Inis; Roscher, Mareike; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf; Debatin, Klaus-Michael; Miltner, Erich

    2014-01-01

    Glioblastoma are the most frequent and malignant human brain tumors, having a very poor prognosis. The enhanced radio- and chemoresistance of glioblastoma and the glioblastoma stem cells might be the main reason why conventional therapies fail. The second messenger cyclic AMP (cAMP) controls cell proliferation, differentiation, and apoptosis. Downregulation of cAMP sensitizes tumor cells for anti-cancer treatment. Opioid receptor agonists triggering opioid receptors can activate inhibitory Gi proteins, which, in turn, block adenylyl cyclase activity reducing cAMP. In this study, we show that downregulation of cAMP by opioid receptor activation improves the effectiveness of anti-cancer drugs in treatment of glioblastoma. The µ-opioid receptor agonist D,L-methadone sensitizes glioblastoma as well as the untreatable glioblastoma stem cells for doxorubicin-induced apoptosis and activation of apoptosis pathways by reversing deficient caspase activation and deficient downregulation of XIAP and Bcl-xL, playing critical roles in glioblastomas’ resistance. Blocking opioid receptors using the opioid receptor antagonist naloxone or increasing intracellular cAMP by 3-isobutyl-1-methylxanthine (IBMX) strongly reduced opioid receptor agonist-induced sensitization for doxorubicin. In addition, the opioid receptor agonist D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux, whereas doxorubicin increased opioid receptor expression in glioblastomas. Furthermore, opioid receptor activation using D,L-methadone inhibited tumor growth significantly in vivo. Our findings suggest that opioid receptor activation triggering downregulation of cAMP is a promising strategy to inhibit tumor growth and to improve the effectiveness of anti-cancer drugs in treatment of glioblastoma and in killing glioblastoma stem cells. PMID:24626197

  1. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer.

    Science.gov (United States)

    Pathak, Sen; Multani, Asha S; Banerji, Pratip; Banerji, Prasanta

    2003-10-01

    Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.

  2. Molecular Basis of the Anti-Cancer Effects of Genistein Isoflavone in LNCaP Prostate Cancer Cells.

    OpenAIRE

    Hartmann J; Zoeller R; Esiobu N; Rathinavelu A; Kumi-Diaka J; Merchant K; Johnson M

    2011-01-01

    Background: Prostate cancer is the most common form of non-skin cancer within the United States and the second leading cause of cancer deaths. Survival rates for the advanced disease remain relatively low, and conventional treatments may be accompanied by significant side effects. As a result, current research is aimed at alternative or adjuvant treatments that will target components of the signal transduction, cell-cycle and apoptosis pathways, to induce cell death with little or no toxic si...

  3. Current progress in immunotherapy for pancreatic cancer.

    Science.gov (United States)

    Foley, Kelly; Kim, Victoria; Jaffee, Elizabeth; Zheng, Lei

    2016-10-10

    Pancreatic cancer remains one of the most lethal cancers with few treatment options. Immune-based strategies to treat pancreatic cancer, such as immune checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies, are showing promise where other approaches have failed. Immune checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, are effective as single agents in immune sensitive cancers like melanoma, but lack efficacy in immune insensitive cancers including pancreatic cancer. However, these inhibitors are showing clinical activity, even in traditionally non-immunogenic cancers, when combined with other interventions, including chemotherapy, radiation therapy, and therapeutic vaccines. Therapeutic vaccines given together with immune modulating agents are of particular interest because vaccines are the most efficient way to induce effective anti-tumor T cell responses, which is required for immunotherapies to be effective. In pancreatic cancer, early studies suggest that vaccines can induce T cells that have the potential to recognize and kill pancreatic cancer cells, but the tumor microenvironment inhibits effective T cell trafficking and function. While progress has been made in the development of immunotherapies for pancreatic cancer over the last several years, additional trials are needed to better understand the signals within the tumor microenvironment that are formidable barriers to T cell infiltration and function. Additionally, as more pancreatic specific antigens are identified, immunotherapies will continue to be refined to provide the most significant clinical benefit.

  4. Perception of Side Effects of Chemotherapy among Cancer Patients in B.P. Koirala Memorial Cancer Hospital Bharatpur, Nepal

    OpenAIRE

    Sharmila Gurung; Radha Acharya Pandey

    2016-01-01

    jdjBackground & Objectives: These side effects of chemotherapy affect the patients’ daily life and quality of life adversely. It affects the different body system resulting in physical and non physical (psychosocial) side effects. Cancer patients demand information to understand chemotherapy-related adverse effects and actions to be taken. The aim of the study is to find out the perception of side effects of chemotherapy among cancer patients.Materials and methods: A descriptive cross-sec...

  5. Response of breast cancer cells and cancer stem cells to metformin and hyperthermia alone or combined.

    Directory of Open Access Journals (Sweden)

    Hyemi Lee

    Full Text Available Metformin, the most widely prescribed drug for treatment of type 2 diabetes, has been shown to exert significant anticancer effects. Hyperthermia has been known to kill cancer cells and enhance the efficacy of various anti-cancer drugs and radiotherapy. We investigated the combined effects of metformin and hyperthermia against MCF-7 and MDA-MB-231 human breast cancer cell, and MIA PaCa-2 human pancreatic cancer cells. Incubation of breast cancer cells with 0.5-10 mM metformin for 48 h caused significant clonogenic cell death. Culturing breast cancer cells with 30 µM metformin, clinically relevant plasma concentration of metformin, significantly reduced the survival of cancer cells. Importantly, metformin was preferentially cytotoxic to CD44(high/CD24(low cells of MCF-7 cells and, CD44(high/CD24(high cells of MIA PaCa-2 cells, which are known to be cancer stem cells (CSCs of MCF-7 cells and MIA PaCa-2 cells, respectively. Heating at 42°C for 1 h was slightly toxic to both cancer cells and CSCs, and it markedly enhanced the efficacy of metformin to kill cancer cells and CSCs. Metformin has been reported to activate AMPK, thereby suppressing mTOR, which plays an important role for protein synthesis, cell cycle progression, and cell survival. For the first time, we show that hyperthermia activates AMPK and inactivates mTOR and its downstream effector S6K. Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K. Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR. It is conclude that the effects of metformin against cancer cells including CSCs can be markedly enhanced by hyperthermia.

  6. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Parvovirus Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine... established as follows: (1) Twenty-five parvovirus susceptible dogs (20 vaccinates and 5 controls) shall...

  7. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bursal Disease Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.212 Bursal Disease Vaccine, Killed Virus. Bursal Disease...

  8. 9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Pseudorabies Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.213 Pseudorabies Vaccine, Killed Virus. Pseudorabies Vaccine,...

  9. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper...

  10. 9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ..., Killed Virus. 113.208 Section 113.208 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian Encephalomyelitis Vaccine, Killed Virus....

  11. 9 CFR 113.204 - Mink Enteritis Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mink Enteritis Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.204 Mink Enteritis Vaccine, Killed Virus. Mink Enteritis...

  12. Killing Vector Fields of Standard Static Space-times

    OpenAIRE

    Dobarro, Fernando; Unal, Bulent

    2008-01-01

    We consider Killing vector fields on standard static space-times and obtain equations for a vector field on a standard static space-time to be Killing. We also provide a characterization of Killing vector fields on standard static space-times with compact Riemannian parts.

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

    International Nuclear Information System (INIS)

    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 A549 and H1299 cells, and the effects of CAF on the radiosensitivity of A549 and H1299 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 A549 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 H1299 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 (SF2) of A549 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 SF2 of H1299 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 A549 cells and H1299 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)

  14. A randomized phase II study of SRL172 (Mycobacterium vaccae) combined with chemotherapy in patients with advanced inoperable non-small-cell lung cancer and mesothelioma

    OpenAIRE

    O’Brien, M E R; Saini, A.; Smith, I. E.; Webb, A.; Gregory, K.; Mendes, R.; Ryan, C.; Priest, K.; Bromelow, K V; Palmer, R. D.; Tuckwell, N; Kennard, D A; Souberbielle, B. E.

    2000-01-01

    Mycobacterial preparations have been used with limited success against cancer apart from superficial bladder cancer. Recently, a therapeutic vaccine derived from Mycobacterium vaccae has been given to patients with prostate cancer and melanoma indicating a possible beneficial effect on disease activity in such patients. We have recently initiated a series of randomized studies to test the feasibility and toxicity of combining a preparation of heat-killed Mycobacterium vaccae (designated SRL17...

  15. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease.

    Science.gov (United States)

    Lamb, Rebecca; Ozsvari, Bela; Lisanti, Camilla L; Tanowitz, Herbert B; Howell, Anthony; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica; Lisanti, Michael P

    2015-03-10

    Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of "stemness", independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known "side-effect", which could be harnessed instead as a "therapeutic effect". Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally, recent

  16. The effect of low level laser on anaplastic thyroid cancer

    Science.gov (United States)

    Rhee, Yun-Hee; Moon, Jeon-Hwan; Ahn, Jin-Chul; Chung, Phil-Sang

    2015-02-01

    Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Here we report that the effects of laser irradiation on anaplastic thyroid cancer cells leads to hyperplasia. 650nm of laser diode was performed with a different time interval (0, 15, 30, 60J/cm2 , 25mW) on anaplastic thyroid cancer cell line FRO in vivo. FRO was orthotopically injected into the thyroid gland of nude mice and the irradiation was performed with the same method described previously. After irradiation, the xenograft evaluation was followed for one month. The thyroid tissues from sacrificed mice were undergone to H&E staining and immunohistochemical staining with HIF-1α, Akt, TGF-β1. We found the aggressive proliferation of FRO on thyroid gland with dose dependent. In case of 60 J/ cm2 of energy density, the necrotic bodies were found in a center of the thyroid. The phosphorylation of HIF-1α and Akt was detected in the thyroid gland, which explained the survival signaling of anaplastic cancer cell was turned on the thyroid gland. Furthermore, TGF-β1 expression was decreased after irradiation. In this study, we demonstrated that insufficient energy density irradiation occurred the decreasing of TGF-β1 which corresponding to the phosphorylation of Akt/ HIF-1α. This aggressive proliferation resulted to the hypoxic condition of tissue for angiogenesis. We suggest that LLLT may influence to cancer aggressiveness associated with a decrease in TGF-β1 and increase in Akt/HIF-1α.

  17. Targeted Anticancer Immunotoxins and Cytotoxic Agents with Direct Killing Moieties

    Directory of Open Access Journals (Sweden)

    Koji Kawakami

    2006-01-01

    Full Text Available Despite the progress of the bioinformatics approach to characterize cell-surface antigens and receptors on tumor cells, it remains difficult to generate novel cancer vaccines or neutralizing monoclonal antibody therapeutics. Among targeted cancer therapeutics, biologicals with targetable antibodies or ligands conjugated or fused to toxins or chemicals for direct cell-killing ability have been developed over the last 2 decades. These conjugated or fused chimeric proteins are termed immunotoxins or cytotoxic agents. Two agents, DAB389IL-2 (ONTAKTM targeting the interleukin-2 receptor and CD33-calicheamicin (Mylotarg®, have been approved by the FDA for cutaneous T-cell lymphoma (CTCL and relapsed acute myeloid leukemia (AML, respectively. Such targetable agents, including RFB4(dsFv-PE38 (BL22, IL13-PE38QQR, and Tf-CRM107, are being tested in clinical trials. Several agents using unique technology such as a cleavable adapter or immunoliposomes with antibodies are also in the preclinical stage. This review summarizes the generation, mechanism, and development of these agents. In addition, possible future directions of this therapeutic approach are discussed.

  18. Effects of repeated mammographic screening on breast cancer stage distribution

    International Nuclear Information System (INIS)

    A randomised controlled trial of mass screening for breast cancer by single-view mammography was begun in Sweden in 1977. All women aged 40 and older and resident in the counties of Koppaberg and Oestergoetland were enrolled. The present report is confined to the Oestergoetland study, which started in 1978 and comprised 92934 women. After randomisation, which was done on the basis of communities rather than individuals, 47001 women were allocated to the study group and offered repeated mammographic screening; 45933 were allocated to the control group. As compliance among women over 74 years of age was poor these were excluded from the present report. The yearly incidence of stage II or more advanced breast cancers after the initial screening round up to and including the second was reduced by 40 per cent in the study group compared with the controls. This effect was less marked in the age group 40-49. After 5.5 years average from the date of entry the absolute number of women with stage II-IV disease in the control group exceeded that for the study group by 44, whereas there was a large excess of cancer in situ and stage I cancer in the study group. (orig.)

  19. Effects of dietary components on cancer of the digestive system.

    Science.gov (United States)

    Zanini, Sara; Marzotto, Marta; Giovinazzo, Francesco; Bassi, Claudio; Bellavite, Paolo

    2015-01-01

    Cancer is the second leading cause of death in developed countries and poor diet and physical inactivity are major risk factors in cancer-related deaths. Therefore, interventions to reduce levels of smoking, improve diet, and increase physical activity must become much higher priorities in the general population's health and health care systems. The consumption of fruit and vegetables exerts a preventive effect towards cancer and in recent years natural dietary agents have attracted great attention in the scientific community and among the general public. Foods, such as tomatoes, olive oil, broccoli, garlic, onions, berries, soy bean, honey, tea, aloe vera, grapes, rosemary, basil, chili peppers, carrots, pomegranate, and curcuma contain active components that can influence the initiation and the progression of carcinogenesis, acting on pathways implied in cell proliferation, apoptosis and metastasis. The present review illustrates the main foods and their active components, including their antioxidant, cytotoxic, and pro-apoptotic properties, with a particular focus on the evidence related to cancers of the digestive system. PMID:24841279

  20. Effect of octreotide on human pancreatic cancer cells after transfected with somatostatin receptor type 2 gene

    Institute of Scientific and Technical Information of China (English)

    Zheng-Ren Liu; Ren-Yi Qin; Gao-Song Wu; Qing Chang; Da-Yu Wang; Sheng-Quan Zou; Fa-Zu Qiu

    2004-01-01

    AIM: To observe the effect of octreotide on apoptosis rate of human pancreatic cancer cells PC-3 after transfected with somatostatin receptor type 2 (SST2) gene.METHODS: SST2 plasmid was transfected into PC-3 cells by liposome. Result of transfection was detected by immunocytochemical staining and Western blotting.Apoptosis rates of PC-3 cells under different dosages of octreotide were measured by MTT assay and flow cytometry (FCM).RESULTS: Apoptosis rate caused by octreotide of transfected PC-3 cells was 7.56±1.06% at the dosage of 0.20 μg/mL, 9.25±1.73% at the dosage of 0.40 μg/mL and 14.18±2.71% at the dosage of 0.80 μg/mL. Apoptosis rate caused by octreotide of non-transfected PC-3 cells was 5.76±0.75% at the dosage of 0.20 μg/mL, 6.69±0.80% at the dosage of 0.40 μg/mL and 7.26±1.28% at the dosage of 0.80 μg/mL. Transfected PC-3 cells growth inhibition rate caused by octreotide was 9.36±1.34% at the dosage of 0.20 μg/mL, 12.03±1.44% at the dosage of 0.40 μg/mL and 20.23±4.21% at the dosage of 0.80 μg/mL. Nontransfected PC-3 cells growth inhibition rate caused by octreotide was 6.44±0.66% at the dosage of 0.20 μg/mL,7.65±0.88% at the dosage of 0.40 μg/mL and 9.29±1.32% at the dosage of 0.80 μg/mL. We found that octreotide caused higher apoptosis rate and inhibition rate in transfected groups than in non-transfected groups (P<0.05)at the tested dosages (0.20, 0.40 and 0.80 μg/mL).CONCLUSION: Deficiency of SST2 was probably the major reason why octreotide had little effect on PC-3 cells.Transfecting SST2 gene could strengthen the ability of octreotide of killing PC-3 cells. It provided an experimental evidence for using both octreotide and transfection with SST2 gene on clinical treatment of pancreatic cancer.

  1. Treatment Options for Nonmelanoma Skin Cancer

    Science.gov (United States)

    ... cells than in normal cells. For skin cancer, laser light is shined onto the skin and the drug becomes active and kills the cancer cells. Photodynamic therapy causes little damage to healthy tissue. Biologic therapy ...

  2. The Effect of Curcumin on Breast Cancer Cells

    OpenAIRE

    Liu, Dongwu; Chen, Zhiwei

    2013-01-01

    Curcumin, which is extracted from the plant Curcuma longa, has been used in the therapeutic arsenal for clinical oncology. Curcumin has chemopreventive and antitumoral activities against some aggressive and recurrent cancers. The expressions and activities of various proteins, such as inflammatory cytokines and enzymes, transcription factors, and gene-products linked with cell survivals and proliferation, can be modified by curcumin. Moreover, curcumin decreases the toxic effect of mitomycin ...

  3. Protective effect of selenium on lung cancer in smelter workers.

    OpenAIRE

    Gerhardsson, L; Brune, D; Nordberg, I G; Wester, P. O.

    1985-01-01

    A possible protective effect of selenium against lung cancer has been indicated in recent studies. Workers in copper smelters are exposed to a combination of airborne selenium and carcinogens. In this study lung tissue concentrations of selenium, antimony, arsenic, cadmium, chromium, cobalt, lanthanum, and lead from 76 dead copper smelter workers were compared with those of 15 controls from a rural area and 10 controls from an urban area. The mean exposure time for the dead workers was 31.2 y...

  4. Antitumor effect of metformin in esophageal cancer: in vitro study.

    Science.gov (United States)

    Kobayashi, Mitsuyoshi; Kato, Kiyohito; Iwama, Hisakazu; Fujihara, Shintaro; Nishiyama, Noriko; Mimura, Shima; Toyota, Yuka; Nomura, Takako; Nomura, Kei; Tani, Joji; Miyoshi, Hisaaki; Kobara, Hideki; Mori, Hirohito; Murao, Koji; Masaki, Tsutomu

    2013-02-01

    Recent studies suggest that metformin, which is a member of the biguanide family and commonly used as an oral anti-hyperglycemic agent, may reduce cancer risk and improve prognosis of numerous types of cancer. However, the mechanisms underlying the antitumor effect of metformin on esophageal cancer remain unknown. The goal of the present study was to evaluate the effects of metformin on the proliferation of human ESCC in vitro, and to study changes in the expression profile of microRNAs (miRNAs), since miRNAs have previously been associated with the antitumor effects of metformin in other human cancers. The human ESCC cell lines T.T, KYSE30 and KYSE70 were used to study the effects of metformin on human ESCC in vitro. In addition, we used miRNA array tips to explore the differences between miRNAs in KYSE30 cells with and without metformin treatment. Metformin inhibited the proliferation of T.T, KYSE30 and KYSE70 cells in vitro. Metformin blocked the cell cycle in G0/G1 in vitro. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, as well as decreases in cyclin-dependent kinase (Cdk)4, Cdk6 and phosphorylated retinoblastoma protein (Rb). In addition, the expression of miRNAs was markedly altered with the treatment of metformin in vitro. Metformin inhibited the growth of three ESCC cell lines, and this inhibition may have involved reductions in cyclin D1, Cdk4 and Cdk6. PMID:23229592

  5. Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4

    OpenAIRE

    Kim, Youn-Jung; Park, Hae-Jeong; Yoon, Seo-Hyun; Kim, Mi-Ja; Leem, Kang-hyun; Chung, Joo-Ho; Kim, Hye-Kyung

    2005-01-01

    AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, SNU-C4.

  6. The Effects of Nimesulide Combined with Cisplatin on Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    邢丽华; 张珍祥; 徐永健; 张惠兰; 刘剑波

    2004-01-01

    To study the effects of cyclooxygenase 2 selective inhibitor Nimesulide (NIM) combined with Cisplatin (DDP) on human lung cancer and the possible mechanisms, the proliferation and apoptosis of human lung cancer cell line A549 were evaluated by MTT reduction assay and flow cytometry respectively. The inhibitory effect on neoplasia in vivo was tested on nude mice subcutaneously implanted tumor. Our results showed that NIM and DDP could inhibit A549 cell proliferation in a concentration dependent pattern; this action was enhanced when NIM (25 μmol/L) was given in combination with DDP and they worked in a synergistic or additive pattern as DDP concentration ≥ 1 μg/ml. NIM and DDP could induce A549 cells apoptosis and the action was augmented when used in combination (P<0.01). NIM and DDP could inhibit the growth of subcutaneously implan ted tumors on nude mice (P<0.05,P<0.01) and the inhibitory rate of NIM combined with DDP was significantly higher than that of NIM orDDPgroup (P<0.01, P<0.01). It is concluded that combined usc of NIM and DDP has significant synergistic antitumor effects on lung cancer cell line A549 and in animals in vivo. The synergy may be achieved by growth inhibition and apoptosis induction.

  7. Cell killing and mutation induction on Chinese hamster cells by photoradiations

    International Nuclear Information System (INIS)

    Applying radiation directly on cells, far-uv is more effective than black light, and black light is more effective than white light in inducing proliferative death and in inducing resistance to 6-thioguanine (6-TG), ouabain and diptheria toxin (DT). Gold light has no killing and mutagenic effects on CHO (Chinese hamster ovary) cells. Use of filters showed that a small percentage of shorter wavelengths in the far-uv region is responsible for most of the killing and mutagenic effects in the unfiltered broad spectra of black and white light

  8. Cell killing and mutation induction on Chinese hamster cells by photoradiations

    Energy Technology Data Exchange (ETDEWEB)

    Lam, C.K.C.

    1982-11-01

    Applying radiation directly on cells, far-uv is more effective than black light, and black light is more effective than white light in inducing proliferative death and in inducing resistance to 6-thioguanine (6-TG), ouabain and diptheria toxin (DT). Gold light has no killing and mutagenic effects on CHO (Chinese hamster ovary) cells. Use of filters showed that a small percentage of shorter wavelengths in the far-uv region is responsible for most of the killing and mutagenic effects in the unfiltered broad spectra of black and white light.

  9. Adjustment of lifetime risks of space radiation-induced cancer by the healthy worker effect and cancer misclassification.

    Science.gov (United States)

    Peterson, Leif E; Kovyrshina, Tatiana

    2015-12-01

    Background. The healthy worker effect (HWE) is a source of bias in occupational studies of mortality among workers caused by use of comparative disease rates based on public data, which include mortality of unhealthy members of the public who are screened out of the workplace. For the US astronaut corp, the HWE is assumed to be strong due to the rigorous medical selection and surveillance. This investigation focused on the effect of correcting for HWE on projected lifetime risk estimates for radiation-induced cancer mortality and incidence. Methods. We performed radiation-induced cancer risk assessment using Poisson regression of cancer mortality and incidence rates among Hiroshima and Nagasaki atomic bomb survivors. Regression coefficients were used for generating risk coefficients for the excess absolute, transfer, and excess relative models. Excess lifetime risks (ELR) for radiation exposure and baseline lifetime risks (BLR) were adjusted for the HWE using standardized mortality ratios (SMR) for aviators and nuclear workers who were occupationally exposed to ionizing radiation. We also adjusted lifetime risks by cancer mortality misclassification among atomic bomb survivors. Results. For all cancers combined ("Nonleukemia"), the effect of adjusting the all-cause hazard rate by the simulated quantiles of the all-cause SMR resulted in a mean difference (not percent difference) in ELR of 0.65% and mean difference of 4% for mortality BLR, and mean change of 6.2% in BLR for incidence. The effect of adjusting the excess (radiation-induced) cancer rate or baseline cancer hazard rate by simulated quantiles of cancer-specific SMRs resulted in a mean difference of [Formula: see text] in the all-cancer mortality ELR and mean difference of [Formula: see text] in the mortality BLR. Whereas for incidence, the effect of adjusting by cancer-specific SMRs resulted in a mean change of [Formula: see text] for the all-cancer BLR. Only cancer mortality risks were adjusted by

  10. An in vitro model of antibody-enhanced killing of the intracellular parasite Leishmania amazonensis.

    Directory of Open Access Journals (Sweden)

    Katherine N Gibson-Corley

    Full Text Available Footpad infection of C3HeB/FeJ mice with Leishmania amazonensis leads to chronic lesions accompanied by large parasite loads. Co-infecting these animals with L. major leads to induction of an effective Th1 immune response that can resolve these lesions. This cross-protection can be recapitulated in vitro by using immune cells from L. major-infected animals to effectively activate L. amazonensis-infected macrophages to kill the parasite. We have shown previously that the B cell population and their IgG2a antibodies are required for effective cross-protection. Here we demonstrate that, in contrast to L. major, killing L. amazonensis parasites is dependent upon FcRγ common-chain and NADPH oxidase-generated superoxide from infected macrophages. Superoxide production coincided with killing of L. amazonensis at five days post-activation, suggesting that opsonization of the parasites was not a likely mechanism of the antibody response. Therefore we tested the hypothesis that non-specific immune complexes could provide a mechanism of FcRγ common-chain/NADPH oxidase dependent parasite killing. Macrophage activation in response to soluble IgG2a immune complexes, IFN-γ and parasite antigen was effective in significantly reducing the percentage of macrophages infected with L. amazonensis. These results define a host protection mechanism effective during Leishmania infection and demonstrate for the first time a novel means by which IgG antibodies can enhance killing of an intracellular pathogen.

  11. Research into the biological effects of ionizing radiation somatic effects II: non-cancer

    International Nuclear Information System (INIS)

    Somatic effects of radiation can be considered in two categories: low and high level effects. In the low level exposure region (defined here arbitrarily as a single dose of the order of 10 rads or less, or higher doses at very low dose rates), the only somatic effects other than cancer known definitely at present to have health significance are those on fertiltiy and on the developing individual from conception to near birth. Knowledge of these effects is inadequate at present, and the bulk of this report will be devoted to discussing the types of additional investigations required. With respect to non-cancer somatic effects of radiation at intermediate to high doses and dose rates, enough is known to describe in general the course of early (over the first days to perhaps six weeks) effects, following different doses of external radiation. In particular, the non-cancer late effects of intermediate to high doses of internal and external radiation need better definition. The distinction between non-cancer and cancer-related somatic effects is blurred, at least at high dose levels

  12. Advance of Cellular Immunotherapy in Clinical and Translational Medicine of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    YAN Fei; YU Shao-rong; FENG Ji-feng

    2016-01-01

    Lung cancer is one of the most common cancers and ranks the ifrst in the mortality worldwide. The core of immunotherapy, especially cellular immunotherapy, is to activate the T cell-mediated tumor-killing effect in patients with tumors, so as to increase their anti-tumor effect. Surgery and radio- and chemotherapy cannot radically eliminate cancerous cells, but immunotherapy is an important supplementary method in killing tumor stem cells and non-proliferating cells. Cellular immunotherapy contains dendritic cells (DC), cytokine-induced killer (CIK), DC-CIK, natural killer T cells (NKT) and γδ T cells, which provides new techniques for the comprehensive treatment of lung cancer. Using CIK combined with DC, radiochemotherapy, radiofrequency ablation and monomers of Chinese medicine to induce CIK cells that directionally migrate to cancerous nest can increase tumor-killing ability and immunoregulatory ability of CIK cells, reduce adverse and toxic reactions and increase patients’ quality of life, and NKT cell and γδ T cell therapies have also been gradually perfected and promoted in clinical translation. This study mainly introduced the clinical translation of DC vaccines, CIK cells and DC-CIK treatment for lung cancer, hoping to provide new pathways and reference for the clinical treatment of lung cancer.

  13. 43. Inhibition effect of Solanum nigrum. L juice on S180 ascites cancer cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To study the action and application of Solanum nigrum.L Juice (abbreviate: S.J) on inhibiting tumors of S180 ascites cancer. Methods: Build mice tumor model through injecting S180 ascites cancer into mice's right armbet .48 male mice from KunMing of four to six weeks were randomly divided into 4 groups: Solanum Nigrum L Juice—high dosage (3mg/ml), middle dosage (1.5mg/ml), low dosage (0.75mg/ml); control group. After taking medicine for 15 days, kill the mice and measure the weight of tumor、spleen and thymus. Result: ①Tumor weights in middle and high dosage group are lighter than control group(P<0.05). ②Spleen index of test groups are different from control group(P<0.05). Conclusion: Solanum. nigrum.L Juice has inhibitory roles to S180 ascites cells.

  14. Coping with side effects from cancer treatment in daily life from the perspective of cancer patients: A qualitative empirical study

    DEFF Research Database (Denmark)

    Pedersen, Birgith; Koktved, Dorte Pallesen; Nielsen, Lene Lyngø

    Aim The aim of this paper is to deepen our understanding of how patients cope with side effects from cancer treatment in daily life. Background Patients receiving cancer treatment experience acute side effects and need individualized information and guidance in order to manage treatment......-related adverse events in everyday life. However development in cancer treatment and the societal demands for efficiency may limit the possibility for individualized support. Methods Nine patients were interviewed from March to July 2009 to explore the patients’ experience of coping with side effects in daily...

  15. Long-term side effects of adjuvant breast cancer treatment

    NARCIS (Netherlands)

    Buijs, Ciska

    2008-01-01

    Breast cancer is the most common malignancy in women. Breast cancer accounts for one-third of all cancers in females and 24% of the patients are younger than 55 years of age. More than 10% all Dutch women will develop breast cancer and 70-80% of all breast cancer patients will survive over 5 years.

  16. Cars kill chimpanzees: case report of a wild chimpanzee killed on a road at Bulindi, Uganda.

    Science.gov (United States)

    McLennan, Matthew R; Asiimwe, Caroline

    2016-07-01

    Roads have broadly adverse impacts on wildlife, including nonhuman primates. One direct effect is mortality from collisions with vehicles. While highly undesirable, roadkills provide valuable information on the health and condition of endangered species. We present a case report of a wild chimpanzee (Pan troglodytes schweinfurthii) killed crossing a road in Bulindi, Uganda, where chimpanzees inhabit forest fragments amid farmland. Details of the collision are constructed from eyewitness accounts of pedestrians. Physical examination of the cadaver indicated good overall body condition; at 40 kg, the deceased female was heavier than usual for an adult female East African chimpanzee. No external wounds or fractures were noted. Coprological assessment demonstrated infection by several gastrointestinal parasites commonly reported in living wild chimpanzees. Histopathology revealed eosinophilic enteritis and biliary hyperplasia potentially caused by parasite infection. However, eosinophilia was not widely spread into the submucosa, while egg/cyst counts suggested low-intensity parasite infections compared to healthy female chimpanzees of similar age in nearby Budongo Forest. No behavioral indicators of ill health were noted in the deceased female in the month prior to the accident. We conclude that cause of death was acute, i.e., shock from the collision, and was probably unrelated to parasite infection or any other underlying health condition. Notably, this female had asymmetrical polythelia, and, while nursing at the time of her death, had one functioning mammary gland only. In Uganda, where primates often inhabit human-dominated landscapes, human population growth and economic development has given rise to increasing motor traffic, while road development is enabling motorists to travel at greater speeds. Thus, the danger of roads to apes and other wildlife is rising, necessitating urgent strategies to reduce risks. Installation of simple speed-bumps-common on Ugandan

  17. Preferential kill of hypoxic EMT6 mammary tumor cells by the bioreductive alkylating agent porfiromycin.

    Science.gov (United States)

    Sartorelli, A C; Belcourt, M F; Hodnick, W F; Keyes, S R; Pritsos, C A; Rockwell, S

    1995-01-01

    Hypoxic cells in solid tumors represent a therapeutically resistant population that limits the curability of many solid tumors by irradiation and by most chemotherapeutic agents. The oxygen deficit, however, creates an environment conducive to reductive processes; this results in a major exploitable difference between normal and neoplastic tissues. The mitomycin antibiotics can be reductively activated by a number of oxidoreductases, in a process required for the production of their therapeutic effects. Preferential activation of these drugs under hypoxia and greater toxicity to oxygen-deficient cells than to their oxygenated counterparts are obtained in most instances. The demonstration that mitomycin C and porfiromycin, used to kill the hypoxic fraction, in combination with irradiation, to eradicate the oxygenated portion of the tumor, produced enhanced cytodestructive effects on solid tumors in animals has led to the clinical evaluation of the mitomycins in combination with radiation therapy in patients with head and neck cancer. The findings from these clinical trials have demonstrated the value of directing a concerted therapeutic attack on the hypoxic fraction of solid tumors as an approach toward enhancing the curability of localized neoplasms by irradiation. PMID:7572339

  18. Killing-Yano forms and Killing tensors on a warped space

    CERN Document Server

    Krtous, Pavel; Kolar, Ivan

    2015-01-01

    We formulate several criteria under which the symmetries associated with the Killing and Killing-Yano tensors on the base space can be lifted to the symmetries of the full warped geometry. The procedure is explicitly illustrated on several examples, providing new prototypes of spacetimes admitting such tensors. In particular, we study a warped product of two Kerr-NUT-(A)dS spacetimes and show that it gives rise to a new class of highly symmetric vacuum (with cosmological constant) black hole solutions that inherit many of the properties of the Kerr-NUT-(A)dS geometry.

  19. Protective effect of selenium on lung cancer in smelter workers.

    Science.gov (United States)

    Gerhardsson, L; Brune, D; Nordberg, I G; Wester, P O

    1985-09-01

    A possible protective effect of selenium against lung cancer has been indicated in recent studies. Workers in copper smelters are exposed to a combination of airborne selenium and carcinogens. In this study lung tissue concentrations of selenium, antimony, arsenic, cadmium, chromium, cobalt, lanthanum, and lead from 76 dead copper smelter workers were compared with those of 15 controls from a rural area and 10 controls from an urban area. The mean exposure time for the dead workers was 31.2 years, and the mean retirement time after the end of exposure 7.2 years. Lung cancer appeared in the workers with the lowest selenium lung tissue levels (selenium median value 71 micrograms/kg wet weight), as compared with both the controls (rural group, median value 110; urban group, median value 136) and other causes of death among the workers (median value 158). The quotient between the metals and selenium was used for comparison: a high quotient indicating a low protective effect of selenium and vice versa. The median values of the quotients between antimony, arsenic, cadmium, lanthanum, lead, chromium, and cobalt versus selenium were all numerically higher among the cases of lung cancer, the first five significantly higher (p less than 0.05) in 28 of the 35 comparisons between the lung cancer group and all other groups of smelter workers and controls. The different lung metal concentrations for each person were weighted according to their carcinogenic potency (Crx4 + Asx3 + Cdx2 + Sbx1 + Cox1 + Lax1 + Pbx1) against their corresponding selenium concentrations. From these calculations the protective effect of selenium was even more pronounced. PMID:4041390

  20. Radiation therapy and Koebner effect in cancer patients with psoriasis

    International Nuclear Information System (INIS)

    Radiation therapy (XRT) may initiate skin side effects that occur more often in patients with skin disorders. One of such diseases is psoriasis - a common disorder in the western communities. In the past Grenz rays and superficial XRT were used to treat psoriatic patients and were reported to initiate the Koebner effect, which is an exacerbation of the underlying disease following a skin trauma. Recently, several case reports revealed a similar response in cancer patients receiving megavoltage XRT. Hence, one may assume that irradiation should be re-considered or re-modified in order to spare the involved skin. To report our experience in radiotherapy of cancer patients with psoriasis. Six patients with prostate adenocarcinoma (3), breast cancer (2) and soft tissue sarcoma (1) suffering from psoriasis were referred for radiotherapy as a part of their anti-cancer treatment. In all patients the irradiation fields included the psoriatic lesions. The irradiation was delivered using linear accelerators operated through 6-8 MV photon and 8 MeV electron beams. The total XRT dose varied from 50 to 70 Gy and the daily fraction was 1.8-2.0 Gy. A close monitoring during and after completion of irradiation was carried out and standard skin care was advised. No change in the irradiated psoriatic lesions as well as in the surrounding area was observed in all patients during the irradiation. Subsequent follow up (up to 24 months) revealed no new skin lesions and no worsening of existing plaques. Megavoltage XRT in a conventional daily fraction has no effect on psoriatic skin lesions

  1. Mothers who kill: evolutionary underpinnings and infanticide law.

    Science.gov (United States)

    Friedman, Susan Hatters; Cavney, James; Resnick, Phillip J

    2012-01-01

    Women who kill their children present a profound challenge to accepted notions of motherhood and the protection offered by mothers to their children. Historically, societies have varied in the sanctions applied to perpetrators of such acts, across both time and place. Where penalties were once severe and punitive for mothers, in modern times some two dozen nations now have infanticide acts that reduce the penalties for mothers who kill their infants. Embedded within these acts are key criteria that relate (a) only to women who are (b) suffering the hormonal or mood effects of pregnancy/lactation at the time of the offence which is (c) usually restricted to within the first year after delivery. Criticisms of infanticide legislation have largely centered on inherent gender bias, misconceptions about the hormonal basis of postpartum psychiatric disorders, and the nexus and contribution of these disorders to the offending in relation to issues of culpability and sentencing. Important differences between female perpetrators relative to the age of the child victim have also highlighted problems in the implementation of infanticide legislation. For example, women who commit neonaticide (murder during the first day of life) differ substantially from mentally ill mothers who kill older children. However, despite these shortcomings, many nations have in recent years chosen to retain their infanticide acts. This article reviews the central controversies of infanticide legislation in relation to current research and fundamental fairness. Using evolutionary psychology as a theoretical framework to organize this discussion, it is argued that infanticide legislation is at best unnecessary and at worst misapplied, in that it exculpates criminal intent and fails to serve those for whom an infanticide defense might otherwise have been intended.

  2. Mothers who kill: evolutionary underpinnings and infanticide law.

    Science.gov (United States)

    Friedman, Susan Hatters; Cavney, James; Resnick, Phillip J

    2012-01-01

    Women who kill their children present a profound challenge to accepted notions of motherhood and the protection offered by mothers to their children. Historically, societies have varied in the sanctions applied to perpetrators of such acts, across both time and place. Where penalties were once severe and punitive for mothers, in modern times some two dozen nations now have infanticide acts that reduce the penalties for mothers who kill their infants. Embedded within these acts are key criteria that relate (a) only to women who are (b) suffering the hormonal or mood effects of pregnancy/lactation at the time of the offence which is (c) usually restricted to within the first year after delivery. Criticisms of infanticide legislation have largely centered on inherent gender bias, misconceptions about the hormonal basis of postpartum psychiatric disorders, and the nexus and contribution of these disorders to the offending in relation to issues of culpability and sentencing. Important differences between female perpetrators relative to the age of the child victim have also highlighted problems in the implementation of infanticide legislation. For example, women who commit neonaticide (murder during the first day of life) differ substantially from mentally ill mothers who kill older children. However, despite these shortcomings, many nations have in recent years chosen to retain their infanticide acts. This article reviews the central controversies of infanticide legislation in relation to current research and fundamental fairness. Using evolutionary psychology as a theoretical framework to organize this discussion, it is argued that infanticide legislation is at best unnecessary and at worst misapplied, in that it exculpates criminal intent and fails to serve those for whom an infanticide defense might otherwise have been intended. PMID:22961624

  3. Randomized trial of the effects of individual nutritional counseling in cancer patients

    DEFF Research Database (Denmark)

    Poulsen, Grith Møller; Pedersen, Louise Lindkvist; Østerlind, Kell;

    2014-01-01

    Cancer-related malnutrition is multifactorial and related to a bad prognosis. The aim of this study was to investigate the effect of intensive, individual dietary counseling of patients in radiotherapy and/or chemotherapy for gynecologic-, gastric-, or esophageal cancer.......Cancer-related malnutrition is multifactorial and related to a bad prognosis. The aim of this study was to investigate the effect of intensive, individual dietary counseling of patients in radiotherapy and/or chemotherapy for gynecologic-, gastric-, or esophageal cancer....

  4. A monoclonal antibody-Pseudomonas toxin conjugate that specifically kills multidrug-resistant cells.

    OpenAIRE

    FitzGerald, D J; Willingham, M C; Cardarelli, C O; Hamada, H; Tsuruo, T.; Gottesman, M M; Pastan, I

    1987-01-01

    One form of multidrug resistance is due to the expression of a 170-kDa energy-dependent drug efflux pump called P-glycoprotein in the plasma membranes of human cancer cells. We have prepared conjugates of Pseudomonas toxin with the anti-P-glycoprotein monoclonal antibody MRK-16. These anti-P-glycoprotein-toxin conjugates specifically kill multidrug-resistant human KB cells. Similar conjugates could be useful in cancer therapy to reduce or eliminate multidrug-resistant tumor populations in tum...

  5. Sildenafil (Viagra) sensitizes prostate cancer cells to doxorubicin-mediated apoptosis through CD95

    OpenAIRE

    Das, Anindita; Durrant, David; Mitchell, Clint; Dent, Paul; Batra, Surinder K.; Kukreja, Rakesh C.

    2015-01-01

    We previously reported that Sildenafil enhances apoptosis and antitumor efficacy of doxorubicin (DOX) while attenuating its cardiotoxic effect in prostate cancer. In the present study, we investigated the mechanism by which sildenafil sensitizes DOX in killing of prostate cancer (PCa) cells, DU145. The death receptor Fas (APO-1 or CD95) induces apoptosis in many carcinoma cells, which is negatively regulated by anti-apoptotic molecules such as FLIP (Fas-associated death domain (FADD) interleu...

  6. Radiobiology effects of radiation-induced horseradish peroxidase/indole-3-acetic suicide gene expression in lung cancer cells

    International Nuclear Information System (INIS)

    Objective: To detect specific cell killing effect of radiation combined with horseradish peroxidase (HRP)/indole-3-acetic (IAA) suicide gene therapy controlled by a novel radio-inducible and cancer-specific chimeric gene promoter in lung cancer. Methods: We constructed a plasmid expressing HRP enzyme under the control of chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 CArG elements, a plasmid expressing HRP enzyme under the control of hTERT promoter carrying single CArG element, and two control plasmids, which named pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControlluc, respectively. After radiation, the proliferation inhibition and apoptosis induction effect of each type of plasmid in lung cancer cells (A549, SPC-A1) and normal lung cells (hEL) was detected by cell counting and Annexin V-FITC staining. The change of radiosensitivity of lung cancer cells with plasmid system was also detected by clonogenic assays. Results: After a single dose radiation of 6 Gy,the average proliferation inhibition rates of pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControlluc systems were 72.92% ,40.60% , 51.00% and 25.19% (F= 67.31, P< 0.01) in A549 cells, 64.63%, 30.02%, 48.23% and 23.16% (F=64.94, P< 0.01) in SPC-A1 cells, and 20.81%, 18.05%, 44.20% and 18.32% (F=52.19, P<0.01) in normal hEL cells, respectively. The average early apoptosis rates of these four plasmid systems were 36.63%, 22.30%, 24.33% and 12.53% (F =50.99, P <0.01) in A549 cells, 33.73%, 17.37%, 22.43% and 11.20% (F = 20. 76, P < 0.01) in SPC-A1 cells, and 13.53 %, 12.5%, 21.93% and 12.16% (F = 15.08, P < 0.01) in normal hEL cells,respectively. The sensitizing enhancement ratios of the four plasmid systems were 3.45, 2.29, 3.05 and 1.21 in A549 cells, while 2.68, 2.15, 3.05 and 1.21 in SPC-A1 cells, respectively. Conclusions: The new suicide gene system controlled by chimeric promoter may provide a novel therapeutic modality for lung cancer. (authors)

  7. Porins facilitate nitric oxide-mediated killing of mycobacteria.

    Science.gov (United States)

    Fabrino, Daniela Leite; Bleck, Christopher K E; Anes, Elsa; Hasilik, Andrej; Melo, Rossana C N; Niederweis, Michael; Griffiths, Gareth; Gutierrez, Maximiliano Gabriel

    2009-09-01

    Non-pathogenic mycobacteria such us Mycobacterium smegmatis reside in macrophages within phagosomes that fuse with late endocytic/lysosomal compartments. This sequential fusion process is required for the killing of non-pathogenic mycobacteria by macrophages. Porins are proteins that allow the influx of hydrophilic molecules across the mycobacterial outer membrane. Deletion of the porins MspA, MspC and MspD significantly increased survival of M. smegmatis in J774 macrophages. However, the mechanism underlying this observation is unknown. Internalization of wild-type M. smegmatis (SMR5) and the porin triple mutant (ML16) by macrophages was identical indicating that the viability of the porin mutant in vivo was enhanced. This was not due to effects on phagosome trafficking since fusion of phagosomes containing the mutant with late endocytic compartments was unaffected. Moreover, in ML16-infected macrophages, the generation of nitric oxide (NO) was similar to the wild type-infected cells. However, ML16 was significantly more resistant to the effects of NO in vitro compared to SMR5. Our data provide evidence that porins render mycobacteria vulnerable to killing by reactive nitrogen intermediates within phagosomes probably by facilitating uptake of NO across the mycobacterial outer membrane. PMID:19460455

  8. Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells

    International Nuclear Information System (INIS)

    Purpose: The effects of a carbon ion beam and X-rays on human pancreatic cancer stem-like cells were examined from the point of view of clonogenic survival and DNA repair. Materials and methods: Human pancreatic cancer stem-like cells were treated with and without carbon ion and X-ray irradiation, and then colony, spheroid and tumor formation assays as well as γH2AX foci formation assay were performed. Results: The relative biological effectiveness (RBE) values of a carbon ion beam relative to X-ray for the MIA PaCa-2 and BxPc-3 cells at the D10 values were 1.85–2.10. The ability for colony, spheroid formation, and tumorigenicity from cancer stem-like CD44+/CD24+ cells is significantly higher than that from non-cancer stem-like CD44−/CD24−cells. FACS data showed that CD44+/CD24+ cells were more highly enriched after X-rays compared to carbon ion irradiation at isoeffective doses. The RBE values for the carbon ion beam relative to X-ray at the D10 levels for CD44+/CD24+ cells were 2.0–2.19. The number of γH2AX foci in CD44−/CD24− cells was higher than that of CD44+/CD24+ cells after irradiation with either X-ray or carbon ion beam. The number of γH2AX foci in CD44+/CD24+ cells was almost the same in the early time, but it persists significantly longer in carbon ion beam irradiated cells compared to X-rays. Conclusions: Carbon ion beam has superior potential to kill pancreatic cancer stem cell-like cells, and prolonged induction of DNA damage might be one of the pivotal mechanisms of its high radiobiological effects compared to X-rays.

  9. Cancer proliferation and therapy: the Warburg effect and quantum metabolism

    Directory of Open Access Journals (Sweden)

    Tuszynski Jack A

    2010-01-01

    Full Text Available Abstract Background Most cancer cells, in contrast to normal differentiated cells, rely on aerobic glycolysis instead of oxidative phosphorylation to generate metabolic energy, a phenomenon called the Warburg effect. Model Quantum metabolism is an analytic theory of metabolic regulation which exploits the methodology of quantum mechanics to derive allometric rules relating cellular metabolic rate and cell size. This theory explains differences in the metabolic rates of cells utilizing OxPhos and cells utilizing glycolysis. This article appeals to an analytic relation between metabolic rate and evolutionary entropy - a demographic measure of Darwinian fitness - to: (a provide an evolutionary rationale for the Warburg effect, and (b propose methods based on entropic principles of natural selection for regulating the incidence of OxPhos and glycolysis in cancer cells. Conclusion The regulatory interventions proposed on the basis of quantum metabolism have applications in therapeutic strategies to combat cancer. These procedures, based on metabolic regulation, are non-invasive, and complement the standard therapeutic methods involving radiation and chemotherapy

  10. Late Effects of Treatment for Childhood Cancer (PDQ)

    Science.gov (United States)

    ... healthy liver are important for survivors of childhood cancer. Pancreas Radiation therapy increases the risk of pancreatic late ... are important for survivors of childhood cancer. Childhood cancer survivors with liver ... Pancreas Radiation therapy increases the risk of pancreatic late ...

  11. Effective screening for early diagnosis of pancreatic cancer.

    Science.gov (United States)

    Hanada, Keiji; Okazaki, Akihito; Hirano, Naomichi; Izumi, Yoshihiro; Minami, Tomoyuki; Ikemoto, Juri; Kanemitsu, Kozue; Hino, Fumiaki

    2015-12-01

    Diagnosis of pancreatic cancer (PC) at an early stage with curative surgery should improve long-term patient outcome. At present, improving survival should lie in identifying those cases with high-risk factors or precursor lesions through an effective screening including ultrasonography, some biological markers, or national familial pancreatic cancer registration. Recently, cases with PC detection was higher on endoscopic ultrasonography (EUS) than on CT or other modalities, and EUS-guided fine needle aspiration was helpful in confirming the histologic diagnosis. Additionally, for the diagnosis of cases with PC in situ, EUS and magnetic resonance cholangiopancreatography (MRCP) may play important roles in detecting the local irregular stenosis of the pancreatic duct. Cytodiagnosis of pancreatic juice using endoscopic nasopancreatic drainage multiple times may be useful in the final diagnosis. PMID:26651254

  12. Anxiolytic Effect of Aromatherapy Massage in Patients with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jiro Imanishi

    2009-01-01

    Full Text Available We examined how aromatherapy massage influenced psychologic and immunologic parameters in 12 breast cancer patients in an open semi-comparative trial. We compared the results 1 month before aromatherapy massage as a waiting control period with those during aromatherapy massage treatment and 1 month after the completion of aromatherapy sessions. The patients received a 30 min aromatherapy massage twice a week for 4 weeks (eight times in total. The results showed that anxiety was reduced in one 30 min aromatherapy massage in State-Trait Anxiety Inventory (STAI test and also reduced in eight sequential aromatherapy massage sessions in the Hospital Anxiety and Depression Scale (HADS test. Our results further suggested that aromatherapy massage ameliorated the immunologic state. Further investigations are required to confirm the anxiolytic effect of aromatherapy in breast cancer patients.

  13. Interferons and the Immunogenic Effects of Cancer Therapy.

    Science.gov (United States)

    Minn, Andy J

    2015-11-01

    Much of our understanding on resistance mechanisms to conventional cancer therapies such as chemotherapy and radiation has focused on cell intrinsic properties that antagonize the detrimental effects of DNA and other cellular damage. However, it is becoming clear that the immune system and/or innate immune signaling pathways can integrate with these intrinsic mechanisms to profoundly influence treatment efficacy. In this context, recent evidence indicates that interferon (IFN) signaling has an important role in this integration by influencing immune and intrinsic/non-immune determinants of therapy response. However, IFN signaling can be both immunostimulatory and immunosuppressive, and the factors determining these outcomes in different disease settings are unclear. Here I discuss the regulation and molecular events in cancer that are associated with these dichotomous functions.

  14. Preliminary study of steep pulse irreversible electroporation technology in human large cell lung cancer cell lines L9981

    Directory of Open Access Journals (Sweden)

    Song Zuoqing

    2013-01-01

    Full Text Available Our aim was to validate the effectiveness of steep pulse irreversible electroporation technology in human large cell lung cancer cells and to screen the optimal treatment of parameters for human large cell lung cancer cells. Three different sets of steep pulse therapy parameters were applied on the lung cancer cell line L9981. The cell line L9981 inhibition rate and proliferation capacity were detected by Vi-Cell vitality analysis and MTT. Steep pulsed irreversible electroporation technology for large cell lung cancer L9981 presents killing effects with various therapy parameters. The optimal treatment parameters are at a voltage amplitude of 2000V/cm, pulse width of 100μs, pulse frequency of 1 Hz, pulse number 10. With this group of parameters, steep pulse could have the best tumor cell-killing effects.

  15. Return to work after early-stage breast cancer : A cohort study into the effects of treatment and cancer-related symptoms

    NARCIS (Netherlands)

    Balak, Fulya; Roelen, Corne A. M.; Koopmans, Petra C.; ten Berge, Elike E.; Groothoff, Johan W.

    2008-01-01

    Introduction Earlier diagnosis and better treatment have increased the survival rates of cancer patients. This warrants research on return to work of cancer survivors. What is the return to work rate following early-stage breast cancer? What is the effect of the type of treatment and cancer-related

  16. The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Clausen, Mathias Porsmose; Bennetzen, Martin;

    2009-01-01

    Tamoxifen resistance is a major clinical problem in the treatment of estrogen receptor a-positive breast tumors. It is, at present, unclear what exactly causes tamoxifen resistance. For decades, chlorpromazine has been used for treating psychotic diseases, such as schizophrenia. However......, the compound is now also recognized as a multitargeting drug with diverse potential applications, for example, it has antiproliferative properties and it can reverse resistance toward antibiotics in bacteria. Furthermore, chlorpromazine can reverse multidrug resistance caused by overexpression of P......-sensitive breast cancer cell line, MCF-7, and in a tamoxifen-resistant cell line, established from the MCF-7 cells. Tamoxifen-sensitive and tamoxifen-resistant cells were killed equally well by combined treatment with chlorpromazine and tamoxifen. This synergistic effect could be prevented by addition of estrogen...

  17. Sodium selenite and cancer related lymphedema: Biological and pharmacological effects.

    Science.gov (United States)

    Pfister, Christina; Dawzcynski, Horst; Schingale, Franz-Josef

    2016-09-01

    A significant percentage of cancer patients develop secondary lymphedema after surgery or radiotherapy. The preferred treatment of secondary lymphedema is complex physical therapy. Pharmacotherapy, for example with diuretics, has received little attention, because they were not effective and only offered short-term solutions. Sodium selenite showed promise as a cost-effective, nontoxic anti-inflammatory agent. Treatment with sodium selenite lowers reactive oxygen species (ROS) production, causes a spontaneous reduction in lymphedema volume, increases the efficacy of physical therapy for lymphedema, and reduces the incidence of erysipelas infections in patients with chronic lymphedema. Besides biological effects in reducing excessive production of ROS, sodium selenite also displays various pharmacological effects. So far the exact mechanisms of these pharmacological effects are mostly unknown, but probably include inhibition of adhesion protein expression. PMID:27267968

  18. Cancer

    Science.gov (United States)

    ... Blood tests (which look for chemicals such as tumor markers) Bone marrow biopsy (for lymphoma or leukemia) Chest ... the case with skin cancers , as well as cancers of the lung, breast, and colon. If the tumor has spread ...

  19. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  20. Effect of Meridian Massage for Cancer Related Fatigue

    Institute of Scientific and Technical Information of China (English)

    In sook Jeoung; Hwa-Seung Yoo

    2008-01-01

    The purpose of this study is to investigate the effectiveness of meridian massage in lessening the fatigue and improving both physical and mental quality of life of cancer patients. Settings and design: This study was conducted at the East-West Cancer Center at Daejeon University; Using a single-arm, waiting list and non-treatment control research design, we compared the results of control group and to that of the experimental group. Materials and methods: From July 2, 2007 to July 28, 2007, eighteen eligible cancer patients were recruited to participate in the experiment. Modified Chalder Fatigue Scale (CFS), Visual Analogue Scale (VAS) and active oxygen level were measured before and after treatment for both control and experimental groups. Lying on their back or stomach inside a room with a temperature of 18-2℃2, the patients received 30 minutes of meridian massages mainly around the trapezius muscles 5 times a week.Statistical analysis used: Data analysis was carried out using independent t-test, paired t-test and One-way ANOVA.Results: Data analysis of modified CFS showed statistically significant results for all groups between before and after treatment. Within CFS, results of physical and psychological analysis showed significant results for all groups except before and after no treatment and secondary treatment. In the analysis of VAS, the experimental group showed a greater decrease in score compared to that of the control group and the average difference was statistically significant (P<0.05). Although the results were not statistically significant (P>0.05), active oxygen levels for the control group showed little difference before and after no treatment (331.11 and 330.78, respectively) while the experimental group observed a decrease in active oxygen level before and after treatment (327.28 and 314.11, respectively). Conclusion: In conclusion, patients who received meridian massage showed decreased cancer related fatigue scores compared to the

  1. Emotional and coping responses to serial killings. The Gainesville murders.

    Science.gov (United States)

    Norvell, N K; Cornell, C E; Limacher, M C

    1993-07-01

    Forensic experts have focused more on the psychological profile of a serial killer rather than on the pronounced effects on the community at large. Coping with a stressful event is thought to influence emotional states. However, little empirical understanding of this process exists. The present study examined changes in psychological factors 9 days after the occurrence of serial killings in a college community. Multivariate analyses of variance conducted on the variables of stress, anxiety, physical symptoms, and depression revealed a significant difference between the group tested after the murders and a cross-sectional cohort group. Univariate analyses revealed that the study class was significantly more depressed compared with the cohort group. The study class was also significantly more depressed compared with their own responses 1 year before the killings. For both classes, depression was significantly correlated with certain coping styles, including escape-avoidance and accept responsibility. Results have implications for certain coping behaviors (i.e., avoidant behaviors), such as that leaving the community may have been maladaptive and perhaps diverted attention from the more necessary active problem-solving behaviors (e.g., increasing security) in addition to increasing depression.

  2. Kinase domain insert containing receptor promotor controlled suicide gene system kills human umbilical vein endothelial cells

    Institute of Scientific and Technical Information of China (English)

    Zong-Hai Huang; Wen-Yu Yang; Qi Cheng; Jing-Long Yu; Zhou Li; Zong-Yan Tong; Hui-Juan Song; Xiao-Yan Che

    2005-01-01

    AIM: To evaluate the killing effect of double suicide gene mediated by adenovirus and regulated under kinase domain insert containing receptor (KDR) promoter on human umbilical vein endothelial cells. METHODS: By PCR technology, human KDR promoter gene, Escherichia coli(E. coli) cytosine deaminase (CD) gene and the herpes simple virus-thymidine kinase (TK) gene were cloned. Plasmid pKDR-CDglyTK was constructed with them. Then, a recombinant adenoviral plasmid pAdKDRCDglyTK was constructed in a "two-step transformation protocol". The newly constructed plasmids were transfected to 293 packaging cells to grow adenoviruses, which were further propagated and purified. Human umbilical vein endothelial cells (HUVEC) were infected with a different multiplicity of infection (MOI) of resultant recombinant adenovirus, the infection rate was measured with the aid of (GFP) expression. Infected cells were cultured in culture media containing different concentrations of (GCV) and/or 5-(FC), and the killing effects were measured.RESULTS: Recombinant adenoviruses AdKDR-CDglyTK were successfully constructed, and they infected HUVEC cells efficiently. Our data indicated that the infection rate was relevant to MOI of recombinant adenoviruses. HUVEC cells infected with AdKDR-CDglyTK were highly sensitive to the prodrugs, their survival rate correlated to both the concentration of the prodrugs and the MOI of recombinant adenoviruses. Our data also indicated that the two prodrugs used in combination were much more effective on killing transgeneic cells than GCV or 5-FC used alone. CONCLUSION: Prodrug/KDR-CDglyTK system is effective on killing HUVEC cells, its killing effect correlates to the concentration of prodrugs and recombinant adenovirus' MOI. Combined use of the two prodrugs confers better killing effects on transgeneic cells.

  3. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2015-07-01

    Full Text Available Astaxanthin (ATX is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and peroxisome proliferator-activated receptor gamma (PPARγ. Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

  4. Effects of Animal Venoms and Toxins on Hallmarks of Cancer.

    Science.gov (United States)

    Chaisakul, Janeyuth; Hodgson, Wayne C; Kuruppu, Sanjaya; Prasongsook, Naiyarat

    2016-01-01

    Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components. PMID:27471574

  5. Effects of Animal Venoms and Toxins on Hallmarks of Cancer

    Science.gov (United States)

    Chaisakul, Janeyuth; Hodgson, Wayne C.; Kuruppu, Sanjaya; Prasongsook, Naiyarat

    2016-01-01

    Animal venoms are a cocktail of proteins and peptides, targeting vital physiological processes. Venoms have evolved to assist in the capture and digestion of prey. Key venom components often include neurotoxins, myotoxins, cardiotoxins, hematoxins and catalytic enzymes. The pharmacological activities of venom components have been investigated as a source of potential therapeutic agents. Interestingly, a number of animal toxins display profound anticancer effects. These include toxins purified from snake, bee and scorpion venoms effecting cancer cell proliferation, migration, invasion, apoptotic activity and neovascularization. Indeed, the mechanism behind the anticancer effect of certain toxins is similar to that of agents currently used in chemotherapy. For example, Lebein is a snake venom disintegrin which generates anti-angiogenic effects by inhibiting vascular endothelial growth factors (VEGF). In this review article, we highlight the biological activities of animal toxins on the multiple steps of tumour formation or hallmarks of cancer. We also discuss recent progress in the discovery of lead compounds for anticancer drug development from venom components. PMID:27471574

  6. Cost-effectiveness analysis of breast cancer control interventions in Peru

    NARCIS (Netherlands)

    Zelle, S.G.; Vidaurre, T.; Abugattas, J.E.; Manrique, J.E.; Sarria, G.; Jeronimo, J.; Seinfeld, J.N.; Lauer, J.A.; Sepulveda, C.R.; Venegas, D.; Baltussen, R.

    2013-01-01

    OBJECTIVES: In Peru, a country with constrained health resources, breast cancer control is characterized by late stage treatment and poor survival. To support breast cancer control in Peru, this study aims to determine the cost-effectiveness of different breast cancer control interventions relevant

  7. Effect of progesterone combined with chemotherapy on epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    陈晓军; 丰有吉

    2003-01-01

    Objective To identify an effective auxiliary therapy for epithelial ovarian cancer. Methods Progesterone acetate given at 250 mg intramuscularly twice a week for 1 month followed by increased administration to 500 mg intramuscularly every two weeks for 3 years was used in combination with platinum based chemotherapy to treat patients with epithelial ovarian cancer as a first-line therapy. Prognoses of the patients receiving progesterone combined with chemotherapy (progesterone group) and those receiving chemotherapy only (control group) were compared. Results Three-year recurrence and survival conditions of the progesterone and control groups were as follows. Stage Ⅰa: no patient relapsed or died in either group. Stage Ⅰb-Ⅰc: three-year recurrence rates were 14.2% and 37.5%, respectively (P=0.2845); three-year survival rates were 92.3% and 87.5% (P=0.7221). Stage Ⅱ: 1 patient relapsed and died among the 3 patients in the progesterone group; among the 4 patients in the control group, 1 patient relapsed, none died. Stage Ⅲ: three-year recurrence rates were 30.8% and 64.3%, respectively (P=0.1170); three-year survival rates were 85.7% and 42.9%, respectively (P=0.005). Stage Ⅳ: 4 patients relapsed and 1 patient died among the 7 patients in the progesterone group; both the patients in the control group relapsed and died. Conclusions The results indicated that progesterone combined with platinum based chemotherapy as a first-line therapy may improve the prognosis of advanced epithelial ovarian cancer, but would not change the prognosis of early stage epithelial ovarian cancer.

  8. Trypanosoma cruzi as an effective cancer antigen delivery vector.

    Science.gov (United States)

    Junqueira, Caroline; Santos, Luara I; Galvão-Filho, Bruno; Teixeira, Santuza M; Rodrigues, Flávia G; DaRocha, Wanderson D; Chiari, Egler; Jungbluth, Achim A; Ritter, Gerd; Gnjatic, Sacha; Old, Lloyd J; Gazzinelli, Ricardo T

    2011-12-01

    One of the main challenges in cancer research is the development of vaccines that induce effective and long-lived protective immunity against tumors. Significant progress has been made in identifying members of the cancer testis antigen family as potential vaccine candidates. However, an ideal form for antigen delivery that induces robust and sustainable antigen-specific T-cell responses, and in particular of CD8(+) T lymphocytes, remains to be developed. Here we report the use of a recombinant nonpathogenic clone of Trypanosoma cruzi as a vaccine vector to induce vigorous and long-term T cell-mediated immunity. The rationale for using the highly attenuated T. cruzi clone was (i) the ability of the parasite to persist in host tissues and therefore to induce a long-term antigen-specific immune response; (ii) the existence of intrinsic parasite agonists for Toll-like receptors and consequent induction of highly polarized T helper cell type 1 responses; and (iii) the parasite replication in the host cell cytoplasm, leading to direct antigen presentation through the endogenous pathway and consequent induction of antigen-specific CD8(+) T cells. Importantly, we found that parasites expressing a cancer testis antigen (NY-ESO-1) were able to elicit human antigen-specific T-cell responses in vitro and solid protection against melanoma in a mouse model. Furthermore, in a therapeutic protocol, the parasites expressing NY-ESO-1 delayed the rate of tumor development in mice. We conclude that the T. cruzi vector is highly efficient in inducing T cell-mediated immunity and protection against cancer cells. More broadly, this strategy could be used to elicit a long-term T cell-mediated immunity and used for prophylaxis or therapy of chronic infectious diseases.

  9. Killing and replacing queen-laid eggs: low cost of worker policing in the honeybee.

    Science.gov (United States)

    Kärcher, Martin H; Ratnieks, Francis L W

    2014-07-01

    Worker honeybees, Apis mellifera, police each other's reproduction by killing worker-laid eggs. Previous experiments demonstrated that worker policing is effective, killing most (∼98%) worker-laid eggs. However, many queen-laid eggs were also killed (∼50%) suggesting that effective policing may have high costs. In these previous experiments, eggs were transferred using forceps into test cells, mostly into unrelated discriminator colonies. We measured both the survival of unmanipulated queen-laid eggs and the proportion of removal errors that were rectified by the queen laying a new egg. Across 2 days of the 3-day egg stage, only 9.6% of the queen-laid eggs in drone cells and 4.1% in worker cells were removed in error. When queen-laid eggs were removed from cells, 85% from drone cells and 61% from worker cells were replaced within 3 days. Worker policing in the honeybee has a high benefit to policing workers because workers are more related to the queen's sons (brothers, r = 0.25) than sister workers' sons (0.15). This study shows that worker policing also has a low cost in terms of the killing of queen-laid eggs, as only a small proportion of queen-laid eggs are killed, most of which are rapidly replaced. PMID:24921604

  10. Two-photon spectroscopic behaviors and photodynamic effect on the BEL-7402 cancer cells of the new chlorophyll photosensitizer

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The spectroscopic properties of a new chlorophyll derivate photosensitizer(CDP) are studied under the excitation wavelengths at 800 and 400 nm using femtosecond pulses from a Ti:sapphire laser.The damaging effect of CDP on the BEL-7402 cancer cells is also investigated upon two-photon illumination at 800 nm.The normalized fluorescence spectra of CDP in tetrahydrofuran(THF) show that two-photon and one-photon spectra have the same distributions and the same emission bands(675 nm).The life-times of two-and one-photon induced fluorescence of this molecule are of the order of 5.0 ns.By comparing the data it is shown that there is some difference between the two lifetimes,but the differ-ence is less than one nanosecond.The two-photon absorption cross section of the molecule is also measured at 800 nm and estimated as about σ′2 ≈ 31.5×10-50 cm4·s·photon-1.The results of two-photon photodynamic therapy(TPPDT) tests show that CDP can kill all of the tested cancer cells according to the usual Eosine assessment.Our results indicate that the two-photon-induced photophysical,photo-chemical and photosensitizing processes of CDP may be basically similar to those of one-photon ex-citation.These behaviors of the sample suggest that one may find other possible methods to estimate some photosensitizers’ effects in details such as their distribution in cells and the reactive targets of the sub-cellular parts of some tumor cells via two-photon excitation techniques.

  11. Radiosensitization effect of folate-conjugated gold nanoparticles on HeLa cancer cells under orthovoltage superficial radiotherapy techniques

    Science.gov (United States)

    Khoshgard, Karim; Hashemi, Bijan; Arbabi, Azim; Javad Rasaee, Mohammad; Soleimani, Masoud

    2014-05-01

    Due to the high atomic number of gold nanoparticles (GNPs), they are known as new radiosensitizer agents for enhancing the efficiency of superficial radiotherapy techniques by increasing the dose absorbed in tumor cells wherein they can be accumulated selectively. The aim of this study was to compare the effect of various common low energy levels of orthovoltage x-rays and megavoltage γ-rays (Co-60) on enhancing the therapeutic efficiency of HeLa cancer cells in the presence of conjugated folate and non-conjugated (pegylated) GNPs. To achieve this, GNPs with an average diameter of 52 nm were synthesized and conjugated to folic acid molecules. Pegylated GNPs with an average diameter of 47 nm were also synthesized and used as non-conjugated folate GNPs. Cytotoxicity assay of the synthesized folate-conjugated and pegylated GNPs was performed using different levels of nanoparticle concentration incubated with HeLa cells for 24 h. The radiosensitizing effect of both the conjugated and pegylated GNPs on the cells at a concentration of 50 µM was compared using MTT as well as clonogenic assays after exposing them to 2 Gy ionizing radiation produced by an orthovoltage x-ray machine at four different kVps and γ-rays of a Co-60 unit. Significant differences were noted among various irradiated groups with and without the folate conjugation, with an average dose enhancement factor (DEF) of 1.64 ± 0.05 and 1.35 ± 0.05 for the folate-conjugated and pegylated GNPs, respectively. The maximum DEF was obtained with the 180 kVp x-ray beam for both of the GNPs. Folate-conjugated GNPs can significantly enhance the cell killing potential of orthovoltage x-ray energies (especially at 180 kVp) in folate receptor-expressing cancer cells, such as HeLa, in superficial radiotherapy techniques.

  12. Effect of Proton Beam on Cancer Progressive and Metastatic Enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Y. H.; Nam, K. S.; Oh, Y. H.; Kim, M. K.; Kim, M. Y.; Jang, J. S. [Dongguk University, Seoul (Korea, Republic of)

    2008-04-15

    The purpose of this study was to investigate the effect of proton beam on enzymes for promotion/progression of carcinogenesis and metastasis of malignant tumor cells to clarify proton beam-specific biological effects. The changes of cancer chemopreventive enzymes in human colorectal adenocarcinoma HT-29 cells irradiated with proton beams were tested by measuring the activities of quinine reductase (QR), glutathione S-transferase (GST), and ornithine decarboxylase (ODC), glutathione (GSH) levels, and expression of cyclooxygenase-2 (COX-2). We also examined the effect of proton beam on the ODC activity and expression of COX-2 in human breast cancer cell. We then assessed the metastatic capabilities of HT-29 and MDA-MB-231 cells irradiated with proton beam by measuring the invasiveness of cells through Matrigel-coated membrane and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP activity in MDA-MB-231 and HT-29 cells. QR activity of irradiated HT-29 cells was slightly increased. Proton irradiation at dose of 32 Gy in HT-29 cells increased GST activity by 1.23-fold. In addition GSH levels in HT-29 cells was significantly increased 1.23- (p<0.05), 1.32- (p<0.01) and 1.34-fold (p<0.01) with the proton irradiation at doses of 8, 16 and 32 Gy, respectively. These results suggest that colon cancer chemopreventive activity was increased with the proton irradiation by increasing QR and GST activities and GSH levels and inhibiting ODC activity. Proton ion irradiation decreased the invasiveness of TPA-treated HT-29 cells and MDA-MB-231 cells through Matrigel-coated membrane. Proton ion irradiation pretreatment decreased TPA-induced MMP activity in MDA-MB-231 and HT-29 cells. Further studies are necessary to investigate if these findings could be translated to in vivo situations

  13. Cytokinetic effects of Wee1 disruption in pancreatic cancer.

    Science.gov (United States)

    Chang, Qing; Chandrashekhar, Megha; Ketela, Troy; Fedyshyn, Yaroslav; Moffat, Jason; Hedley, David

    2016-01-01

    The Wee1 kinase, which is activated in response to DNA damage, regulates exit from G2 through inhibitory phosphorylation of Cdk1/Cdc2, and is an attractive drug target. However, recent work has highlighted effects of Cdk2 phosphorylation by Wee1 on movement through S-phase, suggesting the potential to sensitize to S-phase specific agents by Wee1 inhibitors. In this paper we applied multiparametric flow cytometry to patient-derived pancreatic cancer xenograft tumor cells to study the cell cycle perturbations of Wee1 disruption via the small molecule inhibitor MK-1775, and genetic knockdown. We find that in vitro treatment with MK-1775, and to a lesser degree, Wee1 RNA transcript knockdown, results in the striking appearance of S-phase cells prematurely entering into mitosis. This effect was not seen in vivo in any of the models tested. Here, although we noted an increase of S-phase cells expressing the damage response marker γH2AX, treatment with MK-1775 did not significantly sensitize cells to the cytidine analog gemcitabine. Treatment with MK-1775 did result in a transient but large increase in cells expressing the mitotic marker phosphorylated H3S10 that reached a peak 4 hours after treatment. This suggests a role for Wee1 regulating the progression of genomically unstable cancer cells through G2 in the absence of extrinsically-applied DNA damage. A single dose of 8Gy ionizing radiation resulted in the time-dependent accumulation of Cyclin A2 positive/phosphorylated H3S10 negative cells at the 4N position, which was abrogated by treatment with MK-1775. Consistent with these findings, a genome-scale pooled RNA interference screen revealed that toxic doses of MK-1775 are suppressed by CDK2 or Cyclin A2 knockdown. These findings support G2 exit as the more significant effect of Wee1 inhibition in pancreatic cancers. PMID:26890070

  14. Effect of NS-398 on colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Qing Jia; Ning Zhong; Li-Hui Han; Jing-Hua Wang; Ming Yan; Fan-Li Meng; Shang-Zhong Zhang

    2005-01-01

    AIM: To study the effect of NS-398, a selective cyclooxygenase2 (COX-2) inhibitor, on invasion of colon cancer cell line HT-29 in vitro and to explore its mechanisms.METHODS: Invasive behaviors of the malignant colon cancer cell line HT-29 were investigated in this study.Expressions of COX-2 and CD44v6 in HT-29 cells were detected by flow cytometry. Cellular survival rate was determined by MTT assay. The invasive capacity was quantified by a modified Boyden chamber model. Alterations of cytoskeleton component F-actin were observed by confocal laser scanning microscope.RESULTS: Flow cytometry analysis showed that COX-2was highly expressed in HT-29 cells. The invasive capability of HT-29 cells could be greatly inhibited by NS-398 at the experimental concentrations of 0.1, 1.0 and 10 μmol/L with an inhibitory rate of 22.74%, 42.35% and 58.61% (P<0.01),respectively. MTT assay showed that NS-398 at the experimental concentrations had no significant influence on cellular viability, indicating that such anti-invasive effects had no relationship with cytotoxicity. F-actin was mainly distributed around nuclei forming annular structure in HT-29cells. After exposure to NS-398 of 10 μmol/L, the annular structure around nuclei disappeared and the fluorescence intensity of F-actin decreased obviously. Treatment with NS-398 could down-regulate the expression of CD44v6 as well.CONCLUSION: NS-398 has anti-invasive effects on colon cancer HT-29 cells in vitro, which may be mediated by a novel mechanism of disruption of cytoskeleton. Downregulation of CD44v6 expression may be related to alterations of cytoskeleton.

  15. Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

    2016-02-01

    Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

  16. Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

    2016-02-01

    Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP. PMID:26715289

  17. Effects of Src on Proliferation and Invasion of Lung Cancer Cells

    OpenAIRE

    ZHENG, Rui; Qin, Xiaosong; Li, Wenjie; Kang, Jian

    2011-01-01

    Background and objective It has been proven that Src played pivotal roles in carcinogenesis, cancer progression and metastasis. The aim of this study is to explore the roles of Src phosphorylation on lung cancer cells. Methods Western blot and immunoprecipitation was used to detect the expression and phosphorylation of Src in lung cancer cells. MTT and Boyden chamber assay was used to examine the effects of inhibition of Src phosphorylation on proliferation and invasion of lung cancer cells i...

  18. The eyeball killer: serial killings with postmortem globe enucleation.

    Science.gov (United States)

    Coyle, Julie; Ross, Karen F; Barnard, Jeffrey J; Peacock, Elizabeth; Linch, Charles A; Prahlow, Joseph A

    2015-05-01

    Although serial killings are relatively rare, they can be the cause of a great deal of anxiety while the killer remains at-large. Despite the fact that the motivations for serial killings are typically quite complex, the psychological analysis of a serial killer can provide valuable insight into how and why certain individuals become serial killers. Such knowledge may be instrumental in preventing future serial killings or in solving ongoing cases. In certain serial killings, the various incidents have a variety of similar features. Identification of similarities between separate homicidal incidents is necessary to recognize that a serial killer may be actively killing. In this report, the authors present a group of serial killings involving three prostitutes who were shot to death over a 3-month period. Scene and autopsy findings, including the unusual finding of postmortem enucleation of the eyes, led investigators to recognize the serial nature of the homicides.

  19. The eyeball killer: serial killings with postmortem globe enucleation.

    Science.gov (United States)

    Coyle, Julie; Ross, Karen F; Barnard, Jeffrey J; Peacock, Elizabeth; Linch, Charles A; Prahlow, Joseph A

    2015-05-01

    Although serial killings are relatively rare, they can be the cause of a great deal of anxiety while the killer remains at-large. Despite the fact that the motivations for serial killings are typically quite complex, the psychological analysis of a serial killer can provide valuable insight into how and why certain individuals become serial killers. Such knowledge may be instrumental in preventing future serial killings or in solving ongoing cases. In certain serial killings, the various incidents have a variety of similar features. Identification of similarities between separate homicidal incidents is necessary to recognize that a serial killer may be actively killing. In this report, the authors present a group of serial killings involving three prostitutes who were shot to death over a 3-month period. Scene and autopsy findings, including the unusual finding of postmortem enucleation of the eyes, led investigators to recognize the serial nature of the homicides. PMID:25682709

  20. Geometry of Killing spinors in neutral signature

    CERN Document Server

    Klemm, Dietmar

    2015-01-01

    We classify the supersymmetric solutions of minimal $N=2$ gauged supergravity in four dimensions with neutral signature. They are distinguished according to the sign of the cosmological constant and whether the vector field constructed as a bilinear of the Killing spinor is null or non-null. In neutral signature the bilinear vector field can be spacelike, which is a new feature not arising in Lorentzian signature. In the $\\Lambda0$ non-null case, the manifold is a fibration over a Lorentzian Gauduchon-Tod base space. Finally, in the $\\Lambda>0$ null class, the metric is contained in the Kundt family, and it turns out that the holonomy is reduced to ${\\rm Sim}(1)\\times{\\rm Sim}(1)$. There appear no self-dual solutions in the null class for either sign of the cosmological constant.