Science.gov

Sample records for cancer effects modified

  1. Histone Modifiers in Cancer

    PubMed Central

    Cohen, Idan; Poręba, Elżbieta; Kamieniarz, Kinga; Schneider, Robert

    2011-01-01

    Covalent modifications of histones can regulate all DNA-dependent processes. In the last few years, it has become more and more evident that histone modifications are key players in the regulation of chromatin states and dynamics as well as in gene expression. Therefore, histone modifications and the enzymatic machineries that set them are crucial regulators that can control cellular proliferation, differentiation, plasticity, and malignancy processes. This review discusses the biology and biochemistry of covalent histone posttranslational modifications (PTMs) and evaluates the dual role of their modifiers in cancer: as oncogenes that can initiate and amplify tumorigenesis or as tumor suppressors. PMID:21941619

  2. Studies demonstrate modified T cells effective in treating blood-borne cancers

    Cancer.gov

    At the 2013 American Society of Hematology meeting in Dec. 2013, James Kochenderfer, M.D., NCI, presented findings from two clinical trials evaluating the use of genetically modified immune system T cells as cancer therapy. These reports represent import

  3. Effects of newspaper coverage on public knowledge about modifiable cancer risks.

    PubMed

    Stryker, Jo Ellen; Moriarty, Cortney M; Jensen, Jakob D

    2008-07-01

    This study explores the relationship between cancer newspaper coverage and public knowledge about cancer prevention, confirming self-reported associations between news exposure and cancer prevention knowledge with descriptions of newspaper coverage of modifiable cancer risks. Content analyses (N = 954) revealed that newspapers pay relatively little attention to cancer prevention. However, there is greater newspaper attention to tobacco and diet than to exercise, sun, and alcohol. Survey analysis (the National Cancer Institute's Health Information National Trends Survey) revealed that after controlling for differences based on gender, race, age, income, and education, attention to health news was significantly associated with knowledge about cancer risks associated with food and smoking but not for knowledge about exercise, sun, or alcohol. These findings conform to the findings of the content analysis data and provide a validation of a self-reported measure of media exposure, as well as evidence suggesting a threshold below which news coverage may not generate public knowledge about cancer prevention. PMID:18702002

  4. Body mass index and colon cancer risk in Chinese people: Menopause as an effect modifier

    PubMed Central

    Hou, Lifang; Ji, Bu-Tian; Blair, Aaron; Dai, Qi; Gao, Yu-Tang; Potter, John D.; Chow, Wong-Ho

    2006-01-01

    High body mass index (BMI) has consistently been associated with increased colon cancer risk in men, but not in women. It is hypothesised that menopause-related changes in oestrogen levels play a role in gender-specific risk patterns. Most studies have been conducted in Western countries, where high incidence rates are coupled with a high prevalence of obesity and relatively common use of hormone replacement therapy (HRT) in post-menopausal women. This study evaluated the correlation between body mass index (BMI) and colon cancer risk in a relatively lean population, comprising 931 cases and 1552 controls, in Shanghai, China, where HRT use was extremely rare among women, during 1990–1993. Among men, colon cancer risk significantly increased with increasing BMI (P-trend = 0.005). Among women, the risk varied with age and menopause status in a similar pattern. Within each menopause stratum, however, the BMI-related risk was similar for those aged under 55 years and those aged 55 years and over, indicating a menopause rather than age effect. Among pre-menopausal women, the odds ratios (ORs) for subjects in the highest versus lowest quintile were 1.9 (95% CI 1.1–4.9) for those under 55 years of age, and 2.2 (95% CI 1.4–8.2) for those aged 55 years and over. Among post-menopausal women, the corresponding ORs were 0.6 (95% CI 0.5–0.91) and 0.7 (95% CI 0.5–0.95), respectively. Our findings suggest that BMI predicts colon cancer risk in both genders. Among women, however, the risk is modified by menopause status, possibly through altered endogenous oestrogen levels. PMID:16321519

  5. Anti-tumor effect of RGD modified PTX loaded liposome on prostatic cancer

    PubMed Central

    Cao, Yunjie; Zhou, Yaojun; Zhuang, Qianfeng; Cui, Li; Xu, Xianlin; Xu, Renfang; He, Xiaozhou

    2015-01-01

    In this study, we report an active targeting liposomal formulation directed by a novel peptide (RGD) that specifically binds to the integrins receptors overexpressed on prostatic cancer cells. The objectives of this study were to evaluate the in vitro and in vivo tumor drug targeting delivery of RGD modified liposomes on PC-3 cells and DU145 cells. The uptake efficiency of RGD-LP was 5.2 times higher than that of LP on PC-3 cells. The uptake efficiency of RGD-LP was 3.2 times higher than that of LP on DU145 cells. The anti-proliferative activity of RGD-LP-PTX against PC-3 cells and DU145 cells were much stronger compared to that of LP-PTX and free PTX, respectively. The tumor spheroids experiment revealed that RGD-LP-PTX was more efficaciously internalized into tumor spheroids than LP in both PC-3 cells and DU145 cells. Compared to LP-PTX and free PTX, RGD-LP-PTX showed the greatest tumor growth inhibitory effect in vivo. In brief, the RGD-LP may be an efficient targeting drug delivery system for prostatic cancer. PMID:26550128

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

    PubMed

    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. PMID:21834073

  7. N-Isopropylacrylamide Modified Polyethylenimines as Effective siRNA Carriers for Cancer Therapy.

    PubMed

    Chen, Jie; Lin, Lin; Guo, Zhaopei; Xu, Caina; Li, Yanhui; Tian, Huayu; Tang, Zhaohui; He, Chaoliang; Chen, Xuesi

    2016-06-01

    N-isopropylacrylamide modified PEI (PEN) was synthesized via Michael addition and was developed as an efficient siRNA delivery system both in vitro and in vivo. PEN showed significant enhanced cytocompatibility compared with commercial PEI-25k. The complexation of PEN with siRNA was studied by gel retardation, particle size and zeta potential measurement. The in vitro transfection ability of PEN was measured by qRT-PCR assay, and achieved obviously enhanced gene silencing efficiency compared with PEI-25k. The confocal imaging and flow cytometric analysis further validated its excellent intracellular trafficking ability. For antitumor treatment experiment, PEN mediated siVEGF showed obviously therapeutic effects for the treatment of CT26 tumor. Therefore, the present study demonstrated a useful strategy for constructing efficient siRNA delivery vehicles for antitumor therapy. PMID:27427585

  8. Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts

    PubMed Central

    de Gonzalez, Amy Berrington; Hartge, Patricia; Pfeiffer, Ruth M.; Park, Yikyung; Freedman, D. Michal; Gail, Mitchell H.; Alavanja, Michael C. R.; Albanes, Demetrius; Beane Freeman, Laura E.; Chow, Wong-Ho; Huang, Wen-Yi; Hayes, Richard B.; Hoppin, Jane A.; Ji, Bu-tian; Leitzmann, Michael F.; Linet, Martha S.; Meinhold, Cari L.; Schairer, Catherine; Schatzkin, Arthur; Virtamo, Jarmo; Weinstein, Stephanie J.; Zheng, Wei; Stolzenberg-Solomon, Rachael Z.

    2010-01-01

    Objective To investigate whether the positive association of body mass index (BMI, kg/m2) with risk of pancreatic cancer is modified by age, sex, smoking status, physical activity, and history of diabetes. Methods In a pooled analysis of primary data of seven prospective cohorts including 458,070 men and 485,689 women, we identified 2,454 patients with incident pancreatic cancer during an average 6.9 years of follow-up. Cox proportional hazard regression models were used in data analysis. Results In a random-effects meta-analysis, for every 5 kg/m2 increment in BMI, the summary relative risk (RR) was 1.06 (95% confidence interval (CI) 0.99–1.13) for men and 1.12 (95% CI 1.05–1.19) for women. The aggregate analysis showed that compared with normal weight (BMI: 18.5 to <25), the adjusted RR was 1.13 (95% CI 1.03–1.23) for overweight (BMI: 25 to <30) and 1.19 (95% CI 1.05–1.35) for obesity class I (BMI: 30 to <35). Tests of interactions of BMI effects by other risk factors were not statistically significant. Every 5 kg/m2 increment in BMI was associated with an increased risk of pancreatic cancer among never and former smokers, but not among current smokers (P-interaction = 0.08). Conclusion The present evidence suggests that a high BMI is an independent risk factor of pancreatic cancer. PMID:20383573

  9. Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5-fluorouracil in murine liver cancer model via regulatory T-cells

    PubMed Central

    Cheng, Mingrong; Xu, Hongzhi; Wang, Yong; Chen, Houxiang; He, Bing; Gao, Xiaoyan; Li, Yingchun; Han, Jiang; Zhang, Zhiping

    2013-01-01

    Modified chitosan nanoparticles are a promising platform for drug, such as 5-fluorouracil (5-FU), gene, and vaccine delivery. Here, we used chitosan and hepatoma cell-specific binding molecule glycyrrhetinic acid (GA) to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared spectroscopy and hydrogen nuclear magnetic resonance. By combining GA-CTS and 5-FU, we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 193.7 nm, drug loading of 1.56%, and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained-release system comprising three distinct phases of quick, steady, and slow release. In vitro data indicated that it had a dose- and time-dependent anticancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited cancer cell proliferation, resulting in increased survival time. The antitumor mechanisms for GA-CTS/5-FU nanoparticle were possibly associated with an increased expression of regulatory T-cells, decreased expression of cytotoxic T-cell and natural killer cells, and reduced levels of interleukin-2 and interferon gamma. PMID:24187487

  10. Attitudes towards massage modify effects of manual therapy in breast cancer survivors: a randomised clinical trial with crossover design.

    PubMed

    Fernández-Lao, C; Cantarero-Villanueva, I; Díaz-Rodríguez, L; Cuesta-Vargas, A I; Fernández-Delas-Peñas, C; Arroyo-Morales, M

    2012-03-01

    Our aims were to investigate the immediate effect of myofascial release on heart rate variability and mood state, and the influence of attitude towards massage in breast cancer survivors with cancer-related fatigue. Twenty breast cancer survivors reporting moderate to high cancer-related fatigue participated in this crossover study. All patients presented to the laboratory at the same time of the day on two occasions separated by a 2-week interval. At each session, they received either a massage intervention or control intervention. Holter electrocardiogram recordings and Profile of Mood States questionnaire (six domains: tension-anxiety, depression-dejection, anger-hostility, vigour, fatigue, confusion) were obtained before and immediately after each intervention. The attitude towards massage scale was collected before the first session in all breast cancer survivors. The results showed a significant session × time interaction for standard deviation of the normal-to-normal interval (SDNN) (F= 5.063, P= 0.039), square root of mean squared differences of successive normal-to-normal intervals (RMSSD) (F= 8.273, P= 0.010), high-frequency component (HF) (F= 7.571, P= 0.013), but not for index heart rate variability (F= 3.451, P= 0.080), low-frequency component (LF) (F= 0.014, P= 0.997) and ratio LF/HF (F= 3.680, P= 0.072): significant increases in SDNN, RMSSD and HF domain (P < 0.05) were observed after the manual therapy intervention, with no changes after placebo (P > 0.6). No influence of the attitude scale on heart rate variability results was found. A significant session × time interaction was also found for fatigue (F= 5.101, P= 0.036) and disturbance of mood (F= 6.690, P= 0.018) scales of the Profile of Mood States: patients showed a significant decrease in fatigue and disturbance of mood (P < 0.001) after manual therapy, with no changes after placebo (P > 0.50). A significant influence of the attitude scale was observed in tension-anxiety, depression

  11. A Systematic Review of the Modifying Effect of Anaesthetic Drugs on Metastasis in Animal Models for Cancer

    PubMed Central

    Geessink, Florentine J.; Ritskes-Hoitinga, Merel; Scheffer, Gert Jan

    2016-01-01

    Background Distant metastasis or local recurrence after primary tumour resection remain a major clinical problem. The anaesthetic technique used during oncologic surgery is suggested to influence the metastatic process. While awaiting the results of ongoing randomised controlled trials (RCTs), we have analyzed the evidence regarding the influence of anaesthetic drugs on experimental tumour metastasis in animal studies. Methods PubMed and Embase were searched until April 21st, 2015. Studies were included in the systematic review when they 1) assessed the effect of an anaesthetic drug used in clinical practice on the number or incidence of metastasis in animal models with experimental cancer, 2) included an appropriate control group, and 3) presented unique data. Results 20 studies met the inclusion criteria (published between 1958–2010). Data on number of metastases could be retrieved from 17 studies. These studies described 41 independent comparisons, 33 of which could be included in the meta-analysis (MA). The incidence of metastases was studied in 3 unique papers. From these 3 papers, data on 7 independent comparisons could be extracted and included in the MA. Locally administered local anaesthetics appear to decrease the number of metastases (SMD -6.15 [-8.42; -3.88]), whereas general anaesthetics (RD: 0.136 [0.045, 0.226]), and more specifically volatile anaesthetics (SMD 0.54 [0.24; 0.84]), appear to increase the number and risk of metastases in animal models for cancer. Conclusions Anaesthetics influence the number and incidence of metastases in experimental cancer models. Although more high quality experimental research is necessary, based on the currently available evidence from animal studies, there is no indication to suggest that locally administered local anaesthetics are harmful during surgery in cancer patients. Volatile anaesthetics, however, might increase metastasis in animal models and clinical trials investigating this possibly harmful effect

  12. Lung cancer in French and Czech uranium miners: Radon-associated risk at low exposure rates and modifying effects of time since exposure and age at exposure.

    PubMed

    Tomasek, Ladislav; Rogel, Agnès; Tirmarche, Margot; Mitton, Nicolas; Laurier, Dominique

    2008-02-01

    Radon is recognized as a public health concern for indoor exposure. Precise quantification derived from occupational exposure in miners is still needed for estimating the risk and the factors that modify the dependence on cumulated exposure. The present paper reports on relationship between radon exposure and lung cancer risk in French and Czech cohorts of uranium miners (n = 10,100). Miners from these two cohorts are characterized by low levels of exposure (average cumulated exposure of less than 60 WLM) protracted over a long period (mean duration of exposure of 10 years) and by a good quality of individual exposure estimates (95% of annual exposures based on radon measurements). The modifying effect of the quality of exposure on the risk is analyzed. A total of 574 lung cancer deaths were observed, which is 187% higher than expected from the national statistics. This significantly elevated risk is strongly associated with cumulated radon exposure. The estimated overall excess relative risk per WLM is 0.027 (95% CI: 0.017-0.043, related to measured exposures). For age at exposure of 30 and 20 years since exposure, the ERR/WLM is 0.042, and this value decreases by approximately 50% for each 10-year increase in age at exposure and time since exposure. The present study emphasizes that the quality of exposure estimates is an important factor that may substantially influence results. Time since exposure and simultaneously age at exposure were the most important effect modifiers. No inverse exposure-rate effect below 4 WL was observed. The results are consistent with estimates of the BEIR VI report using the concentration model at an exposure rate below 0.5 WL. PMID:18220460

  13. RGD-modified liposomes enhance efficiency of aclacinomycin A delivery: evaluation of their effect in lung cancer

    PubMed Central

    Feng, Chan; Li, Xiaoyan; Dong, Chunyan; Zhang, Xuemei; Zhang, Xie; Gao, Yong

    2015-01-01

    In this study, long-circulating Arg-Gly-Asp (RGD)-modified aclacinomycin A (ACM) liposomes were prepared by thin film hydration method. Their morphology, particle size, encapsulation efficiency, and in vitro release were investigated. The RGD-ACM liposomes was about 160 nm in size and had the visual appearance of a yellowish suspension. The zeta potential was −22.2 mV and the encapsulation efficiency was more than 93%. The drug-release behavior of the RGD-ACM liposomes showed a biphasic pattern, with an initial burst release and followed by sustained release at a constant rate. After being dissolved in phosphate-buffered saline (pH 7.4) and kept at 4°C for one month, the liposomes did not aggregate and still had the appearance of a milky white colloidal solution. In a pharmacokinetic study, rats treated with RGD-ACM liposomes showed slightly higher plasma concentrations than those treated with ACM liposomes. Maximum plasma concentrations of RGD-ACM liposomes and ACM liposomes were 4,532 and 3,425 ng/mL, respectively. RGD-ACM liposomes had a higher AUC0–∞ (1.54-fold), mean residence time (2.09-fold), and elimination half-life (1.2-fold) when compared with ACM liposomes. In an in vivo study in mice, both types of liposomes inhibited growth of human lung adenocarcinoma (A549) cells and markedly decreased tumor size when compared with the control group. There were no obvious pathological tissue changes in any of the treatment groups. Our results indicate that RGD-modified ACM liposomes have a better antitumor effect in vivo than their unmodified counterparts. PMID:26316700

  14. Polymorphisms in base excision repair genes as colorectal cancer risk factors and modifiers of the effect of diets high in red meat

    PubMed Central

    Brevik, Asgeir; Joshi, Amit D.; Corral, Román; Onland-Moret, N. Charlotte; Siegmund, Kimberly D.; Le Marchand, Loïc; Baron, John A.; Martinez, Maria Elena; Haile, Robert W.; Ahnen, Dennis J.; Sandler, Robert S.; Lance, Peter; Stern, Mariana C.

    2010-01-01

    Background A diet high in red meat is an established colorectal cancer (CRC) risk factor. Carcinogens generated during meat cooking have been implicated as causal agents, and can induce oxidative DNA damage, which elicits repair by the base excision repair (BER) pathway. Methods Using a family-based study we investigated the role of polymorphisms in four BER genes (APEX1 Gln51His, Asp148Glu; OGG1 Ser236Cys; PARP Val742Ala; XRCC1 Arg194Trp, Arg280His, Arg399Gln) as potential CRC risk factors and modifiers of the association between high-red meat or poultry diets and CRC risk. We tested for gene-environment interactions using case-only analyses (N = 577) and compared statistically significant results to those obtained using case-unaffected sibling comparisons (N = 307 sibships). Results Carriers of the APEX1 codon 51 Gln/His genotype had a reduced CRC risk compared to carriers of the Gln/Gln genotype (OR 0.15, 95% CI 0.03-0.69, p = 0.015). The association between higher red meat intake (>3 servings/week) and CRC was modified by the PARP Val762Ala SNP (case-only interaction p = 0.026). This SNP also modified the association between higher intake of high-temperature cooked red meat (case-only interaction p = 0.0009). Conclusions We report evidence that the BER pathway PARP gene modifies the association of diets high in red meat cooked at high temperatures with risk of CRC. Impact Our findings suggest a contribution to colorectal carcinogenesis of free radical damage as one of the possible harmful effects of a high-red meat diet. PMID:21037106

  15. Magainin II modified polydiacetylene micelles for cancer therapy

    NASA Astrophysics Data System (ADS)

    Yang, Danling; Zou, Rongfeng; Zhu, Yu; Liu, Ben; Yao, Defan; Jiang, Juanjuan; Wu, Junchen; Tian, He

    2014-11-01

    Polydiacetylene (PDA) micelles have been widely used to deliver anticancer drugs in the treatment of a variety of tumours and for imaging living cells. In this study, we developed an effective strategy to directly conjugate magainin II (MGN-II) to the surface of PDA micelles using a fluorescent dye. These stable and well-defined PDA micelles had high cytotoxicity in cancer cell lines, and were able to reduce the tumour size in mice. The modified PDA micelles improved the anticancer effects of MGN-II in the A549 cell line only at a concentration of 16.0 μg mL-1 (IC50). In addition, following irradiation with UV light at 254 nm, the PDA micelles gave rise to an energy transfer from the fluorescent dye to the backbone of PDA micelles to enhance the imaging of living cells. Our results demonstrate that modified PDA micelles can not only be used in the treatment of tumors in vitro and in vivo in a simple and directed way, but also offer a new platform for designing functional liposomes to act as anticancer agents.Polydiacetylene (PDA) micelles have been widely used to deliver anticancer drugs in the treatment of a variety of tumours and for imaging living cells. In this study, we developed an effective strategy to directly conjugate magainin II (MGN-II) to the surface of PDA micelles using a fluorescent dye. These stable and well-defined PDA micelles had high cytotoxicity in cancer cell lines, and were able to reduce the tumour size in mice. The modified PDA micelles improved the anticancer effects of MGN-II in the A549 cell line only at a concentration of 16.0 μg mL-1 (IC50). In addition, following irradiation with UV light at 254 nm, the PDA micelles gave rise to an energy transfer from the fluorescent dye to the backbone of PDA micelles to enhance the imaging of living cells. Our results demonstrate that modified PDA micelles can not only be used in the treatment of tumors in vitro and in vivo in a simple and directed way, but also offer a new platform for

  16. Photothermal effects of immunologically modified carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Griswold, Ryan T.; Henderson, Brock; Goddard, Jessica; Tan, Yongqiang; Hode, Tomas; Liu, Hong; Nordquist, Robert E.; Chen, Wei R.

    2013-02-01

    Carbon nanotubes have a great potential in the biomedical applications. To use carbon nanotubes in the treatment of cancer, we synthesized an immunologically modified single-walled carbon nanotube (SWNT) using a novel immunomodifier, glycated chitosan (GC), as an effective surfactant for SWNT. This new composition SWNT-GC was stable due to the strong non-covalent binding between SWNT and GC. The structure of SWNT-GC is presented in this report. The photothermal effect of SWNT-GC was investigated under irradiation of a near-infrared laser. SWNT-GC retained the optical properties of SWNT and the immunological properties of GC. Specifically, the SWNT-GC could selectively absorb a 980-nm light and induce desirable thermal effects in tissue culture and in animals. It could also induce tumor cell destruction, controlled by the laser settings and the doses of SWNT and GC. Laser+SWNT-GC treatment could also induce strong expression of heat shock proteins on the surface of tumor cells. This immunologically modified carbon nanotube could be used for selective photothermal interactions in noninvasive tumor treatment.

  17. The Modifier Effect and Property Mutability

    ERIC Educational Resources Information Center

    Hampton, James A.; Passanisi, Alessia; Jonsson, Martin L.

    2011-01-01

    The modifier effect is the reduction in perceived likelihood of a generic property sentence, when the head noun is modified. We investigated the prediction that the modifier effect would be stronger for mutable than for central properties, without finding evidence for this predicted interaction over the course of five experiments. However…

  18. Age and cancer risk: a potentially modifiable relationship.

    PubMed

    White, Mary C; Holman, Dawn M; Boehm, Jennifer E; Peipins, Lucy A; Grossman, Melissa; Henley, S Jane

    2014-03-01

    This article challenges the idea that cancer cannot be prevented among older adults by examining different aspects of the relationship between age and cancer. Although the sequential patterns of aging cannot be changed, several age-related factors that contribute to disease risk can be. For most adults, age is coincidentally associated with preventable chronic conditions, avoidable exposures, and modifiable risk behaviors that are causally associated with cancer. Midlife is a period of life when the prevalence of multiple cancer risk factors is high and incidence rates begin to increase for many types of cancer. However, current evidence suggests that for most adults, cancer does not have to be an inevitable consequence of growing older. Interventions that support healthy environments, help people manage chronic conditions, and promote healthy behaviors may help people make a healthier transition from midlife to older age and reduce the likelihood of developing cancer. Because the number of adults reaching older ages is increasing rapidly, the number of new cancer cases will also increase if current incidence rates remain unchanged. Thus, the need to translate the available research into practice to promote cancer prevention, especially for adults at midlife, has never been greater. PMID:24512933

  19. Bauhinia purprea agglutinin-modified liposomes for human prostate cancer treatment.

    PubMed

    Ikemoto, Keisuke; Shimizu, Kosuke; Ohashi, Kento; Takeuchi, Yoshihito; Shimizu, Motohiro; Oku, Naoto

    2016-01-01

    Bauhinia purprea agglutinin (BPA) is a well-known lectin that recognizes galactosyl glycoproteins and glycolipids. In the present study, we firstly found that BPA bound to human prostate cancer specimens but not to normal prostate ones. Therefore, we sought to develop BPA-PEG-modified liposomes (BPA-PEG-LP) encapsulating anticancer drugs for the treatment of prostate cancer. We examined the tumor targetability of BPA-PEG-LP with human prostate cancer DU145 cells, and observed that fluorescently labeled BPA-PEG-LP dominantly associated with the cells via the interaction between liposome-surface BPA and cell-surface galactosyl molecules. We also observed that BPA-PEG-LP accumulated in the prostate cancer tissue after the i.v. injection to DU145 solid cancer-bearing mice, and strongly bound to the cancer cells. In a therapeutic study, DU145 solid cancer-bearing mice were i.v. injected thrice with BPA-PEG-LP encapsulating doxorubicin (BPA-PEG-LPDOX, 2 mg/kg/day as the DOX dosage) or PEG-modified liposomes encapsulating DOX (PEG-LPDOX). As a result, BPA-PEG-LPDOX significantly suppressed the growth of the DU145 cancer cells, whereas PEG-LPDOX at the same dosage as DOX showed little anti-cancer effect. The present study suggested that BPA-PEG-LP could be a useful drug carrier for the treatment of human prostate cancers. PMID:26495901

  20. Factors that modify risks of radiation-induced cancer

    SciTech Connect

    Fabrikant, J.I.

    1988-11-01

    The collective influence of biologic and physical factors that modify risks of radiation-induced cancer introduces uncertainties sufficient to deny precision of estimates of human cancer risk that can be calculated for low-dose radiation in exposed populations. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, minimum latent period, time-to-tumor recognition, and the influence of individual host (age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Other modifying factors include other carcinogens, and other biological sources (hormonal status, immune status, hereditary factors).

  1. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression.

    PubMed

    Feinberg, Andrew P; Koldobskiy, Michael A; Göndör, Anita

    2016-05-01

    This year is the tenth anniversary of the publication in this journal of a model suggesting the existence of 'tumour progenitor genes'. These genes are epigenetically disrupted at the earliest stages of malignancies, even before mutations, and thus cause altered differentiation throughout tumour evolution. The past decade of discovery in cancer epigenetics has revealed a number of similarities between cancer genes and stem cell reprogramming genes, widespread mutations in epigenetic regulators, and the part played by chromatin structure in cellular plasticity in both development and cancer. In the light of these discoveries, we suggest here a framework for cancer epigenetics involving three types of genes: 'epigenetic mediators', corresponding to the tumour progenitor genes suggested earlier; 'epigenetic modifiers' of the mediators, which are frequently mutated in cancer; and 'epigenetic modulators' upstream of the modifiers, which are responsive to changes in the cellular environment and often linked to the nuclear architecture. We suggest that this classification is helpful in framing new diagnostic and therapeutic approaches to cancer. PMID:26972587

  2. Effects of modified gravity in galactic clustering

    NASA Astrophysics Data System (ADS)

    Verma, Murli; Krishna Yadav, Bal

    2016-07-01

    We discuss the distinct effects of the modified gravity, especially f(R) gravity in structure formation. The small redshift as well as high redshift epochs are studied with a potential set of diagnostics distinguishing between the standard general relativistic and the modified gravity. These diagnostics are further put to test against the observations obtained in clustering surveys.

  3. The Effects of Pre Modified Input, Interactionally Modified Input, and Modified Output on EFL Learners' Comprehension of New Vocabularies

    ERIC Educational Resources Information Center

    Maleki, Zinat; Pazhakh, AbdolReza

    2012-01-01

    The present study was an attempt to investigate the effects of premodified input, interactionally modified input and modified output on 80 EFL learners' comprehension of new words. The subjects were randomly assigned into four groups of pre modified input, interactionally modified input, modified output and unmodified (control) groups. Each group…

  4. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression

    PubMed Central

    Feinberg, Andrew P.; Koldobskiy, Michael A.; Göndör, Anita

    2016-01-01

    This year is the tenth anniversary of the publication in this journal of a model suggesting the existence of ‘tumour progenitor genes’. These genes are epigenetically disrupted at the earliest stages of malignancies, even before mutations, and thus cause altered differentiation throughout tumour evolution. The past decade of discovery in cancer epigenetics has revealed a number of similarities between cancer genes and stem cell reprogramming genes, widespread mutations in epigenetic regulators, and the part played by chromatin structure in cellular plasticity in both development and cancer. In the light of these discoveries, we suggest here a framework for cancer epigenetics involving three types of genes: ‘epigenetic mediators’, corresponding to the tumour progenitor genes suggested earlier; ‘epigenetic modifiers’ of the mediators, which are frequently mutated in cancer; and ‘epigenetic modulators’ upstream of the modifiers, which are responsive to changes in the cellular environment and often linked to the nuclear architecture. We suggest that this classification is helpful in framing new diagnostic and therapeutic approaches to cancer. PMID:26972587

  5. Modified nucleosides as biomarkers for early cancer diagnose in exposed populations.

    PubMed

    Seidel, Annerose; Seidel, Peter; Manuwald, Olaf; Herbarth, Olf

    2015-07-01

    There is increasing worldwide interest in developing of markers for tumor diagnosis and identification of individuals who are at high cancer risk. Cancer, like other diseases accompanied by metabolic disorders, causes characteristic effects on cell turnover rate, activity of modifying enzymes, and RNA/DNA modifications. This results in an increased excretion of modified nucleosides in cancer patients. Therefore, for many years modified nucleosides have been suggested as tumor markers. The aim of the study was to elucidate further the usefulness of urinary nucleosides as possible markers at early detection of cancer in persons which are exposed against tumor promoting influences during their working life. Uranium miners are exposed to many kinds of pollutants that can cause health damage even lead to carcinogenesis. We analyzed modified nucleosides in urine samples from 92 miners who are at high risk for lung cancer to assess the levels of nucleosides by a multilayer perceptron (MLP) classifier - a neural network model. Eighteen nucleosides/metabolites were detected with reversed-phase high-pressure liquid chromatography (RP-HPLC). A valid set of urinary metabolites were selected and multivariate statistical technique of multilayer perceptron neural network were applied. In a previous study, MLP shows a sensitivity and specificity of 97 and 85%, respectively. MLP classification including the most relevant markers/nucleosides clearly demonstrates the elevation of RNA metabolism in miners, which is associated with possible malignant disease. We found that there were 30 subjects with early health disorders among 92 uranium workers based on MLP technique using modified nucleosides. The combination of RP-HPLC analysis of modified nucleosides and subsequent MLP analyses represents a promising tool for the development of a non-invasive prediction system and may assist in developing management and surveillance procedures. PMID:24615900

  6. Anti-cancer activities of pH- or heat-modified pectin

    PubMed Central

    Leclere, Lionel; Cutsem, Pierre Van; Michiels, Carine

    2013-01-01

    Despite enormous efforts that have been made in the search for novel drugs and treatments, cancer continues to be a major public health problem. Moreover, the emergence of resistance to cancer chemotherapy often prevents complete remission. Researchers have thus turned to natural products mainly from plant origin to circumvent resistance. Pectin and pH- or heat-modified pectin have demonstrated chemopreventive and antitumoral activities against some aggressive and recurrent cancers. The focus of this review is to describe how pectin and modified pectin display these activities and what are the possible underlying mechanisms. The failure of conventional chemotherapy to reduce mortality as well as serious side effects make natural products, such as pectin-derived products, ideal candidates for exerting synergism in combination with conventional anticancer drugs. PMID:24115933

  7. Socioeconomic status, negative affect, and modifiable cancer risk factors in African-American smokers.

    PubMed

    Kendzor, Darla E; Cofta-Woerpel, Ludmila M; Mazas, Carlos A; Li, Yisheng; Vidrine, Jennifer Irvin; Reitzel, Lorraine R; Costello, Tracy J; Businelle, Michael S; Ahluwalia, Jasjit S; Cinciripini, Paul M; Wetter, David W

    2008-10-01

    The purpose of the present study was to describe the prevalence, patterns, and predictors of cooccurring modifiable cancer risk factors among African-Americans seeking smoking cessation treatment and to evaluate previously hypothesized models of the relationship between socioeconomic status (SES) and health behavior. Overweight/obesity, at-risk alcohol consumption, and insufficient physical activity were measured in 399 African-American smokers. Analyses indicated that 92.8% of participants had at least one cancer risk factor in addition to smoking. Univariate ordinal logistic regression analyses revealed that female gender, unemployment, lower positive affect, and greater negative affect were associated with having a greater number of cancer risk factors. Multivariate analyses yielded similar findings. A structural equation modeling approach indicated that stress/negative affect may function as one pathway linking SES and modifiable cancer risk factors among African-American smokers and that gender has a direct effect on modifiable cancer risk factors. Thus, risk patterns identified within each gender group may guide the development of multiple risk factor interventions for African-American smokers. Stress and negative affect may be an important treatment target within behavioral interventions for African-American smokers of low SES. PMID:18842995

  8. Modified sugar beet pectin induces apoptosis of colon cancer cells via an interaction with the neutral sugar side-chains.

    PubMed

    Maxwell, Ellen G; Colquhoun, Ian J; Chau, Hoa K; Hotchkiss, Arland T; Waldron, Keith W; Morris, Victor J; Belshaw, Nigel J

    2016-01-20

    Pectins extracted from a variety of sources and modified with heat and/or pH have previously been shown to exhibit activity towards several cancer cell lines. However, the structural basis for the anti-cancer activity of modified pectin requires clarification. Sugar beet and citrus pectin extracts have been compared. Pectin extracted from sugar beet pulp only weakly affected the viability of colon cancer cells. Alkali treatment increased the anti-cancer effect of sugar beet pectin via an induction of apoptosis. Alkali treatment decreased the degree of esterification (DE) and increased the ratio of rhamnogalacturonan I (RGI) to homogalacturonan. Low DE per se did not play a significant role in the anti-cancer activity. However, the enzymatic removal of galactose and, to a lesser extent, arabinose from the pectin decreased the effect on cancer cells indicating that the neutral sugar-containing RGI regions are important for pectin bioactivity. PMID:26572430

  9. Clinical application of genetically modified T cells in cancer therapy

    PubMed Central

    Kershaw, Michael H; Westwood, Jennifer A; Slaney, Clare Y; Darcy, Phillip K

    2014-01-01

    Immunotherapies are emerging as highly promising approaches for the treatment of cancer. In these approaches, a variety of materials are used to boost immunity against malignant cells. A key component of many of these approaches is functional tumor-specific T cells, but the existence and activity of sufficient T cells in the immune repertoire is not always the case. Recent methods of generating tumor-specific T cells include the genetic modification of patient lymphocytes with receptors to endow them with tumor specificity. These T cells are then expanded in vitro followed by infusion of the patient in adoptive cell transfer protocols. Genes used to modify T cells include those encoding T-cell receptors and chimeric antigen receptors. In this review, we provide an introduction to the field of genetic engineering of T cells followed by details of their use against cancer in the clinic. PMID:25505964

  10. Engineering chemically modified viruses for prostate cancer cell recognition.

    PubMed

    Mohan, K; Weiss, G A

    2015-12-01

    Specific detection of circulating tumor cells and characterization of their aggressiveness could improve cancer diagnostics and treatment. Metastasis results from such tumor cells, and causes the majority of cancer deaths. Chemically modified viruses could provide an inexpensive and efficient approach to detect tumor cells and quantitate their cell surface biomarkers. However, non-specific adhesion between the cell surface receptors and the virus surface presents a challenge. This report describes wrapping the virus surface with different PEG architectures, including as fusions to oligolysine, linkers, spacers and scaffolded ligands. The reported PEG wrappers can reduce by >75% the non-specific adhesion of phage to cell surfaces. Dynamic light scattering verified the non-covalent attachment by the reported wrappers as increased sizes of the virus particles. Further modifications resulted in specific detection of prostate cancer cells expressing PSMA, a key prostate cancer biomarker. The approach allowed quantification of PSMA levels on the cell surface, and could distinguish more aggressive forms of the disease. PMID:26463253

  11. Do Environmental Factors Modify the Genetic Risk of Prostate Cancer?

    PubMed Central

    Loeb, Stacy; Peskoe, Sarah B.; Joshu, Corinne E.; Huang, Wen-Yi; Hayes, Richard B.; Carter, H. Ballentine; Isaacs, William B.; Platz, Elizabeth A.

    2015-01-01

    Background Many SNPs influence prostate cancer risk. To what extent genetic risk can be reduced by environmental factors is unknown. Methods We evaluated effect modification by environmental factors of the association between susceptibility SNPs and prostate cancer in 1,230 incident prostate cancer cases and 1,361 controls, all white and similar ages, nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Trial. Genetic risk scores were calculated as number of risk alleles for 20 validated SNPs. We estimated the association between higher genetic risk (≥ 12 SNPs) and prostate cancer within environmental factor strata and tested for interaction. Results Men with ≥12 risk alleles had 1.98, 2.04, and 1.91 times the odds of total, advanced, and nonadvanced prostate cancer, respectively. These associations were attenuated with the use of selenium supplements, aspirin, ibuprofen, and higher vegetable intake. For selenium, the attenuation was most striking for advanced prostate cancer: compared with <12 alleles and no selenium, the OR for ≥12 alleles was 2.06 [95% confidence interval (CI), 1.67–2.55] in nonusers and 0.99 (0.38–2.58) in users (Pinteraction = 0.031). Aspirin had the most marked attenuation for nonadvanced prostate cancer: compared with <12 alleles and nonusers, the OR for ≥12 alleles was 2.25 (1.69–3.00) in nonusers and 1.70 (1.25–2.32) in users (Pinteraction = 0.009). This pattern was similar for ibuprofen (Pinteraction = 0.023) and vegetables (Pinteraction = 0.010). Conclusions This study suggests that selenium supplements may reduce genetic risk of advanced prostate cancer, whereas aspirin, ibuprofen, and vegetables may reduce genetic risk of nonadvanced prostate cancer. PMID:25342390

  12. Effective co-delivery of doxorubicin and curcumin using a glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer micelle for combination cancer chemotherapy.

    PubMed

    Yan, Tingsheng; Li, Dalong; Li, Jiwei; Cheng, Feng; Cheng, Jinju; Huang, Yudong; He, Jinmei

    2016-09-01

    A glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer (PCL-SS-CTS-GA) micelle was developed for the co-delivery of doxorubicin (DOX) and curcumin (CCM) to hepatoma cells. Glycyrrhetinic acid (GA) was used as a targeting unit to ensure specific delivery. Co-encapsulation of DOX and CCM was facilitated by the incorporation of poly(ε-caprolactone) (PCL) groups. The highest drug loading content was 19.8% and 8.9% (w/w) for DOX and CCM, respectively. The PCL-SS-CTS-GA micelle presented a spherical or ellipsoidal geometry with a mean diameter of approximately 110nm. The surface charge of the micelle changed from negative to positive, when the pH value of the solution decreased from 7.4 to 6.8. Meanwhile, it also exhibited a character of redox-responsive drug release and GA/pH-mediated endocytosis in vitro. In simulated body fluid with 10mM glutathione, the release rate in 12h was 80.6% and 67.2% for DOX and CCM, respectively. The cell uptake of micelles was significantly higher at pH 6.8 than pH 7.4. The combined administration of DOX and CCM was facilitated by PCL-SS-CTS-GA micelle. Results showed that there was strong synergic effect between the two drugs. The PCL-SS-CTS-GA micelle might turn into a promising and effective carrier for improved combination chemotherapy. PMID:27281238

  13. Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in non–small cell lung cancer

    SciTech Connect

    Pedicini, Piernicola; Strigari, Lidia; Benassi, Marcello; Caivano, Rocchina; Fiorentino, Alba; Nappi, Antonio; Salvatore, Marco; Storto, Giovanni

    2014-04-01

    To increase the efficacy of radiotherapy for non–small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new “toxicity index” (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volume histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.

  14. A modified thymosin alpha 1 inhibits the growth of breast cancer both in vitro and in vivo: suppressment of cell proliferation, inducible cell apoptosis and enhancement of targeted anticancer effects.

    PubMed

    Lao, Xingzhen; Li, Bin; Liu, Meng; Shen, Chen; Yu, Tingting; Gao, Xiangdong; Zheng, Heng

    2015-10-01

    Thymosin alpha 1 (Tα1) is commonly used for treating several diseases; however its usage has been limited because of poor penetration of the target tissue, such as tumor cells. In the present study, Tα1-iRGD, a peptide by conjugating Tα1 with the iRGD fragment, was evaluated its performance in MCF-7 and MDA-MB-231 human breast cancer cells. Compared with the wild-type peptide, Tα1-iRGD was more selective in binding tumor cells in the cell attachment assay. Furthermore, the MTT assay confirmed that Tα1-iRGD proved more effective in significantly inhibiting the growth of MCF-7 cells in contrast to the general inhibition displayed by Tα1. Further, conjugation of Tα1 with iRGD preserved the immunomodulatory activity of the drug by increasing the proliferation of mouse spleen lymphocytes. Further, compared with Tα1 treatment, Tα1-iRGD treatment of MCF-7 cells considerably increased the number of cells undergoing apoptosis, resulting in a dose-dependent inhibition of cancer cell growth, which was associated with a much better effect on up-regulation of the expression of BCL2-associated X protein (Bax), caspase 9, etc. More importantly, treatment with Ta1-iRGD was more efficacious than treatment with Ta1 in vivo. This study highlights the importance of iRGD on enhancement of cell penetration and tumor accumulation. In summary, our findings demonstrate that the novel modified Tα1 developed in this study has the potential to be used for treating breast cancer. PMID:26283169

  15. Peptide-modified gold nanoparticles for improved cancer therapeutics

    NASA Astrophysics Data System (ADS)

    Yang, Celina; Prooijen, Monique V.; Chithrani, Devika B.

    2014-03-01

    The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options. These nanostructures further provide strategies for improving loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy. Our recent results show enhancement of cell death during radiation therapy when GNPs are targeted to nucleus. In addition, we have seen enhanced therapeutic effects when GNPs are used as anticancer drug carriers. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents will hold the possibility of promising directions in cancer research.

  16. The effect of the cyclin D1 (CCND1) A870G polymorphism on colorectal cancer risk is modified by glutathione-S-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese Health Study.

    PubMed

    Probst-Hensch, Nicole M; Sun, Can-Lan; Van Den Berg, David; Ceschi, Michela; Koh, Woon-Puay; Yu, Mimi C

    2006-12-01

    Cyclin D1 (CCND1) regulates cellular decision between proliferation and growth arrest. Despite the functional relevance of the CCND1 A870G single nucleotide polymorphism (SNP) published results on its association with colorectal cancer (CRC) were inconsistent. We examined the association between this CCND1 genotype and CRC in the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63,000 Chinese men and women. We explored the hypothesis that inconsistency regarding the CCND1/CRC association may be attributable to the modifying effect of additional CRC risk factors. Since GSTM1/GSTT1 genotype and dietary isothiocyanate (ITC) intake had previously been identified as CRC risk factors in this cohort, we now explored if they influenced the CCND1/CRC association. In a nested case-control study within the Singapore Cohort, genomic DNA collected from 300 incident CRC cases and 1169 controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 polymorphisms. Unconditional logistic regression was used to assess genotype effects on cancer risk. No main effect of CCND1 was observed, yet the CCND1 effect was influenced by ITC intake and GST genotypes. The presence of at least one CCND1 A-allele was associated with increased risk among low dietary ITC consumers (intake below median value for the cohort) with a high-activity GST profile (>or=2 of the 3 GST genotypes classified non-null or high-activity) [odds ratio (OR)=2.05; 95% confidence interval (CI), 1.10-3.82]. In contrast, the presence of at least one A-allele was associated with a decreased risk among all remaining subjects (OR=0.56; 0.36-0.86) (P for interaction=0.01). Recent studies indicate that ITCs inhibit cell proliferation and cause apoptosis through pro-oxidant properties. The results of our current study on CRC and those of our previous breast cancer study are compatible with the notion of oxidative stress in target cells as important determinant of direction and magnitude of the CCND1

  17. Inhibition of metastatic tumor growth and metastasis via targeting metastatic breast cancer by chlorotoxin-modified liposomes.

    PubMed

    Qin, Chao; He, Bing; Dai, Wenbing; Zhang, Hua; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Wang, Guangji; Yin, Lifang; Zhang, Qiang

    2014-10-01

    A liposome system modified with chlorotoxin (ClTx), a scorpion venom peptide previously utilized for targeting brain tumors, was established. Its targeting efficiency and antimetastasis behavior against metastatic breast cancer highly expressed MMP-2, the receptor of ClTx, were investigated. 4T1, a metastatic breast cancer cell line derived from a murine breast tumor, was selected as the cell model. As results, the ClTx-modified liposomes displayed specific binding to 4T1 as determined by flow cytometry and confocal imaging. The cytotoxicity assay revealed that the ClTx modification increased the toxicity compared with nonmodified liposomes. In addition, the modified liposomes also exhibited high in vivo targeting efficiency in the BALB/c mice bearing 4T1 tumors. Importantly, this system inhibited the growth of metastatic tumor and prevented the incidence of lung metastasis in mice bearing 4T1 tumors with only low systemic toxicity. The data obtained from the in vitro and in vivo studies confirmed that the ClTx-modified liposomes increased the drug delivery to metastatic breast cancers. This study proved that the ClTx-modified liposomes had targeting ability to metastatic breast cancer in addition to brain cancer, and displayed an obvious antimetastasis effect. Generally, it may provide a promising strategy for metastatic breast cancer therapy. PMID:24559485

  18. Wnt Lipidation and Modifiers in Intestinal Carcinogenesis and Cancer

    PubMed Central

    Kaemmerer, Elke; Gassler, Nikolaus

    2016-01-01

    The wingless (Wnt) signaling is suggested as a fundamental hierarchical pathway in regulation of proliferation and differentiation of cells. The Wnt ligands are small proteins of about 40 kDa essentially for regulation and initiation of the Wnt activity. They are secreted proteins requiring acylation for activity in the Wnt signaling cascade and for functional interactivity with transmembrane proteins. Dual lipidation is important for posttranslational activation of the overwhelming number of Wnt proteins and is probably involved in their spatial distribution. The intestinal mucosa, where Wnt signaling is essential in configuration and maintenance, is an established model to study Wnt proteins and their role in carcinogenesis and cancer. The intestinal crypt-villus/crypt-plateau axis, a cellular system with self-renewal, proliferation, and differentiation, is tightly coordinated by a Wnt gradient. In the review, some attention is given to Wnt3, Wnt3A, and Wnt2B as important members of the Wnt family to address the role of lipidation and modifiers of Wnt proteins in intestinal carcinogenesis. Wnt3 is an important player in establishing the Wnt gradient in intestinal crypts and is mainly produced by Paneth cells. Wnt2B is characterized as a mitochondrial protein and shuttles between mitochondria and the nucleus. Porcupine and ACSL5, a long-chain fatty acid activating enzyme, are introduced as modifiers of Wnts and as interesting strategy to targeting Wnt-driven carcinogenesis. PMID:27438855

  19. Wnt Lipidation and Modifiers in Intestinal Carcinogenesis and Cancer.

    PubMed

    Kaemmerer, Elke; Gassler, Nikolaus

    2016-01-01

    The wingless (Wnt) signaling is suggested as a fundamental hierarchical pathway in regulation of proliferation and differentiation of cells. The Wnt ligands are small proteins of about 40 kDa essentially for regulation and initiation of the Wnt activity. They are secreted proteins requiring acylation for activity in the Wnt signaling cascade and for functional interactivity with transmembrane proteins. Dual lipidation is important for posttranslational activation of the overwhelming number of Wnt proteins and is probably involved in their spatial distribution. The intestinal mucosa, where Wnt signaling is essential in configuration and maintenance, is an established model to study Wnt proteins and their role in carcinogenesis and cancer. The intestinal crypt-villus/crypt-plateau axis, a cellular system with self-renewal, proliferation, and differentiation, is tightly coordinated by a Wnt gradient. In the review, some attention is given to Wnt3, Wnt3A, and Wnt2B as important members of the Wnt family to address the role of lipidation and modifiers of Wnt proteins in intestinal carcinogenesis. Wnt3 is an important player in establishing the Wnt gradient in intestinal crypts and is mainly produced by Paneth cells. Wnt2B is characterized as a mitochondrial protein and shuttles between mitochondria and the nucleus. Porcupine and ACSL5, a long-chain fatty acid activating enzyme, are introduced as modifiers of Wnts and as interesting strategy to targeting Wnt-driven carcinogenesis. PMID:27438855

  20. Modifiable Prostate Cancer Risk Reduction and Early Detection Behaviors in Black Men

    ERIC Educational Resources Information Center

    Odedina, Folakemi T.; Scrivens, John J., Jr.; Larose-Pierre, Margareth; Emanuel, Frank; Adams, Angela Denise; Dagne, Getachew A.; Pressey, Shannon Alexis; Odedina, Oladapo

    2011-01-01

    Objective: To explore the personal factors related to modifiable prostate cancer risk-reduction and detection behaviors among black men. Methods: Three thousand four hundred thirty (3430) black men were surveyed and structural equation modeling employed to test study hypotheses. Results: Modifiable prostate cancer risk-reduction behavior was found…

  1. Mercier criterion modified by kinetic effects

    SciTech Connect

    Rosenbluth, M.N.; Porcelli, F.

    1996-12-31

    The ideal MHD Mercier criterion for the stability of localized interchange modes is easily violated by modest pressure gradients in the central region of a Tokamak plasma where the magnetic winding index q drops below unity. However, kinetic effects can substantially modify this criterion, allowing for stable peaked pressure profiles. In this paper, we discuss the modifications to the Mercier criterion brought about by the fusion alpha particles and by the thermal trapped ions in the collisionless Kruskal-Oberman limit.

  2. Breast cancer survival among young women: a review of the role of modifiable lifestyle factors.

    PubMed

    Brenner, Darren R; Brockton, Nigel T; Kotsopoulos, Joanne; Cotterchio, Michelle; Boucher, Beatrice A; Courneya, Kerry S; Knight, Julia A; Olivotto, Ivo A; Quan, May Lynn; Friedenreich, Christine M

    2016-04-01

    Almost 7% of breast cancers are diagnosed among women age 40 years and younger in Western populations. Clinical outcomes among young women are worse. Early age-of-onset increases the risk of contralateral breast cancer, local and distant recurrence, and subsequent mortality. Breast cancers in young women (BCYW) are more likely to present with triple-negative (TNBC), TP53-positive, and HER-2 over-expressing tumors than among older women. However, despite these known differences in breast cancer outcomes and tumor subtypes, there is limited understanding of the basic biology, epidemiology, and optimal therapeutic strategies for BCYW. Several modifiable lifestyle factors associated with reduced risk of developing breast cancer have also been implicated in improved prognosis among breast cancer survivors of all ages. Given the treatment-related toxicities and the extended window for late effects, long-term lifestyle modifications potentially offer significant benefits to BCYW. In this review, we propose a model identifying three main areas of lifestyle factors (energy imbalance, inflammation, and dietary nutrient adequacy) that may influence survival in BCYW. In addition, we provide a summary of mechanisms of action and a synthesis of previous research on each of these topics. PMID:26970739

  3. Radiation-induced cancer and its modifying factor among A-bomb survivors

    SciTech Connect

    Kato, H.

    1987-01-01

    The Atomic Bomb Casualty Commission (ABCC) and its successor, the Radiation Effects Research Foundation, have conducted a long-term follow-up study of a cohort of 120,000 atomic bomb (A-bomb) survivors and non-exposed controls since 1950. The most recent findings regarding cancer mortality and incidence in this cohort can be briefly summarized as follows: 1) An increase in leukemia mortality among A-bomb survivors peaked 5-6 years after the bombing and has decreased with time thereafter. In addition to leukemia, the incidence of cancer of the lung, breast, esophagus, stomach, colon, thyroid, ovary, urinary tract, and multiple myeloma increases with dose. At present, there is no indication of an increase in cancer of the rectum or uterus among A-bomb survivors. In general, radiation-induced solid cancers begin to appear after the age at which they are normally prone to develop, and have continued to increase with time in proportion to the natural increase in mortality of the control group. 2) There are factors which modify the effects of radiation, such as age at the time of bombing (ATB) and sex. Sensitivity to radiation, in terms of cancer induction, is higher for persons who were young ATB in general, than for those who were older ATB. 3) There was no increase in childhood cancer among those exposed while in utero, but there is a recent indication of an increase in cancer incidence among these persons as they age. 4) There seems to be no interaction in a multiplicative way between radiation and smoking and lung cancer induction.

  4. Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy

    PubMed Central

    Dai, Hanren; Wang, Yao; Lu, Xuechun

    2016-01-01

    The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. PMID:26819347

  5. Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy.

    PubMed

    Dai, Hanren; Wang, Yao; Lu, Xuechun; Han, Weidong

    2016-07-01

    The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. PMID:26819347

  6. Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy

    PubMed Central

    Dai, Hanren; Wang, Yao; Lu, Xuechun

    2016-01-01

    The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy.

  7. p53 status as effect modifier of the association between pre-treatment fasting glucose and breast cancer outcomes in non diabetic, HER2 positive patients treated with trastuzumab

    PubMed Central

    Maugeri-Saccà, Marcello; Melucci, Elisa; Benedetto, Anna Di; Lauro, Luigi Di; Pizzuti, Laura; Sergi, Domenico; Terrenato, Irene; Esposito, Luca; Iannuzzi, Carmelina Antonella; Pasquale, Raffaella; Botti, Claudio; Fuhrman, Barbara; Giordano, Antonio

    2014-01-01

    Mounting evidence supports the role of p53 in metabolic processes involved in breast carcinogenesis. We investigated whether p53 status affects the association of pre-treatment fasting glucose with treatment outcomes in 106 non diabetic, HER2 positive breast cancer patients treated with trastuzumab. p53 status was validated against gene sequencing of selected codons in 49 patients. The Kaplan–Meier method and log rank test were used to compare survival by categories of fasting glucose in the overall population and separate settings. Cox models included age and body mass index. Direct sequencing confirmed the lack of mutations in 73.7% of p53 negative patients and their presence in 53.3% of p53 positive cases. At 66 months, 88.3% of patients with glucose ≤ 89.0 mg/dl (median value) did not experiment disease progression compared with 70.0% in the highest category (p=0.034), with glucose being an independent predictor (p=0.046). Stratified analysis confirmed this association in p53 negative patients only (p=0.01). In the early setting, data suggested longer disease free survival in p53 negative patients in the lowest glucose category (p=0.053). In our study, p53 status acted as effect modifier of the investigated association. This may help differentiate target sub-groups and affect outcomes interpretation in similarly characterized patients. PMID:25071015

  8. Aptamer-modified PLGA nanoparticle delivery of triplex forming oligonucleotide for targeted prostate cancer therapy.

    PubMed

    Jiao, J; Zou, Q; Zou, M H; Guo, R M; Zhu, S; Zhang, Y

    2016-01-01

    Presented study aimed to prepare A10 aptamer-modified poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with triplex forming oligonucleotides(TFO) for targeted prostate cancer therapy. We first synthesized a PLGA-PEG-Apt copolymer. The PLGA-PEG-Apt nanoparticles (NP-Apt) were loaded with TFO using double emulsion solvent evaporation method. Carboxy-fluorescein labeled TFO-NP-Apt, TFO-NP and TFO were prepared for cellular uptake experiments. Cell counting kit-8 (CCK-8) test was used to determine the ability of TFO-NP-Apt to inhibit LNCaP cell proliferation. RT-PCR and Western blot was conducted to analyze AR gene expressing. Then, a mouse model of prostate cancer was used to evaluate the anti-cancer effect of TFO-NP-Apt in vivo. We confirmed that the PLGA-PEG-Apt conjugation was successful. The TFO encapsulation efficiency and drug loading percentage were 46.1± 3.6% and 40.8±5.3%, respectively. TFO-NP-Apt showed a more efficient cellular uptake than TFO-NP or TFO in LNCaP cells. TFO-NP-Apt was significantly more cytotoxic than TFO-NP and TFO in the CCK-8 test (p<0.001). TFO-NP-Apt silenced the AR gene better than unconjugated Apt, naked TFO, NP or saline. TFO-NP-Apt were more effective than TFO-NP, naked TFO, NP and saline at inhibiting prostate cancer growth in vivo (p<0.05). Aptamer-modified TFO-loaded PLGA nanoparticles may prove useful in targeted therapy for advanced prostate cancer. PMID:27268920

  9. Folate-Modified Lipoplexes Delivering the Interleukin-12 Gene for Targeting Colon Cancer Immunogene Therapy.

    PubMed

    Luo, Min; Liang, Xiao; Luo, Shun-Tao; Wei, Xia-Wei; Liu, Ting; Ren, Jun; Ma, Cui-Cui; Yang, Yu-Han; Wang, Bi-Lan; Liu, Li; Song, Xiang-Rong; He, Zhi-Yao; Wei, Yu-Quan

    2015-11-01

    The incidence and mortality rate of colorectal cancer increase every year, making it a serious threat to human health. Targeted immunogene therapy is a novel method of treating this type of cancer. Colon cancer overexpresses folate receptor α (FRα) and folate-modified liposomes for colon cancer immunogene therapy may suppress tumor growth effectively. In this study, F-PLP/pIL12, an FRα-targeted lipoplex loading plasmid interleukin-12 (pIL12) was prepared and its physicochemical properties were characterized. Then the antitumor effect of F-PLP/pIL12 was studied in an in vivo model of CT-26 colon cancer. F-PLP/pIL12 was associated with about 56.6% tumor growth inhibition compared with the saline control. The production of malignant ascites was significantly less pronounced than in controls, and there were fewer tumor nodules and less overall tumor mass (P < 0.01). There was more IL12 expression and IFN-γ secretion in F-PLP/pIL12-treated tumor tissues, but there was less FRα expression. The antitumor mechanisms involved inducing tumor cell apoptosis, reducing microvessel density, and stimulating TNF-α secretion. In addition, there were fewer M2 macrophages in the tumor microenvironment of tissues stimulated with F-PLP/pIL12, which also activated the natural killer cells. H&E staining of vital organs suggested that F-PLP/pIL12 is safe for use in intraperitoneally administered cancer therapy. It was here concluded that F-PLP/plL12 may be a suitable targeting formulation for colon cancer immunogene therapy. PMID:26554159

  10. Modifiers of exposure-response estimates for lung cancer among miners exposed to radon progeny.

    PubMed Central

    Hornung, R W; Deddens, J; Roscoe, R

    1995-01-01

    The association between lung cancer and exposure to radon decay products has been well established. Despite agreement on this point, there is still some degree of uncertainty regarding characteristics of the exposure-response relationship. The use of studies of underground miners to estimate lung cancer risks due to residential radon exposure depends upon a better understanding of factors potentially modifying the exposure-response relationship. Given the diversity in study populations regarding smoking status, mining conditions, risk analysis methodology, and referent populations, the risk estimates across studies are quite similar. However, several factors partially contributing to differences in risk estimates are modified by attained age, time since last exposure, exposure rate, and cigarette smoking patterns. There is growing agreement across studies that relative risk decreases with attained age and time since last exposure. Several studies have also found an inverse exposure-rate effect, i.e., low exposure rates for protracted duration of exposure are more hazardous than equivalent cumulative exposures received at higher rates for shorter periods of time. Additionally, the interaction between radon exposure and cigarette smoking appears to be intermediate between additive and multiplicative in a growing number of studies. Quantitative estimates of these modifying factors are given using a new analysis of data from the latest update of the Colorado Plateau uranium miners cohort. PMID:7614947

  11. Cancer targeted magic bullets for effective treatment of cancer.

    PubMed

    Aneja, Preeti; Rahman, Mahfoozur; Beg, Sarwar; Aneja, Shivali; Dhingra, Vishal; Chugh, Rupali

    2014-01-01

    Cancer is a multifaceted disorder with serious threat across the globe. The vision for accomplishing an effective treatment strategy for cancer has always been a major concern worldwide. Although conventional drug therapy, esp. the chemotherapeutics provide benefits upto certain extent for treatment and management of cancers, yet it possesses umpteen challenges in terms of the associated side effects and adverse effects, lack of targeting ability, multi-drug resistance, poor patient acceptance and compliance, etc. at the desired site. To overcome these problems, the nanomedicines have been evolved as an effective and cost-effectual alternative for treatment of cancer. Inspiring from the concept of magic bullet, the world is moving towards developing the surface modified nanocarriers, which not only provide effective drug delivery but also allows site-specific monitoring of the cancer cells through in vivo diagnostic imaging. The present review endeavors to provide an explicit account on various drug targeting strategies employed for nanomedicines like active targeting, passive targeting, magnetic targeting, physical targeting and ultrasound targeting, etc, followed by their utility in the treatment of a particular type of cancer. According to the recent market survey, many nanocarrier-based drug delivery systems have been approved by USFDA, EMEA, MHRA and other global regulatory agencies, testify the high degrees of acceptance of the nanomedicines for treatment of cancer, while many products are under the preclinical and clinical development phases. Thus, for the translation of such technologies into the clinic, the pharma industry needs to be metamorphosing for a change in its culture of developing the traditional therapeutics. PMID:25876849

  12. A Multicountry Ecological Study of Cancer Incidence Rates in 2008 with Respect to Various Risk-Modifying Factors

    PubMed Central

    Grant, William B.

    2013-01-01

    Observational and ecological studies are generally used to determine the presence of effect of cancer risk-modifying factors. Researchers generally agree that environmental factors such as smoking, alcohol consumption, poor diet, lack of physical activity, and low serum 25-hdyroxyvitamin D levels are important cancer risk factors. This ecological study used age-adjusted incidence rates for 21 cancers for 157 countries (87 with high-quality data) in 2008 with respect to dietary supply and other factors, including per capita gross domestic product, life expectancy, lung cancer incidence rate (an index for smoking), and latitude (an index for solar ultraviolet-B doses). The factors found to correlate strongly with multiple types of cancer were lung cancer (direct correlation with 12 types of cancer), energy derived from animal products (direct correlation with 12 types of cancer, inverse with two), latitude (direct correlation with six types, inverse correlation with three), and per capita gross national product (five types). Life expectancy and sweeteners directly correlated with three cancers, animal fat with two, and alcohol with one. Consumption of animal products correlated with cancer incidence with a lag time of 15–25 years. Types of cancer which correlated strongly with animal product consumption, tended to correlate weakly with latitude; this occurred for 11 cancers for the entire set of countries. Regression results were somewhat different for the 87 high-quality country data set and the 157-country set. Single-country ecological studies have inversely correlated nearly all of these cancers with solar ultraviolet-B doses. These results can provide guidance for prevention of cancer. PMID:24379012

  13. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    EPA Science Inventory

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
    Cancer Responses
    .
    There has been a concerted effort in the field of radiation biology to better understand cellular
    responses that could have an impact on the estin1ation of cancer...

  14. Nucleotide excision repair polymorphisms may modify ionizing radiation-related breast cancer risk in US radiologic technologists.

    PubMed

    Rajaraman, Preetha; Bhatti, Parveen; Doody, Michele Morin; Simon, Steven L; Weinstock, Robert M; Linet, Martha S; Rosenstein, Marvin; Stovall, Marilyn; Alexander, Bruce H; Preston, Dale L; Sigurdson, Alice J

    2008-12-01

    Exposure to ionizing radiation has been consistently associated with increased risk of female breast cancer. Although the majority of DNA damage caused by ionizing radiation is corrected by the base-excision repair pathway, certain types of multiple-base damage can only be repaired through the nucleotide excision repair pathway. In a nested case-control study of breast cancer in US radiologic technologists exposed to low levels of ionizing radiation (858 cases, 1,083 controls), we examined whether risk of breast cancer conferred by radiation was modified by nucleotide excision gene polymorphisms ERCC2 (XPD) rs13181, ERCC4 (XPF) rs1800067 and rs1800124, ERCC5 (XPG) rs1047769 and rs17655; and ERCC6 rs2228526. Of the 6 ERCC variants examined, only ERCC5 rs17655 showed a borderline main effect association with breast cancer risk (OR(GC) = 1.1, OR(CC) = 1.3; p-trend = 0.08), with some indication that individuals carrying the C allele variant were more susceptible to the effects of occupational radiation (EOR/Gy(GG) = 1.0, 95% CI = <0, 6.0; EOR/Gy(GC/CC) = 5.9, 95% CI = 0.9, 14.4; p(het) = 0.10). ERCC2 rs13181, although not associated with breast cancer risk overall, statistically significantly modified the effect of occupational radiation dose on risk of breast cancer (EOR/Gy(AA) = 9.1, 95% CI = 2.1-21.3; EOR/Gy(AC/CC) = 0.6, 95% CI = <0, 4.6; p(het) = 0.01). These results suggest that common variants in nucleotide excision repair genes may modify the association between occupational radiation exposure and breast cancer risk. PMID:18767034

  15. A modified method by differential adhesion for enrichment of bladder cancer stem cells

    PubMed Central

    Zhu, Yong-tong; Pang, Shi-yu; Luo, Yang; Chen, Wei; Bao, Ji-ming; Tan, Wan-long

    2016-01-01

    ABSTRACT Purpose: In a previous study the vaccine was effective against bladder cancer in a mouse model. However, a small portion of tumors regrew because the vaccine could not eliminate bladder cancer stem cells (CSCs). In this study, we showed a modified method for the isolation of bladder CSCs using a combination of differential adhesion method and serum-free culture medium (SFM) method. Materials and Methods: Trypsin-resistant cells and trypsin-sensitive cells were isolated from MB49, EJ and 5637 cells by a combination of differential adhesion method and SFM method. The CSCs characterizations of trypsin-resistant cells were verified by the flow cytometry, the western blotting, the quantitative polymerase chain reaction, the resistance to chemotherapy assay, the transwell assay, and the tumor xenograft formation assay. Results: Trypsin-resistant cells were isolated and identified in CSCs characters, with high expression of CSCs markers, higher resistance to chemotherapy, greater migration in vitro, and stronger tumorigenicity in vivo. Conclusion: Trypsin-resistant cells displayed specific CSCs properties. Our study showed trypsin-resistant cells were isolated successfully with a modified method using a combination of differential adhesion method and SFM method. PMID:27564296

  16. Enhanced anti-cancer efficacy to cancer cells by doxorubicin loaded water-soluble amino acid-modified β-cyclodextrin platinum complexes.

    PubMed

    Zhao, Mei-Xia; Zhao, Meng; Zeng, Er-Zao; Li, Yang; Li, Jin-Ming; Cao, Qian; Tan, Cai-Ping; Ji, Liang-Nian; Mao, Zong-Wan

    2014-08-01

    The effective targeted delivery of insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. In this system, two water-soluble amino acid-modified β-cyclodextrin (β-CD) platinum complexes were reported. They showed preferable binding ability to DNA and effective inhibition to cancer cells, and they could bind and unwind pBR322 DNA in a manner which was similar to cisplatin. Besides, our platinum complexes could effectively deliver the anticancer drug doxorubicin (Dox) into cells and had higher cell inhibition ratio, but less toxicity on the normal cells, compared with cancer cells. In this combination system, Dox was encapsulated into the hydrophobic cavities of β-CD at the optimum molar ratio of 1:1, which were validated by UV-visible (UV-vis) absorption spectroscopy, fluorescence spectroscopy and MTT experiments. Moreover, the combination system had higher cell inhibition ratio than free Dox and amino acid-modified β-CD platinum complexes, and the results of high content screening (HCS) showed that Dox-loaded amino acid-modified β-CD platinum complexes could permeate the cell membrane and enter cells, suggesting the efficient transport of Dox across the membranes with the aid of the β-CD. We expect that the amino acid-modified β-CD platinum complexes will deliver the antitumor drug Dox to enhance intracellular drug accumulation and such combination system showed great potential as an antitumor drug. PMID:24803024

  17. Childbearing Recency and Modifiers of Premenopausal Breast Cancer Risk

    PubMed Central

    Peterson, Neeraja B.; Huang, Yifan; Newcomb, Polly A.; Titus-Ernstoff, Linda; Trentham-Dietz, Amy; Anic, Gabriella; Egan, Kathleen M.

    2009-01-01

    The purpose of this study was to examine the risk of premenopausal breast cancer for women in relation to childbearing recency, and whether this association differs by breastfeeding history and/or the amount of weight gained during pregnancy. This analysis was based on data from a population-based case-control study comprised of 1,706 incident cases of invasive breast cancer and 1,756 population controls from Wisconsin, New Hampshire, and Massachusetts. In a telephone interview conducted from 1996 to 2001, information was gathered on established breast cancer risk factors, as well as reproductive history, including amount of weight gained during the last full-term pregnancy, and whether or not the child was breast-fed. Unconditional logistic regression was used to estimate odds ratios (ORs) and Wald 95% confidence intervals (CIs) for the risk of breast cancer. When compared to nulliparous women, women that had given birth within the past 5 years prior to breast cancer diagnosis in the cases or a comparable period in controls had a non-significant 35% increased risk of invasive breast cancer (OR=1.35; 95% CI: 0.90–2.04) adjusting for age and known breast cancer risk factors (p trend = 0.14). We did not find a significant interaction with breast-feeding (p for interaction = 0.30) or pregnancy weight gain (p for interaction = 0.09). PMID:18990773

  18. Diagnosis of Brain Metastases from Lung Cancer Using a Modified Electromagnetism like Mechanism Algorithm.

    PubMed

    Chen, Kun-Huang; Wang, Kung-Jeng; Adrian, Angelia Melani; Wang, Kung-Min; Teng, Nai-Chia

    2016-01-01

    Brain metastases are commonly found in patients that are diagnosed with primary malignancy on their lung. Lung cancer patients with brain metastasis tend to have a poor survivability, which is less than 6 months in median. Therefore, an early and effective detection system for such disease is needed to help prolong the patients' survivability and improved their quality of life. A modified electromagnetism-like mechanism (EM) algorithm, MEM-SVM, is proposed by combining EM algorithm with support vector machine (SVM) as the classifier and opposite sign test (OST) as the local search technique. The proposed method is applied to 44 UCI and IDA datasets, and 5 cancers microarray datasets as preliminary experiment. In addition, this method is tested on 4 lung cancer microarray public dataset. Further, we tested our method on a nationwide dataset of brain metastasis from lung cancer (BMLC) in Taiwan. Since the nature of real medical dataset to be highly imbalanced, the synthetic minority over-sampling technique (SMOTE) is utilized to handle this problem. The proposed method is compared against another 8 popular benchmark classifiers and feature selection methods. The performance evaluation is based on the accuracy and Kappa index. For the 44 UCI and IDA datasets and 5 cancer microarray datasets, a non-parametric statistical test confirmed that MEM-SVM outperformed the other methods. For the 4 lung cancer public microarray datasets, MEM-SVM still achieved the highest mean value for accuracy and Kappa index. Due to the imbalanced property on the real case of BMLC dataset, all methods achieve good accuracy without significance difference among the methods. However, on the balanced BMLC dataset, MEM-SVM appears to be the best method with higher accuracy and Kappa index. We successfully developed MEM-SVM to predict the occurrence of brain metastasis from lung cancer with the combination of SMOTE technique to handle the class imbalance properties. The results confirmed that MEM

  19. Autologous, hapten-modified vaccine as a treatment for human cancers.

    PubMed

    Berd, D; Kairys, J; Dunton, C; Mastrangelo, M J; Sato, T; Maguire, H C

    1998-12-01

    We have devised a novel approach to active immunotherapy based on modification of autologous cancer cells with the hapten, dinitrophenyl (DNP). The treatment program consists of multiple intradermal injections of DNP-modified autologous tumor cells mixed with BCG. Administration of DNP-vaccine to patients with metastatic melanoma induces a unique reaction- the development of inflammation in metastatic masses. Histologically, this consists of infiltration of T lymphocytes, most of which are CD8+. These T cells usually produce interferon-gamma in situ. Moreover, they represent expansion of T-cell clones with novel T-cell receptor (TCR) structures. Occasionally, administration of DNP-vaccine results in regression of measurable metastases. The most common site of regression has been small lung metastases. Administration of DNP-vaccine to patients in the postsurgical adjuvant setting produces a more striking clinical effect. Of 62 patients with clinically evident stage III melanoma who had undergone lymphadenectomy, the 5-year relapse-free survival rate was 45% and the overall survival rate was 58%. These results appear to be better than those obtained with high-dose interferon, although a randomized phase III trial is required to prove that point. A recent phase I study suggests that this therapeutic approach is also applicable to stage III ovarian cancer. There appear to be no insurmountable impediments to applying this approach to much larger numbers of patients or to developing it as a standard cancer treatment. PMID:9865679

  20. Proportion of Invasive Breast Cancer Attributable to Risk Factors Modifiable after Menopause

    PubMed Central

    Sprague, Brian L.; Egan, Kathleen M.; Titus-Ernstoff, Linda; Hampton, John M.; Newcomb, Polly A.

    2008-01-01

    A number of breast cancer risk factors are modifiable later in life, yet the combined impact of the population changes in these risk factors on breast cancer incidence is not known to have been evaluated. The population attributable risk (PAR) associated with individual risk factors and the summary PAR for sets of modifiable and nonmodifiable risk factors were estimated by using data on 3,499 invasive breast cancer cases and 4,213 controls from a population-based study in Wisconsin, Massachusetts, and New Hampshire, conducted from 1997 to 2001. The summary PAR for factors modifiable after menopause, including current postmenopausal hormone use, recent alcohol consumption, adult weight gain, and recent recreational physical activity, was 40.7%. Of the individual modifiable factors, the highest PARs were observed for weight gain (21.3%) and recreational physical activity (15.7%), which together showed a summary PAR of 33.6%. The summary PAR for factors not modifiable after menopause, including family history of breast cancer, personal history of benign breast disease, height at age 25 years, age at menarche, age at menopause, age at first birth, and parity, was 57.3%. These findings suggest that a substantial fraction of postmenopausal breast cancer may be avoided by purposeful changes in lifestyle later in life. PMID:18552361

  1. Acetate as a Metabolic and Epigenetic Modifier of Cancer Therapy.

    PubMed

    Jaworski, Diane M; Namboodiri, Aryan M A; Moffett, John R

    2016-03-01

    Metabolic networks are significantly altered in neoplastic cells. This altered metabolic program leads to increased glycolysis and lipogenesis and decreased dependence on oxidative phosphorylation and oxygen consumption. Despite their limited mitochondrial respiration, cancer cells, nonetheless, derive sufficient energy from alternative carbon sources and metabolic pathways to maintain cell proliferation. They do so, in part, by utilizing fatty acids, amino acids, ketone bodies, and acetate, in addition to glucose. The alternative pathways used in the metabolism of these carbon sources provide opportunities for therapeutic manipulation. Acetate, in particular, has garnered increased attention in the context of cancer as both an epigenetic regulator of posttranslational protein modification, and as a carbon source for cancer cell biomass accumulation. However, to date, the data have not provided a clear understanding of the precise roles that protein acetylation and acetate oxidation play in carcinogenesis, cancer progression or treatment. This review highlights some of the major issues, discrepancies, and opportunities associated with the manipulation of acetate metabolism and acetylation-based signaling in cancer development and treatment. PMID:26251955

  2. pH-sensitive, polymer modified, plasma stable niosomes: promising carriers for anti-cancer drugs

    PubMed Central

    Tila, Dena; Yazdani-Arazi, Seyede Narjes; Ghanbarzadeh, Saeed; Arami, Sanam; Pourmoazzen, Zhaleh

    2015-01-01

    The aim of this study was the design and evaluation of a novel plasma stable, pH-sensitive niosomal formulation of Mitoxantrone by a modified ethanol injection method. Cholesterol hemisuccinate was added instead of cholesterol in order to produce pH-sensitivity property and using PEG-Poly (monomethyl itaconate)-CholC6 (PEG-PMMI-CholC6) copolymer introduced simultaneously pH-sensitivity and plasma stability properties in prepared niosomes. The pH-sensitivity and cytotoxicity of Mitoxantrone niosomes were evaluated in vitro in phosphate buffer with different pHs as well as using human ovarian cancer cell line (OVCAR-3), human breast cancer cell line (MCF-7) and human umbilical vein endothelial cells (HUVEC). Results showed that both cholesterol derivatives bearing formulations had pH-sensitive property and were found to release their contents under mild acidic conditions rapidly. In addition, the PEG-PMMI-CholC6-based niosomes could reserve the pH-sensitivity after incubation in plasma. Both Mitoxantrone-loaded pH-sensitive niosomes showed higher cytotoxicity than the conventional niosomes on OVCAR-3 and MCF-7 cell lines. However, both pH-sensitive niosomes exhibited lower cytotoxic effect on HUVEC cell line. Plasma stable, pH-sensitive niosomes could improve the cytotoxic effect and reduce the side effects of anti-tumor drugs. PMID:26417350

  3. Air pollution: a potentially modifiable risk factor for lung cancer.

    PubMed

    Fajersztajn, Laís; Veras, Mariana; Barrozo, Ligia Vizeu; Saldiva, Paulo

    2013-09-01

    Economic growth and increased urbanization pose a new risk for cancer development: the exposure of high numbers of people to ambient air pollution. Epidemiological evidence that links air pollution to mortality from lung cancer is robust. An ability to produce high-quality scientific research that addresses these risks and the ability of local health authorities to understand and respond to these risks are basic requirements to solve the conflict between economic development and the preservation of human health. However, this is currently far from being achieved. Thus, this Science and Society article addresses the possibilities of expanding scientific networking to increase awareness of the risk of lung cancer that is promoted by air pollution. PMID:23924644

  4. Effects of preparation process on performance of rubber modified asphalt

    NASA Astrophysics Data System (ADS)

    Liu, Hanbing; Luo, Guobao; Wang, Xianqiang; Jiao, Yubo

    2015-06-01

    The rational utilization of waste rubber tire is essential for the environmental protection. Utilizing rubber particles to modify asphalt can not only improve asphalt performance, but also help the recycling of waste materials. Considering the effect of different preparation process parameters on the performance of rubber modified asphalt, this paper analyzes the effects of the shear temperature, shear time and shear rate on the performance of rubber modified asphalt, and provided a reference for its preparation.

  5. Cancers in Australia in 2010 attributable to modifiable factors: summary and conclusions

    PubMed Central

    Whiteman, David C; Webb, Penelope M; Green, Adele C; Neale, Rachel E; Fritschi, Lin; Bain, Christopher J; Parkin, D Max; Wilson, Louise F; Olsen, Catherine M; Nagle, Christina M; Pandeya, Nirmala; Jordan, Susan J; Antonsson, Annika; Kendall, Bradley J; Hughes, Maria Celia B; Ibiebele, Torukiri I; Miura, Kyoko; Peters, Susan; Carey, Renee N

    2015-01-01

    Objective To estimate the numbers and proportions of cancers occurring in Australia in 2010 attributable to modifiable causal factors. Methods We estimated the population attributable fraction (PAF) of cancers associated with exposure to 13 causal factors using standard formulae incorporating exposure prevalence and relative risk data. We also calculated the potential impact of changing exposure to some factors. Results A total of 32% of all cancers diagnosed in Australia in 2010 (excluding keratinocyte cancers) were attributable to the 13 factors assessed (men 33%; women 31%). Leading factors were tobacco smoke (PAF all cancers: 13.4%), solar radiation (6.2%), inadequate diet (6.1%) and overweight/obesity (3.4%). Factors conferring highest PAFs differed by sex: highest PAFs for men were tobacco smoke (15.8%), solar radiation (7.1%) and alcohol (3.0%); while highest PAFs for women were tobacco smoke (10.1%), solar radiation (5.0%) and overweight/obesity (4.5%). Sites with the highest counts of potentially preventable cancers were lung (8,569), colorectal (7,404), melanoma of the skin (7,220) and breast (3,233). Conclusions At least one in three cancers in Australia is attributable to exposure to known modifiable factors. Implications Up to 37,000 cancers could be prevented in Australia each year if the population avoided exposure to 13 common factors known or strongly suspected to cause cancer. PMID:26437735

  6. dbEM: A database of epigenetic modifiers curated from cancerous and normal genomes

    PubMed Central

    Singh Nanda, Jagpreet; Kumar, Rahul; Raghava, Gajendra P. S.

    2016-01-01

    We have developed a database called dbEM (database of Epigenetic Modifiers) to maintain the genomic information of about 167 epigenetic modifiers/proteins, which are considered as potential cancer targets. In dbEM, modifiers are classified on functional basis and comprise of 48 histone methyl transferases, 33 chromatin remodelers and 31 histone demethylases. dbEM maintains the genomic information like mutations, copy number variation and gene expression in thousands of tumor samples, cancer cell lines and healthy samples. This information is obtained from public resources viz. COSMIC, CCLE and 1000-genome project. Gene essentiality data retrieved from COLT database further highlights the importance of various epigenetic proteins for cancer survival. We have also reported the sequence profiles, tertiary structures and post-translational modifications of these epigenetic proteins in cancer. It also contains information of 54 drug molecules against different epigenetic proteins. A wide range of tools have been integrated in dbEM e.g. Search, BLAST, Alignment and Profile based prediction. In our analysis, we found that epigenetic proteins DNMT3A, HDAC2, KDM6A, and TET2 are highly mutated in variety of cancers. We are confident that dbEM will be very useful in cancer research particularly in the field of epigenetic proteins based cancer therapeutics. This database is available for public at URL: http://crdd.osdd.net/raghava/dbem. PMID:26777304

  7. Novel therapeutic approaches for various cancer types using a modified sleeping beauty-based gene delivery system.

    PubMed

    Hong, In-Sun; Lee, Hwa-Yong; Kim, Hyun-Pyo

    2014-01-01

    Successful gene therapy largely depends on the selective introduction of therapeutic genes into the appropriate target cancer cells. One of the most effective and promising approaches for targeting tumor tissue during gene delivery is the use of viral vectors, which allow for high efficiency gene delivery. However, the use of viral vectors is not without risks and safety concerns, such as toxicities, a host immune response towards the viral antigens or potential viral recombination into the host's chromosome; these risks limit the clinical application of viral vectors. The Sleeping Beauty (SB) transposon-based system is an attractive, non-viral alternative to viral delivery systems. SB may be less immunogenic than the viral vector system due to its lack of viral sequences. The SB-based gene delivery system can stably integrate into the host cell genome to produce the therapeutic gene product over the lifetime of a cell. However, when compared to viral vectors, the non-viral SB-based gene delivery system still has limited therapeutic efficacy due to the lack of long-lasting gene expression potential and tumor cell specific gene transfer ability. These limitations could be overcome by modifying the SB system through the introduction of the hTERT promoter and the SV40 enhancer. In this study, a modified SB delivery system, under control of the hTERT promoter in conjunction with the SV40 enhancer, was able to successfully transfer the suicide gene (HSV-TK) into multiple types of cancer cells. The modified SB transfected cancer cells exhibited a significantly increased cancer cell specific death rate. These data suggest that our modified SB-based gene delivery system can be used as a safe and efficient tool for cancer cell specific therapeutic gene transfer and stable long-term expression. PMID:24466025

  8. Novel Therapeutic Approaches for Various Cancer Types Using a Modified Sleeping Beauty-Based Gene Delivery System

    PubMed Central

    Kim, Hyun-Pyo

    2014-01-01

    Successful gene therapy largely depends on the selective introduction of therapeutic genes into the appropriate target cancer cells. One of the most effective and promising approaches for targeting tumor tissue during gene delivery is the use of viral vectors, which allow for high efficiency gene delivery. However, the use of viral vectors is not without risks and safety concerns, such as toxicities, a host immune response towards the viral antigens or potential viral recombination into the host's chromosome; these risks limit the clinical application of viral vectors. The Sleeping Beauty (SB) transposon-based system is an attractive, non-viral alternative to viral delivery systems. SB may be less immunogenic than the viral vector system due to its lack of viral sequences. The SB-based gene delivery system can stably integrate into the host cell genome to produce the therapeutic gene product over the lifetime of a cell. However, when compared to viral vectors, the non-viral SB-based gene delivery system still has limited therapeutic efficacy due to the lack of long-lasting gene expression potential and tumor cell specific gene transfer ability. These limitations could be overcome by modifying the SB system through the introduction of the hTERT promoter and the SV40 enhancer. In this study, a modified SB delivery system, under control of the hTERT promoter in conjunction with the SV40 enhancer, was able to successfully transfer the suicide gene (HSV-TK) into multiple types of cancer cells. The modified SB transfected cancer cells exhibited a significantly increased cancer cell specific death rate. These data suggest that our modified SB-based gene delivery system can be used as a safe and efficient tool for cancer cell specific therapeutic gene transfer and stable long-term expression. PMID:24466025

  9. Genetically modified T cells in cancer therapy: opportunities and challenges

    PubMed Central

    Sharpe, Michaela; Mount, Natalie

    2015-01-01

    Tumours use many strategies to evade the host immune response, including downregulation or weak immunogenicity of target antigens and creation of an immune-suppressive tumour environment. T cells play a key role in cell-mediated immunity and, recently, strategies to genetically modify T cells either through altering the specificity of the T cell receptor (TCR) or through introducing antibody-like recognition in chimeric antigen receptors (CARs) have made substantial advances. The potential of these approaches has been demonstrated in particular by the successful use of genetically modified T cells to treat B cell haematological malignancies in clinical trials. This clinical success is reflected in the growing number of strategic partnerships in this area that have attracted a high level of investment and involve large pharmaceutical organisations. Although our understanding of the factors that influence the safety and efficacy of these therapies has increased, challenges for bringing genetically modified T-cell immunotherapy to many patients with different tumour types remain. These challenges range from the selection of antigen targets and dealing with regulatory and safety issues to successfully navigating the routes to commercial development. However, the encouraging clinical data, the progress in the scientific understanding of tumour immunology and the improvements in the manufacture of cell products are all advancing the clinical translation of these important cellular immunotherapies. PMID:26035842

  10. Breast Cancer Risk and 6q22.33: Combined Results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2

    PubMed Central

    Antoniou, Antonis C.; McGuffog, Lesley; Humphreys, Manjeet K.; Dunning, Alison M.; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Dork, Thilo; Schürmann, Peter; Karstens, Johann H.; Hillemanns, Peter; Couch, Fergus J.; Olson, Janet; Vachon, Celine; Wang, Xianshu; Cox, Angela; Brock, Ian; Elliott, Graeme; Reed, Malcolm W.R.; Burwinkel, Barbara; Meindl, Alfons; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Broeks, Annegien; Schmidt, Marjanka K.; Van ‘t Veer, Laura J.; Braaf, Linde M.; Johnson, Nichola; Fletcher, Olivia; Gibson, Lorna; Peto, Julian; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Rahman, Nazneen; Wu, Pei-Ei; Yu, Jyh-Cherng; Hsiung, Chia-Ni; Shen, Chen-Yang; Southey, Melissa C.; Hopper, John L.; Hammet, Fleur; Van Dorpe, Thijs; Dieudonne, Anne-Sophie; Hatse, Sigrid; Lambrechts, Diether; Andrulis, Irene L.; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Juri I.; Prokofieva, Daria; Bermisheva, Marina; Khusnutdinova, Elza; van Asperen, Christi J.; Tollenaar, Robert A.E.M.; Hooning, Maartje J.; Devilee, Peter; Margolin, Sara; Lindblom, Annika; Milne, Roger L.; Arias, José Ignacio; Zamora, M. Pilar; Benítez, Javier; Severi, Gianluca; Baglietto, Laura; Giles, Graham G.; kConFab; Group, AOCS Study; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Healey, Sue; Wang-Gohrke, Shan; Chang-Claude, Jenny; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Agnarsson, Bjarni A.; Caligo, Maria A.; Godwin, Andrew K.; Nevanlinna, Heli; Heikkinen, Tuomas; Fredericksen, Zachary; Lindor, Noralane; Nathanson, Katherine L.; Domchek, Susan M.; SWE-BRCA; Loman, Niklas; Karlsson, Per; Askmalm, Marie Stenmark; Melin, Beatrice; von Wachenfeldt, Anna; HEBON; Hogervorst, Frans B. L.; Verheus, Martijn; Rookus, Matti A.; Seynaeve, Caroline; Oldenburg, Rogier A.; Ligtenberg, Marjolijn J.; Ausems, Margreet G.E.M.; Aalfs, Cora M.; Gille, Hans J.P.; Wijnen, Juul T.; Gómez García, Encarna B.; EMBRACE; Peock, Susan; Cook, Margaret; Oliver, Clare T.; Frost, Debra; Luccarini, Craig; Pichert, Gabriella; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Ong, Kai-Ren; Cook, Jackie; Douglas, Fiona; Hodgson, Shirley; Evans, D. Gareth; Eeles, Rosalind; Gold, Bert; Pharoah, Paul D.P.; Offit, Kenneth; Chenevix-Trench, Georgia; Easton, Douglas F.

    2012-01-01

    Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00–1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I2 = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80–1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk. PMID:22768030

  11. Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2.

    PubMed

    Kirchhoff, Tomas; Gaudet, Mia M; Antoniou, Antonis C; McGuffog, Lesley; Humphreys, Manjeet K; Dunning, Alison M; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Dork, Thilo; Schürmann, Peter; Karstens, Johann H; Hillemanns, Peter; Couch, Fergus J; Olson, Janet; Vachon, Celine; Wang, Xianshu; Cox, Angela; Brock, Ian; Elliott, Graeme; Reed, Malcolm W R; Burwinkel, Barbara; Meindl, Alfons; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Broeks, Annegien; Schmidt, Marjanka K; Van 't Veer, Laura J; Braaf, Linde M; Johnson, Nichola; Fletcher, Olivia; Gibson, Lorna; Peto, Julian; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Rahman, Nazneen; Wu, Pei-Ei; Yu, Jyh-Cherng; Hsiung, Chia-Ni; Shen, Chen-Yang; Southey, Melissa C; Hopper, John L; Hammet, Fleur; Van Dorpe, Thijs; Dieudonne, Anne-Sophie; Hatse, Sigrid; Lambrechts, Diether; Andrulis, Irene L; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Juri I; Prokofieva, Daria; Bermisheva, Marina; Khusnutdinova, Elza; van Asperen, Christi J; Tollenaar, Robert A E M; Hooning, Maartje J; Devilee, Peter; Margolin, Sara; Lindblom, Annika; Milne, Roger L; Arias, José Ignacio; Zamora, M Pilar; Benítez, Javier; Severi, Gianluca; Baglietto, Laura; Giles, Graham G; Spurdle, Amanda B; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Healey, Sue; Wang-Gohrke, Shan; Chang-Claude, Jenny; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Agnarsson, Bjarni A; Caligo, Maria A; Godwin, Andrew K; Nevanlinna, Heli; Heikkinen, Tuomas; Fredericksen, Zachary; Lindor, Noralane; Nathanson, Katherine L; Domchek, Susan M; Loman, Niklas; Karlsson, Per; Stenmark Askmalm, Marie; Melin, Beatrice; von Wachenfeldt, Anna; Hogervorst, Frans B L; Verheus, Martijn; Rookus, Matti A; Seynaeve, Caroline; Oldenburg, Rogier A; Ligtenberg, Marjolijn J; Ausems, Margreet G E M; Aalfs, Cora M; Gille, Hans J P; Wijnen, Juul T; Gómez García, Encarna B; Peock, Susan; Cook, Margaret; Oliver, Clare T; Frost, Debra; Luccarini, Craig; Pichert, Gabriella; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Ong, Kai-Ren; Cook, Jackie; Douglas, Fiona; Hodgson, Shirley; Evans, D Gareth; Eeles, Rosalind; Gold, Bert; Pharoah, Paul D P; Offit, Kenneth; Chenevix-Trench, Georgia; Easton, Douglas F

    2012-01-01

    Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk. PMID:22768030

  12. Gene-modified hematopoietic stem cells for cancer immunotherapy

    PubMed Central

    Larson, Sarah; De Oliveira, Satiro N

    2014-01-01

    The rapid expansion of available cancer immunotherapies has resulted in favorable early outcomes. Specifically the use of gene therapy to introduce chimeric antigen receptors (CARs) and T cell receptors (TCRs) in T cells creates new immunotherapy options for patients. While showing early success with these approaches, limitations remain that can be overcome by the use of modification of hematopoietic stem cells (HSCs) to express CARs and TCRs. With modern gene therapy technologies, increased safety and control of the modification of the HSCs can be achieved through the use of a suicide gene. PMID:24398603

  13. Polyaniline modified flexible conducting paper for cancer detection

    NASA Astrophysics Data System (ADS)

    Kumar, Saurabh; Sen, Anindita; Kumar, Suveen; Augustine, Shine; Yadav, Birendra K.; Mishra, Sandeep; Malhotra, Bansi D.

    2016-05-01

    We report results of studies relating to the fabrication of a flexible, disposable, and label free biosensing platform for detection of the cancer biomarker (carcinoembryonic antigen, CEA). Polyaniline (PANI) has been electrochemically deposited over gold sputtered paper (Au@paper) for covalent immobilization of monoclonal carcinoembryonic antibodies (anti-CEA). The bovine serum albumin (BSA) has been used for blocking nonspecific binding sites at the anti-CEA conjugated PANI/Au@Paper. The PANI/Au@Paper, anti-CEA/PANI/Au@Paper, and BSA/anti-CEA/PANI/Au@Paper platforms have been characterized using scanning electron microscopy, X-ray diffraction, Fourier transmission infrared spectroscopy, chronoamperometry, and electrochemical impedance techniques. The results of the electrochemical response studies indicate that this BSA/anti-CEA/PANI/Au@paper electrode has sensitivity of 13.9 μA ng-1 ml cm2, shelf life of 22 days, and can be used to estimate CEA in the range of 2-20 ng ml-1. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.

  14. Modified sugar beet pectin induces apoptosis of colon cancer cells via interaction with the neutral sugar side-chains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pectins extracted from a variety of sources and modified with heat and/or pH have previously been shown to exhibit activity towards several cancer cell lines. However, the structural basis for the anti-cancer activity of modified pectin requires clarification. Sugar beet and citrus pectin extracts h...

  15. The use of genetically modified mice in cancer risk assessment: Challenges and limitations*

    PubMed Central

    Eastmond, David A.; Vulimiri, Suryanarayana V.; French, John E.; Sonawane, Babasaheb

    2015-01-01

    The use of genetically modified (GM) mice to assess carcinogenicity is playing an increasingly important role in the safety evaluation of chemicals. While progress has been made in developing and evaluating mouse models such as the Trp53+/−, Tg.AC and the rasH2, the suitability of these models as replacements for the conventional rodent cancer bioassay and for assessing human health risks remains uncertain. The objective of this research was to evaluate the use of accelerated cancer bioassays with GM mice for assessing the potential health risks associated with exposure to carcinogenic agents. We compared the published results from the GM bioassays to those obtained in the National Toxicology Program’s conventional chronic mouse bioassay for their potential use in risk assessment. Our analysis indicates that the GM models are less efficient in detecting carcinogenic agents but more consistent in identifying non-carcinogenic agents. We identified several issues of concern related to the design of the accelerated bioassays (e.g., sample size, study duration, genetic stability and reproducibility) as well as pathway-dependency of effects, and different carcinogenic mechanisms operable in GM and non-GM mice. The use of the GM models for dose-response assessment is particularly problematic as these models are, at times, much more or less sensitive than the conventional rodent cancer bioassays. Thus, the existing GM mouse models may be useful for hazard identification, but will be of limited use for dose-response assessment. Hence, caution should be exercised when using GM mouse models to assess the carcinogenic risks of chemicals. PMID:23985072

  16. Proteomics analysis of cancer exosomes using a novel modified aptamer-based array (SOMAscan™) platform.

    PubMed

    Webber, Jason; Stone, Timothy C; Katilius, Evaldas; Smith, Breanna C; Gordon, Bridget; Mason, Malcolm D; Tabi, Zsuzsanna; Brewis, Ian A; Clayton, Aled

    2014-04-01

    We have used a novel affinity-based proteomics technology to examine the protein signature of small secreted extracellular vesicles called exosomes. The technology uses a new class of protein binding reagents called SOMAmers® (slow off-rate modified aptamers) and allows the simultaneous precise measurement of over 1000 proteins. Exosomes were highly purified from the Du145 prostate cancer cell line, by pooling selected fractions from a continuous sucrose gradient (within the density range of 1.1 to 1.2 g/ml), and examined under standard conditions or with additional detergent treatment by the SOMAscan™ array (version 3.0). Lysates of Du145 cells were also prepared, and the profiles were compared. Housekeeping proteins such as cyclophilin-A, LDH, and Hsp70 were present in exosomes, and we identified almost 100 proteins that were enriched in exosomes relative to cells. These included proteins of known association with cancer exosomes such as MFG-E8, integrins, and MET, and also those less widely reported as exosomally associated, such as ROR1 and ITIH4. Several proteins with no previously known exosomal association were confirmed as exosomally expressed in experiments using individual SOMAmer® reagents or antibodies in micro-plate assays. Western blotting confirmed the SOMAscan™-identified enrichment of exosomal NOTCH-3, L1CAM, RAC1, and ADAM9. In conclusion, we describe here over 300 proteins of hitherto unknown association with prostate cancer exosomes and suggest that the SOMAmer®-based assay technology is an effective proteomics platform for exosome-associated biomarker discovery in diverse clinical settings. PMID:24505114

  17. Validation of a modified clinical risk score to predict cancer-specific survival for stage II colon cancer

    PubMed Central

    Oliphant, Raymond; Horgan, Paul G; Morrison, David S; McMillan, Donald C

    2015-01-01

    Many patients with stage II colon cancer will die of their disease despite curative surgery. Therefore, identification of patients at high risk of poor outcome after surgery for stage II colon cancer is desirable. This study aims to validate a clinical risk score to predict cancer-specific survival in patients undergoing surgery for stage II colon cancer. Patients undergoing surgery for stage II colon cancer in 16 hospitals in the West of Scotland between 2001 and 2004 were identified from a prospectively maintained regional clinical audit database. Overall and cancer-specific survival rates up to 5 years were calculated. A total of 871 patients were included. At 5 years, cancer-specific survival was 81.9% and overall survival was 65.6%. On multivariate analysis, age ≥75 years (hazard ratio (HR) 2.11, 95% confidence intervals (CI) 1.57–2.85; P<0.001) and emergency presentation (HR 1.97, 95% CI 1.43–2.70; P<0.001) were independently associated with cancer-specific survival. Age and mode of presentation HRs were added to form a clinical risk score of 0–2. The cancer-specific survival at 5 years for patients with a cumulative score 0 was 88.7%, 1 was 78.2% and 2 was 65.9%. These results validate a modified simple clinical risk score for patients undergoing surgery for stage II colon cancer. The combination of these two universally documented clinical factors provides a solid foundation for the examination of the impact of additional clinicopathological and treatment factors on overall and cancer-specific survival. PMID:25487740

  18. Shielding effectiveness of original and modified building materials

    NASA Astrophysics Data System (ADS)

    Frenzel, T.; Stumpf, J.; Koch, M.

    2007-06-01

    This contribution deals with the determination of the shielding effectiveness of building materials used for office, factory and government buildings. Besides the examination of standard materials, measurements were also performed on modified materials, e.g. ferro concrete with enhanced shielding effectiveness due to a changed mixture or structure of the reinforcement. The measurements of original and modified materials were carried out in a fully anechoic room (FAR) according to IEEE 299-1997 from 80 MHz up to 10 GHz.

  19. Cancers in Australia in 2010 attributable to modifiable factors: introduction and overview

    PubMed Central

    Whiteman, David C; Webb, Penelope M; Green, Adele C; Neale, Rachel E; Fritschi, Lin; Bain, Christopher J; Parkin, D Max; Wilson, Louise F; Olsen, Catherine M; Nagle, Christina M; Pandeya, Nirmala; Jordan, Susan J; Antonsson, Annika; Kendall, Bradley J; Hughes, Maria Celia B; Ibiebele, Torukiri I; Miura, Kyoko; Peters, Susan; Carey, Renee N

    2015-01-01

    Objective To describe the approach underpinning a national project to estimate the numbers and proportions of cancers occurring in Australia in 2010 that are attributable to modifiable causal factors. Methods We estimated the population attributable fraction (PAF) (or prevented fraction) of cancers associated with exposure to causal (or preventive) factors using standard formulae. Where possible, we also estimated the potential impact on cancer incidence resulting from changes in prevalence of exposure. Analyses were restricted to factors declared causal by international agencies: tobacco smoke; alcohol; solar radiation; infectious agents; obesity; insufficient physical activity; insufficient intakes of fruits, vegetables and fibre; red and processed meat; menopausal hormone therapy (MHT); oral contraceptive pill (OCP); and insufficient breast feeding. Separately, we estimated numbers of cancers prevented by: aspirin; sunscreen; MHT; and OCP use. We discuss assumptions pertaining to latent periods between exposure and cancer onset, choices of prevalence data and risk estimates, and approaches to sensitivity analyses. Results Numbers and population attributable fractions of cancer are presented in accompanying papers. Conclusions This is the first systematic assessment of population attributable fractions of cancer in Australia. PMID:26437722

  20. Synthesis of Biomolecule-Modified Mesoporous Silica Nanoparticles for Targeted Hydrophobic Drug Delivery to Cancer Cells

    PubMed Central

    Ferris, Daniel P.; Lu, Jie; Gothard, Chris; Yanes, Rolando; Thomas, Courtney R.; Olsen, John-Carl; Stoddart, J. Fraser; Tamanoi, Fuyuhiko; Zink, Jeffrey I.

    2011-01-01

    Synthetic methodologies integrating hydrophobic drug delivery and biomolecular targeting with mesoporous silica nanoparticles are described. Transferrin and cyclic-RGD peptides are covalently attached to the nanoparticles utilizing different techniques and provide selectivity between primary and metastatic cancer cells. The increase in cellular uptake of the targeted particles is examined using fluorescence microscopy and flow cytometry. Transferrin-modified silica nanoparticles display enhancement in particle uptake by Panc-1 cancer cells over that of normal HFF cells. The endocytotic pathway for these particles is further investigated through plasmid transfection of the transferrin receptor into the normal HFF cell line, which results in an increase in particle endocytosis as compared to unmodified HFF cells. By designing and attaching a synthetic cyclic-RGD, selectivity between primary cancer cells (BT-549) and metastatic cancer cells (MDA-MB 435) is achieved with enhanced particle uptake by the metastatic cancer cell line. Incorporation of the hydrophobic drug Camptothecin into these two types of biomolecular-targeted nanoparticles causes an increase in mortality of the targeted cancer cells compared to that caused by both the free drug and nontargeted particles. These results demonstrate successful biomolecular-targeted hydrophobic drug delivery carriers that selectively target specific cancer cells and result in enhanced drug delivery and cell mortality. PMID:21595023

  1. How Leucocyte Cell Membrane Modified Janus Microcapsules are Phagocytosed by Cancer Cells.

    PubMed

    He, Wenping; Frueh, Johannes; Wu, Zhenwei; He, Qiang

    2016-02-01

    Modern drug delivery systems rely on either antibody-based single-surface recognition or on surface-hydrophobicity-based approaches. For a tumor showing various surface mutations, both approaches fail. This publication hereby presents Janus capsules based on polyelectrolyte multilayer microcapsules exhibiting human leucocyte (THP-1 cell line) cell membranes for discriminating HUVEC cells from three different cancer cell lines. Despite destroying the cellular integrity of leucocyte cells, the modified Janus capsules are able to adhere to cancer cells. Leucocyte cell-membrane-coated Janus capsules are phagocytosed with the cellular membrane part pointing to the cells. PMID:26824329

  2. Perspective on a Modified Developmental and Reproductive Toxicity Testing Strategy for Cancer Immunotherapy.

    PubMed

    Prell, Rodney A; Halpern, Wendy G; Rao, Gautham K

    2016-05-01

    The intent of cancer immunotherapy (CIT) is to generate and enhance T-cell responses against tumors. The tumor microenvironment establishes several inhibitory pathways that lead to suppression of the local immune response, which is permissive for tumor growth. The efficacy of different CITs, alone and in combination, stems from reinvigorating the tumor immune response via several mechanisms, including costimulatory agonists, checkpoint inhibitors, and vaccines. However, immune responses to other antigens (self and foreign) may also be enhanced, resulting in potentially undesired effects. In outbred mammalian pregnancies, the fetus expresses paternally derived alloantigens that are recognized as foreign by the maternal immune system. If unchecked or enhanced, maternal immunity to these alloantigens represents a developmental and reproductive risk and thus is a general liability for cancer immunotherapeutic molecules. We propose a tiered approach to confirm this mechanistic reproductive liability for CIT molecules. A rodent allopregnancy model is based on breeding 2 different strains of mice so that paternally derived alloantigens are expressed by the fetus. When tested with a cross-reactive biotherapeutic, small molecule drug, or surrogate molecule, this model should reveal on-target reproductive liabilities if the pathway is involved in maintaining pregnancy. Alternatively, allopregnancy models with genetically modified mice can be interrogated for exquisitely specific biotherapeutics with restricted species reactivity. The allopregnancy model represents a relatively straightforward approach to confirm an expected on-target reproductive risk for CIT molecules. For biotherapeutics, it could potentially replace more complex developmental and reproductive toxicity testing in nonhuman primates when a pregnancy hazard is confirmed or expected. PMID:26786669

  3. Activation of the Ubiquitin Proteasome Pathway by Silk Fibroin Modified Chitosan Nanoparticles in Hepatic Cancer Cells

    PubMed Central

    Yang, Ming-Hui; Chung, Tze-Wen; Lu, Yi-Shan; Chen, Yi-Ling; Tsai, Wan-Chi; Jong, Shiang-Bin; Yuan, Shyng-Shiou; Liao, Pao-Chi; Lin, Po-Chiao; Tyan, Yu-Chang

    2015-01-01

    Silk fibroin (SF) is a protein with bulky hydrophobic domains and can be easily purified as sericin-free silk-based biomaterial. Silk fibroin modified chitosan nanoparticle (SF-CSNP), a biocompatible material, has been widely used as a potential drug delivery system. Our current investigation studied the bio-effects of the SF-CSNP uptake by liver cells. In this experiment, the characterizations of SF-CSNPs were measured by particle size analysis and protein assay. The average size of the SF-CSNP was 311.9 ± 10.7 nm, and the average zeta potential was +13.33 ± 0.3 mV. The SF coating on the SF-CSNP was 6.27 ± 0.17 μg/mL. Moreover, using proteomic approaches, several proteins involved in the ubiquitin proteasome pathway were identified by analysis of differential protein expressions of HepG2 cell uptake the SF-CSNP. Our experimental results have demonstrated that the SF-CSNP may be involved in liver cancer cell survival and proliferation. PMID:25588218

  4. Activation of the ubiquitin proteasome pathway by silk fibroin modified chitosan nanoparticles in hepatic cancer cells.

    PubMed

    Yang, Ming-Hui; Chung, Tze-Wen; Lu, Yi-Shan; Chen, Yi-Ling; Tsai, Wan-Chi; Jong, Shiang-Bin; Yuan, Shyng-Shiou; Liao, Pao-Chi; Lin, Po-Chiao; Tyan, Yu-Chang

    2015-01-01

    Silk fibroin (SF) is a protein with bulky hydrophobic domains and can be easily purified as sericin-free silk-based biomaterial. Silk fibroin modified chitosan nanoparticle (SF-CSNP), a biocompatible material, has been widely used as a potential drug delivery system. Our current investigation studied the bio-effects of the SF-CSNP uptake by liver cells. In this experiment, the characterizations of SF-CSNPs were measured by particle size analysis and protein assay. The average size of the SF-CSNP was 311.9 ± 10.7 nm, and the average zeta potential was +13.33 ± 0.3 mV. The SF coating on the SF-CSNP was 6.27 ± 0.17 μg/mL. Moreover, using proteomic approaches, several proteins involved in the ubiquitin proteasome pathway were identified by analysis of differential protein expressions of HepG2 cell uptake the SF-CSNP. Our experimental results have demonstrated that the SF-CSNP may be involved in liver cancer cell survival and proliferation. PMID:25588218

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

    PubMed

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

    2015-07-01

    Clinical risk assessment involves absolute risk measures, but information on modifying risk and preventing cancer is often communicated in relative terms. To illustrate the potential impact of risk factor modification in model-based risk assessment, we evaluated the performance of the IBIS Breast Cancer Risk Evaluation Tool, with and without current body mass index (BMI), for predicting future breast cancer occurrence in a prospective cohort of 665 postmenopausal women. Overall, IBIS's accuracy (overall agreement between observed and assigned risks) and discrimination (AUC concordance between assigned risks and outcomes) were similar with and without the BMI information. However, in women with BMI > 25 kg/m(2), adding BMI information improved discrimination (AUC = 63.9 % and 61.4 % with and without BMI, P < 0.001). The model-assigned 10-year risk difference for a woman with high (27 kg/m(2)) versus low (21 kg/m(2)) BMI was only 0.3 % for a woman with neither affected first-degree relatives nor BRCA1 mutation, compared to 4.5 % for a mutation carrier with three such relatives. This contrast illustrates the value of using information on modifiable risk factors in risk assessment and in sharing information with patients of their absolute risks with and without modifiable risk factors. PMID:26012643

  6. Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers

    PubMed Central

    2010-01-01

    Introduction Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene approach, based on knowledge of gene functions, or the development of large genome-wide association studies. In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies. Methods We successfully genotyped 24 SNPs in a cohort of up to 4,724 BRCA1 and 2,693 BRCA2 female mutation carriers from 15 study groups and assessed whether these variants were associated with risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Results SNPs in five of the 14 candidate genes showed evidence of association with breast cancer risk for BRCA1 or BRCA2 carriers (P < 0.05). Notably, the minor alleles of two SNPs (rs7166081 and rs3825977) in high linkage disequilibrium (r2 = 0.77), located at the SMAD3 locus (15q22), were each associated with increased breast cancer risk for BRCA2 mutation carriers (relative risk = 1.25, 95% confidence interval = 1.07 to 1.45, Ptrend = 0.004; and relative risk = 1.20, 95% confidence interval = 1.03 to 1.40, Ptrend = 0.018). Conclusions This study provides evidence that the SMAD3 gene, which encodes a key regulatory protein in the transforming growth factor beta signalling pathway and is known to interact directly with BRCA2, may contribute to increased risk of breast cancer in BRCA2 mutation carriers. This finding suggests that genes with expression associated with BRCA1 and BRCA2 mutation status are enriched for the presence of common genetic modifiers of breast cancer risk in these populations. PMID:21114847

  7. Cetuximab-modified mesoporous silica nano-medicine specifically targets EGFR-mutant lung cancer and overcomes drug resistance.

    PubMed

    Wang, Yuetong; Huang, Hsin-Yi; Yang, Liu; Zhang, Zhanxia; Ji, Hongbin

    2016-01-01

    Drug resistance to tyrosine kinase inhibitor (TKI) is the main obstacle for efficient treatment of epidermal growth factor receptor (EGFR)-mutant lung cancer patients. Here we design a cetuximab-capped mesoporous silica nanoparticle (MP-SiO2 NP) as the drug carrier to specifically target EGFR-mutant lung cancer cells and efficiently release loaded drugs including doxorubicin and gefitinib. This innovative nano-medicine can specifically target lung cancer cells with high EGFR expression rather than those with low EGFR level. Treatment of a gefitinib-resistant cell line derived from PC9 cell (PC9-DR) with the gefitinib-loaded cetuximab-capped MP-SiO2 NP showed a significant inhibition of cell growth. Moreover, this nano-medicine successfully suppressed the progression of PC9-DR xenograft tumors. This tumor suppression was due to the endocytosis of large amount of nano-medicine and the effective gefitinib release induced by high glutathione (GSH) level in PC9-DR cells. Collectively, our study provides a novel approach to overcome EGFR-TKI resistance using cetuximab modified MP-SiO2 NP, which holds strong potential for effective management of EGFR-mutant lung cancer. PMID:27151505

  8. Cetuximab-modified mesoporous silica nano-medicine specifically targets EGFR-mutant lung cancer and overcomes drug resistance

    PubMed Central

    Wang, Yuetong; Huang, Hsin-Yi; Yang, Liu; Zhang, Zhanxia; Ji, Hongbin

    2016-01-01

    Drug resistance to tyrosine kinase inhibitor (TKI) is the main obstacle for efficient treatment of epidermal growth factor receptor (EGFR)-mutant lung cancer patients. Here we design a cetuximab-capped mesoporous silica nanoparticle (MP-SiO2 NP) as the drug carrier to specifically target EGFR-mutant lung cancer cells and efficiently release loaded drugs including doxorubicin and gefitinib. This innovative nano-medicine can specifically target lung cancer cells with high EGFR expression rather than those with low EGFR level. Treatment of a gefitinib-resistant cell line derived from PC9 cell (PC9-DR) with the gefitinib-loaded cetuximab-capped MP-SiO2 NP showed a significant inhibition of cell growth. Moreover, this nano-medicine successfully suppressed the progression of PC9-DR xenograft tumors. This tumor suppression was due to the endocytosis of large amount of nano-medicine and the effective gefitinib release induced by high glutathione (GSH) level in PC9-DR cells. Collectively, our study provides a novel approach to overcome EGFR-TKI resistance using cetuximab modified MP-SiO2 NP, which holds strong potential for effective management of EGFR-mutant lung cancer. PMID:27151505

  9. Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

    NASA Astrophysics Data System (ADS)

    Jiang, Liqin; Li, Xuemin; Liu, Lingrong; Zhang, Qiqing

    2013-02-01

    Oral chemotherapy is a key step towards `chemotherapy at home', a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-PCL-TPGS) random copolymer were prepared in this research for oral delivery of antitumor agents, including thiolated chitosan-modified PCL nanoparticles, unmodified PLA-PCL-TPGS nanoparticles, and thiolated chitosan-modified PLA-PCL-TPGS nanoparticles. Firstly, the PLA-PCL-TPGS random copolymer was synthesized and characterized. Thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The PLA-PCL-TPGS nanoparticles were found by FESEM that they are of spherical shape and around 200 nm in diameter. The surface charge of PLA-PCL-TPGS nanoparticles was reversed from anionic to cationic after thiolated chitosan modification. The thiolated chitosan-modified PLA-PCL-TPGS nanoparticles have significantly higher level of the cell uptake than that of thiolated chitosan-modified PLGA nanoparticles and unmodified PLA-PCL-TPGS nanoparticles. In vitro cell viability studies showed advantages of the thiolated chitosan-modified PLA-PCL-TPGS nanoparticles over Taxol® in terms of cytotoxicity against A549 cells. It seems that the mucoadhesive nanoparticles can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein. In conclusion, PLA-PCL-TPGS nanoparticles modified by thiolated chitosan could enhance the cellular uptake and cytotoxicity, which revealed a potential application for oral chemotherapy of lung cancer.

  10. Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer.

    PubMed

    Jiang, Liqin; Li, Xuemin; Liu, Lingrong; Zhang, Qiqing

    2013-01-01

    Oral chemotherapy is a key step towards 'chemotherapy at home', a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-PCL-TPGS) random copolymer were prepared in this research for oral delivery of antitumor agents, including thiolated chitosan-modified PCL nanoparticles, unmodified PLA-PCL-TPGS nanoparticles, and thiolated chitosan-modified PLA-PCL-TPGS nanoparticles. Firstly, the PLA-PCL-TPGS random copolymer was synthesized and characterized. Thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The PLA-PCL-TPGS nanoparticles were found by FESEM that they are of spherical shape and around 200 nm in diameter. The surface charge of PLA-PCL-TPGS nanoparticles was reversed from anionic to cationic after thiolated chitosan modification. The thiolated chitosan-modified PLA-PCL-TPGS nanoparticles have significantly higher level of the cell uptake than that of thiolated chitosan-modified PLGA nanoparticles and unmodified PLA-PCL-TPGS nanoparticles. In vitro cell viability studies showed advantages of the thiolated chitosan-modified PLA-PCL-TPGS nanoparticles over Taxol® in terms of cytotoxicity against A549 cells. It seems that the mucoadhesive nanoparticles can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein. In conclusion, PLA-PCL-TPGS nanoparticles modified by thiolated chitosan could enhance the cellular uptake and cytotoxicity, which revealed a potential application for oral chemotherapy of lung cancer. PMID:23394588

  11. Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

    PubMed Central

    2013-01-01

    Oral chemotherapy is a key step towards ‘chemotherapy at home’, a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-PCL-TPGS) random copolymer were prepared in this research for oral delivery of antitumor agents, including thiolated chitosan-modified PCL nanoparticles, unmodified PLA-PCL-TPGS nanoparticles, and thiolated chitosan-modified PLA-PCL-TPGS nanoparticles. Firstly, the PLA-PCL-TPGS random copolymer was synthesized and characterized. Thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The PLA-PCL-TPGS nanoparticles were found by FESEM that they are of spherical shape and around 200 nm in diameter. The surface charge of PLA-PCL-TPGS nanoparticles was reversed from anionic to cationic after thiolated chitosan modification. The thiolated chitosan-modified PLA-PCL-TPGS nanoparticles have significantly higher level of the cell uptake than that of thiolated chitosan-modified PLGA nanoparticles and unmodified PLA-PCL-TPGS nanoparticles. In vitro cell viability studies showed advantages of the thiolated chitosan-modified PLA-PCL-TPGS nanoparticles over Taxol® in terms of cytotoxicity against A549 cells. It seems that the mucoadhesive nanoparticles can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein. In conclusion, PLA-PCL-TPGS nanoparticles modified by thiolated chitosan could enhance the cellular uptake and cytotoxicity, which revealed a potential application for oral chemotherapy of lung cancer. PMID:23394588

  12. Effects of Dipole Potential Modifiers on Heterogenic Lipid Bilayers.

    PubMed

    Efimova, Svetlana S; Malev, Valery V; Ostroumova, Olga S

    2016-04-01

    In this work, we examine the ability of dipole modifiers, flavonoids, and RH dyes to affect the dipole potential (φ d) and phase separation in membranes composed of ternary mixtures of POPC with different sphingolipids and sterols. Changes in the steady-state conductance induced by cation-ionophore complexes have been measured to evaluate the changes in dipole potential of planar lipid bilayers. Confocal fluorescence microscopy has been employed to investigate lipid segregation in giant unilamellar vesicles. The effects of flavonoids on φ d depend on lipid composition and dipole modifier type. The effectiveness of RH dyes to increase φ d depends on sphingolipid type but is not influenced by sterol content. Tested modifiers lead to partial or complete disruption of gel domains in bilayers composed of POPC, sphingomyelin, and cholesterol. Substitution of cholesterol to ergosterol or 7-dehydrocholesterol leads to a loss of fluidizing effects of modifiers except phloretin. This may be due to various compositions of gel domains. The lack of influence of modifiers on phase scenario in vesicles composed of ternary mixtures of POPC, cholesterol, and phytosphingosine or sphinganine is related to an absence of gel-like phase. It was concluded that the membrane lateral heterogeneity affects the dipole-modifying abilities of the agents that influence the magnitude of φ d by intercalation into the bilayer and orientation of its own large dipole moments (phloretin and RH dyes). The efficacy of modifiers that do not penetrate deeply and affect φ d through water adsorption (phlorizin, quercetin, and myricetin) is not influenced by lateral heterogeneity of membrane. PMID:26454655

  13. Effective Einstein cosmological spaces for non-minimal modified gravity

    NASA Astrophysics Data System (ADS)

    Elizalde, Emilio; Vacaru, Sergiu I.

    2015-06-01

    Certain off-diagonal vacuum and nonvacuum configurations in Einstein gravity can mimic physical effects of modified gravitational theories of type. We prove this statement by constructing exact and approximate solutions which encode certain models of covariant Hořava type gravity with dynamical Lorentz symmetry breaking. Off-diagonal generalizations of de Sitter and nonholonomic CDM universes are constructed which are generated through nonlinear gravitational polarization of fundamental physical constants and which model interactions with non-constant exotic fluids and effective matter. The problem of possible matter instability for such off-diagonal deformations in (modified) gravity theories is discussed.

  14. Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors

    NASA Astrophysics Data System (ADS)

    Almeida, Patrick V.; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Kaasalainen, Martti; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A.

    2014-08-01

    Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi-HA+ relies on the capability of the conjugated HA+ to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA+-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery.Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of Un

  15. WCRF/AICR recommendation adherence and breast cancer incidence among postmenopausal women with and without non-modifiable risk factors.

    PubMed

    Nomura, Sarah J O; Inoue-Choi, Maki; Lazovich, DeAnn; Robien, Kim

    2016-06-01

    Taller height, family history of breast cancer, greater number of years of potential fertility and nulliparity are established non-modifiable risk factors for postmenopausal breast cancer. Greater adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) diet, physical activity and body weight recommendations has previously been shown to be associated with lower breast cancer risk. However, no prior studies have evaluated whether women with non-modifiable risk factors receive similar benefits from recommendation adherence compared to women without these risk factors. In the Iowa Women's Health Study prospective cohort, we investigated whether associations of WCRF/AICR recommendation adherence differed by the presence/absence of non-modifiable breast cancer risk factors. Baseline (1986) questionnaire data from 36,626 postmenopausal women were used to create adherence scores for the WCRF/AICR recommendations (maximum score = 8.0). Overall and single recommendation adherence in relation to breast cancer risk (n = 3,189 cases) across levels of non-modifiable risk factors were evaluated using proportional hazards regression. Mean adherence score was 5.0 points (range: 0.5-8.0). Higher adherence scores (score ≥ 6.0 vs. ≤ 3.5, HR = 0.76, 95% CI = 0.67-0.87), and adherence to the individual recommendations for body weight and alcohol intake were associated with a lower breast cancer incidence. While not statistically significant among women with more non-modifiable risk factors (score ≥ 6.0 vs. ≤ 3.5, HR = 0.76, 95% CI = 0.36-1.63), hazard ratios were comparable to women with the no non-modifiable risk factors (score ≥ 6.0 vs. ≤ 3.5, HR = 0.74, 95% CI = 0.49-0.93) (p-interaction = 0.57). WCRF/AICR recommendation adherence is associated with lower breast cancer risk, regardless of non-modifiable risk factor status. PMID:26756307

  16. Antibacterial effect of silver nanofilm modified stainless steel surface

    NASA Astrophysics Data System (ADS)

    Fang, F.; Kennedy, J.; Dhillon, M.; Flint, S.

    2015-03-01

    Bacteria can attach to stainless steel surfaces, resulting in the colonization of the surface known as biofilms. The release of bacteria from biofilms can cause contamination of food such as dairy products in manufacturing plants. This study aimed to modify stainless steel surfaces with silver nanofilms and to examine the antibacterial effectiveness of the modified surface. Ion implantation was applied to produce silver nanofilms on stainless steel surfaces. 35 keV Ag ions were implanted with various fluences of 1 × 1015 to 1 × 1017 ions•cm-2 at room temperature. Representative atomic force microscopy characterizations of the modified stainless steel are presented. Rutherford backscattering spectrometry spectra revealed the implanted atoms were located in the near-surface region. Both unmodified and modified stainless steel coupons were then exposed to two types of bacteria, Pseudomonas fluorescens and Streptococcus thermophilus, to determine the effect of the surface modification on bacterial attachment and biofilm development. The silver modified coupon surface fluoresced red over most of the surface area implying that most bacteria on coupon surface were dead. This study indicates that the silver nanofilm fabricated by the ion implantation method is a promising way of reducing the attachment of bacteria and delay biofilm formation.

  17. Biochemical basis of the effects of modified and controlled atmospheres

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review provides updated information on the biochemical and physiological effects of modified and controlled atmospheres (MA & CA) on fruits and vegetables. In addition to conventional MA and CA storage which uses low oxygen and high carbon dioxide, there has been some interest recently in usin...

  18. C1GALT1 overexpression promotes the invasive behavior of colon cancer cells through modifying O-glycosylation of FGFR2.

    PubMed

    Hung, Ji-Shiang; Huang, John; Lin, Yo-Chuen; Huang, Miao-Juei; Lee, Po-Huang; Lai, Hong-Shiee; Liang, Jin-Tung; Huang, Min-Chuan

    2014-04-30

    Core 1 β1,3-galactosyltransferase (C1GALT1) transfers galactose (Gal) to N-acetylgalactosamine (GalNAc) to form Galβ1,3GalNAc (T antigen). Aberrant O-glycans, such as T antigen, are commonly found in colorectal cancer. However, the role of C1GALT1 in colorectal cancer remains unclear. Here we showed that C1GALT1 was frequently overexpressed in colorectal tumors and is associated with poor survival. C1GALT1 overexpression promoted cell survival, migration, invasion, and sphere formation as well as tumor growth and metastasis of colon cancer cells. Conversely, knockdown of C1GALT1 with small interference (si) RNA was sufficient to suppress these malignant phenotypes in vitro and in vivo. Moreover, we are the first to show that fibroblast growth factor receptor (FGFR) 2 carried O-glycans in colon cancer cells. Mechanistic investigations showed that C1GALT1 modified the O-glycans on FGFR2 and enhanced bFGF-triggered activation of FGFR2 as well as increased bFGF-mediated malignant phenotypes. In addition, BGJ398, a selective inhibitor of FGFR, blocked the effects of C1GALT1. These findings suggest that C1GALT1 overexpression modifies O-glycans on FGFR2 and enhances its phosphorylation to promote the invasive behavior and cancer stem-like property in colon cancer cells, indicating a critical role of O-glycosylation in the pathogenesis of colorectal cancer. PMID:24758762

  19. C1GALT1 overexpression promotes the invasive behavior of colon cancer cells through modifying O-glycosylation of FGFR2

    PubMed Central

    Hung, Ji-Shiang; Huang, John; Lin, Yo-Chuen; Huang, Miao-Juei; Lee, Po-Huang; Lai, Hong-Shiee; Liang, Jin-Tung; Huang, Min-Chuan

    2014-01-01

    Core 1 β1,3-galactosyltransferase (C1GALT1) transfers galactose (Gal) to N-acetylgalactosamine (GalNAc) to form Galβ1,3GalNAc (T antigen). Aberrant O-glycans, such as T antigen, are commonly found in colorectal cancer. However, the role of C1GALT1 in colorectal cancer remains unclear. Here we showed that C1GALT1 was frequently overexpressed in colorectal tumors and is associated with poor survival. C1GALT1 overexpression promoted cell survival, migration, invasion, and sphere formation as well as tumor growth and metastasis of colon cancer cells. Conversely, knockdown of C1GALT1 with small interference (si) RNA was sufficient to suppress these malignant phenotypes in vitro and in vivo. Moreover, we are the first to show that fibroblast growth factor receptor (FGFR) 2 carried O-glycans in colon cancer cells. Mechanistic investigations showed that C1GALT1 modified the O-glycans on FGFR2 and enhanced bFGF-triggered activation of FGFR2 as well as increased bFGF-mediated malignant phenotypes. In addition, BGJ398, a selective inhibitor of FGFR, blocked the effects of C1GALT1. These findings suggest that C1GALT1 overexpression modifies O-glycans on FGFR2 and enhances its phosphorylation to promote the invasive behavior and cancer stem-like property in colon cancer cells, indicating a critical role of O-glycosylation in the pathogenesis of colorectal cancer. PMID:24758762

  20. Cancer immunotherapy utilizing gene-modified T cells: From the bench to the clinic.

    PubMed

    Duong, Connie P M; Yong, Carmen S M; Kershaw, Michael H; Slaney, Clare Y; Darcy, Phillip K

    2015-10-01

    The immune system plays a critical role in the elimination and suppression of pathogens. Although the endogenous immune system is capable of immune surveillance resulting in the elimination of cancer cells, tumor cells have developed a variety of mechanisms to escape immune recognition often resulting in tumor outgrowth. The presence of immune infiltrate in tumors has been correlated with a good prognosis following treatment (Sato et al., 2005; Loi et al., 2013; Clemente et al., 1996; Galon et al., 2006). As such, immune cells such as T cells, have been harnessed in order to target cancer. Tumor reactive lymphocytes, called tumor-infiltrating lymphocytes (TILs) have been isolated and expanded from the tumor and reinfused back into patients for the treatment of melanoma. The promise of adoptive immunotherapy utilizing TILs as a robust treatment for cancer has been highlighted in patients with advanced melanoma with greater than 50% of patients responding to treatment (Dudley et al., 2005). Although TIL therapy has shown promising results in melanoma patients, it has proved difficult to translate this approach to other cancers, given that the numbers of TILs that can be isolated are generally low. To broaden this therapy for other cancers, T cells have been genetically modified to endow them with tumor reactivity using either a T cell receptor (TCR) (Parkhurst et al., 2009, 2011; Chinnasamy et al., 2011) or a chimeric antigen receptor (CAR) (Grupp et al., 2013; Park et al., 2007). This review will outline the origins and development of adoptive immunotherapy utilizing TILs leading to genetic modification strategies to redirect T cells to cancer. Potential hurdles and novel strategies will be discussed for realizing the full potential of adoptive immunotherapy becoming a standard of care treatment for cancer. PMID:25595028

  1. Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors

    PubMed Central

    Almeida, Patrick V.; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Kaasalainen, Martti; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A.

    2014-01-01

    Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi–HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi–HA+ relies on the capability of the conjugated HA+ to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA+-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery. PMID:25074521

  2. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

    PubMed Central

    Cox, David G.; Simard, Jacques; Sinnett, Daniel; Hamdi, Yosr; Soucy, Penny; Ouimet, Manon; Barjhoux, Laure; Verny-Pierre, Carole; McGuffog, Lesley; Healey, Sue; Szabo, Csilla; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Thomassen, Mads; Gerdes, Anne-Marie; Caligo, Maria A.; Friedman, Eitan; Laitman, Yael; Kaufman, Bella; Paluch, Shani S.; Borg, Åke; Karlsson, Per; Stenmark Askmalm, Marie; Barbany Bustinza, Gisela; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Benítez, Javier; Hamann, Ute; Rookus, Matti A.; van den Ouweland, Ans M.W.; Ausems, Margreet G.E.M.; Aalfs, Cora M.; van Asperen, Christi J.; Devilee, Peter; Gille, Hans J.J.P.; Peock, Susan; Frost, Debra; Evans, D. Gareth; Eeles, Ros; Izatt, Louise; Adlard, Julian; Paterson, Joan; Eason, Jacqueline; Godwin, Andrew K.; Remon, Marie-Alice; Moncoutier, Virginie; Gauthier-Villars, Marion; Lasset, Christine; Giraud, Sophie; Hardouin, Agnès; Berthet, Pascaline; Sobol, Hagay; Eisinger, François; Bressac de Paillerets, Brigitte; Caron, Olivier; Delnatte, Capucine; Goldgar, David; Miron, Alex; Ozcelik, Hilmi; Buys, Saundra; Southey, Melissa C.; Terry, Mary Beth; Singer, Christian F.; Dressler, Anne-Catharina; Tea, Muy-Kheng; Hansen, Thomas V.O.; Johannsson, Oskar; Piedmonte, Marion; Rodriguez, Gustavo C.; Basil, Jack B.; Blank, Stephanie; Toland, Amanda E.; Montagna, Marco; Isaacs, Claudine; Blanco, Ignacio; Gayther, Simon A.; Moysich, Kirsten B.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Gadzicki, Dorothea; Fiebig, Britta; Caldes, Trinidad; Laframboise, Rachel; Nevanlinna, Heli; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan C.; Couch, Fergus J.; Wang, Xianshu; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Radice, Paolo; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Sinilnikova, Olga M.

    2011-01-01

    Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77–0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription. PMID:21890493

  3. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers.

    PubMed

    Cox, David G; Simard, Jacques; Sinnett, Daniel; Hamdi, Yosr; Soucy, Penny; Ouimet, Manon; Barjhoux, Laure; Verny-Pierre, Carole; McGuffog, Lesley; Healey, Sue; Szabo, Csilla; Greene, Mark H; Mai, Phuong L; Andrulis, Irene L; Thomassen, Mads; Gerdes, Anne-Marie; Caligo, Maria A; Friedman, Eitan; Laitman, Yael; Kaufman, Bella; Paluch, Shani S; Borg, Åke; Karlsson, Per; Askmalm, Marie Stenmark; Bustinza, Gisela Barbany; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Benítez, Javier; Hamann, Ute; Rookus, Matti A; van den Ouweland, Ans M W; Ausems, Margreet G E M; Aalfs, Cora M; van Asperen, Christi J; Devilee, Peter; Gille, Hans J J P; Peock, Susan; Frost, Debra; Evans, D Gareth; Eeles, Ros; Izatt, Louise; Adlard, Julian; Paterson, Joan; Eason, Jacqueline; Godwin, Andrew K; Remon, Marie-Alice; Moncoutier, Virginie; Gauthier-Villars, Marion; Lasset, Christine; Giraud, Sophie; Hardouin, Agnès; Berthet, Pascaline; Sobol, Hagay; Eisinger, François; Bressac de Paillerets, Brigitte; Caron, Olivier; Delnatte, Capucine; Goldgar, David; Miron, Alex; Ozcelik, Hilmi; Buys, Saundra; Southey, Melissa C; Terry, Mary Beth; Singer, Christian F; Dressler, Anne-Catharina; Tea, Muy-Kheng; Hansen, Thomas V O; Johannsson, Oskar; Piedmonte, Marion; Rodriguez, Gustavo C; Basil, Jack B; Blank, Stephanie; Toland, Amanda E; Montagna, Marco; Isaacs, Claudine; Blanco, Ignacio; Gayther, Simon A; Moysich, Kirsten B; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Gadzicki, Dorothea; Fiebig, Britta; Caldes, Trinidad; Laframboise, Rachel; Nevanlinna, Heli; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B; Neuhausen, Susan L; Ding, Yuan C; Couch, Fergus J; Wang, Xianshu; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Radice, Paolo; Easton, Douglas F; Chenevix-Trench, Georgia; Antoniou, Antonis C; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Sinilnikova, Olga M

    2011-12-01

    Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription. PMID:21890493

  4. Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells

    PubMed Central

    Chen, Feng; Zhang, Xiao Hong; Hu, Xiao Dan; Zhang, Wei; Lou, Zhi Chao; Xie, Li Hua; Liu, Pei Dang; Zhang, Hai Qian

    2015-01-01

    Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue. PMID:26316742

  5. Dietary effects on breast cancer

    SciTech Connect

    Stevens, R.G. )

    1991-07-20

    Professor Lee and colleagues show a significant effect of dietary red meat intake, no effect of fat, and a protective effect of soya protein on the risk of breast cancer in young women in Singapore. They do not ascribe the red-meat effect to fat in the meat, and offer no alternative explanation. Red meat contains the most readily absorbed form of dietary iron, and there is evidence that increased body iron stores raise cancer risk, perhaps by one or both of two possible mechanisms: (1) boosting the availability of an essential nutrient for cancer cells, and (2) increasing the production of oxygen radicals. In addition, there is some evidence from studies in animals for a role for iron in mammary-tumor induction. Thompson et al administered 1-methyl-1-nitrosourea to groups of rats receiving normal rat chow, a low-iron diet, or an iron-supplemented diet. The group receiving dietary iron supplementation had the greatest mammary-tumor burden, whereas that receiving an iron-restricted diet had fewer tumors than the group on the normal diet (although this latter effect may have resulted merely from reduced body weight in the rats on an iron-restricted diet). The protective effect of soya protein seen by Lee et al may also be related to iron metabolism. Soy beans are a source of phytate, a constituent of most cereals, nuts, and legumes, that avidly binds iron in such a way that it is incapable of catalyzing the production of oxygen radicals. The protective effect of soya protein may be shared by increased intakes of other plant products that are high in phytate but either not consumed in quantity in Singapore or not assessed in the questionnaire Lee et al administered.

  6. Effects of Chemically Modified Messenger RNA on Protein Expression.

    PubMed

    Li, Bin; Luo, Xiao; Dong, Yizhou

    2016-03-16

    Chemically modified nucleotides play significant roles in the effectiveness of mRNA translation. Here, we describe the synthesis of two sets of chemically modified mRNAs [encoding firefly Luciferase (FLuc) and enhanced green fluorescent protein (eGFP), respectively], evaluation of protein expression, and correlation analysis of expression level under various conditions. The results indicate that chemical modifications of mRNAs are able to significantly improve protein expression, which is dependent on cell types and coding sequences. Moreover, eGFP mRNAs with N1-methylpseudouridine (me(1)ψ), 5-methoxyuridine (5moU), and pseudouridine (ψ) modifications ranked top three in cell lines tested. Interestingly, 5moU-modified eGFP mRNA was more stable than other eGFP mRNAs. Consequently, me(1)ψ, 5moU, and ψ are promising nucleotides for chemical modification of mRNAs. PMID:26906521

  7. Kinetic Sunyaev-Zel'dovich effect in modified gravity

    NASA Astrophysics Data System (ADS)

    Bianchini, Federico; Silvestri, Alessandra

    2016-03-01

    We investigate the impact of modified theories of gravity on the kinetic Sunyaev-Zel'dovich (kSZ) effect of the cosmic microwave background. We focus on a specific class of f (R ) models of gravity and compare their predictions for the kSZ power spectrum to that of the Λ CDM model. We use a publicly available modified version of Halofit to properly include the nonlinear matter power spectrum of f (R ) in the modeling of the kSZ signal. We find that the well-known modifications of the growth rate of structure in f (R ) can indeed induce sizable changes in the kSZ signal, which are more significant than the changes induced by modifications of the expansion history. We discuss prospects of using the kSZ signal as a complementary probe of modified gravity, giving an overview of assumptions and possible caveats in the modeling.

  8. Effects of irradiation for cervical cancer on subsequent breast cancer

    SciTech Connect

    Harlan, L.C.M.

    1985-01-01

    Previous research suggests that cervical cancer patients have a lower risk of breast cancer than women in the general population. Possible explanations include opposing risk factors for cervical cancer and breast cancer, the effect of irradiation used to treat cervical cancer, or both. The purpose of this study was to explore the relationship between irradiation for cervical cancer and the subsequent development of breast cancer. There was no statistically significant relationship between radiation to the ovarian area and the risk of breast cancer in this study. However, the results were consistent with a 19% reduction in risk for women irradiated for cervical cancer when compared to nonirradiated women. In a dose-response analysis, there was a nonsignificant trend of decreased risk of breast cancer with increased radiation up to 1800 rad. There was no consistent pattern for higher doses. The trend, although nonsignificant, differed by age. Women <60 years of age at irradiation were generally at a lower risk of breast cancer than nonirradiated women. Women over 59 years were at an increased risk. There are some potentially important findings from this study which might influence medical care. These should be examined in the larger International Radiation Study.

  9. Effects of the modified uncertainty principle on the inflation parameters

    NASA Astrophysics Data System (ADS)

    Majumder, Barun

    2012-03-01

    In this Letter we study the effects of the Modified Uncertainty Principle as proposed in Ali et al. (2009) [7] on the inflationary dynamics of the early universe in both standard and Randall-Sundrum type II scenarios. We find that the quantum gravitational effect increase the amplitude of density fluctuation, which is oscillatory in nature, with an increase in the tensor-to-scalar ratio.

  10. A fiber-modified adenovirus co-expressing HSV-TK and Coli.NTR enhances antitumor activities in breast cancer cells

    PubMed Central

    Zhan, Yang; Yu, Bin; Wang, Zhen; Zhang, Yu; Zhang, Hai-Hong; Wu, Hao; Feng, Xiao; Geng, Ran-Shen; Kong, Wei; Yu, Xiang-Hui

    2014-01-01

    Breast cancers especially in late and metastatic stages remain refractory to treatment despite advances in surgical techniques and chemotherapy. Suicide gene therapy based on adenoviral technology will be promising strategies for such advanced diseases. We previously showed that co-expression of herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli nitroreductase (Coli.NTR) by an hTERT-driven adenovirus vector resulted in additive anti-tumor effects in breast cancer cells in vitro and in vivo. As many tumor tissue and cancer cells express low level of coxsackie-adenovirus receptor (CAR), which is the functional receptor for the fiber protein of human adenovirus serotype 5 (Ad5), novel Ad5 vectors containing genetically modifi ed fiber are attractive vehicles for achieving targeted gene transfer and improving suicide gene expression in these cancer cells. In the present study, we first built a simplified Ad5 vector platform for fiber modification and quick detection for gene transfer. Then a fiber-modified adenovirus vector containing an RGD motif in the HI loop of the fiber knob was constructed. After recombined with HSV-TK and Coli.NTR gene, this fiber-modified Ad5 vector (Ad-RGD-hT-TK/NTR) was compared with that of our previously constructed Ad5 vector (Ad-hT-TK/NTR) for its therapeutic effects in human breast cancer cell lines. The anti-tumor activity of Ad-RGD-hT-TK/NTR was significantly enhanced compared with Ad-hT-TK/NTR both in vitro and in vivo. This new vector platform provided a robust and simplified approach for capsid modification, and the fiber-modified Ad5 with double suicide genes under the control of hTERT promoter would be a useful gene therapy strategy for breast cancer. PMID:25031704

  11. Codelivery of paclitaxel and small interfering RNA by octadecyl quaternized carboxymethyl chitosan-modified cationic liposome for combined cancer therapy.

    PubMed

    Zhang, Ran; Wang, Shi-Bin; Chen, Ai-Zheng; Chen, Wei-Guang; Liu, Yuan-Gang; Wu, Wen-Guo; Kang, Yong-Qiang; Ye, Shi-Fu

    2015-09-01

    Conventional therapeutic approaches for cancer are limited by cancer cell resistance, which has impeded their clinical applications. The main goal of this work was to investigate the combined antitumor effect of paclitaxel with small interfering RNA modified by cationic liposome formed from modified octadecyl quaternized carboxymethyl chitosan. The cationic liposome was composed of 3β-[N-(N', N'-dimethylaminoethane)-carbamoyl]-cholesterol, dioleoylphosphatidylethanolamine, and octadecyl quaternized carboxymethyl chitosan. The cationic liposome properties were characterized by Fourier transform infrared spectroscopy, dynamic light scattering and zeta potential measurements, transmission electron microscopy, atomic force microscopy, and gel retardation assay. The cationic liposome exhibited good properties, such as a small particle size, a narrow particle size distribution, a good spherical shape, a smooth surface, and a good binding ability with small interfering RNA. Most importantly, when combined with paclitaxel and small interfering RNA, the composite cationic liposome induced a great enhancement in the antitumor activity, which showed a significantly higher in vitro cytotoxicity in Bcap-37 cells than liposomal paclitaxel or small interfering RNA alone. In conclusion, the results indicate that cationic liposome could be further developed as a codelivery system for chemotherapy drugs and therapeutic small interfering RNAs. PMID:25838353

  12. Development and evaluation of bevacizumab-modified pegylated cationic liposomes using cellular and in vivo models of human pancreatic cancer

    NASA Astrophysics Data System (ADS)

    Kuesters, Geoffrey M.

    Targeting the tumor vascular supply in a homogenous manner is a difficult task to achieve with the use of pegylated cationic liposomes (PCLs) alone. Our formulation consisting of bevacizumab conjugated to the distal end of PEG on PCLs was thus developed in an effort to eliminate some of this heterogeneity as well as to increase tumor targeting overall. This study focuses on pancreatic cancer, which has the poorest five-year survival rate of all cancers because of its late diagnosis. The addition of bevacizumab will target tumor areas because it binds to VEGF which is secreted by tumors in high levels. In vitro, we showed that pancreatic cancer cells (Capan-1, HPAF-II and PANC-1) all secrete VEGF into media at different levels, with Capan-1 producing the most and HPAF-II producing the least. A murine endothelial cell line, MS1-VEGF, produces and secretes the most VEGF. A human microvascular endothelial cell line (HMEC-1) was grown in two different conditions, with and without VEGF in the media. Modifying PCLs with bevacizumab enhanced the binding and uptake of PCLs by some pancreatic and endothelial cells in vitro, particularly the cells that had or secreted the most significant amount of VEGF in the media. This translated into enhanced tumor targeting in a biodistribution study using a Capan-1 subcutaneous pancreatic tumor model. This also showed enhanced blood retention compared to the unmodified PCLs while it diminished uptake by the spleen and increased uptake by the kidney. To test the therapeutic benefit of this enhanced uptake and targeting, an anti-angiogenic agent, 2-methoxyestradiol was incorporated into the formulation with 20% incorporation efficiency. Both the unmodified and modified drug-loaded PCLs were the least efficacious against Capan-1, moderately effective against HPAF-II, PANC-1, MS1-VEGF and HMEC-1 grown without VEGF in the media and most efficacious against HMEC-1 grown with VEGF which had the most VEGF present in the media. Multiple in vivo

  13. Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines.

    PubMed

    Vieweg, J; Rosenthal, F M; Bannerji, R; Heston, W D; Fair, W R; Gansbacher, B; Gilboa, E

    1994-04-01

    Adenocarcinoma of the prostate is the most common cancer in men. The majority of cancers are discovered once they have already metastasized, and there is no effective therapy for prostatic cancer at this stage. The use of cytokine-secreting tumor cell preparations as therapeutic vaccines for the treatment of advanced prostate cancer was investigated in the Dunning rat R3327-MatLyLu prostatic tumor model. IL-2 secreting, irradiated, tumor cell preparations were capable of curing animals with s.c. established tumors, and induced immunological memory that protected animals from subsequent tumor challenge. Immunotherapy was less effective when tumors were induced orthotopically, but nevertheless led to improved outcome, significantly delaying, and occasionally preventing, recurrence of tumors after resection of the cancerous prostate. Granulocyte-macrophage colony stimulating factor secreting tumor cell preparations were less effective, and interferon-gamma secreting cells had only a marginal effect. Induction of a potent immune response in tumor bearing animals against the nonimmunogenic MatLyLu tumor supports the view that active immunotherapy warrants further investigation as a potential therapeutic approach to prostate cancer. PMID:8137291

  14. Neurological Toxicity in Metastatic Colorectal Cancer Patients Treated with Modified FOLFOX6 Plus Bevacizumab

    PubMed Central

    Otsu, Satoshi; Hirashima, Yoshinori; Nishikawa, Kazuo; Sakashita, Hiroyuki; Morinaga, Ryotaro; Watanabe, Koichiro; Shirao, Kuniaki

    2014-01-01

    This study was conducted to investigate the toxicity and efficacy of modified FOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer with particular regard to oxaliplatin-induced neuropathy. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (version 3.0). The evaluation was especially focused on grade 2 oxaliplatin-induced neuropathy. The estimated median treatment time to occurrence of grade 2 sensory neuropathy was 7.3 months. The estimated median cumulative dose to occurrence of grade 2 sensory neuropathy was 931 mg/m2. This study clarified the treatment time from first dose as well as the cumulative dose of oxaliplatin leading to grade 2 neuropathy. It may be important to institute some clinical countermeasures when grade 2 neuropathy occurs so as to reduce the chance of progression to irreversible grade 3 neuropathy. PMID:25210489

  15. Ubiquitin-Fold Modifier 1 Acts as a Positive Regulator of Breast Cancer

    PubMed Central

    Yoo, Hee Min; Park, Jong Ho; Jeon, Young Joo; Chung, Chin Ha

    2015-01-01

    Estrogen receptor-α (ERα) is a steroid hormone-sensitive transcription factor that plays a critical role in development of breast cancer. The binding of estrogen to ERα triggers the recruitment of transcriptional co-activators as well as chromatin remodeling factors to estrogen-responsive elements (ERE) of ERα target genes. This process is tightly associated with post-translational modifications (PTMs) of ERα and its co-activators for promotion of transcriptional activation, which leads to proliferation of a large subset of breast tumor cells. These PTMs include phosphorylation, acetylation, methylation, and conjugation by ubiquitin and ubiquitin-like proteins. Ubiquitin-fold modifier 1 (UFM1), one of ubiquitin-like proteins, has recently been shown to be ligated to activating signal co-integrator 1 (ASC1), which acts as a transcriptional co-activator of nuclear receptors. Here, we discuss the mechanistic connection between ASC1 modification by UFM1 and ERα transactivation, and highlight how the interplay of these processes is involved in development of breast cancer. We also discuss potential use of UFM1-conjugating system as therapeutic targets against not only breast cancer but also other nuclear receptor-mediated cancers. PMID:25852645

  16. Targeting Warburg Effect in Cancers with PEGylated Glucose.

    PubMed

    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

  17. Physical, Heritable and Age-Related Factors as Modifiers of Radiation Cancer Risk in Patched Heterozygous Mice

    SciTech Connect

    Pazzaglia, Simonetta Pasquali, Emanuela M.Sc.; Tanori, Mirella; Mancuso, Mariateresa; Leonardi, Simona; Di Majo, Vincenzo; Rebessi, Simonetta; Saran, Anna

    2009-03-15

    Purpose: To address the tumorigenic potential of exposure to low/intermediate doses of ionizing radiation and to identify biological factors influencing tumor response in a mouse model highly susceptible to radiogenic cancer. Methods and Materials: Newborn Ptc1 heterozygous mice were exposed to X-ray doses of 100, 250, and 500 mGy, and tumor development was monitored for their lifetime. Additional groups were irradiated with the same doses and sacrificed at fixed times for determination of short-term endpoints, such as apoptosis and early preneoplastic lesions in cerebellum. Finally, groups of Ptc1 heterozygous mice were bred on the C57BL/6 background to study the influence of common variant genes on radiation response. Results: We have identified a significant effect of low-intermediate doses of radiation (250 and 500 mGy) in shortening mean survival and inducing early and more progressed stages of tumor development in the cerebellum of Ptc1{sup +/-} mice. In addition, we show that age at exposure and heritable factors are potent modifiers of radiation-related cancer risk. Conclusions: The Ptc1 knockout mouse model offers a highly sensitive system that may potentially help to improve understanding and quantification of risk at low doses, such as doses experienced in occupational and medical exposures, and clarify the complex interactions between genetic and environmental factors underlying cancer susceptibility.

  18. Three Measurable and Modifiable Enteric Microbial Biotransformations Relevant to Cancer Prevention and Treatment

    PubMed Central

    2014-01-01

    Interdisciplinary scientific evaluation of the human microbiota has identified three enteric microbial biotransformations of particular relevance for human health and well-being, especially cancer. Two biotransformations are counterproductive; one is productive. First, selective bacteria can reverse beneficial hepatic hydroxylation to produce toxic secondary bile acids, especially deoxycholic acid. Second, numerous bacterial species can reverse hepatic detoxification—in a sense, retoxify hormones and xeonobiotics—by deglucuronidation. Third, numerous enteric bacteria can effect a very positive biotransformation through the production of butyrate, a small chain fatty acid with anti-cancer activity. Each biotransformation is addressed in sequence for its relevance in representative gastrointestinal and extra-intestinal cancers. This is not a complete review of their connection with every type of cancer. The intent is to introduce the reader to clinically relevant microbial biochemistry plus the emerging evidence that links these to both carcinogenesis and treatment. Included is the evidence base to guide counseling for potentially helpful dietary adjustments. PMID:24891992

  19. No evidence that GATA3 rs570613 SNP modifies breast cancer risk

    PubMed Central

    Johnatty, Sharon E.; Couch, Fergus J.; Fredericksen, Zachary; Tarrell, Robert; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Gschwantler-Kaulich, Daphne; Singer, Christian F.; Fuerhauser, Christine; Fink-Retter, Anneliese; Domchek, Susan M.; Nathanson, Katherine L.; Pankratz, Vernon S.; Lindor, Noralane M.; Godwin, Andrew K.; Caligo, Maria A.; Hopper, John; Southey, Melissa C.; Giles, Graham G.; Justenhoven, Christina; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Heikkinen, Tuomas; Aaltonen, Kirsimari; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli; Hall, Per; Czene, Kamila; Liu, Jianjun; Peock, Susan; Cook, Margaret; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Rosalind; Pichert, Gabriella; Eccles, Diana; Davidson, Rosemarie; Cole, Trevor; Cook, Jackie; Douglas, Fiona; Chu, Carol; Hodgson, Shirley; Paterson, Joan; Hogervorst, Frans B.L.; Rookus, Matti A.; Seynaeve, Caroline; Wijnen, Juul; Vreeswijk, Maaike; Ligtenberg, Marjolijn; Luijt, Rob B. van der; van Os, Theo A.M.; Gille, Hans J.P.; Blok, Marinus J.; Issacs, Claudine; Humphreys, Manjeet K.; McGuffog, Lesley; Healey, Sue; Sinilnikova, Olga; Antoniou, Antonis C.; Easton, Douglas F.; Chenevix-Trench, Georgia

    2009-01-01

    GATA-binding protein 3 (GATA3) is a transcription factor that is crucial to mammary gland morphogenesis and differentiation of progenitor cells, and has been suggested to have a tumor suppressor function. The rs570613 single nucleotide polymorphism (SNP) in intron 4 of GATA3 was previously found to be associated with a reduction in breast cancer risk in the Cancer Genetic Markers of Susceptibility project and in pooled analysis of two case-control studies from Norway and Poland (Ptrend =0.004), with some evidence for a stronger association with estrogen receptor (ER) negative tumours [1]. We genotyped GATA3 rs570613 in 6,388 cases and 4,995 controls from the Breast Cancer Association Consortium (BCAC) and 5,617 BRCA1 and BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). We found no association between this SNP and breast cancer risk in BCAC cases overall (ORper-allele = 1.00, 95% CI 0.94 − 1.05), in ER negative BCAC cases (ORper-allele = 1.02, 95% CI 0.91−1.13), in BRCA1 mutation carriers RRper-allele = 0.99, 95% CI 0.90−1.09) or BRCA2 mutation carriers (RRper-allele = 0.93, 95% CI 0.80−1.07). We conclude that there is no evidence that either GATA3 rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women. PMID:19082709

  20. Evaulation of cancer and non-cancer effects of cumene

    EPA Science Inventory

    Cumene, also known as isopropyl benzene, is a volatile liquid. We have systematically reviewed published literature to evaluate cancer and noncancer effects of cumene. Cumene, readily absorbed via inhalation is distributed in several tissues, metabolized extensively by cytochrome...

  1. CAR-modified T-cell therapy for cancer: an updated review.

    PubMed

    Haji-Fatahaliha, Mostafa; Hosseini, Maryam; Akbarian, Asiye; Sadreddini, Sanam; Jadidi-Niaragh, Farhad; Yousefi, Mehdi

    2016-09-01

    The use of chimeric antigen receptor (CAR)-modified T cells is a promising approach for cancer immunotherapy. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in T-cell activation subsequent to antigen binding. Optimal tumor removal through CAR-modified T cells requires suitable target antigen selection, co-stimulatory signaling domain, and the ability of CAR T cells to traffic, persist, and retain antitumor function after adoptive transfer. There are several elements which can improve antitumor function of CAR T cells, including signaling, conditioning chemotherapy and irradiation, tumor burden of the disease, T-cell phenotype, and supplementary cytokine usage. This review outlines four generations of CAR. The pre-clinical and clinical studies showed that this technique has a great potential for treatment of solid and hematological malignancies. The main purpose of the current review is to focus on the pre-clinical and clinical developments of CAR-based immunotherapy. PMID:26068778

  2. Modifiable risk factors for the prevention of bladder cancer: a systematic review of meta-analyses.

    PubMed

    Al-Zalabani, Abdulmohsen H; Stewart, Kelly F J; Wesselius, Anke; Schols, Annemie M W J; Zeegers, Maurice P

    2016-09-01

    Each year, 430,000 people are diagnosed with bladder cancer. Due to the high recurrence rate of the disease, primary prevention is paramount. Therefore, we reviewed all meta-analyses on modifiable risk factors of primary bladder cancer. PubMed, Embase and Cochrane database were systematically searched for meta-analyses on modifiable risk factors published between 1995 and 2015. When appropriate, meta-analyses (MA) were combined in meta-meta-analysis (MMA). If not, the most comprehensive MA was selected based on the number of primary studies included. Probability of causation was calculated for individual factors and a subset of lifestyle factors combined. Of 1496 articles identified, 5 were combined in MMA and 21 were most comprehensive on a single risk factor. Statistically significant associations were found for current (RR 3.14) or former (RR 1.83) cigarette smoking, pipe (RR 1.9) or cigar (RR 2.3) smoking, antioxidant supplementation (RR 1.52), obesity (RR 1.10), higher physical activity levels (RR 0.86), higher body levels of selenium (RR 0.61) and vitamin D (RR 0.75), and higher intakes of: processed meat (RR 1.22), vitamin A (RR 0.82), vitamin E (RR 0.82), folate (RR 0.84), fruit (RR 0.77), vegetables (RR 0.83), citrus fruit (RR 0.85), and cruciferous vegetables (RR 0.84). Finally, three occupations with the highest risk were tobacco workers (RR 1.72), dye workers (RR 1.58), and chimney sweeps (RR 1.53). The probability of causation for individual factors ranged from 4 to 68 %. The combined probability of causation was 81.8 %. Modification of lifestyle and occupational exposures can considerably reduce the bladder cancer burden. While smoking remains one of the key risk factors, also several diet-related and occupational factors are very relevant. PMID:27000312

  3. No evidence for a genetic modifier for renal cell cancer risk in HLRCC syndrome.

    PubMed

    Vahteristo, Pia; Koski, Taru A; Näätsaari, Laura; Kiuru, Maija; Karhu, Auli; Herva, Riitta; Sallinen, Satu-Leena; Vierimaa, Outi; Björck, Erik; Richard, Stéphane; Gardie, Betty; Bessis, Didier; Van Glabeke, Emmanuel; Blanco, Ignacio; Houlston, Richard; Senter, Leigha; Hietala, Marja; Aittomäki, Kristiina; Aaltonen, Lauri A; Launonen, Virpi; Lehtonen, Rainer

    2010-06-01

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. Cutaneous and uterine leiomyomas are the most common clinical manifestations of HLRCC, whereas only approximately 20% of the families display renal cell cancer (RCC). The number of RCC cases in these families varies from one to five. Interestingly, families with multiple RCC cases are mainly found in Finland and the USA. Such aggregation of RCC in only some families and populations has led to the hypothesis that besides FH mutations also other inherited genetic and/or environmental factors may contribute to the malignant kidney tumor formation. To search for such a genetic modifier we have performed a genome-wide linkage analysis in two and an identical by descent analysis in four Finnish HLRCC families with several RCC patients. Additional Finnish and French families were used in fine-mapping and haplotype analyses. The only region compatible with linkage was the locus surrounding the FH gene itself in chromosome 1q43. The genes in the putative candidate region were screened, but no potentially pathogenic alterations were observed. Although these data do not rule out the existence of a genetic modifier, they emphasize the contribution of the FH genotype in HLRCC related RCC. Therefore, as all FH mutation carriers may have an increased risk for developing renal cancer, counseling and genetic testing should be offered for all HLRCC family members and clinical follow-up should be organized for the mutation carriers. PMID:20091131

  4. Attractive Casimir effect in an infrared modified gluon bag model

    SciTech Connect

    Oxman, L.E.; Amaral, R.L.P.G.

    2005-12-15

    In this work, we are motivated by previous attempts to derive the vacuum contribution to the bag energy in terms of familiar Casimir energy calculations for spherical geometries. A simple infrared modified model is introduced which allows studying the effects of the analytic structure as well as the geometry in a clear manner. In this context, we show that if a class of infrared vanishing effective gluon propagators is considered, then the renormalized vacuum energy for a spherical bag is attractive, as required by the bag model to adjust hadron spectroscopy.

  5. Reviewing Cancer Care Team Effectiveness

    PubMed Central

    Taplin, Stephen H.; Weaver, Sallie; Salas, Eduardo; Chollette, Veronica; Edwards, Heather M.; Bruinooge, Suanna S.; Kosty, Michael P.

    2015-01-01

    Purpose: The management of cancer varies across its type, stage, and natural history. This necessitates involvement of a variety of individuals and groups across a number of provider types. Evidence from other fields suggests that a team-based approach helps organize and optimize tasks that involve individuals and groups, but team effectiveness has not been fully evaluated in oncology-related care. Methods: We undertook a systematic review of literature published between 2009 and 2014 to identify studies of all teams with clear membership, a comparator group, and patient-level metrics of cancer care. When those teams included two or more people with specialty training relevant to the care of patients with cancer, we called them multidisciplinary care teams (MDTs). After reviews and exclusions, 16 studies were thoroughly evaluated: two addressing screening and diagnosis, 11 addressing treatment, two addressing palliative care, and one addressing end-of-life care. The studies included a variety of end points (eg, adherence to quality indicators, patient satisfaction with care, mortality). Results: Teams for screening and its follow-up improved screening use and reduced time to follow-up colonoscopy after an abnormal screen. Discussion of cases within MDTs improved the planning of therapy, adherence to recommended preoperative assessment, pain control, and adherence to medications. We did not see convincing evidence that MDTs affect patient survival or cost of care, or studies of how or which MDT processes and structures were associated with success. Conclusion: Further research should focus on the association between team processes and structures, efficiency in delivery of care, and mortality. PMID:25873056

  6. Climate Effects of Cloud Modified CCN-Cloud Interactions

    NASA Astrophysics Data System (ADS)

    Noble, S. R., Jr.; Hudson, J. G.

    2015-12-01

    Cloud condensation nuclei (CCN) play an important role in the climate system through the indirect aerosol effect (IAE). IAE is one of the least understood aspects of the climate system as many cloud processes are complicated. Many studies of aerosol-cloud interaction involve CCN interaction with cloud droplet concentrations (Nc), cloud microphysics, and radiative properties. However, fewer studies investigate how cloud processes modify CCN. Upon evaporation from non-precipitating clouds, CCN distributions develop bimodal shaped distributions (Hoppel et al. 1986). Activated CCN participate in cloud processing that is either chemical: aqueous oxidation; or physical: Brownian scavenging, collision and coalescence. Chemical processing does not change CCN concentration (NCCN) but reduces critical supersaturations (Sc; larger size) (Feingold and Kreidenweis, 2000) while physical processing reduces NCCN and Sc. These processes create the minima in the bimodal CCN distributions (Hudson et al., 2015). Updraft velocity (W) and NCCN are major factors on how these modified CCN distributions affect clouds. Panel a shows two nearby CCN distributions in the MArine Stratus/stratocumulus Experiment (MASE), which have similar concentrations, but the bimodal one (red) has been modified by cloud processing. In a simplified cloud droplet model, the modified CCN then produces higher Nc (panel b) and smaller droplet mean diameters (MD; panel c) when compared to the unmodified CCN (black) for W lower than 50 cm/s. The better CCN (lower Sc) increase competition among droplets reducing MD and droplet distribution spread (σ) which acts to reduce drizzle. Competition is created by limited available condensate due to lower S created by the low W (<50 cm/s) typical of stratus. The increased Nc of the modified CCN in stratus then increases IAE in the climate system. At higher W (>50 cm/s) typical of cumuli, Ncis reduced and MD is increased from the modified CCN distribution (panels b & c). Here

  7. Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer

    PubMed Central

    2014-01-01

    Background Renal cell carcinoma (RCC) is a malignant disease that demonstrates resistance to standard chemotherapeutic agents. Yet Active immunization using genetically modified dendritic cells holds promise for the adjuvant treatment of malignancies to eradicate or control residual disease. Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD8+ T cells with diverse TCR specificities, possessing non-MHC-restricted cytolytic activities against tumor cells. Clinical studies have confirmed benefit and safety of CIK cell-based therapy for patients with malignancies. This clinical trial was conducted to evaluate efficacy and safety of genetically modified dendritic cells in combination with Cytokine-Induced Killer Cell (gmDCs-CIK) treatment of patients with RCC. Methods 28 patients with advanced renal cancer were admitted to Affiliated Hospital of Academy of Military Medical Sciences from December 2010 to March 2012 and treated by gmDCs-CIK. Clinical efficacy and safety between pre- and post-treatment were compared. Results This analysis showed an objective response rate (ORR) of 39% and a disease control rate (DCR) of as 75%. There is no significant relationship between clinical efficacy and whether metastasis occurred or not (P > 0.05). There is no significant relationship between ORR and cycles of treatment (P > 0.05), but DCR was significantly related with cycles of treatment (P < 0.05). No clinically significant side effects were observed. There were no significant changes of T cell subsets including CD3+, CD4+, CD8+, CD4+ CD25+ Treg cells except Th1 in peripheral blood between day 30 after immunotherapy and 1 day before immunotherapy in 11 patients. Conclusion DC-CIK is feasible and effective in treating advanced renal cancer and thus provides a new approach. Trial registration ClinicalTrials.gov Identifier: NCT01924156. Registration date: August 14, 2013. PMID:24720900

  8. [Modified posterior exenteration (radical oophorectomy type II) as a part of an extensive surgery of ovarian cancer--case report].

    PubMed

    Knapp, Paweł; Łukaszewicz, Jerzy; Knapp, Piotr

    2013-06-01

    Epithelial ovarian cancer remains to be the most deadly gynecologic cancer among the female population. Carcinogenesis and abdomen extension are the reasons why ovarian cancer is still examined in advances stages. Ovarian cancer frequent metastasizes to the uterus, rectosigmoid colon, and other pelvic structures by intraperitoneal seeding of tumor deposits, as well as direct extension. Multiple modalities of therapy are utilized in the management of the disease. Numerous medical trials and research programs have demonstrated the most important role of surgery in the treatment of this disease. A vast majority of authors are of the opinion that the surgical interventions have a major influence on the overall survival (OS) and progression free survival (PFS) in ovarian cancer cases. The paper presents a case of a 35-year-old woman diagnosed with advanced ovarian cancer who underwent modified posterior exenteration as a part of extensive cytoreductive surgery PMID:24032266

  9. Allelopathic effect of methanolic extracts of genetically modified and non-genetically modified canola on soybean.

    PubMed

    Syed, Kashmala; Shinwari, Zabta Khan

    2016-03-01

    This study on the effect of genetically modified (GM) and non-GM canola on soybean was carried out for physiological and biochemical biosafety assessment of GM canola. Methanolic extracts of GM and non-GM canola were assessed on seed germination and growth of soybean (Glycine max L.) under sterilized conditions. The extracts applied were of 3, 5, and 10% concentrations. The results showed that methanolic extracts of both GM and non-GM canola improved the germination percentage. However, germination rate index was significantly decreased with concomitant increase in mean germination time of soybean. A significant rate of decrease was observed in root fresh weight while increase in shoot length took place; when treatment of GM canola extracts were applied, however, no effect was observed in shoot fresh weight. A significant increase in protein contents, as well as phenolic, carotenoids, proline, and chlorophyll a content, was observed when different GM canola treatments (3, 5, and 10%) were applied to soybean; however, a significant rate of reduction in chlorophyll b content was observed by the application of GM canola treatment. Similar results were observed for superoxide dismutase, peroxidase, and catalase activities. A significant increase in the sugar content levels was observed when GM canola treatments (3, 5, and 10%) were applied to soybean. PMID:24105070

  10. [THE EFFECT OF PREGNANCY ON BREAST CANCER].

    PubMed

    Matalon, Shelly Tartakover; Shochet, Gali Epstein; Drucker, Liat; Lishner, Michael

    2015-08-01

    Cancer and pregnancy coincide in about one in 1,000 pregnancies. One of the most common malignancies associated with pregnancy is breast cancer. Women with pregnancy-associated breast cancer (PABC) have a higher likelihood of being diagnosed with metastatic disease and estrogen receptor (ER) negative tumors than do non-pregnant women. Controversies exist regarding the effect of pregnancy on breast cancer prognosis. Some researchers suggest that pregnancy does not affect breast cancer prognosis, whereas others claim the opposite. Although PABC is usually discovered in an advanced stage, breast cancer metastasis on the placenta is a rare event. During cancer progression, the surrounding microenvironment co-evolves into an activated state through continuous communication with the malignant cells, thereby promoting tumor growth. The effect of pregnancy and placental environment on breast cancer biology is the issue of this review. Placental and cancer cells implantation processes share similar molecular pathways. This suggests that placental factors may affect breast cancer cells biology. Previously, we analyzed the effect of first trimester human placenta on breast cancer cells. Breast cancer cells were co-cultured with placental explants during their implantation on matrigel substrate. We found that the placenta reduced ER expression on the cancer cells and induced their migration and invasion abilities. As a result of it, breast cancer cells migrated away from the placental implantation sites. Hormonal pathways were involved in these phenomena. These results may explain the high incidence of metastases during pregnancy in on the one hand and the rarity of metastases on the placenta on the other hand. PMID:26480621

  11. A non-synonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

    PubMed Central

    Ding, Yuan C.; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Shani-Shimon–Paluch; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Cajal, Teresa Ramóny; Stavropoulou, Alexandra V; Benítez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M.; de Lange, Judith L.; Meijers-Heijboer, Hanne E.J.; Oosterwijk, Jan C.; van Asperen, Christi J.; García, Encarna B. Gómez; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B.; Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Godwin, Andrew K.; Pathak, Harsh; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure; Léoné, Mélanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnès; Berthet, Pascaline; Dreyfus, Hélène; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnès; Sokolowska, Johanna; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Maria, Muy-Kheng Tea; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Hansen, Thomas v. O.; Ejlertsen, Bent; Johannsson, Oskar Th.; Offit, Kenneth; Sarrel, Kara; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion R; Andrews, Lesley; Cohn, David; DeMars, Leslie R.; DiSilvestro, Paul; Rodriguez, Gustavo; Toland, Amanda Ewart; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Ramus, Susan J; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Ganz, Patricia A.; Beattie, Mary S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Tomlinson, Gail E.; Weitzel, Jeffrey; Garber, Judy E.; Olopade, Olufunmilayo I.; Rubinstein, Wendy S.; Tung, Nadine; Blum, Joanne L.; Narod, Steven A.; Brummel, Sean; Gillen, Daniel L.; Lindor, Noralane; Fredericksen, Zachary; Pankratz, Vernon S.; Couch, Fergus J.; Radice, Paolo; Peterlongo, Paolo; Greene, Mark H.; Loud, Jennifer T.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Gerdes, Anne-Marie; Thomassen, Mads; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Lee, Andrew; Chenevix-Trench, Georgia; Antoniou, Antonis C; Neuhausen, Susan L.

    2012-01-01

    Background We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. Methods IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Results Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 [Hazard ratio (HR) = 1.43; 95% CI: 1.06–1.92; p = 0.019] and BRCA2 mutation carriers (HR=2.21; 95% CI: 1.39–3.52, p=0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class 2 mutations than class 1 (mutations (class 2 HR=1.86, 95% CI: 1.28–2.70; class 1 HR=0.86, 95%CI:0.69–1.09; p-for difference=0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class 2 mutation carriers (HR = 2.42; p = 0.03). Conclusion The IRS1 Gly972Arg SNP, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class 2 mutation carriers. Impact These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. PMID:22729394

  12. Technical hints and potential pitfalls in modified radical neck dissection for thyroid cancer

    PubMed Central

    Lorente, Leyre; Sancho, Juan J.

    2013-01-01

    Modified radical neck dissection (MRND) is often performed in conjunction with total thyroidectomy for the management of thyroid cancer. Prevention of postoperative sequelae after MRND is closely dependent on the avoidance of technical mistakes that may lead to significant complications and long-term morbidity. A thorough technical discussion with emphasis on potential pitfalls is made of the most relevant steps of MRND using the extrafascial approach: fascial dissection, approach to the accessory nerve, posterior limits, upper internal jugular vein (IJV), transverse cervical vessels, thoracic duct and compartment V dissection. Some anatomical hints are emphasized to help the novice surgeon to develop a refined surgical technique, the key to an uneventful postoperative course. PMID:25083480

  13. Endostatin and irradiation modifies the activity of ADAM10 and neprilysin in breast cancer cells.

    PubMed

    Aydemir, Esra Arslan; Şimşek, Ece; Korcum, Aylin Fidan; Fişkin, Kayahan

    2016-09-01

    Angiogenesis, the formation of new blood vessels, is regarded as a key cancer cell property. Endostatin (ES) is a potential antiangiogenic agent and it may be useful when implemented in combination with other cancer therapeutic strategies. The present study investigated the in vitro effects of ES, radiotherapy (RT) or combination therapy (ES + RT) on two important proteases, a disintegrin and metalloproteinase domain‑containing protein 10 (ADAM10) and neprilysin (NEP) in 4T1 mouse breast cancer cells and the more metastatic phenotype of 4THMpc breast cancer cells. 4T1 and 4THMpc cells were treated with recombinant murine ES (4 µg/ml) alone, RT (45 Gy) alone or with ES + RT. ADAM10 enzyme activity was determined using a tumor necrosis factor‑α converting enzyme (α‑secretase) activity assay kit, and NEP enzyme activity was measured with a fluorometric assay based on the generation of free dansyl‑D‑Ala‑Gly from N-dansyl-Ala-Gly-D-nitro-Phe-Gly, the substrate of NEP. Western blotting analysis was performed to determine whether the altered enzyme activity levels of the two cell lines occurred due to changes in expression level. These data indicate that ES independently potentiates the activity of ADAM10 and NEP enzymes in 4T1 and 4THMpc breast cancer cells. PMID:27430992

  14. Low penetrance alleles as risk modifiers in familial and sporadic breast cancer.

    PubMed

    Esteban Cardeñosa, Eva; de Juan Jiménez, Inmaculada; Palanca Suela, Sarai; Chirivella González, Isabel; Segura Huerta, Angel; Santaballa Beltran, Ana; Casals El Busto, María; Barragán González, Eva; Fuster Lluch, Oscar; Bermúdez Edo, José; Bolufer Gilabert, Pascual

    2012-12-01

    The aim of the study is to investigate the relevance of rs1056663 and rs2708861 HUS1 polymorphisms, and rs104548, rs2981582 and rs2910164 polymorphisms of CASP8, FGFR2 and micro RNA 146A genes, respectively, as risk modifiers in hereditary breast or ovarian cancer (BC/OC) and risk factors in sporadic BC. We performed a case-control study in 189 healthy controls (CG) and 538 BC/OC cases, 340 with familial history of BC/OC (130 carriers of BRCA1/2 mutations and 210 non-carriers) and 198 sporadic BC/OC. The polymorphisms were assessed by real-time PCR using primers and fluorescent-labelled hybridization probes. We found statistically significant differences between familial BC/OC and CG for rs1056663 and rs2708861 HSU1 polymorphisms and rs2981582 FGFR2 polymorphism, particularly in non-carriers of BRCA1/2 mutations. In this group we found statistical differences for rs1056663 HSU1 and rs2981582 FGFR2 polymorphisms (p-trend < 0.006). The logistic regression confirmed that rs2981582 FGFR2 polymorphism (OR = 2.09; 95 % CI 1.35, 3.20) and the interaction between rs1056663 and rs2708861 HUS1 polymorphisms increased the risk of cancer (OR = 1.87; 95 % CI 1.19, 2.92). Furthermore, we found that the presence of rs1056663 and rs2708861 HUS1 polymorphisms is associated with early age of presentation of BC (p = 0.015) in the group of non-carriers of BRCA1/2 mutations. In addition, no association of the polymorphisms studied in sporadic BC was observed. In conclusion, the HUS1 and FGFR2 polymorphisms act as risk BC modifiers in familial BC/OC, particularly in the group of non-carriers of BRCA1/2 mutations. PMID:22926736

  15. Cancer preventive effects of vitamin E.

    PubMed

    Wada, Sayori

    2012-01-01

    Vitamin E is well known as an antioxidant, with 8 natural isoforms, such as α-, bgr;-, γ- and δ-tocopherols and α-, β-, gamma;- and δ-tocotrienols. It has been suggested that both tocopherols and tocotrienols have anti-tumor effects due to the antioxidant effect. The results of several studies have indicated that the tocotrienols may have a stronger bioactivity than the tocopherols. Both types have shown antiproliferative, proapoptotic and cyclooxygenase-2- inhibiting effects in in vitro studies. Several animal studies have demonstrated that vitamin E has cancer-preventing effects. However, clinical trials have not shown similar results for the cancer prevention effect of tocopherol. Although the Linxian Trials demonstrated that the supplementation of β-carotene, α-tocopherol and selenium reduced cancer risk, the beneficial effects of α- tocopherol on prostate cancer disappeared after several years in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Vitamin E, especially tocotrienols, seems to be a potent agent for cancer prevention, however no large-scale clinical trial on the cancer prevention effect of tocotrienols has been conducted yet. Therefore it is expected that clinical trials overcoming the lower bioavailability of tocotrienols will be conducted, and it is urgently needed to assess the safety and the efficacy of the administration of the tocotrienols as a part of a cancer prevention regimen. PMID:21466429

  16. Rare alleles of the HRAS polymorphism do not modify the risk of breast or ovarian cancer in BRCA1 carriers

    SciTech Connect

    Phelan, C.; Tonin, P.; Lynch, H.T.

    1994-09-01

    The presence of one of the rare alleles of a minisatellite polymorphism at the HRAS locus on chromosome 11p15 has been associated with a roughly two-fold increase in the risk of breast cancer. The BRCA1 gene on chromosome 17q12-21 is responsible for the majority of the families with the breast-ovarian cancer syndrome. It is estimated that 87% of BRCA1 carriers will be affected with breast cancer by age 70. The relative risk for premenopausal breast cancer in carriers, compared to non-carriers, is roughly 100. Because of the wide range in ages of onset of cancer among BRCA1 carriers, it is likely that additional factors modify the risk of cancer. The role of other modifying genetic loci has not been studied. Through haplotype analysis we have identified 199 female BRCA1 carriers above the age of 20 years in 25 linked families. 127 of these women have been diagnosed with cancer and 72 are currently healthy. DNA was available on 59 carriers. Each sample was typed for the HRAS polymorphism by PCR, using primers flanking the minisatellite. Rare alleles were identified in 18 carriers. The penetrance of the BRCA1 gene was not higher among those women who carried a rare HRAS allele (mean age of onset 49 years) than among those who carried two common alleles (mean age of onset 43 years) (p= 0.59; log rank test). Similar results were obtained for ovarian cancer. These data do not support the hypothesis that the HRAS locus modified the risk of cancer among carriers of mutations in BRCA1.

  17. Assessment of truncal edema following breast cancer treatment using modified Harpenden skinfold calipers.

    PubMed

    Roberts, C C; Levick, J R; Stanton, A W; Mortimer, P S

    1995-06-01

    After initial treatment for breast cancer, lymphedema often affects the trunk as well as the arm. Evaluation of truncal swelling by the clinical "pinch test" of the posterior axillary fold is unreliable. Our aim was to develop an objective measurement, using modified Harpenden skinfold calipers. Standard Harpenden skinfold calipers exert a pressure of 12.6 g.mm-2, which rapidly squeezes edema fluid out of the skinfold. Springs were substituted to exert a lighter but relatively constant load (3.7 g.mm-2). Repeated skinfold thickness measurements on the same, normal subject then gave a relative standard deviation (r.s.d.) or coefficient of variation of 5%. The posterior axillary folds of 14 patients (age 56 +/- 13 (s.d.) years) with an average 30% arm swelling were measured using the same procedure. Readings were taken at 10 s, and again after 60 s of sustained application to assess the rate of creep, or deformation with time, attributed to displacement of pressurized interstitial fluid. Two patients had clinically observable axillary fold swelling. Eight patients, including the above two, showed axillary fold swelling by caliper measurement, defined as a 10% increase over the contralateral side (2 r.s.d.'s). Creep was greater on the affected side in all 14 patients. Thus, modified calipers can detect axillary fold edema, and thereby provide an objective method for assessing changes in swelling after lymphedema treatment. PMID:7564495

  18. [Construction of biotin-modified polymeric micelles for pancreatic cancer targeted photodynamic therapy].

    PubMed

    Deng, Chun-yue; Long, Ying-ying; Liu, Sha; Chen, Zhang-bao; Li, Chong

    2015-08-01

    In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ± 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 ± 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy. PMID:26669006

  19. Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    NASA Astrophysics Data System (ADS)

    Yu, Meihua; Jambhrunkar, Siddharth; Thorn, Peter; Chen, Jiezhong; Gu, Wenyi; Yu, Chengzhong

    2012-12-01

    In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs). HA-MSNs possess a specific affinity to CD44 over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells). The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis. Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake via HA receptor mediated endocytosis. An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles. Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs. It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors.

  20. Dark energy or modified gravity? An effective field theory approach

    SciTech Connect

    Bloomfield, Jolyon; Flanagan, Éanna É.; Park, Minjoon; Watson, Scott E-mail: eef3@cornell.edu E-mail: gswatson@syr.edu

    2013-08-01

    We take an Effective Field Theory (EFT) approach to unifying existing proposals for the origin of cosmic acceleration and its connection to cosmological observations. Building on earlier work where EFT methods were used with observations to constrain the background evolution, we extend this program to the level of the EFT of the cosmological perturbations — following the example from the EFT of Inflation. Within this framework, we construct the general theory around an assumed background which will typically be chosen to mimic ΛCDM, and identify the parameters of interest for constraining dark energy and modified gravity models with observations. We discuss the similarities to the EFT of Inflation, but we also identify a number of subtleties including the relationship between the scalar perturbations and the Goldstone boson of the spontaneously broken time translations. We present formulae that relate the parameters of the fundamental Lagrangian to the speed of sound, anisotropic shear stress, effective Newtonian constant, and Caldwell's varpi parameter, emphasizing the connection to observations. It is anticipated that this framework will be of use in constraining individual models, as well as for placing model-independent constraints on dark energy and modified gravity model building.

  1. Cancer Basics

    MedlinePlus

    ... 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 ...

  2. Antitumor drug effect of betulinic acid mediated by polyethylene glycol modified liposomes.

    PubMed

    Liu, Yanping; Gao, Dawei; Zhang, Xuwu; Liu, Zhiwei; Dai, Kun; Ji, Bingshuo; Wang, Qianqian; Luo, Liyao

    2016-07-01

    Betulinic acid (BA), as a natural pentacyclic lupine-type triterpene, principally derives from bark of white birch, due to its potent pharmacological properties and low side-effect, which has been demonstrated a prominent efficiency on cancer therapy. However, the poor solubility and low bioavailability limit its pharmaceutical effect. Herein, we reported the rapid efficient synthesis of the polyethylene glycol modified (PEGylated) BA liposomes using ethanol injection technique for the first time. In the study, hydrophobic BA was encapsulated in the lipid bilayer of liposomes, meanwhile hydrophilic PEG layer covered the surface of liposomes. The mean diameter of PEGylated BA liposomes was 142nm, which can effectively accumulate in the tumor tissues. In vitro drug release study showed that the PEGylated BA liposomes had a better sustained drug release effect than BA liposomes. The PEGylated BA liposomes also exhibited a better tumor inhibitory effect compared with those of free BA or BA liposomes in vitro and in vivo experiments. Therefore, the PEGylated BA liposomes could serve as a better alternative for the cancer therapy in future. PMID:27127036

  3. Anti-Tumor Effects after Adoptive Transfer of IL-12 Transposon-Modified Murine Splenocytes in the OT-I-Melanoma Mouse Model.

    PubMed

    Galvan, Daniel L; O'Neil, Richard T; Foster, Aaron E; Huye, Leslie; Bear, Adham; Rooney, Cliona M; Wilson, Matthew H

    2015-01-01

    Adoptive transfer of gene modified T cells provides possible immunotherapy for patients with cancers refractory to other treatments. We have previously used the non-viral piggyBac transposon system to gene modify human T cells for potential immunotherapy. However, these previous studies utilized adoptive transfer of modified human T cells to target cancer xenografts in highly immunodeficient (NOD-SCID) mice that do not recapitulate an intact immune system. Currently, only viral vectors have shown efficacy in permanently gene-modifying mouse T cells for immunotherapy applications. Therefore, we sought to determine if piggyBac could effectively gene modify mouse T cells to target cancer cells in a mouse cancer model. We first demonstrated that we could gene modify cells to express murine interleukin-12 (p35/p40 mIL-12), a transgene with proven efficacy in melanoma immunotherapy. The OT-I melanoma mouse model provides a well-established T cell mediated immune response to ovalbumin (OVA) positive B16 melanoma cells. B16/OVA melanoma cells were implanted in wild type C57Bl6 mice. Mouse splenocytes were isolated from C57Bl6 OT-I mice and were gene modified using piggyBac to express luciferase. Adoptive transfer of luciferase-modified OT-I splenocytes demonstrated homing to B16/OVA melanoma tumors in vivo. We next gene-modified OT-I cells to express mIL-12. Adoptive transfer of mIL-12-modified mouse OT-I splenocytes delayed B16/OVA melanoma tumor growth in vivo compared to control OT-I splenocytes and improved mouse survival. Our results demonstrate that the piggyBac transposon system can be used to gene modify splenocytes and mouse T cells for evaluating adoptive immunotherapy strategies in immunocompetent mouse tumor models that may more directly mimic immunotherapy applications in humans. PMID:26473608

  4. Anti-Tumor Effects after Adoptive Transfer of IL-12 Transposon-Modified Murine Splenocytes in the OT-I-Melanoma Mouse Model

    PubMed Central

    Foster, Aaron E.; Huye, Leslie; Bear, Adham; Rooney, Cliona M.; Wilson, Matthew H.

    2015-01-01

    Adoptive transfer of gene modified T cells provides possible immunotherapy for patients with cancers refractory to other treatments. We have previously used the non-viral piggyBac transposon system to gene modify human T cells for potential immunotherapy. However, these previous studies utilized adoptive transfer of modified human T cells to target cancer xenografts in highly immunodeficient (NOD-SCID) mice that do not recapitulate an intact immune system. Currently, only viral vectors have shown efficacy in permanently gene-modifying mouse T cells for immunotherapy applications. Therefore, we sought to determine if piggyBac could effectively gene modify mouse T cells to target cancer cells in a mouse cancer model. We first demonstrated that we could gene modify cells to express murine interleukin-12 (p35/p40 mIL-12), a transgene with proven efficacy in melanoma immunotherapy. The OT-I melanoma mouse model provides a well-established T cell mediated immune response to ovalbumin (OVA) positive B16 melanoma cells. B16/OVA melanoma cells were implanted in wild type C57Bl6 mice. Mouse splenocytes were isolated from C57Bl6 OT-I mice and were gene modified using piggyBac to express luciferase. Adoptive transfer of luciferase-modified OT-I splenocytes demonstrated homing to B16/OVA melanoma tumors in vivo. We next gene-modified OT-I cells to express mIL-12. Adoptive transfer of mIL-12-modified mouse OT-I splenocytes delayed B16/OVA melanoma tumor growth in vivo compared to control OT-I splenocytes and improved mouse survival. Our results demonstrate that the piggyBac transposon system can be used to gene modify splenocytes and mouse T cells for evaluating adoptive immunotherapy strategies in immunocompetent mouse tumor models that may more directly mimic immunotherapy applications in humans. PMID:26473608

  5. A Phosphorylation-Related Variant ADD1-rs4963 Modifies the Risk of Colorectal Cancer

    PubMed Central

    Shen, Na; Liu, Cheng; Li, Jiaoyuan; Chen, Xueqin; Yang, Yang; Zhu, Ying; Gong, Yajie; Gong, Jing; Zhong, Rong; Cheng, Liming; Miao, Xiaoping

    2015-01-01

    It is well-established that abnormal protein phosphorylation could play an essential role in tumorgenesis by disrupting a variety of physiological processes such as cell growth, signal transduction and cell motility. Moreover, increasing numbers of phosphorylation-related variants have been identified in association with cancers. ADD1 (α-adducin), a versatile protein expressed ubiquitously in eukaryotes, exerts an important influence on membrane cytoskeleton, cell proliferation and cell-cell communication. Recently, a missense variant at the codon of ADD1’s phosphorylation site, rs4963 (Ser586Cys), was reported to modify the risk of non-cardia gastric cancer. To explore the role of ADD1-rs4963 in colorectal cancer (CRC), we conducted a case-control study with a total of 1054 CRC cases and 1128 matched controls in a Chinese population. After adjustment for variables including age, gender, smoking and drinking, it was demonstrated that this variant significantly conferred susceptibility to CRC (G versus C: OR = 1.16, 95% CI = 1.03–1.31, P = 0.016; CG versus CC: OR = 1.25, 95% CI = 1.02–1.55, P = 0.036; GG versus CC: OR = 1.35, 95% CI = 1.06–1.72, P = 0.015). We further investigated the interaction of ADD1-rs4963 with smoking or drinking exposure, but found no significant result. This study is the first report of an association between ADD1 and CRC risk, promoting our knowledge of the genetics of CRC. PMID:25816007

  6. Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: A genome-wide interaction study

    PubMed Central

    Rudolph, Anja; Hein, Rebecca; Lindström, Sara; Beckmann, Lars; Behrens, Sabine; Liu, Jianjun; Aschard, Hugues; Bolla, Manjeet K.; Wang, Jean; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Brüning, Thomas; Harth, Volker; Severi, Gianluca; Baglietto, Laura; Southey, Melissa; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Eriksson, Mikael; Humpreys, Keith; Darabi, Hatef; Olson, Janet E.; Stevens, Kristen N.; Vachon, Celine M.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Webb, Penny M.; Guénel, Pascal; Brauch, Hiltrud; Giles, Graham; García-Closas, Montserrat; Czene, Kamila; Chenevix-Trench, Georgia; Couch, Fergus J.; Andrulis, Irene L.; Swerdlow, Anthony; Hunter, David J.; Flesch-Janys, Dieter; Easton, Douglas F.; Hall, Per; Nevanlinna, Heli; Kraft, Peter; Chang-Claude, Jenny

    2013-01-01

    Women using menopausal hormone therapy (MHT) are at increased risk to develop breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in eleven case-control studies. We used a case-only design to assess interactions between single nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2,920 cases (541 lobular) from four genome-wide association studies. The top 1,391 SNPs showing P-values for interaction (Pint) <3.0×10−03 were selected for replication using pooled case-control data from eleven studies of the Breast Cancer Association Consortium, including 7,689 cases (676 lobular) and 9,266 controls. Fixed effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9×10−06), two SNPs in SLC25A21 (combined Pint≤4.8×10−05), and three SNPs in PLCG2 (combined Pint≤4.5×10−05). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7×10−05), one SNP in CD80 (combined Pint≤8.2×10−06), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10−06), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6×10−05). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies. PMID:24080446

  7. Lifestyle and cancer: effect of parental divorce.

    PubMed

    Hemminki, Kari; Chen, Bowang

    2006-12-01

    According to previous studies, divorced individuals have increased risks of cancers related to alcohol and tobacco consumption and sexual habits, but the increases are balanced with decreased risks of many common cancers. In the present study, cancer risks were analyzed for 0-70-year-old offspring of divorced parents, on the basis the Swedish Family-Cancer Database with cancer data from the years 1958 to 2002. We calculated standardized incidence ratios for cancer among offspring of divorced parents (19,000 cancer patients) and compared them with offspring of stably married parents (121,000 cancer patients). Standardized incidence ratios were adjusted for many factors, including socio-economic status. Offspring of divorced parents were divided into groups depending on whether their mothers, fathers or both had had children with different partners. Offspring of divorced parents had an increased risk of upper aerodigestive tract, esophageal, anal, pancreatic, lung and cervical cancers. Decreased risks were noted for Hodgkin's disease and bone cancer. For Hodgkin's disease, the data suggest protective effects through early exposure to childhood pathogens but for bone cancer mechanisms remain to be established. The overall cancer risk for offspring of divorced parents was at or above unity. The results show that offspring of divorced parents have increased cancer risks at tobacco-related, alcohol-related and sex-related sites, in analogy to their parent, but they lack decreased risks at common sites, experienced by their parents. Divorce is becoming increasingly common in many countries and any deviant cancer patterns among offspring of divorced parents will have an impact on the population risk. PMID:17106333

  8. Generation of more effective cancer vaccines

    PubMed Central

    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

  9. GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation.

    PubMed

    Cheng, Liang; Huang, Fa-Zhen; Cheng, Li-Fang; Zhu, Ya-Qin; Hu, Qing; Li, Ling; Wei, Lin; Chen, Da-Wei

    2014-01-01

    Non-small cell lung cancer (NSCLC) is a serious threat to human health, and 40%-80% of NSCLCs express high levels of epidermal growth factor receptor (EGFR). GE11 is a novel peptide and exhibits high affinity for EGFR binding. The aim of this study was to construct and evaluate GE11-modified liposomes for targeted drug delivery to EGFR-positive NSCLC. Doxorubicin, a broad-spectrum antitumor agent, was chosen as the payload. GE11 was conjugated to the distal end of DSPE-PEG2000-Mal by an addition reaction with a conjugation efficiency above 90%. Doxorubicin-loaded liposomes containing GE11 (GE11-LP/DOX) at densities ranging from 0% to 15% were prepared by combination of a thin film hydration method and a post insertion method. Irrespective of GE11 density, the physicochemical properties of these targeted liposomes, including particle size, zeta potential, and drug entrapment efficiency, were nearly identical. Interestingly, the cytotoxic effect of the liposomes on A549 tumor cells was closely related to GE11 density, and liposomes with 10% GE11 had the highest tumor cell killing activity and a 2.6-fold lower half maximal inhibitory concentration than that of the nontargeted counterpart (PEG-LP/DOX). Fluorescence microscopy and flow cytometry analysis revealed that GE11 significantly increased cellular uptake of the liposomes, which could be ascribed to specific EGFR-mediated endocytosis. It was found that multiple endocytic pathways were involved in entry of GE11-LP/DOX into cells, but GE11 assisted in cellular internalization mainly via the clathrin-mediated endocytosis pathway. Importantly, the GE11-modified liposomes showed enhanced accumulation and prolonged retention in tumor tissue, as evidenced by a 2.2-fold stronger mean fluorescence intensity in tumor tissue than the unmodified liposomes at 24 hours. In summary, GE11-modified liposomes may be a promising platform for targeted delivery of chemotherapeutic drugs in NSCLC. PMID:24611009

  10. Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

    PubMed Central

    Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B.; Rudolph, Anja; Schmutzler, Rita K.; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A.; Easton, Douglas F.; Hamann, Ute; Wilkening, Stefan; Chen, Bowang; Rookus, Matti A.; Schmidt, Marjanka K; van der Baan, Frederieke H.; Spurdle, Amanda B.; Walker, Logan C.; Lose, Felicity; Maia, Ana-Teresa; Montagna, Marco; Matricardi, Laura; Lubinski, Jan; Jakubowska, Anna; Gómez Garcia, Encarna B.; Olopade, Olufunmilayo I.; Nussbaum, Robert L.; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Arun, Banu K.; Karlan, Beth Y.; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K.; Miron, Alex; Southey, Melissa C.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Ding, Yuan Chun; Neuhausen, Susan L.; Hansen, Thomas V. O.; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martínez-Bouzas, Cristina; Benitez, Javier; Conway, Edye E.; Blazer, Kathleen R.; Weitzel, Jeffrey N.; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Martayan, Aline; Tibiletti, Maria Grazia; Radice, Paolo; Vratimos, Athanassios; Fostira, Florentia; Garber, Judy E.; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D. Gareth R.; Frost, Debra; Eccles, Diana; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E.; Kennedy, M. John; Rogers, Mark T.; Porteous, Mary E.; Morrison, Patrick J.; Platte, Radka; Davidson, Rosemarie; Hodgson, Shirley V.; Ellis, Steve; Cole, Trevor; Godwin, Andrew K.; Claes, Kathleen; Van Maerken, Tom; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wang-Gohrke, Shan; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Boutry-Kryza, Nadia; Sinilnikova, Olga M.; Caron, Olivier; Pujol, Pascal; Mazoyer, Sylvie; Belotti, Muriel; Piedmonte, Marion; Friedlander, Michael L.; Rodriguez, Gustavo C.; Copeland, Larry J; de la Hoya, Miguel; Segura, Pedro Perez; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A.M.; Meijers-Heijboer, Hanne E.J.; van der Hout, Annemarie H.; Vreeswijk, Maaike P.G.; Hoogerbrugge, Nicoline; Ausems, Margreet G.E.M.; van Doorn, Helena C.; Collée, J. Margriet; Olah, Edith; Diez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Feliubadalo, Lidia; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Arason, Adalgeir; Chiquette, Jocelyne; Teixeira, Manuel R.; Olswold, Curtis; Couch, Fergus J.; Lindor, Noralane M.; Wang, Xianshu; Szabo, Csilla I.; Offit, Kenneth; Corines, Marina; Jacobs, Lauren; Robson, Mark E.; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M.; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Mulligan, Anna Marie; Glendon, Gord; Tchatchou, Sandrine; Andrulis, Irene L.; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Laitman, Yael; Rantala, Johanna; von Wachenfeldt, Anna; Ehrencrona, Hans; Askmalm, Marie Stenmark; Borg, Åke; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D.P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Friedman, Eitan

    2014-01-01

    Background BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and non-genetic modifying factors. In this study we evaluated the putative role of variants in many candidate modifier genes. Methods Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n=3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results The observed p-values of association ranged between 0.005-1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. PMID:25336561

  11. Effect of three biological response modifiers on chemical carcinogenesis in mice.

    PubMed

    Bogdanović, Z; Culo, F; Marusić, M

    1993-01-01

    The modulation of chemical carcinogenesis by three biological response modifiers was assessed in a mouse model. CBA mice given 20-methylcholanthrene s.c. were treated with peptidoglycan monomer, azure B and indomethacin for one month, either from day 0 or 75 after methylcholanthrene injection to assess their effects on tumor incidence (on days 150 and 300), time of tumor appearance, time of death, and duration and dynamics of tumor growth. All three agents significantly influenced some of the parameters of tumor growth, except tumor incidence on day 300. Highly significant sex differences in tumor appearance and growth were observed. Tumors with late appearance grew faster in comparison to tumors with early appearance. The data presented indicate that the effectiveness of anti-cancer body defense mechanisms can be best defined by the time of tumor appearance. PMID:8272149

  12. Proteomics Analysis of Cancer Exosomes Using a Novel Modified Aptamer-based Array (SOMAscanTM) Platform*

    PubMed Central

    Webber, Jason; Stone, Timothy C.; Katilius, Evaldas; Smith, Breanna C.; Gordon, Bridget; Mason, Malcolm D.; Tabi, Zsuzsanna; Brewis, Ian A.; Clayton, Aled

    2014-01-01

    We have used a novel affinity-based proteomics technology to examine the protein signature of small secreted extracellular vesicles called exosomes. The technology uses a new class of protein binding reagents called SOMAmers® (slow off-rate modified aptamers) and allows the simultaneous precise measurement of over 1000 proteins. Exosomes were highly purified from the Du145 prostate cancer cell line, by pooling selected fractions from a continuous sucrose gradient (within the density range of 1.1 to 1.2 g/ml), and examined under standard conditions or with additional detergent treatment by the SOMAscanTM array (version 3.0). Lysates of Du145 cells were also prepared, and the profiles were compared. Housekeeping proteins such as cyclophilin-A, LDH, and Hsp70 were present in exosomes, and we identified almost 100 proteins that were enriched in exosomes relative to cells. These included proteins of known association with cancer exosomes such as MFG-E8, integrins, and MET, and also those less widely reported as exosomally associated, such as ROR1 and ITIH4. Several proteins with no previously known exosomal association were confirmed as exosomally expressed in experiments using individual SOMAmer® reagents or antibodies in micro-plate assays. Western blotting confirmed the SOMAscanTM-identified enrichment of exosomal NOTCH-3, L1CAM, RAC1, and ADAM9. In conclusion, we describe here over 300 proteins of hitherto unknown association with prostate cancer exosomes and suggest that the SOMAmer®-based assay technology is an effective proteomics platform for exosome-associated biomarker discovery in diverse clinical settings. PMID:24505114

  13. Classifying linearly shielded modified gravity models in effective field theory.

    PubMed

    Lombriser, Lucas; Taylor, Andy

    2015-01-23

    We study the model space generated by the time-dependent operator coefficients in the effective field theory of the cosmological background evolution and perturbations of modified gravity and dark energy models. We identify three classes of modified gravity models that reduce to Newtonian gravity on the small scales of linear theory. These general classes contain enough freedom to simultaneously admit a matching of the concordance model background expansion history. In particular, there exists a large model space that mimics the concordance model on all linear quasistatic subhorizon scales as well as in the background evolution. Such models also exist when restricting the theory space to operators introduced in Horndeski scalar-tensor gravity. We emphasize that whereas the partially shielded scenarios might be of interest to study in connection with tensions between large and small scale data, with conventional cosmological probes, the ability to distinguish the fully shielded scenarios from the concordance model on near-horizon scales will remain limited by cosmic variance. Novel tests of the large-scale structure remedying this deficiency and accounting for the full covariant nature of the alternative gravitational theories, however, might yield further insights on gravity in this regime. PMID:25658988

  14. Individual Effect Modifiers of Dust Exposure Effect on Cardiovascular Morbidity

    PubMed Central

    Vodonos, Alina; Friger, Michael; Katra, Itzhak; Krasnov, Helena; Zahger, Doron; Schwartz, Joel; Novack, Victor

    2015-01-01

    Background High concentrations of particulate matter (PM) air pollution have been associated with death and hospital admissions due to cardiovascular morbidity. However, it is not clear a) whether high levels of non-anthropogenic PM from dust storms constitute a health risk; and b) whether these health risks are exacerbated in a particular demographic. Methods This study comprised all patients above 18 years old admitted to Soroka University Medical Center (1000 bed tertiary hospital, Be’er- Sheva, Israel, 2001–2010) with a primary diagnosis of acute coronary syndrome (ACS). Data on meteorological parameters and PM10 (particulate matter <10 μm in aerodiameter) were obtained from monitoring stations in the city of Be'er-Sheva. Data were analyzed using a case crossover analysis to examine the effect of dust exposure on hospitalization due to ACS and the interaction with co-morbidities and demographic factors. Results There were 16,734 hospitalizations due to ACS during the study period. The estimated odds of hospitalization due to ACS was significantly associated with PM10 during non dust storm days at the same day of the exposure (lag0); OR = 1.014 (95%CI 1.001–1.027) for a 10 μg/m3 increase, while a delayed response (lag1) was found during the dust storm days; OR = 1.007 (95%CI 1.002–1.012). The effect size for the dust exposure association was larger for older (above the age of 65), female or Bedouin patients. Conclusions Exposure to non-anthropogenic PM is associated with cardiovascular morbidity. Health risk associated dust exposure is gender and age specific with older women and Bedouin patients being the most vulnerable groups. PMID:26381397

  15. Rapid, Effective DNA Isolation from Osmanthus via Modified Alkaline Lysis.

    PubMed

    Alexander, Lisa

    2016-07-01

    Variability of leaf structure and presence of secondary metabolites in mature leaf tissue present a challenge for reliable DNA extraction from Osmanthus species and cultivars. The objective of this study was to develop a universal rapid, effective, and cost-efficient method of DNA isolation for Osmanthus mature leaf tissue. Four different methods were used to isolate DNA from 8 cultivars of Osmanthus. Absorbance spectra, DNA concentration, appearance on agarose gel, and performance in PCR were used to analyze quality, quantity, and integrity of isolated DNA. Methods were ranked in order, based on total quantity, quality, and performance points as the following: 1) solid-phase extraction (SPE), 2) modified alkaline lysis (SDS), 3) cetyltrimethylammonium bromide (CTAB) with chloroform (CHL), and 4) CTAB with phenol/chloroform (PHE). Total DNA, isolated via SPE, showed the least contamination but the lowest mean quantity (9.6 ± 3.4 μg) and highest cost. The highest quantity of DNA was isolated via SDS (117 ± 54.1 μg). SPE and SDS resolved the most individuals on agarose gel, whereas the 2 CTAB methods had poorly resolved gels. All methods except PHE performed well in PCR. Additions to the modified alkaline lysis method increased A260:A230 by up to 59% without affecting yield. With the use of SDS, an average of 1000 μg/g DNA was isolated from fresh leaf tissue of 18 samples in ∼1.5 h at a cost of 0.74 U.S. dollars (USD)/sample. We recommend improved alkaline lysis as a rapid, effective, and cost-efficient method of isolating DNA from Osmanthus species. PMID:26816495

  16. Rapid, Effective DNA Isolation from Osmanthus via Modified Alkaline Lysis

    PubMed Central

    2016-01-01

    Variability of leaf structure and presence of secondary metabolites in mature leaf tissue present a challenge for reliable DNA extraction from Osmanthus species and cultivars. The objective of this study was to develop a universal rapid, effective, and cost-efficient method of DNA isolation for Osmanthus mature leaf tissue. Four different methods were used to isolate DNA from 8 cultivars of Osmanthus. Absorbance spectra, DNA concentration, appearance on agarose gel, and performance in PCR were used to analyze quality, quantity, and integrity of isolated DNA. Methods were ranked in order, based on total quantity, quality, and performance points as the following: 1) solid-phase extraction (SPE), 2) modified alkaline lysis (SDS), 3) cetyltrimethylammonium bromide (CTAB) with chloroform (CHL), and 4) CTAB with phenol/chloroform (PHE). Total DNA, isolated via SPE, showed the least contamination but the lowest mean quantity (9.6 ± 3.4 μg) and highest cost. The highest quantity of DNA was isolated via SDS (117 ± 54.1 μg). SPE and SDS resolved the most individuals on agarose gel, whereas the 2 CTAB methods had poorly resolved gels. All methods except PHE performed well in PCR. Additions to the modified alkaline lysis method increased A260:A230 by up to 59% without affecting yield. With the use of SDS, an average of 1000 μg/g DNA was isolated from fresh leaf tissue of 18 samples in ∼1.5 h at a cost of 0.74 U.S. dollars (USD)/sample. We recommend improved alkaline lysis as a rapid, effective, and cost-efficient method of isolating DNA from Osmanthus species. PMID:26816495

  17. Modified effective range analysis of electron scattering from krypton

    NASA Astrophysics Data System (ADS)

    Fedus, Kamil

    2014-10-01

    The elastic cross sections for electron scattering on krypton from zero energy up to 10 eV have been analyzed by the modified effective range method. A simple model based on the analytical solution of the Schrödinger equation with the polarization potential using explicitly determined scattering phase shifts for the three lowest partial waves describes the elastic differential, integral and momentum transfer cross sections up to the energy threshold of the first inelastic process well. In detail, the contribution of the long-range polarization potential to the scattering phase shift is exactly expressed, while the contribution of the short-range effects is modelled by simple quadratic expressions (the effective range expansions). The effective range parameters are determined empirically by comparison with the latest experimental differential cross sections. Presently, the calculated integral and momentum transfer cross sections are validated against numerous electron scattering experiments and the most recent quantum-mechanical theories. To complete the picture, the two-term Boltzmann analysis is employed to determine the electron transport coefficients; the agreement with the electron swarm experimental data is found to be very good.

  18. MATERNAL EFFECTS IN ADVANCED HYBRIDS OF GENETICALLY MODIFIED AND NON-GENETICALLY MODIFIED BRASSICA SPECIES

    EPA Science Inventory

    Identification of fitness traits potentially impacted by gene flow from genetically modified (GM) crops to compatible relatives is of interest in risk assessments for GM crops. Reciprocal crosses were made between GM canola, Brassica napus cv. RaideRR that expresses CP4 EPSPS fo...

  19. Socioeconomic Status Modifies the Seasonal Effect on Blood Pressure

    PubMed Central

    Cois, Annibale; Ehrlich, Rodney

    2015-01-01

    Abstract Seasonal variations in blood pressure have been consistently reported. However, uncertainty remains about the size of the seasonal effect in different regions, and about factors that explain the differences observed across and within populations. Using data from a national panel study, we investigated seasonal variations in blood pressure in the South African adult population, and whether these variations differed across socioeconomic strata. We estimated age-specific seasonal effects on blood pressure using a multilevel structural equation model, with repeated measurements nested within subjects. Effect modification by socioeconomic status was assessed by repeating the analyses in the subpopulations defined by levels of education, household income per capita, and type of housing. In men and women, season had a statistically significant effect on blood pressure, with higher levels in winter and lower levels in summer. For systolic blood pressure, the magnitude of the seasonal effect was 4.25/4.21 mmHg (women/men) and was higher in the older age groups. For diastolic blood pressure, the effect size was 4.00/4.01 mmHg, with no evident age trend. Seasonal effects were higher among subjects in the lowest socioeconomic classes than in the highest, with differences between 2.4 and 7.7 mmHg, depending on gender, whether systolic or diastolic blood pressure, and socioeconomic status indicator. In the South African adult population, blood pressure shows seasonal variation modified by age and socioeconomic status. These variations have epidemiological, clinical, and public health implications, including the prospect of population level intervention to reduce elevated risk of cold weather cardiovascular morbidity. PMID:26334893

  20. Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers

    PubMed Central

    Wang, Xianshu; Pankratz, V. Shane; Fredericksen, Zachary; Tarrell, Robert; Karaus, Mary; McGuffog, Lesley; Pharaoh, Paul D.P.; Ponder, Bruce A.J.; Dunning, Alison M.; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Houdayer, Claude; Hogervorst, Frans B.L.; Hooning, Maartje J.; Ligtenberg, Marjolijn J.; Spurdle, Amanda; Chenevix-Trench, Georgia; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Singer, Christian F.; Gschwantler-Kaulich, Daphne; Dressler, Catherina; Fink, Anneliese; Szabo, Csilla I.; Zikan, Michal; Foretova, Lenka; Claes, Kathleen; Thomas, Gilles; Hoover, Robert N.; Hunter, David J.; Chanock, Stephen J.; Easton, Douglas F.; Antoniou, Antonis C.; Couch, Fergus J.

    2010-01-01

    Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these risk modifiers were originally identified as genetic risk factors for breast cancer in genome-wide association studies (GWASs), additional risk modifiers for BRCA1 and BRCA2 may be identified from promising signals discovered in breast cancer GWAS. A total of 350 SNPs identified as candidate breast cancer risk factors (P < 1 × 10−3) in two breast cancer GWAS studies were genotyped in 3451 BRCA1 and 2006 BRCA2 mutation carriers from nine centers. Associations with breast cancer risk were assessed using Cox models weighted for penetrance. Eight SNPs in BRCA1 carriers and 12 SNPs in BRCA2 carriers, representing an enrichment over the number expected, were significantly associated with breast cancer risk (Ptrend < 0.01). The minor alleles of rs6138178 in SNRPB and rs6602595 in CAMK1D displayed the strongest associations in BRCA1 carriers (HR = 0.78, 95% CI: 0.69–0.90, Ptrend = 3.6 × 10−4 and HR = 1.25, 95% CI: 1.10–1.41, Ptrend = 4.2 × 10−4), whereas rs9393597 in LOC134997 and rs12652447 in FBXL7 showed the strongest associations in BRCA2 carriers (HR = 1.55, 95% CI: 1.25–1.92, Ptrend = 6 × 10−5 and HR = 1.37, 95% CI: 1.16–1.62, Ptrend = 1.7 × 10−4). The magnitude and direction of the associations were consistent with the original GWAS. In subsequent risk assessment studies, the loci appeared to interact multiplicatively for breast cancer risk in BRCA1 and BRCA2 carriers. Promising candidate SNPs from GWAS were identified as modifiers of breast cancer risk in BRCA1 and BRCA2 carriers. Upon further validation, these SNPs together with other genetic and environmental factors may improve breast cancer risk assessment in these populations. PMID:20418484

  1. Interleukin-2 administration after modified radical mastectomy in breast cancer therapy increases peripheral regulatory T cells

    PubMed Central

    Li, Yunli; Zhou, Lei; Sun, Bei; Li, Xiaoxiao; Duan, Kaiming; Wu, Yuhui; Ouyang, Wen

    2015-01-01

    Background: Breast cancer (BC) deaths are a major concern worldwide, and modified radical mastectomy (MRM) still represents a primary therapeutic strategy. Post-surgery administration of interleukin (IL)-2 for BC therapy has been implemented in China recently. Although its impact on regulatory T cells (Tregs) has been documented in some cancer types, such as melanoma, the IL-2-mediated changes in the Treg composition after MRM in BC treatment remain unknown. Methods: As registered with the Chinese Clinical Trial Registry, 34 newly diagnosed BC patients, aged 20-65 years, were enrolled in this trial. Patients were randomized to the IL-2-treated group (n=15) and the untreated control group (n=19). Peripheral blood mononuclear cells were isolated at time points of pre-operation (PreOP) and post-operation Day 1 (POD1), POD3, and POD7. Cells were subjected to flow cytometric assays to identify CD4+ CD25+ Foxp3+ Tregs, as well as real-time quantitative polymerase chain reaction analysis of FOXP3 expression. Results: We found that the surgery caused a significant decrease in the percentage of Tregs on POD1, followed by a significant increase characterized by a peak value on POD7 with a more than 18% increase relative to the Pre-OP levels. We observed that the Treg percentages in the IL-2-treated group were significantly greater than those in the control group on POD3 and POD7, whereas no such statistical difference was observed on POD1. The FOXP3 expression analysis revealed consistent trends as observed by flow cytometry. Conclusions: Post-operative administration of IL-2 amplifies the surgery-induced augmentation of both Tregs and FOXP3 expression in BC therapy. PMID:26221334

  2. Modified gold nanoparticles for intracellular delivery of anti-liver cancer siRNA.

    PubMed

    Shaat, Hanan; Mostafa, Amany; Moustafa, Moustafa; Gamal-Eldeen, Amira; Emam, Ahmed; El-Hussieny, Enas; Elhefnawi, Mahmoud

    2016-05-17

    To overcome the rapid enzymatic degradation and low transfection efficiency of siRNA, the delivery carriers for siRNA is a therapeutic demand to increase its stability. Gold nanoparticles (AuNPs) modified by branched polyethyleneimine (bPEI) were developed as an efficient and safe intracellular delivery carriers for siRNA. The current study implied that siRNA designed against an oncogene c-Myc could be delivered by a modified AuNPs complex without significant cytotoxicity. The comparative semi-quantitative and quantitative real time PCR were used to measure the c-Myc gene expression after transfection with naked siRNA and siRNA/bPEI/AuNPs, but AuNPs interfered with PCR. However, the c-Myc protein translation was successfully detected in the transfected HuH7 cells with naked siRNA and siRNA/bPEI/AuNPs and it was found to be inhibited by siRNA/bPEI/AuNPs more than naked siRNA. The results validate the successful silencing of c-Myc gene. Accordingly, it may confirm the promising and effective delivery of siRNA by bPEI/AuNPs. The complex enhances the cellular uptake of siRNA without significant cytotoxicity and confirms that bPEI modified AuNPs could be used as a good candidate for safe cellular delivery of siRNA. PMID:27036397

  3. Modified international e-Delphi survey to define healthcare professional competencies for working with teenagers and young adults with cancer

    PubMed Central

    Taylor, Rachel M; Feltbower, Richard G; Aslam, Natasha; Raine, Rosalind; Whelan, Jeremy S; Gibson, Faith

    2016-01-01

    Objectives To provide international consensus on the competencies required by healthcare professionals in order to provide specialist care for teenagers and young adults (TYA) with cancer. Design Modified e-Delphi survey. Setting International, multicentre study. Participants Experts were defined as professionals having worked in TYA cancer care for more than 12 months. They were identified through publications and professional organisations. Methods Round 1, developed from a previous qualitative study, included 87 closed-ended questions with responses on a nine-point Likert scale and further open-ended responses to identify other skills, knowledge and attitudes. Round 2 contained only items with no consensus in round 1 and suggestions of additional items of competency. Consensus was defined as a median score ranging from 7 to 9 and strength of agreement using mean absolute deviation of the median. Results A total of 179 registered to be members of the expert panel; valid responses were available from 158 (88%) in round 1 and 136/158 (86%) in round 2. The majority of participants were nurses (35%) or doctors (39%) from Europe (55%) or North America (35%). All 87 items in round 1 reached consensus with an additional 15 items identified for round 2, which also reached consensus. The strength of agreement was mostly high for statements. The areas of competence rated most important were agreed to be: ‘Identify the impact of disease on young people's life’ (skill), ‘Know about side effects of treatment and how this might be different to those experienced by children or older adults’ (knowledge), ‘Honesty’ (attitude) and ‘Listen to young people's concerns’ (aspect of communication). Conclusions Given the high degree of consensus, this list of competencies should influence education curriculum, professional development and inform workforce planning. Variation in strength of agreement for some competencies between professional groups should be explored

  4. Vitamin D receptor gene polymorphism as an important modifier of positive family history related breast cancer risk.

    PubMed

    Sillanpää, Pia; Hirvonen, Ari; Kataja, Vesa; Eskelinen, Matti; Kosma, Veli-Matti; Uusitupa, Matti; Vainio, Harri; Mitrunen, Katja

    2004-04-01

    The association between vitamin D receptor (VDR) gene polymorphisms and diseases such as breast cancer, prostate cancer and osteoporosis has been extensively investigated during recent years. To date, several polymorphisms have been found in the VDR gene. In this Finnish case-control study, comprising 483 breast cancer patients and 482 healthy population controls, we investigated the association between altered breast cancer risk and two polymorphisms in the 3' end of the gene detectable with ApaI and TaqI restriction enzymes. A statistically significant difference was observed in the ApaI genotype distribution between cases and controls. Women with the VDR variant a allele containing genotypes showed a decreased risk for breast cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.54-0.98] compared to women with the AA genotype. This association was especially strong among women with a positive family history of breast cancer (OR 0.14, 95% CI 0.03-0.76). Moreover, there was a trend (P for trend = 0.0007) for decreased risk with increasing number of variant alleles. The lowest risk of breast cancer was seen for the women with the aa genotype (OR 0.03, 95% CI 0.003-0.31) compared to women with the AA genotype. A tendency of decreased risk of breast cancer was also observed for the TaqI T allele containing genotypes (Tt and TT) (OR 0.68, 95% CI 0.41-1.12), but because the distribution of Taql alleles in the controls missed the Hardy-Weinberg equilibrium (P = 0.01), we were unable to properly assess the potential impact of the TaqI polymorphism in breast cancer susceptibility. In conclusion, our results suggest that the VDR ApaI genotype may be an important modifier of individual breast cancer risk among Finnish women, especially if they have a positive family history of breast cancer. PMID:15083068

  5. Treatment of childhood cancers: late effects.

    PubMed

    2015-10-01

    In France, about 1 in 1000 young adults aged 20 to 30 years is a survivor of childhood cancer and is thus faced with late effects of their cancer and its treatment (radiation therapy and/or chemotherapy). What are the late effects of childhood cancer therapy? A systematic review by the Scottish Intercollegiate Guidelines Network (SIGN) provides useful information based on European and North American data. Cancer treatments can have many long-term consequences that depend on the drugs and doses used, radiation therapy protocols and irradiated organs, and age at the time of treatment. Cytotoxic drugs and radiation can both cause infertility. Abdominopelvic radiation therapy in girls has been linked to an increased risk of premature delivery and other complications of pregnancy. No increase in birth defects has been reported among children born to childhood cancer survivors. Anthracyclines and radiation therapy can cause cardiomyopathy. Neck irradiation can lead to thyroid disorders, and cranial irradiation to growth retardation. Chemotherapy can cause osteonecrosis and loss of bone density, but without an increased risk of fracture. The risk of cognitive impairment and structural abnormalities of the brain is higher when the child is younger or receives a high cumulative dose of cranial irradiation or total irradiation dosage. Some cytotoxic drugs can damage the kidneys. Cranial radiation therapy can cause long-term neuroendocrine disorders and growth disorders, especially when the dose exceeds 18 Gy. Cytotoxic drugs (alkylating agents, etoposide, etc.) and radiation therapy can cause second cancers of a different histological type. One analysis of second cancers showed a median time to onset of 7 years for solid tumours and 2.5 years for lymphoma and leukaemia. Better knowledge of the late effects of childhood cancer therapy can help orient the choice of treatment towards less harmful options or, if necessary, implement measures aimed at preventing late adverse

  6. Lung cancer biomarkers for the assessment of modified risk tobacco products: an oxidative stress perspective

    PubMed Central

    Luettich, Karsta; Gregg, Evan O.

    2013-01-01

    Manufacturers have developed prototype cigarettes yielding reduced levels of some tobacco smoke toxicants, when tested using laboratory machine smoking under standardised conditions. For the scientific assessment of modified risk tobacco products, tests that offer objective, reproducible data, which can be obtained in a much shorter time than the requirements of conventional epidemiology are needed. In this review, we consider whether biomarkers of biological effect related to oxidative stress can be used in this role. Based on published data, urinary 8-oxo-7,8-dihydro-2-deoxyguanosine, thymidine glycol, F2-isoprostanes, serum dehydroascorbic acid to ascorbic acid ratio and carotenoid concentrations show promise, while 4-hydroxynonenal requires further qualification. PMID:23530763

  7. [Assessment of Cachexia in Head and Neck Cancer Patients Based on a Modified Glasgow Prognostic Score].

    PubMed

    Matsuzuka, Takashi; Suzuki, Masahiro; Saijoh, Satoshi; Ikeda, Masakazu; Imaizumi, Mitsumasa; Nomoto, Yukio; Matsui, Takamichi; Tada, Yasuhiro; Omori, Koichi

    2016-02-01

    We retrospectively analyzed 54 patients who died of head and neck squamous cell caricinoma regarding the process and duration of cachexia using the modified Glasgow Prognostic Score (mGPS). The patients were classified as having cachexia when the serum albumin level was less than 3.5 mg/dL and the C-reactive protein (CRP) level was more than 0.5 mg/dL. The number of patients with cachexia was eight (8%) at the first visit and 50 (93%) at the time of death. In the 50 patients, the median and average time of having cachexia was 59 and 95 days, respectively. Thirty-two of the 50 patients (64%) died within three months after the presence of cachexia was confirmed. In this study, the time of having cachexia was so short, then the policy of care should be converted from aggressive into supportive in patients classified as having cachexia. mGPS would be an accurate assessment tool for cachexia and ascertain the end stage of head and neck cancer patients. PMID:27149710

  8. Genetic modifiers of EGFR dependence in non-small cell lung cancer

    PubMed Central

    Sharifnia, Tanaz; Rusu, Victor; Piccioni, Federica; Bagul, Mukta; Imielinski, Marcin; Cherniack, Andrew D.; Pedamallu, Chandra Sekhar; Wong, Bang; Wilson, Frederick H.; Garraway, Levi A.; Altshuler, David; Golub, Todd R.; Root, David E.; Subramanian, Aravind; Meyerson, Matthew

    2014-01-01

    Lung adenocarcinomas harboring activating mutations in the epidermal growth factor receptor (EGFR) represent a common molecular subset of non-small cell lung cancer (NSCLC) cases. EGFR mutations predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs) and thus represent a dependency in NSCLCs harboring these alterations, but the genetic basis of EGFR dependence is not fully understood. Here, we applied an unbiased, ORF-based screen to identify genetic modifiers of EGFR dependence in EGFR-mutant NSCLC cells. This approach identified 18 kinase and kinase-related genes whose overexpression can substitute for EGFR in EGFR-dependent PC9 cells, and these genes include seven of nine Src family kinase genes, FGFR1, FGFR2, ITK, NTRK1, NTRK2, MOS, MST1R, and RAF1. A subset of these genes can complement loss of EGFR activity across multiple EGFR-dependent models. Unbiased gene-expression profiling of cells overexpressing EGFR bypass genes, together with targeted validation studies, reveals EGFR-independent activation of the MEK-ERK and phosphoinositide 3-kinase (PI3K)-AKT pathways. Combined inhibition of PI3K-mTOR and MEK restores EGFR dependence in cells expressing each of the 18 EGFR bypass genes. Together, these data uncover a broad spectrum of kinases capable of overcoming dependence on EGFR and underscore their convergence on the PI3K-AKT and MEK-ERK signaling axes in sustaining EGFR-independent survival. PMID:25512530

  9. Effects of modified atmosphere on crop productivity and mineral content

    NASA Astrophysics Data System (ADS)

    Chagvardieff, P.; Dimon, B.; Souleimanov, A.; Massimino, D.; Le Bras, S.; Péan, M.; Louche-Teissandier, D.

    1997-01-01

    Wheat, potato, pea and tomato crops were cultivated from seeding to harvest in a controlled and confined growth chamber at elevated CO_2 concentration (3700 muL.L^-1) to examine the effects on biomass production and edible part yields. Different responses to high CO_2 were recorded, ranging from a decline in productivity for wheat, to slight stimulation for potatoes, moderate increase for tomatoes, and very large enhancement for pea. Mineral content in wheat and pea seeds was not greatly modified by the elevated CO_2. Short-term experiments (17 d) were conducted on potato at high (3700 muL.L^-1) and very high (20,000 muL.L^-1) CO_2 concentration and/or low O_2 partial pressure (~ 20,600 muL.L^-1 or 2 kPa). Low O_2 was more effective than high CO_2 in total biomass accumulation, but development was affected: Low O_2 inhibited tuberization, while high CO_2 significantly increased production of tubers.

  10. Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk

    PubMed Central

    Vijai, Joseph; Klein, Robert J.; Kirchhoff, Tomas; McGuffog, Lesley; Barrowdale, Daniel; Dunning, Alison M.; Lee, Andrew; Dennis, Joe; Healey, Sue; Dicks, Ed; Soucy, Penny; Sinilnikova, Olga M.; Pankratz, Vernon S.; Wang, Xianshu; Eldridge, Ronald C.; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Hogervorst, Frans B. L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Schmutzler, Rita K.; Nathanson, Katherine L.; Piedmonte, Marion; Singer, Christian F.; Thomassen, Mads; Hansen, Thomas v. O.; Neuhausen, Susan L.; Blanco, Ignacio; Greene, Mark H.; Garber, Judith; Weitzel, Jeffrey N.; Andrulis, Irene L.; Goldgar, David E.; D'Andrea, Emma; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; van Rensburg, Elizabeth J.; Arason, Adalgeir; Rennert, Gad; van den Ouweland, Ans M. W.; van der Hout, Annemarie H.; Kets, Carolien M.; Aalfs, Cora M.; Wijnen, Juul T.; Ausems, Margreet G. E. M.; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Jacobs, Chris; Adlard, Julian; Tischkowitz, Marc; Porteous, Mary E.; Damiola, Francesca; Golmard, Lisa; Barjhoux, Laure; Longy, Michel; Belotti, Muriel; Ferrer, Sandra Fert; Mazoyer, Sylvie; Spurdle, Amanda B.; Manoukian, Siranoush; Barile, Monica; Genuardi, Maurizio; Arnold, Norbert; Meindl, Alfons; Sutter, Christian; Wappenschmidt, Barbara; Domchek, Susan M.; Pfeiler, Georg; Friedman, Eitan; Jensen, Uffe Birk; Robson, Mark; Shah, Sohela; Lazaro, Conxi; Mai, Phuong L.; Benitez, Javier; Southey, Melissa C.; Schmidt, Marjanka K.; Fasching, Peter A.; Peto, Julian; Humphreys, Manjeet K.; Wang, Qin; Michailidou, Kyriaki; Sawyer, Elinor J.; Burwinkel, Barbara; Guénel, Pascal; Bojesen, Stig E.; Milne, Roger L.; Brenner, Hermann; Lochmann, Magdalena; Aittomäki, Kristiina; Dörk, Thilo; Margolin, Sara; Mannermaa, Arto; Lambrechts, Diether; Chang-Claude, Jenny; Radice, Paolo; Giles, Graham G.; Haiman, Christopher A.; Winqvist, Robert; Devillee, Peter; García-Closas, Montserrat; Schoof, Nils; Hooning, Maartje J.; Cox, Angela; Pharoah, Paul D. P.; Jakubowska, Anna; Orr, Nick; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Hall, Per; Couch, Fergus J.; Simard, Jacques; Altshuler, David; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Offit, Kenneth

    2013-01-01

    Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80–0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical

  11. Menopausal Status Modifies Breast Cancer Risk Associated with the Myeloperoxidase (MPO) G463A Polymorphism in Caucasian Women: A Meta-Analysis

    PubMed Central

    Pabalan, Noel; Jarjanazi, Hamdi; Sung, Lillian; Li, Hong; Ozcelik, Hilmi

    2012-01-01

    Background Breast cancer susceptibility may be modulated partly through polymorphisms in oxidative enzymes, one of which is myeloperoxidase (MPO). Association of the low transcription activity variant allele A in the G463A polymorphism has been investigated for its association with breast cancer risk, considering the modifying effects of menopausal status and antioxidant intake levels of cases and controls. Methodology/Principal Findings To obtain a more precise estimate of association using the odds ratio (OR), we performed a meta-analysis of 2,975 cases and 3,427 controls from three published articles of Caucasian populations living in the United States. Heterogeneity among studies was tested and sensitivity analysis was applied. The lower transcriptional activity AA genotype of MPO in the pre-menopausal population showed significantly reduced risk (OR 0.56–0.57, p = 0.03) in contrast to their post-menopausal counterparts which showed non-significant increased risk (OR 1.14; p = 0.34–0.36). High intake of antioxidants (OR 0.67–0.86, p = 0.04–0.05) and carotenoids (OR 0.68–0.86, p = 0.03–0.05) conferred significant protection in the women. Stratified by menopausal status, this effect was observed in pre-menopausal women especially those whose antioxidant intake was high (OR 0.42–0.69, p = 0.04). In post-menopausal women, effect of low intake elicited susceptibility (OR 1.19–1.67, p = 0.07–0.17) to breast cancer. Conclusions/Significance Based on a homogeneous Caucasian population, the MPO G463A polymorphism places post-menopausal women at risk for breast cancer, where this effect is modified by diet. PMID:22427832

  12. Modifiable Risk of Breast Cancer in Northeast Iran: Hope for the Future. A Case-Control Study.

    PubMed

    Motie, Mohammad R; Besharat, Sima; Torkjazi, Reza; Shojaa, Mahdieh; Besharat, Mahsa; Keshtkar, Abbasali; Roshandel, Gholamreza; Besharat, Saba; Fateme, Arab Ameri

    2011-12-01

    BACKGROUND: Breast cancer is the most common cancer in women. Its prevalence is increasing annually by 2%. The determination of modifiable risk factors has been the subject of various studies. The aim of this study was to determine risk factors of breast cancer in women in Golestan Province. PATIENTS AND METHODS: This case-control study was conducted among women with breast cancer recorded in the cancer registry system between 2004 and 2006 (n = 134), and their age-matched healthy neighbors (n = 133). Data were statistically analyzed. RESULTS: Age at marriage, menarche and pregnancy, breast feeding, positive family history, marital status, and educational level were not significantly correlated with risk of breast cancer, but age at menopause (< 46.6 years) was significantly correlated (95% confidence interval 1.15-7.37; p = 0.021). Live births, still births, and infant deaths were not significantly different between the 2 groups. For other variables, such as smoking history, no odds ratio was calculated. CONCLUSION: Results show that there is no significant correlation between variables and risk of breast cancer in our population, except for age at menopause. A large cohort study is recommended. PMID:22419899

  13. Effects of Using Modified Items to Test Students with Persistent Academic Difficulties

    ERIC Educational Resources Information Center

    Elliott, Stephen N.; Kettler, Ryan J.; Beddow, Peter A.; Kurz, Alexander; Compton, Elizabeth; McGrath, Dawn; Bruen, Charles; Hinton, Kent; Palmer, Porter; Rodriguez, Michael C.; Bolt, Daniel; Roach, Andrew T.

    2010-01-01

    This study investigated the effects of using modified items in achievement tests to enhance accessibility. An experiment determined whether tests composed of modified items would reduce the performance gap between students eligible for an alternate assessment based on modified achievement standards (AA-MAS) and students not eligible, and the…

  14. Modifying effect of the County Level Health Indices on Cardiopulmonary Effects Associated with Wildfire Exposure

    EPA Science Inventory

    Background and Aims: Socioeconomic status (SES) is a known risk factor for cardiopulmonary health and some studies suggest SES may be an effect modifier for health effects associated with exposure to air pollution. We investigated the synergistic impact of health disparities on ...

  15. Hyaluronic Acid Modified Hollow Prussian Blue Nanoparticles Loading 10-hydroxycamptothecin for Targeting Thermochemotherapy of Cancer

    PubMed Central

    Jing, Lijia; shao, shangmin; Wang, Yang; Yang, Yongbo; Yue, Xiuli; Dai, Zhifei

    2016-01-01

    This paper reported the fabrication of a multifunctional nanoplatform by modifying hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene glycol, followed by loading 10-hydroxycamptothecin for tumor-targeted thermochemotherapy. It was found that the surface modification of hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene endowed a great colloidal stability, long blood circulation time and the capability for targeting Hela cells over-expressing the CD44 receptor. The obtained nanoagent exhibited efficient photothermal effect and a light triggered and stepwise release behavior of 10-hydroxycamptothecin due to the strong optical absorption in the near-infrared region. The investigations on the body weight change, histological injury and blood biochemical indexes showed that such nanoagent had excellent biocompatibility for medical application. Both in vitro and in vivo experiments proved that the combination of chemotherapy and photothermal therapy through the agent of hyaluronic acid modified Prussian blue nanoparticles loading 10-hydroxycamptothecin could significantly improve the therapeutic efficacy compared with either therapy alone because of a good synergetic effect. PMID:26722372

  16. Ferrocene-Modified Phospholipid: An Innovative Precursor for Redox-Triggered Drug Delivery Vesicles Selective to Cancer Cells.

    PubMed

    Noyhouzer, Tomer; L'Homme, Chloé; Beaulieu, Isabelle; Mazurkiewicz, Stephanie; Kuss, Sabine; Kraatz, Heinz-Bernhard; Canesi, Sylvain; Mauzeroll, Janine

    2016-05-01

    Controlled payload release is one of the key elements in the creation of a reliable drug delivery system. We report the discovery of a drug delivery vessel able to transport chemotherapeutic agents to target cancer cells and selectively trigger their release using the electrochemical activity of a ferrocene-modified phospholipid. Supported by in vitro assays, the competitive advantages of this discovery are (i) the simple one step scalability of the synthetic process, (ii) the stable encapsulation of toxic drugs (doxorubicin) during transport, and (iii) the selective redox triggering of the liposomes to harness their cytotoxic payload at the cancer site. Specifically, the redox-modified giant unilamellar vesicle and liposomes were characterized using advanced methods such as scanning electrochemical microscopy (SECM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and fluorescent imaging. PMID:26987014

  17. Paradoxical effects of antioxidants on cancer.

    PubMed

    Mendelsohn, Andrew R; Larrick, James W

    2014-06-01

    Antioxidants have had a checkered history concerning their reported ability to prevent or treat cancer. Early studies that showed ascorbate had benefit in cancer were followed by more definitive studies that demonstrated no benefit. Recent work suggests that biological context may be key to predicting whether antioxidants impede or even promote tumorigenesis. In a recent report, the antioxidants N-acetylcysteine and vitamin E accelerated tumorigenesis of lung cancer in mice. antioxidants decrease reactive oxygen species (ROS) levels, which paradoxically increase the proliferation rate of lung cancer cells, resulting in greater tumor burdens and reduced survival. Increased proliferation rates result from decreased expression of the genomic watchdog protein p53. In mice lacking p53, neither anti-oxidant affects tumor growth. But antioxidants can be used to kill cancer, at least in rodents. High concentrations of the "antioxidant" ascorbate, achievable only by injection in vivo, result in the production of ascorbate radicals and hydrogen peroxide in the extracellular fluid that kills cancer cells, but not normal cells. In preliminary human trials, ascorbate reduced the toxicity of chemotherapy, but showed no statistical benefit on disease progression. Vitamin C is beneficial when it acts as an oxidant. These studies are consistent with others that suggest that even tumor suppressor genes, such as Nrf2, which stimulate innate cellular stress protection pathways that reduce ROS, can promote cancer progression. Nrf2 is required for the cancer preventive effects of compounds such as sulforaphane, but Nrf2 can help maintain an aggressive tumor phenotype by stimulating proliferation and offering protection from chemotherapy. Context determines whether a specific gene is a tumor enhancer or a suppressor. Such paradoxical behavior creates difficult problems for the development of conventional therapeutics to fight cancer. Personal genomic analysis may provide the means to

  18. Testosterone regulates thyroid cancer progression by modifying tumor suppressor genes and tumor immunity

    PubMed Central

    Zhang, Lisa J.; Xiong, Yin; Nilubol, Naris; He, Mei; Bommareddi, Swaroop; Zhu, Xuguang; Jia, Li; Xiao, Zhen; Park, Jeong-Won; Xu, Xia; Patel, Dhaval; Willingham, Mark C.; Cheng, Sheue-yann; Kebebew, Electron

    2015-01-01

    Cancer gender disparity has been observed for a variety of human malignancies. Thyroid cancer is one such cancer with a higher incidence in women, but more aggressive disease in men. There is scant evidence on the role of sex hormones on cancer initiation/progression. Using a transgenic mouse model of follicular thyroid cancer (FTC), we found castration led to lower rates of cancer in females and less advanced cancer in males. Mechanistically, less advanced cancer in castrated males was due to increased expression of tumor suppressor (Glipr1, Sfrp1) and immune-regulatory genes and higher tumor infiltration with M1 macrophages and CD8 cells. Functional study showed that GLIPR1 reduced cell growth and increased chemokine secretion (Ccl5) that activates immune cells. Our data demonstrate that testosterone regulates thyroid cancer progression by reducing tumor suppressor gene expression and tumor immunity. PMID:25576159

  19. The effects of cancer and cancer therapy on male fertility

    SciTech Connect

    Thachil, J.V.; Jewett, M.A.; Rider, W.D.

    1981-08-01

    Multimodality treatments have increased the survival of cancer patients in recent years. With cure the quality of life also should be taken into consideration. Maintenance of the reproductive capacity is of great concern to many young patients. Until now the cause of sterility was attributed to the long-term side effects of treatment when recovery could not be predicted. Pre-treatment sperm banking is advised routinely for many of these patients. Our own observation as well as a few other reports show that cancer itself seems to have an adverse effect on fertility before any form of treatment. As assessed by semen quality the majority of our patients were subfertile when first seen. Hence, sperm banking may be a poor guarantee for future reproduction in these patients.

  20. Nanoparticles Modified With Tumor-targeting scFv Deliver siRNA and miRNA for Cancer Therapy

    PubMed Central

    Chen, Yunching; Zhu, Xiaodong; Zhang, Xiaoju; Liu, Bin; Huang, Leaf

    2010-01-01

    Targeted delivery of RNA-based therapeutics for cancer therapy remains a challenge. We have developed a LPH (liposome-polycation-hyaluronic acid) nanoparticle formulation modified with tumor-targeting single-chain antibody fragment (scFv) for systemic delivery of small interfering RNA (siRNA) and microRNA (miRNA) into experimental lung metastasis of murine B16F10 melanoma. The siRNAs delivered by the scFv targeted nanoparticles efficiently downregulated the target genes (c-Myc/MDM2/VEGF) in the lung metastasis. Two daily intravenous injections of the combined siRNAs in the GC4-targeted nanoparticles significantly reduced the tumor load in the lung. miRNA-34a (miR-34a) induced apoptosis, inhibited survivin expression, and downregulated MAPK pathway in B16F10 cells. miR-34a delivered by the GC4-targeted nanoparticles significantly downregulated the survivin expression in the metastatic tumor and reduced tumor load in the lung. When miR-34a and siRNAs were co-formulated in GC4-targeted nanoparticles, an enhanced anticancer effect was observed. PMID:20606648

  1. The effects of laser immunotherapy on cancer cell migration

    NASA Astrophysics Data System (ADS)

    Bahavar, Cody F.; Zhou, Feifan; Hasanjee, Aamr M.; Layton, Elivia; Lam, Anh; Chen, Wei R.; Vaughan, Melville B.

    2016-03-01

    Laser immunotherapy (LIT) uses laser irradiation and immunological stimulation to target all types of metastases and creates a long-term tumor resistance. Glycated chitosan (GC) is the immunological stimulant used in LIT. Interestingly, GC can act as a surfactant for single-walled carbon nanotubes (SWNTs) to immunologically modify SWNTs. SWNT-GC retains the optical properties of SWNTs and the immunological functions of GC to help increase the selectivity of the laser and create a more optimal immune response. One essential aspect of understanding this immune response is knowing how laser irradiation affects cancer cells' ability to metastasize. In this experiment, a cell migration assay was performed. A 2mm circular elastomer plugs were placed at the bottom of multi-well dishes. Pre-cancerous keratinocytes, different tumor cells, and fibroblasts were then plated separately in treated wells. Once the cells reached 100% confluence, they were irradiated by either a 980nm or 805nm wavelength laser. The goal was to determine the effects of laser irradiation and immunological stimulation on cancer cell migration in vitro, paying the way to understand the mechanism of LIT in treating metastatic tumors in cancer patients.

  2. The effect of meteorological factors on adolescent hand, foot, and mouth disease and associated effect modifiers

    PubMed Central

    Wu, Haixia; Wang, Hongchun; Wang, Qingzhou; Xin, Qinghua; Lin, Hualiang

    2014-01-01

    Background Hand, foot, and mouth disease (HFMD) is a contagious viral illness that commonly affects infants and children. This infection is an emerging infectious disease in Rizhao in recent years. The present study examined the short-term effects of meteorological factors on adolescent HFMD in Rizhao. Design A generalized additive Poisson model was applied to estimate the effects of meteorological factors on adolescent HFMD occurrence in 2010–2012. Subgroup analyses were also conducted to examine the potential effect modifiers of the association in terms of age, sex, and occupation. Results A positive effect of temperature was observed (ER [excess risk]=1.93%, 95% CI: 1.05 to 2.82% for 1°C increase on lag 5 day). A negative effect of relative humidity at lag 1 day and positive effects were found on lag 5–7 days, and an adverse effect was observed for sunshine at lag days 3–4 (ER=−0.71%, 95% CI: −1.25 to −0.17% on lag day 4). We also found that age, sex, and occupation might be important effect modifiers of the effects of weather variables on HFMD. Conclusions This study suggests that meteorological factors might be an important predictor of adolescent HFMD occurrence in Rizhao. Age, sex, and occupation might be important effect modifiers of the effects. PMID:25098727

  3. Modifiable risk factors associated with bone deficits in childhood cancer survivors

    PubMed Central

    2012-01-01

    Background To determine the prevalence and severity of bone deficits in a cohort of childhood cancer survivors (CCS) compared to a healthy sibling control group, and the modifiable factors associated with bone deficits in CCS. Methods Cross-sectional study of bone health in 319 CCS and 208 healthy sibling controls. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). Generalized estimating equations were used to compare measures between CCS and controls. Among CCS, multivariable logistic regression was used to evaluate odds ratios for BMD Z-score ≤ -1. Results All subjects were younger than 18 years of age. Average time since treatment was 10.1 years (range 4.3 - 17.8 years). CCS were 3.3 times more likely to have whole body BMD Z-score ≤ -1 than controls (95% CI: 1.4-7.8; p = 0.007) and 1.7 times more likely to have lumbar spine BMD Z-score ≤ -1 than controls (95% CI: 1.0-2.7; p = 0.03). Among CCS, hypogonadism, lower lean body mass, higher daily television/computer screen time, lower physical activity, and higher inflammatory marker IL-6, increased the odds of having a BMD Z-score ≤ -1. Conclusions CCS, less than 18 years of age, have bone deficits compared to a healthy control group. Sedentary lifestyle and inflammation may play a role in bone deficits in CCS. Counseling CCS and their caretakers on decreasing television/computer screen time and increasing activity may improve bone health. PMID:22455440

  4. A modified VMAT adaptive radiotherapy for nasopharyngeal cancer patients based on CT-CT image fusion

    PubMed Central

    2013-01-01

    Background To investigate the feasibility and benefits of a modified adaptive radiotherapy (ART) by replanning in the initial CT (iCT) with new contours from a repeat CT (rCT) based on CT-CT image fusion for nasopharyngeal cancer (NPC) patients underwent volumetric modulated arc radiotherapy (VMAT). Materials and methods Nine NPC patients underwent VMAT treatment with a rCT at 23rd fraction were enrolled in this study. Dosimetric differences for replanning VMAT plans in the iCT and in the rCT were compared. Volumetric and dosimetric changes of gross tumor volume (GTV) and organs at risk (OARs) of this modified ART were also investigated. Results No dosimetric differences between replanning in the iCT and in the rCT were observed. The average volume of GTV decreased from 78.83 ± 38.42 cm3 in the iCT to 71.44 ± 37.46 cm3 in the rCT, but with no significant difference (p = 0.42).The average volume of the left and right parotid decreased from 19.91 ± 4.89 cm3 and 21.58 ± 6.16 cm3 in the iCT to 11.80 ± 2.79 cm3 and 13.29 ± 4.17 cm3 in the rCT (both p < 0.01), respectively. The volume of other OARs did not shrink very much. No significant differences on PTVGTV and PTVCTV coverage were observed for replanning with this modified ART. Compared to the initial plans, the average mean dose of the left and right parotid after re-optimization were decreased by 62.5 cGy (p = 0.05) and 67.3 cGy (p = 0.02), respectively, and the V5 (the volume receiving 5 Gy) of the left and right parotids were decreased by 7.8% (p = 0.01) and 11.2% (p = 0.001), respectively. There was no significant difference on the dose delivered to other OARs. Conclusion Patients with NPC undergoing VMAT have significant anatomic and dosimetric changes to parotids. Repeat CT as an anatomic changes reference and re-optimization in the iCT based on CT-CT image fusion was accurate enough to identify the volume changes and to ensure safe dose to

  5. Surface modified multifunctional nanomedicines for simultaneous imaging and therapy of cancer

    PubMed Central

    Barar, Jaleh; Omidi, Yadollah

    2014-01-01

    Introduction: To date, a growing number of advanced anticancer nanomedicines (e.g., Doxil®, Lipoxal®, DepoCyte®) have entered into different phases of clinical trials. However, most of these medicaments fail to differentiate between diseased and normal cells. They also do not have capability of real time monitoring of disease status trough on-demand imaging/sensing of target molecule(s). Multifunctional nanomedicines and theranostics can resolve such limitations, while formulation of these advanced seamless systems appear to involve various sophisticated process, exploiting several bioconjugations. Methods: Recent works upon multifunctional nanomedicines for simultaneous imaging and therapy of cancer have been systematically reviewed, focusing on surface modification and application of advanced nanobiomaterials. Results: Ultimate therapy of malignancies, as complex systems, demands implementation of seamless nanosystems (NSs) that can specifically target the cancerous cells and smartly deliver the anticancer agent(s) into the desired target site. Engineering of such NSs requires in-situ coordination of various technologies (e.g., synthesis, surface modification and bioconjugation) in order to achieve improved pharmacokinetics and pharmacodynamics outcomes. Conclusion: Seamless multimodal NSs have potential to simultaneously target and monitor the tumor cells through homing and imaging/sensing devices and deliver the therapeutic agents. However, to achieve superior pharmacokinetics with maximal efficacy and minimal side effects, these advanced NSs need to become much more intelligent to sense the disease condition and liberate therapeutics on demand. PMID:24790893

  6. Targeting Cancer Metabolism - Revisiting the Warburg Effects

    PubMed Central

    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

  7. Targeting Cancer Metabolism - Revisiting the Warburg Effects.

    PubMed

    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

  8. Effect of modified yam (Dioscorea esculenta) flour on some physicochemical and sensory properties of synbiotic yoghurt

    NASA Astrophysics Data System (ADS)

    Handayani, M. N.; Cakrawati, D.; Handayani, S.

    2016-04-01

    The aim of the study were to know characteristics of yam modified flour; to know the effect of modified yam flour on some physicochemical and sensory properties of synbiotic yoghurt and to determine the concentration level of modified yam flour to produce symbiotic yoghurt preferred by panelists. The reasearch was conducted using one factor complete randomized design. Modified yam flour was added to yoghurt at concentration of 2%, 4%, 6%. The effect of physical modification were investigated. Proximate analysis showed modified yam flour consist of 7.66% moisture content, 1.42% ash content, 10.16%, dietary fiber, 7.49% inulin, and 71.78% total starch content. Result obtained that modified yam flour has yield of 10.54%, the modified yam flour showed solubility and water absopsion of 77,63% and 136,65 respectively. The addition of modified yam flour on yoghurt resulted significantly difference effect on texture, but did not have significantly difference on colour, flavour and aroma. Modified yam flour added yoghurt thickness because it was gelatinized when added to yoghurt at 40°C. Sensory analysis conducted with hedonic test showed synbiotic yoghurt added with 2% of modified yam flour most preferred by panellists. Synbiotic yoghurt with 2% of modified yam flour has pH number of 4, 8 and total acid tirated of 1, 7%.

  9. Systemic delivery of siRNA by T7 peptide modified core-shell nanoparticles for targeted therapy of breast cancer.

    PubMed

    Yu, Min-Zhi; Pang, Wen-Hao; Yang, Ting; Wang, Jian-Cheng; Wei, Lin; Qiu, Chong; Wu, Yi-Fan; Liu, Wei-Zhong; Wei, Wei; Guo, Xi-Ying; Zhang, Qiang

    2016-09-20

    Systemic delivery of siRNA is the most challenging step to transfer RNAi to clinical application for breast cancer therapy. In this study, the tumor targeted, T7 peptide modified core-shell nanoparticles (named as T7-LPC/siRNA NPs) were constructed to achieve effective systemic delivery of siRNA. The core-shell structure of T7-LPC/siRNA NPs enables them to encapsulate siRNA in the core and protect it from RNase degradation during circulation. In vitro cellular uptake and gene silencing experiments demonstrated that T7-LPC/siEGFR NPs could deliver EGFR siRNA into breast cancer cells through receptor mediated endocytosis and effectively down-regulate the EGFR expression. In vivo distribution study proved the T7-LPC/siRNA NPs could deliver fluorescence labeled siRNA to the tumor site more efficiently than the non-targeted PEG-LPC/siRNA NPs after intravenous administration. Furthermore, the experiments of in vivo tumor therapy confirmed that intravenous administration of T7-LPC/siEGFR NPs led to an effective EGFR down-regulation and an obvious inhibition of breast tumor growth, with little activation of immune responses and negligible body weight loss. These results suggested that T7-LPC/siRNA NPs could be an effective and safe systemic siRNA delivery system for RNAi-based breast cancer therapy. PMID:27355138

  10. Modifying normal tissue damage postirradiation. Report of a workshop sponsored by the Radiation Research Program, National Cancer Institute, Bethesda, Maryland, September 6-8, 2000.

    PubMed

    Stone, Helen B; McBride, William H; Coleman, C Norman

    2002-02-01

    Late effects that develop in normal tissues adjacent to the tumor site in the months to years after radiotherapy can reduce the quality of life of cancer survivors. They can be dose-limiting and debilitating or life-threatening. There is now evidence that some late effects may be preventable or partially reversible. A workshop, "Modifying Normal Tissue Damage Postirradiation", was sponsored by the Radiation Research Program of the National Cancer Institute to identify the current status of and research needs and opportunities in this area. Mechanistic, genetic and physiological studies of the development of late effects are needed and will provide a rational basis for development of treatments. Interdisciplinary teams will be needed to carry out this research, including pathologists, physiologists, geneticists, molecular biologists, experts in functional imaging, wound healing, burn injury, molecular biology, and medical oncology, in addition to radiation biologists, physicists and oncologists. The participants emphasized the need for developing and choosing appropriate models, and for radiation dose-response studies to determine whether interventions remain effective at the radiation doses used clinically. Both preclinical and clinical studies require long-term follow-up, and easier-to-use, more objective clinical scoring systems must be developed and standardized. New developments in biomedical imaging should provide useful tools in all these endeavors. The ultimate goals are to improve the quality of life and efficacy of treatment for cancer patients treated with radiotherapy. PMID:11835685

  11. Effective Removal of Heavy Metals from Wastewater Using Modified Clay.

    PubMed

    Song, Mun-Seon; Vijayarangamuthu, K; Han, EunJi; Jeon, Ki-Joon

    2016-05-01

    We report an economical and eco-friendly way to remove the heavy metal pollutant using modified clay. The modification of clay was done by calcining the natural clay from Kyushu region in Japan. Further, the removal efficiency for various pH and contact time was evaluated. The morphology of the clays was studied using the scanning electron microscopy (SEM). The structural and chemical analyses of modified clay were done by using X-ray diffraction (XRD), Raman spectroscopy, and Energy dispersion analysis (EDAX) to understand the properties related to the removal of heavy metal pollutant. Further, we studied the absorption efficiency of clay for various pH and contacting time using Ni polluted water. The modified clays show better removal efficiency for all pH with different saturation time. The adsorption follows pseudo-second order kinetics and the adsorption capacity of modified clay is 1.5 times larger than that of natural clay. The increase in the adsorption efficiency of modified clay was correlated to the increase in hematite phase along with increase in surface area due to surface morphological changes. PMID:27483775

  12. Ultrasound Effect on Cancerous versus Non-Cancerous Cells.

    PubMed

    Azagury, Aharon; Amar-Lewis, Eliz; Yudilevitch, Yana; Isaacson, Carol; Laster, Brenda; Kost, Joseph

    2016-07-01

    Previous studies have found that cancer cells whose metastatic potential is low are more vulnerable to mechanical stress-induced trauma to their cytoskeleton compared with benign cells. Because ultrasound induces mechanical stresses on cells and tissues, it is postulated that there may be a way to apply ultrasound to tumors to reduce their ability to metastasize. The difference between low-malignant-potential cancer cells and benign cells could be a result of their different responses to the mechanical stress insonation induced. This hypothesis was tested in vitro and in vivo. Low-malignant-potential cells were found to be more sensitive to insonation, resulting in a significantly higher mortality rate compared with that of benign cells, 89% versus 21%, respectively. This effect can be controlled by varying ultrasound parameters: intensity, duration, and duty cycle. Thus, the results presented in this study suggest the application of ultrasound to discriminate between benign and malignant cells. PMID:27067417

  13. Components and modifiers of the healthy worker effect: evidence from three occupational cohorts and implications for industrial compensation

    SciTech Connect

    Howe, G.R.; Chiarelli, A.M.; Lindsay, J.P.

    1988-12-01

    The authors examined the components and modifiers of the healthy worker effect using mortality data from three occupational cohorts: the employees of Atomic Energy of Canada Limited followed between 1950 and 1981, a 10% sample of the Canadian labor force followed between 1965 and 1979, and workers at the Eldorado Resources Limited Beaverlodge uranium mine followed between 1950 and 1980. Two important components of the healthy worker effect have been identified in these cohorts, namely, initial selection of and continuing employment of healthy individuals. There is less evidence for a contribution from the existence of differential risk factors among employed individuals as compared with the general population. The healthy worker effect is, however, substantially modified by time since employment, sex, age, specific cause of death, and specific occupation. Because of this variation, it is inappropriate to account for the healthy worker effect by a single parameter, and all of the above factors must be taken into account in any appropriate analysis. When the only available comparison group for an occupational cohort is the general population, the healthy worker effect is unlikely to have any substantial influence on the process of assessing causality for any observed association or attributing cause in an individual case. This would be particularly true for cancer, and even more so for lung cancer, a disease often associated with industrial compensation cases.

  14. Monodisperse magnetite (Fe3O4) nanoparticles modified with water soluble polymers for the diagnosis of breast cancer by MRI method

    NASA Astrophysics Data System (ADS)

    Rezayan, Ali Hossein; Mosavi, Majid; Kheirjou, Somayyeh; Amoabediny, Ghasem; Ardestani, Mehdi Shafiee; Mohammadnejad, Javad

    2016-12-01

    In this study, magnetic nanoparticles (MNPs) were synthesized via co-precipitation method. To enhance the biocompatibility and colloidal stability of the synthesized nanoparticles, they were modified with carboxyl functionalized PEG via dopamine (DPA) linker. Both modified and unmodified Fe3O4 nanoparticles exhibited super paramagnetic behavior (particle size below 20 nm). The saturation magnetization (Ms) of PEGdiacid-modified Fe3O4 was 45 emu/g, which was less than the unmodified Fe3O4 nanoparticles (70 emu/g). This difference indicated that PEGdiacid polymer was immobilized on the surface of Fe3O4 nanoparticles successfully. To evaluate the efficiency of the resulting nanoparticles as contrast agents for magnetic resonance imaging (MRI), different concentration of MNPs and different value of echo time TE were investigated. The results showed that by increasing the concentration of the nanoparticles, transverse relaxation time (T2) decreased, which subsequently resulted in MR signal enhancement. T2-weighted MR images of the different concentration of MNPs in different value of echo time TE indicated that MR signal intensity increased with increase in TE value up to 66 and then remained constant. The cytotoxicity effect of the modified and unmodified nanoparticles was evaluated in three different concentrations (12, 60 and 312 mg l-1) on MDA-MB-231 cancer cells for 24 and 48 h. In both tested time (24 and 48 h) for all three samples, the modified nanoparticles had long life time than unmodified nanoparticles. Cellular uptake of modified MNPs was 80% and reduced to 9% by the unmodified MNPs.

  15. Hyaluronic acid modified mesoporous carbon nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    NASA Astrophysics Data System (ADS)

    Wan, Long; Jiao, Jian; Cui, Yu; Guo, Jingwen; Han, Ning; Di, Donghua; Chang, Di; Wang, Pu; Jiang, Tongying; Wang, Siling

    2016-04-01

    In this paper, hyaluronic acid (HA) functionalized uniform mesoporous carbon spheres (UMCS) were synthesized for targeted enzyme responsive drug delivery using a facile electrostatic attraction strategy. This HA modification ensured stable drug encapsulation in mesoporous carbon nanoparticles in an extracellular environment while increasing colloidal stability, biocompatibility, cell-targeting ability, and controlled cargo release. The cellular uptake experiments of fluorescently labeled mesoporous carbon nanoparticles, with or without HA functionalization, demonstrated that HA-UMCS are able to specifically target cancer cells overexpressing CD44 receptors. Moreover, the cargo loaded doxorubicin (DOX) and verapamil (VER) exhibited a dual pH and hyaluronidase-1 responsive release in the tumor microenvironment. In addition, VER/DOX/HA-UMCS exhibited a superior therapeutic effect on an in vivo HCT-116 tumor in BALB/c nude mice. In summary, it is expected that HA-UMCS will offer a new method for targeted co-delivery of drugs to tumors overexpressing CD44 receptors.

  16. The cancer preventive effects of edible mushrooms.

    PubMed

    Xu, Tongtong; Beelman, Robert B; Lambert, Joshua D

    2012-12-01

    An increasing body of scientific literature suggests that dietary components may exert cancer preventive effects. Tea, soy, cruciferous vegetables and other foods have been investigated for their cancer preventive potential. Some non-edible mushrooms like Reishi (Ganoderma lucidum) have a history use, both alone and in conjunction with standard therapies, for the treatment of various diseases including cancer in some cultures. They have shown efficacy in a number of scientific studies. By comparison, the potential cancer preventive effects of edible mushrooms have been less well-studied. With similar content of putative effective anticancer compounds such as polysaccharides, proteoglycans, steroids, etc., one might predict that edible mushrooms would also demonstrate anticancer and cancer preventive activity. In this review, available data for five commonly-consumed edible mushrooms: button mushrooms (Agaricus bisporus), A. blazei, oyster mushrooms (Pleurotus ostreatus), shiitake mushrooms (Lentinus edodes), and maitake (Grifola frondosa) mushrooms is discussed. The results of animal model and human intervention studies, as well as supporting in vitro mechanistic studies are critically evaluated. Weaknesses in the current data and topics for future work are highlighted. PMID:22583406

  17. Biological effects of progestins in breast cancer.

    PubMed

    Pasqualini, J R; Ebert, C

    1999-06-01

    Developments in the synthesis of different progestins have opened up new possibilities for the biological effects and therapeutic uses of these compounds. The actions of progestins are a function of their structure, affinity to the progesterone receptor or to other steroid receptors, the target tissue considered, the biological response, the experimental conditions, dose, and metabolic transformation. Data on the action of progestins in breast cancer patients are very limited. A positive response with the progestins medroxyprogesterone acetate and megestrol acetate has been obtained in postmenopausal patients with advanced breast cancer. However, extensive information on the effect of progestins was obtained in in vitro studies using hormone-dependent and hormone-independent human mammary cancer cell lines. It was demonstrated that in hormone-dependent breast cancer cells, various progestins (nomegestrol acetate, medrogestone, promegestone) as well as tibolone, are potent sulfatase-inhibitory agents. Progestins may also be involved in the inhibition of the mRNA of this enzyme. In another series of studies, it was also demonstrated that various progestins are very active in inhibiting the 17 beta-hydroxysteroid dehydrogenase for the conversion of estrone to estradiol. More recently, it has been observed that promegestone or medrogestone stimulates the sulfotransferase for the formation of estrogen sulfates. Clinical trials of these enzymatic effects on the formation and transformation of estradiol in breast cancer patients could be the next step to investigate new therapeutic possibilities for this disease. PMID:12227897

  18. The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers.

    PubMed

    Kotsopoulos, Joanne; Ghadirian, Parviz; El-Sohemy, Ahmed; Lynch, Henry T; Snyder, Carrie; Daly, Mary; Domchek, Susan; Randall, Susan; Karlan, Beth; Zhang, Phil; Zhang, Shiyu; Sun, Ping; Narod, Steven A

    2007-05-01

    We have recently reported that, among BRCA1 mutation carriers, the consumption of caffeinated coffee was associated with a significant reduction in breast cancer risk. Because the metabolism of caffeine is primarily by CYP1A2, we examined whether or not the CYP1A2 genotype modifies the association between a history of coffee consumption and the risk of breast cancer. A common A to C polymorphism in the CYP1A2 gene is associated with decreased enzyme inducibility and impaired caffeine metabolism. Information regarding coffee consumption habits and the CYP1A2 genotype was available for 411 BRCA1 mutation carriers (170 cases and 241 controls). We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer associated with the CYP1A2 genotype and a history of coffee consumption before age 35, adjusting for potential confounders. The CYP1A2 genotype did not affect breast cancer risk. Among women with at least one variant C allele (AC or CC), those who consumed coffee had a 64% reduction in breast cancer risk, compared with women who never consumed coffee (OR, 0.36; 95% CI, 0.18-0.73). A significant protective effect of coffee consumption was not observed among women with the CYP1A2 AA genotype (OR, 0.93; 95% CI, 0.49-1.77). Similar results were obtained when the analysis was restricted to caffeinated coffee. This study suggests that caffeine protects against breast cancer in women with a BRCA1 mutation and illustrates the importance of integrating individual genetic variability when assessing diet-disease associations. PMID:17507615

  19. Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients.

    PubMed

    Knights, Ashley J; Nuber, Natko; Thomson, Christopher W; de la Rosa, Olga; Jäger, Elke; Tiercy, Jean-Marie; van den Broek, Maries; Pascolo, Steve; Knuth, Alexander; Zippelius, Alfred

    2009-03-01

    The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions. PMID:18663444

  20. Mechanistic Effects of Calcitriol in Cancer Biology

    PubMed Central

    Díaz, Lorenza; Díaz-Muñoz, Mauricio; García-Gaytán, Ana Cristina; Méndez, Isabel

    2015-01-01

    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. PMID:26102214

  1. Late endocrine effects of childhood cancer.

    PubMed

    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

  2. Effects of Chemotherapy on the Brain in Women With Newly Diagnosed Early-Stage Breast Cancer

    ClinicalTrials.gov

    2016-05-12

    Breast Cancer; Chemotherapeutic Agent Toxicity; Cognitive/Functional Effects; Fatigue; Long-term Effects Secondary to Cancer Therapy in Adults; Neurotoxicity; Psychosocial Effects of Cancer and Its Treatment

  3. Modelling intervention effects after cancer relapses

    PubMed Central

    González, Juan R.; Peña, Edsel A.; Slate, Elizabeth H.

    2014-01-01

    Summary This article addresses the problem of incorporating information regarding the effects of treatments or interventions into models for repeated cancer relapses. In contrast to many existing models, our approach permits the impact of interventions to differ after each relapse. We adopt the general model for recurrent events proposed by Peña and Hollander, in which the effect of interventions is represented by an effective age process acting on the baseline hazard rate function. To accommodate the situation of cancer relapse, we propose an effective age function that encodes three possible therapeutic responses: complete remission, partial remission, and null response. The proposed model also incorporates the effect of covariates, the impact of previous relapses, and heterogeneity among individuals. We use our model to analyse the times to relapse for 63 patients with a particular subtype of indolent lymphoma and compare the results to those obtained using existing methods. PMID:16320269

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

    ClinicalTrials.gov

    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

  5. Neurocognitive Effects of Treatment for Childhood Cancer

    ERIC Educational Resources Information Center

    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…

  6. Biological effects of progestins in breast cancer.

    PubMed

    Pasqualini, J R; Ebert, C; Chetrite, G S

    2001-12-01

    The action of progestins is derived from many factors: structure, affinity for the progesterone receptor or for other steroid receptors, the target tissue considered, the biological response, the experimental conditions, the dose and metabolic transformation. The proliferative response to progestins in human breast cancer cells is contradictory: some progestins inhibit, others stimulate, have no effect at all, or have a dual action. For instance, medroxyprogesterone acetate has a stimulatory effect on breast cancer cells after a short period of treatment, but this effect becomes inhibitory when treatment is prolonged. It has been demonstrated that, in hormone-dependent breast cancer cells, various progestins (nomegestrol acetate, medrogestone, promegestone) are potent sulfatase inhibitory agents. The progestins can also involve the inhibition of the mRNA expression of this enzyme. In another series of studies it was also demonstrated that some progestins are very active in inhibiting 17beta-hydroxysteroid dehydrogenase for the conversion of estrone to estradiol. More recently it was observed that the progestins promegestone and medrogestone stimulate sulfotransferase for the formation of estrogen sulfates. Consequently, the action of progestins in blocking estradiol formation via sulfatase, or in stimulating the effect on sulfotransferase activity, can open interesting and new possibilities in clinical applications in breast cancer. PMID:12227886

  7. Effects of Brassicaceae Isothiocyanates on Prostate Cancer.

    PubMed

    Novío, Silvia; Cartea, María Elena; Soengas, Pilar; Freire-Garabal, Manuel; Núñez-Iglesias, María Jesús

    2016-01-01

    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. PMID:27187332

  8. In vitro and in vivo targeting imaging of pancreatic cancer using a Fe3O4@SiO2 nanoprobe modified with anti-mesothelin antibody.

    PubMed

    Liu, Fang; Le, Wenjun; Mei, Tianxiao; Wang, Tiegong; Chen, Luguang; Lei, Yi; Cui, Shaobin; Chen, Bingdi; Cui, Zheng; Shao, Chengwei

    2016-01-01

    Pancreatic cancer is a highly malignant disease with a 5-year survival rate <5% mainly due to lack of early diagnosis and effective therapy. In an effort to improve the early diagnostic rate of pancreatic cancer, a nanoprobe Fe3O4@SiO2 modified with anti-mesothelin antibody (A-MFS) was prepared to target cells and tumor tissues highly expressing mesothelin in vitro (human pancreatic cancer cell line SW1990) and in vivo (subcutaneously transplanted tumors) studies. The A-MFS probe was successfully prepared and was spherical and uniform with a hydrodynamic diameter between 110 and 130 nm. Cell Counting Kit-8 testing indicated that A-MFS was nontoxic in vitro and in vivo studies. The in vitro study showed that the A-MFS probe specifically targeted SW1990 cells with high mesothelin expression. The in vivo study was conducted in Siemens 3.0 T magnetic resonance imaging. The average T2-weighted signal values of the xenografts were 966.533±31.56 before injecting A-MFS and 691.133±56.84 before injecting saline solution. After injection of 0.1 mL A-MFS via nude mouse caudal vein for 2.5 hours, the average T2-weighted signal of the xenograft decreased by 342.533±42.6. The signal value decreased by -61.233±33.9 and -58.7±19.4 after injection of the saline and Fe3O4@SiO2. The decrease of tumor signal by A-MFS was much more significant than that by saline and Fe3O4@SiO2 (P<0.05). The results demonstrated the high stability and nontoxicity of A-MFS, which effectively targeted pancreatic cancer in vitro and in vivo. A-MFS is a promising agent for diagnosis of pancreatic cancer. PMID:27274243

  9. In vitro and in vivo targeting imaging of pancreatic cancer using a Fe3O4@SiO2 nanoprobe modified with anti-mesothelin antibody

    PubMed Central

    Liu, Fang; Le, Wenjun; Mei, Tianxiao; Wang, Tiegong; Chen, Luguang; Lei, Yi; Cui, Shaobin; Chen, Bingdi; Cui, Zheng; Shao, Chengwei

    2016-01-01

    Pancreatic cancer is a highly malignant disease with a 5-year survival rate <5% mainly due to lack of early diagnosis and effective therapy. In an effort to improve the early diagnostic rate of pancreatic cancer, a nanoprobe Fe3O4@SiO2 modified with anti-mesothelin antibody (A-MFS) was prepared to target cells and tumor tissues highly expressing mesothelin in vitro (human pancreatic cancer cell line SW1990) and in vivo (subcutaneously transplanted tumors) studies. The A-MFS probe was successfully prepared and was spherical and uniform with a hydrodynamic diameter between 110 and 130 nm. Cell Counting Kit-8 testing indicated that A-MFS was nontoxic in vitro and in vivo studies. The in vitro study showed that the A-MFS probe specifically targeted SW1990 cells with high mesothelin expression. The in vivo study was conducted in Siemens 3.0 T magnetic resonance imaging. The average T2-weighted signal values of the xenografts were 966.533±31.56 before injecting A-MFS and 691.133±56.84 before injecting saline solution. After injection of 0.1 mL A-MFS via nude mouse caudal vein for 2.5 hours, the average T2-weighted signal of the xenograft decreased by 342.533±42.6. The signal value decreased by −61.233±33.9 and −58.7±19.4 after injection of the saline and Fe3O4@SiO2. The decrease of tumor signal by A-MFS was much more significant than that by saline and Fe3O4@SiO2 (P<0.05). The results demonstrated the high stability and nontoxicity of A-MFS, which effectively targeted pancreatic cancer in vitro and in vivo. A-MFS is a promising agent for diagnosis of pancreatic cancer. PMID:27274243

  10. Heparanase multiple effects in cancer.

    PubMed

    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

  11. [A Case of Locally Advanced Breast Cancer Treated with Modified Radical Mastectomy with Immediate Reconstruction Using a Tissue Expander after Endocrine Therapy].

    PubMed

    Aomatsu, Naoki; Tei, Seika; Haraoka, Goichi; Hosoi, Kosuke; Fujii, Naho; Tsujio, Gen; Hiramatsu, Soichiro; Wang, En; Iwauchi, Takehiko; Morimoto, Junya; Nishii, Takafumi; Kosaka, Kinshi; Uchima, Yasutake; Takeuchi, Kazuhiro

    2015-11-01

    We experienced a case of locally advanced breast cancer treated with modified radical mastectomy with immediate reconstruction using a tissue expander after endocrine therapy. A 64-year-old postmenopausal woman had a 50 mm tumor in her right breast with extensive reddening of the skin. She had axillary lymph node metastasis. Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+, PgR+) and negative HER2 status. The patient was diagnosed with locally-advanced breast cancer (cT4bN1M0, stage ⅢB). She was treated with anastrozole at a dose of 1 mg per day. The tumor decreased in size gradually and became operable after 7 months of anastrozole monotherapy. She underwent modified radical mastectomy with immediate reconstruction using a tissue expander. The resected specimen was a 30 mm tumor; adverse effects due to endocrine therapy were of Grade 1a severity. Seven months after adjuvant chemotherapy (FEC→DTX), the tissue expander was removed, and the right breast was reconstructed using an implant. No complications were noted, and the patient was treated with radiation therapy. Ten months have passed since surgery, and no local recurrence or distant metastasis has been noted. PMID:26805181

  12. Lung cancer: chemoprevention and intermediate effect markers.

    PubMed

    Tockman, M S

    2001-01-01

    Even after smoking cessation, genetic damage in the airways epithelium may lead to focal progression of lung carcinogenesis. Some centres now report as many new lung cancer cases among former smokers as among current smokers. Chemoprevention is a potential approach to diminish the progression of pre-clinical genetic damage. The most intensively studied lung cancer chemoprevention agents are the retinoids, including vitamin A and its synthetic analogues and precursors. While effective in suppressing lung carcinogenesis in animal models, retinoids have failed to inhibit carcinogenesis in human chemoprevention trials with premalignant end-points (sputum atypia, bronchial metaplasia). In trials with lung cancer end-points, administration of retinoids either was ineffective or, in the case of beta-carotene, led to greater lung cancer incidence and mortality. In view of these findings, markers of specific retinoid effect (i.e., levels of RAR-beta) become less relevant. Other markers of genetic instability and proliferation may be useful for both early detection and potentially as intermediate-effect markers for new chemoprevention trials. Cytological atypia, bronchial metaplasia, protein (hnRNP A2/B1) overexpression, ras oncogene activation and tumour-suppressor gene deletion, genomic instability (loss of heterozygosity, microsatellite alterations), abnormal methylation, helical CT detection of atypical adenomatous hyperplasia and fluorescent bronchoscopic detection of angiogenic squamous dysplasia offer great promise for molecular diagnosis of lung cancer far in advance of clinical presentation. These end-points can now be evaluated as monitors of response to chemoprevention as potential intermediate-effect markers. PMID:11220665

  13. Cell-Penetrating Peptide-Modified Gold Nanoparticles for the Delivery of Doxorubicin to Brain Metastatic Breast Cancer.

    PubMed

    Morshed, Ramin A; Muroski, Megan E; Dai, Qing; Wegscheid, Michelle L; Auffinger, Brenda; Yu, Dou; Han, Yu; Zhang, Lingjiao; Wu, Meijing; Cheng, Yu; Lesniak, Maciej S

    2016-06-01

    As therapies continue to increase the lifespan of patients with breast cancer, the incidence of brain metastases has steadily increased, affecting a significant number of patients with metastatic disease. However, a major barrier toward treating these lesions is the inability of therapeutics to penetrate into the central nervous system and accumulate within intracranial tumor sites. In this study, we designed a cell-penetrating gold nanoparticle platform to increase drug delivery to brain metastatic breast cancer cells. TAT peptide-modified gold nanoparticles carrying doxorubicin led to improved cytotoxicity toward two brain metastatic breast cancer cell lines with a decrease in the IC50 of at least 80% compared to free drug. Intravenous administration of these particles led to extensive accumulation of particles throughout diffuse intracranial metastatic microsatellites with cleaved caspase-3 activity corresponding to tumor foci. Furthermore, intratumoral administration of these particles improved survival in an intracranial MDA-MB-231-Br xenograft mouse model. Our results demonstrate the promising application of gold nanoparticles for improving drug delivery in the context of brain metastatic breast cancer. PMID:27169484

  14. Multifunctional hyaluronic acid modified graphene oxide loaded with mitoxantrone for overcoming drug resistance in cancer

    NASA Astrophysics Data System (ADS)

    Hou, Lin; Feng, Qianhua; Wang, Yating; Yang, Xiaomin; Ren, Junxiao; Shi, Yuyang; Shan, Xiaoning; Yuan, Yujie; Wang, Yongchao; Zhang, Zhenzhong

    2016-01-01

    Multifunctional nanosheets (HA-GO/Pluronic) with targeted chemo-photothermal properties were successfully developed for controlled delivery of mitoxantrone (MIT) to overcome multidrug resistance (MDR). In vitro release profiles displayed that both an acidic environment and a NIR laser could trigger and accelerate the release of a drug, which ensured nanosheets were stable in blood circulation and released MIT within tumor cells under laser irradiation. HA-GO/Pluronic nanosheets were taken up into MCF-7/ADR cells via receptor-mediated endocytosis, which further facilitated escapement of P-gp efflux. Compared with MIT solution, MIT/HA-GO/Pluronic showed greater cytotoxicity and increase in cellular MIT accumulation in MCF-7/ADR cells. Cell apoptosis and cell cycle arrest studies also revealed that MIT/HA-GO/Pluronic was more potent than MIT/GO/Pluronic and MIT solution. The anticancer efficacy in vivo was evaluated in MCF-7 and MCF-7/ADR-bearing mice, and inhibition of tumors by MIT/HA-GO/Pluronic with NIR laser irradiation was the most effective among all MIT formulations. In summary, the MIT/HA-GO/Pluronic system had striking functions such as P-gp reversible inhibitor and anticancer efficacy, and could present a promising platform for drug-resistant cancer treatment.

  15. Hyaluronic acid modified mesoporous carbon nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells.

    PubMed

    Wan, Long; Jiao, Jian; Cui, Yu; Guo, Jingwen; Han, Ning; Di, Donghua; Chang, Di; Wang, Pu; Jiang, Tongying; Wang, Siling

    2016-04-01

    In this paper, hyaluronic acid (HA) functionalized uniform mesoporous carbon spheres (UMCS) were synthesized for targeted enzyme responsive drug delivery using a facile electrostatic attraction strategy. This HA modification ensured stable drug encapsulation in mesoporous carbon nanoparticles in an extracellular environment while increasing colloidal stability, biocompatibility, cell-targeting ability, and controlled cargo release. The cellular uptake experiments of fluorescently labeled mesoporous carbon nanoparticles, with or without HA functionalization, demonstrated that HA-UMCS are able to specifically target cancer cells overexpressing CD44 receptors. Moreover, the cargo loaded doxorubicin (DOX) and verapamil (VER) exhibited a dual pH and hyaluronidase-1 responsive release in the tumor microenvironment. In addition, VER/DOX/HA-UMCS exhibited a superior therapeutic effect on an in vivo HCT-116 tumor in BALB/c nude mice. In summary, it is expected that HA-UMCS will offer a new method for targeted co-delivery of drugs to tumors overexpressing CD44 receptors. PMID:26901756

  16. Oral Delivery of DMAB-Modified Docetaxel-Loaded PLGA-TPGS Nanoparticles for Cancer Chemotherapy

    NASA Astrophysics Data System (ADS)

    Chen, Hongbo; Zheng, Yi; Tian, Ge; Tian, Yan; Zeng, Xiaowei; Liu, Gan; Liu, Kexin; Li, Lei; Li, Zhen; Mei, Lin; Huang, Laiqiang

    2011-12-01

    Three types of nanoparticle formulation from biodegradable PLGA-TPGS random copolymer were developed in this research for oral administration of anticancer drugs, which include DMAB-modified PLGA nanoparticles, unmodified PLGA-TPGS nanoparticles and DMAB-modified PLGA-TPGS nanoparticles. Firstly, the PLGA-TPGS random copolymer was synthesized and characterized. DMAB was used to increase retention time at the cell surface, thus increasing the chances of particle uptake and improving oral drug bioavailability. Nanoparticles were found to be of spherical shape with an average particle diameter of around 250 nm. The surface charge of PLGA-TPGS nanoparticles was changed to positive after DMAB modification. The results also showed that the DMAB-modified PLGA-TPGS nanoparticles have significantly higher level of the cellular uptake than that of DMAB-modified PLGA nanoparticles and unmodified PLGA-TPGS nanoparticles. In vitro, cytotoxicity experiment showed advantages of the DMAB-modified PLGA-TPGS nanoparticle formulation over commercial Taxotere® in terms of cytotoxicity against MCF-7 cells. In conclusion, oral chemotherapy by DMAB-modified PLGA-TPGS nanoparticle formulation is an attractive and promising treatment option for patients.

  17. Biological activity of ruthenium and osmium arene complexes with modified paullones in human cancer cells.

    PubMed

    Mühlgassner, Gerhard; Bartel, Caroline; Schmid, Wolfgang F; Jakupec, Michael A; Arion, Vladimir B; Keppler, Bernhard K

    2012-11-01

    In an attempt to combine the ability of indolobenzazepines (paullones) to inhibit cyclin-dependent kinases (Cdks) and that of platinum-group metal ions to interact with proteins and DNA, ruthenium(II) and osmium(II) arene complexes with paullones were prepared, expecting synergies and an increase of solubility of paullones. Complexes with the general formula [M(II)Cl(η(6)-p-cymene)L]Cl, where M=Ru (1, 3) or Os (2, 4), and L=L(1) (1, 2) or L(2) (3, 4), L(1)=N-(9-bromo-7,12-dihydroindolo[3,2-d][1]-benzazepin-6(5H)-yliden-N'-(2-hydroxybenzylidene)azine and L(2)=N-(9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6-yl)-N'-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl-methylene]azinium chloride (L(2)(*)HCl), were now investigated regarding cytotoxicity and accumulation in cancer cells, impact on the cell cycle, capacity of inhibiting DNA synthesis and inducing apoptosis as well as their ability to inhibit Cdk activity. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay yielded IC(50) values in the nanomolar to low micromolar range. In accordance with cytotoxicity data, the BrdU assay showed that 1 is the most and 4 the least effective of these compounds regarding inhibition of DNA synthesis. Effects on the cell cycle are minor, although concentration-dependent inhibition of Cdk2/cyclin E activity was observed in cell-free experiments. Induction of apoptosis is most pronounced for complex 1, accompanied by a low fraction of necrotic cells, as observed by annexin V-fluorescein isothiocyanate/propidium iodide staining and flow cytometric analysis. PMID:23037896

  18. Biological activity of ruthenium and osmium arene complexes with modified paullones in human cancer cells

    PubMed Central

    Mühlgassner, Gerhard; Bartel, Caroline; Schmid, Wolfgang F.; Jakupec, Michael A.; Arion, Vladimir B.; Keppler, Bernhard K.

    2012-01-01

    In an attempt to combine the ability of indolobenzazepines (paullones) to inhibit cyclin-dependent kinases (Cdks) and that of platinum-group metal ions to interact with proteins and DNA, ruthenium(II) and osmium(II) arene complexes with paullones were prepared, expecting synergies and an increase of solubility of paullones. Complexes with the general formula [MIICl(η6-p-cymene)L]Cl, where M = Ru (1, 3) or Os (2, 4), and L = L1 (1, 2) or L2 (3, 4), L1 = N-(9-bromo-7,12-dihydroindolo[3,2-d][1]-benzazepin-6(5H)-yliden-N′-(2-hydroxybenzylidene)azine and L2 = N-(9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6-yl)-N′-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl-methylene]azinium chloride (L2*HCl), were now investigated regarding cytotoxicity and accumulation in cancer cells, impact on the cell cycle, capacity of inhibiting DNA synthesis and inducing apoptosis as well as their ability to inhibit Cdk activity. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay yielded IC50 values in the nanomolar to low micromolar range. In accordance with cytotoxicity data, the BrdU assay showed that 1 is the most and 4 the least effective of these compounds regarding inhibition of DNA synthesis. Effects on the cell cycle are minor, although concentration-dependent inhibition of Cdk2/cyclin E activity was observed in cell-free experiments. Induction of apoptosis is most pronounced for complex 1, accompanied by a low fraction of necrotic cells, as observed by annexin V–fluorescein isothiocyanate/propidium iodide staining and flow cytometric analysis. PMID:23037896

  19. Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer.

    PubMed

    Marcello, Marjory Alana; Calixto, Antonio Ramos; de Almeida, Jacqueline Fatima Martins; Martins, Mariana Bonjiorno; Cunha, Lucas Leite; Cavalari, Camila Ayume Amano; Etchebehere, Elba C S; da Assumpção, Ligia Vera Montalli; Geloneze, Bruno; Carvalho, Andre Lopes; Ward, Laura Sterian

    2015-01-01

    Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98 ng/mL) than those with AG genotype (10.07 ± 0.60 ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59 ng/mL) than the subjects with GG genotype (9.52 ± 0.79 ng/mL; P < 0.05). A multivariate logistic regression adjusted for gender, age, and BMI showed that the AG genotype of rs7799039 was an independent risk for DTC (OR, 11.689; P = 0.0183; 95% CI, 1.516-90.119). Similarly, AG and GG genotypes of rs1137101 increased the susceptibility to DTC (OR, 3.747; P = 0.027; 95% CI, 1.161-12.092 and OR, 5.437; P = 0.013; 95% CI, 1.426-20.729). Conclusions. We demonstrated that rs7799039 and rs2167270 polymorphisms modify the serum leptin concentrations in patients with DTC. Furthermore, polymorphisms rs7799039 and rs1137101 increase the risk of DTC development, although they do not correlate with tumor aggressiveness. PMID:25810718

  20. Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer

    PubMed Central

    Marcello, Marjory Alana; Calixto, Antonio Ramos; de Almeida, Jacqueline Fatima Martins; Cunha, Lucas Leite; Cavalari, Camila Ayume Amano; Etchebehere, Elba C. S.; da Assumpção, Ligia Vera Montalli; Geloneze, Bruno; Carvalho, Andre Lopes; Ward, Laura Sterian

    2015-01-01

    Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98 ng/mL) than those with AG genotype (10.07 ± 0.60 ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59 ng/mL) than the subjects with GG genotype (9.52 ± 0.79 ng/mL; P < 0.05). A multivariate logistic regression adjusted for gender, age, and BMI showed that the AG genotype of rs7799039 was an independent risk for DTC (OR, 11.689; P = 0.0183; 95% CI, 1.516–90.119). Similarly, AG and GG genotypes of rs1137101 increased the susceptibility to DTC (OR, 3.747; P = 0.027; 95% CI, 1.161–12.092 and OR, 5.437; P = 0.013; 95% CI, 1.426–20.729). Conclusions. We demonstrated that rs7799039 and rs2167270 polymorphisms modify the serum leptin concentrations in patients with DTC. Furthermore, polymorphisms rs7799039 and rs1137101 increase the risk of DTC development, although they do not correlate with tumor aggressiveness. PMID:25810718

  1. [A Case of Advanced Rectal Cancer Resected Successfully after Induction Chemotherapy with Modified FOLFOX6 plus Panitumumab].

    PubMed

    Yukawa, Yoshimi; Uchima, Yasutake; Kawamura, Minori; Takeda, Osami; Hanno, Hajime; Takayanagi, Shigenori; Hirooka, Tomoomi; Dozaiku, Toshio; Hirooka, Takashi; Aomatsu, Naoki; Hirakawa, Toshiki; Iwauchi, Takehiko; Nishii, Takafumi; Morimoto, Junya; Nakazawa, Kazunori; Takeuchi, Kazuhiro

    2016-05-01

    We report a case of advanced colon cancer that was effectively treated with mFOLFOX6 plus panitumumab combination chemotherapy. The patient was a 54-year-old man who had type 2 colon cancer of the rectum. An abdominal CT scan demonstrated rectal cancer with bulky lymph node metastasis and 1 hepatic node(rectal cancer SI[bladder retroperitoneum], N2M0H1P0, cStage IV). He was treated with mFOLFOX6 plus panitumumab as neoadjuvant chemotherapy. After 4 courses of chemotherapy, CT revealed that the primary lesion and regional metastatic lymph nodes had reduced in size(rectal cancer A, N1H1P0M0, cStage IV). Anterior rectal resection with D3 nodal dissection and left lateral segmentectomy of the liver was performed. The histological diagnosis was tubular adenocarcinoma(tub2-1), int, INF a, pMP, ly0, v0, pDM0, pPM0, R0. He was treated with 4 courses of mFOLFOX6 after surgery. The patient has been in good health without a recurrence for 2 years and 5 months after surgery. This case suggests that induction chemotherapy with mFOLFOX6 plus panitumumab is a potentially effective regimen for advanced colon cancer. PMID:27210100

  2. Radiation effects on cancer risks in the Life Span Study cohort.

    PubMed

    Kodama, Kazunori; Ozasa, Kotaro; Katayama, Hiroaki; Shore, Roy E; Okubo, Toshiteru

    2012-10-01

    To determine late health effects of radiation in atomic bomb survivors, the Radiation Effects Research Foundation has been conducting studies on the Life Span Study (LSS) population, which consists of 93,000 atomic bomb survivors and 27,000 controls. A recent report on the incidence of solid cancers estimates that at the age of 70 y, after exposure at the age of 30 y, solid-cancer rates increase by about 35% per Gy for men and 58% per Gy for women. The age-at-exposure is an important risk modifier. Furthermore, it seems that radiation-associated increases in cancer rates persist throughout life. In addition, radiation has similar effects upon first-primary and second-primary cancer risks. A recent report on leukemia mortality suggested that the effect of radiation on leukemia mortality persisted for more than five decades. In addition, a significant dose-response for myelodysplastic syndrome is found in Nagasaki LSS members 40-60 y after radiation exposure. In view of the nature of the continuing increase in solid cancers, the LSS should continue to provide important new information on cancer risks, as most survivors still alive today were exposed to the atomic bomb radiation under the age of 20 y and are now entering their cancer-prone years. PMID:22908358

  3. Loss of PTEN stabilizes the lipid modifying enzyme cytosolic phospholipase A2α via AKT in prostate cancer cells

    PubMed Central

    Vignarajan, Soma; Xie, Chanlu; Yao, Mu; Sun, Yuting; Simanainen, Ulla; Sved, Paul; Liu, Tao; Dong, Qihan

    2014-01-01

    Aberrant increase in pAKT, due to a gain-of-function mutation of PI3K or loss-of-function mutation or deletion of PTEN, occurs in prostate cancer and is associated with poor patient prognosis. Cytosolic phospholipase A2α (cPLA2α) is a lipid modifying enzyme by catalyzing the hydrolysis of membrane arachidonic acid. Arachidonic acid and its metabolites contribute to survival and proliferation of prostate cancer cells. We examined whether AKT plays a role in promoting cPLA2α action in prostate cancer cells. We found a concordant increase in pAKT and cPLA2α levels in prostate tissue of prostate epithelial-specific PTEN-knockout but not PTEN-wide type mice. Restoration of PTEN expression or inhibition of PI3K action decreased cPLA2α expression in PTEN-mutated or deleted prostate cancer cells. An increase in AKT by Myr-AKT elevated cPLA2α protein levels, which could be diminished by inhibition of AKT phosphorylation without noticeable change in total AKT levels. pAKT levels had no influence on cPLA2α at mRNA levels but reduced cPLA2α protein degradation. Anti-AKT antibody co-immunoprecipitated cPLA2α and vice versa. Hence, AKT plays a role in enhancing cPLA2α protein stability in PTEN-null prostate cancer cells, revealing a link between oncogenic pathway and lipid metabolism. PMID:25026288

  4. Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

    PubMed Central

    Osorio, A; Milne, R L; Pita, G; Peterlongo, P; Heikkinen, T; Simard, J; Chenevix-Trench, G; Spurdle, A B; Beesley, J; Chen, X; Healey, S; Neuhausen, S L; Ding, Y C; Couch, F J; Wang, X; Lindor, N; Manoukian, S; Barile, M; Viel, A; Tizzoni, L; Szabo, C I; Foretova, L; Zikan, M; Claes, K; Greene, M H; Mai, P; Rennert, G; Lejbkowicz, F; Barnett-Griness, O; Andrulis, I L; Ozcelik, H; Weerasooriya, N; Gerdes, A-M; Thomassen, M; Cruger, D G; Caligo, M A; Friedman, E; Kaufman, B; Laitman, Y; Cohen, S; Kontorovich, T; Gershoni-Baruch, R; Dagan, E; Jernström, H; Askmalm, M S; Arver, B; Malmer, B; Domchek, S M; Nathanson, K L; Brunet, J; Ramón y Cajal, T; Yannoukakos, D; Hamann, U; Hogervorst, F B L; Verhoef, S; García, EB Gómez; Wijnen, J T; van den Ouweland, A; Easton, D F; Peock, S; Cook, M; Oliver, C T; Frost, D; Luccarini, C; Evans, D G; Lalloo, F; Eeles, R; Pichert, G; Cook, J; Hodgson, S; Morrison, P J; Douglas, F; Godwin, A K; Sinilnikova, O M; Barjhoux, L; Stoppa-Lyonnet, D; Moncoutier, V; Giraud, S; Cassini, C; Olivier-Faivre, L; Révillion, F; Peyrat, J-P; Muller, D; Fricker, J-P; Lynch, H T; John, E M; Buys, S; Daly, M; Hopper, J L; Terry, M B; Miron, A; Yassin, Y; Goldgar, D; Singer, C F; Gschwantler-Kaulich, D; Pfeiler, G; Spiess, A-C; Hansen, Thomas v O; Johannsson, O T; Kirchhoff, T; Offit, K; Kosarin, K; Piedmonte, M; Rodriguez, G C; Wakeley, K; Boggess, J F; Basil, J; Schwartz, P E; Blank, S V; Toland, A E; Montagna, M; Casella, C; Imyanitov, E N; Allavena, A; Schmutzler, R K; Versmold, B; Engel, C; Meindl, A; Ditsch, N; Arnold, N; Niederacher, D; Deißler, H; Fiebig, B; Varon-Mateeva, R; Schaefer, D; Froster, U G; Caldes, T; de la Hoya, M; McGuffog, L; Antoniou, A C; Nevanlinna, H; Radice, P; Benítez, J

    2009-01-01

    Background: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. Methods: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. Results: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93–1.04, P=0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89–1.06, P=0.5) mutation carriers. Conclusion: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out. PMID:19920816

  5. Evaluation of Modified Categorical Data Fuzzy Clustering Algorithm on the Wisconsin Breast Cancer Dataset.

    PubMed

    Ahmad, Amir

    2016-01-01

    The early diagnosis of breast cancer is an important step in a fight against the disease. Machine learning techniques have shown promise in improving our understanding of the disease. As medical datasets consist of data points which cannot be precisely assigned to a class, fuzzy methods have been useful for studying of these datasets. Sometimes breast cancer datasets are described by categorical features. Many fuzzy clustering algorithms have been developed for categorical datasets. However, in most of these methods Hamming distance is used to define the distance between the two categorical feature values. In this paper, we use a probabilistic distance measure for the distance computation among a pair of categorical feature values. Experiments demonstrate that the distance measure performs better than Hamming distance for Wisconsin breast cancer data. PMID:27022504

  6. [A case report of residual gastric cancer 15 years after pancreatoduodenectomy with modified child's reconstruction].

    PubMed

    Yamada, Masanori; Nakai, Koji; Inoue, Kentaro; Matsuura, Takashi; Yanagida, Hidesuke; Kitade, Hiroaki; Yoshioka, Kazuhiko; Hamada, Madoka; Kwon, A-Hon

    2014-11-01

    A 75-year-old man underwent pancreatoduodenectomy for pancreatic cancer. He had presented with epigastralgia in June 2008. Gastrointestinal endoscopy revealed type 2 gastric cancer in the cardiac area. Enhanced abdominal CT scanning confirmed an enhanced mass in the cardiac area. Gastrectomy with Roux-en-Y reconstruction was performed for residual gastric cancer. Histopathological findings revealed, pT3(SS), pN0, pH0, pP0, pStageIIA. Single-agent TS-1 therapy was chosen as adjuvant chemotherapy but was changed to TS-1+CDDP because of CT-detected recurrence 3 months after the second operation. After a 6 month course of chemotherapy, complete reduction of the tumor was obtained. PMID:25731550

  7. Cyclodextrin-Modified Porous Silicon Nanoparticles for Efficient Sustained Drug Delivery and Proliferation Inhibition of Breast Cancer Cells.

    PubMed

    Correia, Alexandra; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Almeida, Sérgio; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

    2015-10-21

    Over the past decade, the potential of polymeric structures has been investigated to overcome many limitations related to nanosized drug carriers by modulating their toxicity, cellular interactions, stability, and drug-release kinetics. In this study, we have developed a successful nanocomposite consisting of undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with an anticancer drug, sorafenib, and surface-conjugated with heptakis(6-amino-6-deoxy)-β-cyclodextrin (HABCD) to show the impact of the surface polymeric functionalization on the physical and biological properties of the drug-loaded nanoparticles. Cytocompatibility studies showed that the UnTHCPSi-HABCD NPs were not toxic to breast cancer cells. HABCD also enhanced the suspensibility and both the colloidal and plasma stabilities of the UnTHCPSi NPs. UnTHCPSi-HABCD NPs showed a significantly increased interaction with breast cancer cells compared to bare NPs and also sustained the drug release. Furthermore, the sorafenib-loaded UnTHCPSi-HABCD NPs efficiently inhibited cell proliferation of the breast cancer cells. PMID:26440739

  8. [A case of hyperammonemic encephalopathy in a patient with recurrent colon cancer treated with modified FOLFOX6].

    PubMed

    Teraishi, Fuminori; Suzuki, Takeo; Nakamoto, Masako; Chikuba, Akira; Nezu, Masashi; Shimamura, Hiroshi; Watanabe, Takamasa; Matsuda, Tadakazu; Takiue, Takao; Chikuba, Hiroshi

    2009-05-01

    FOLFOX therapy is a commonly used chemotherapeutic regimen against recurrent and unresectable colon cancer. However, its acute neurotoxicity is rare and not well recognized. We herein report a case of mFOLFOX6-induced hyperammonemic encephalopathy in a patient having recurrent colon cancer. A 74-year-old female with a history of sigmoid colon cancer was diagnosed as liver, lung, and peritoneal recurrences by surveillance CT and PET/CT. She was initially treated with modified FOLFOX6 therapy. After completing treatment, she presented with sudden onset of confusion, cognitive disturbances, and repeated seizures. None of the other radiographic examinations and laboratory tests provided an explanation for her symptoms except hyperammonemia. She was treated with branched-chain amino acid solutions and high-volume drip infusion, 6 hours after which the encephalopathy resolved. Clinicians should be aware of the adverse hyperammonemia induced by mFOLFOX6 when patients treated with mFOLFOX6 present with neurological disorders. PMID:19461197

  9. Regulatory Match Effects on a Modified Wisconsin Card Sort Task

    PubMed Central

    Maddox, W. Todd; Filoteo, J. Vincent; Glass, Brian D.; Markman, Arthur B.

    2009-01-01

    The Wisconsin Card Sorting Task (WCST; Heaton, 1980) is commonly used to assess concept formation and set shifting. Cognitive research suggests that set shifting performance is enhanced by a match between a person’s regulatory focus (promotion focus: attempting to earn an entry into a cash drawing; prevention focus: attempting to avoid losing an entry into the drawing) and the task reward structure (gains: attempting to maximize points gained; losses: attempting to minimize points lost). A regulatory match results when attempting to earn an entry by maximizing points or attempting to avoid losing an entry by minimizing losses. We test the hypothesis that performance on a modified WCST is accentuated in younger, healthy participants when there is a match between the global performance incentive and the local task reward structure. As predicted, participants in a match showed better set shifting but equivalent initial concept formation when compared to participants in a mismatch. Further, relative to a baseline control group, mismatch participants were significantly worse at set shifting than were participants in a regulatory match. These results suggest that set shifting performance might be impacted by incentive and task reward factors in ways that have not been considered previously. PMID:20128935

  10. Toxicity and therapy of cisplatin-loaded EGF modified mPEG-PLGA-PLL nanoparticles for SKOV3 cancer in mice.

    PubMed

    Wang, Yunfei; Liu, Peifeng; Qiu, Lihua; Sun, Ying; Zhu, Mingjie; Gu, Liying; Di, Wen; Duan, Yourong

    2013-05-01

    Construction on the nanoparticles with lower toxicity and specific tumor targeting properties is challenging and requires careful design of composition, size, physicochemical properties tailored for the nanoparticles. Here the epidermal growth factor (EGF) modified methoxy polyethylene glycol-polylactic-co-glycolic acid-polylysine (mPEG-PLGA-PLL) encapsulated cisplatin (CDDP) nanoparticles (CDDP-NPs-EGF) was prepared to for solving the toxicity of CDDP and improving therapeutic efficiency. The remarkable features of CDDP-NPs-EGF are increasing cytotoxicity that attribute to effective cell cycle arrest and high cell apoptosis in vitro. In vivo, the CDDP-NPs-EGF change drug distribution, decrease the nephrotoxicity of CDDP and improve significantly therapeutic efficiency without inducing obvious system toxicity, verifying its key role of the CDDP-NPs-EGF in lowering drug toxicity and enhancing the antitumor efficiency for SKOV3 cancer in mice. PMID:23480957

  11. Modified Logistic Regression Models Using Gene Coexpression and Clinical Features to Predict Prostate Cancer Progression

    PubMed Central

    Zhao, Hongya; Logothetis, Christopher J.; Gorlov, Ivan P.; Zeng, Jia; Dai, Jianguo

    2013-01-01

    Predicting disease progression is one of the most challenging problems in prostate cancer research. Adding gene expression data to prediction models that are based on clinical features has been proposed to improve accuracy. In the current study, we applied a logistic regression (LR) model combining clinical features and gene co-expression data to improve the accuracy of the prediction of prostate cancer progression. The top-scoring pair (TSP) method was used to select genes for the model. The proposed models not only preserved the basic properties of the TSP algorithm but also incorporated the clinical features into the prognostic models. Based on the statistical inference with the iterative cross validation, we demonstrated that prediction LR models that included genes selected by the TSP method provided better predictions of prostate cancer progression than those using clinical variables only and/or those that included genes selected by the one-gene-at-a-time approach. Thus, we conclude that TSP selection is a useful tool for feature (and/or gene) selection to use in prognostic models and our model also provides an alternative for predicting prostate cancer progression. PMID:24367394

  12. Non-cancer health effects of pesticides

    PubMed Central

    Sanborn, M.; Kerr, K.J.; Sanin, L.H.; Cole, D.C.; Bassil, K.L.; Vakil, C.

    2007-01-01

    OBJECTIVE To investigate whether there are associations between exposure to pesticides and 4 chronic non-cancer health effects: dermatologic, neurologic, reproductive, and genotoxic effects. DATA SOURCES We searched PreMedline, MEDLINE, and LILACS using the key word pesticide combined with the term for the specific health effect being searched. Reviewers scanned the references of all articles for additional relevant studies. STUDY SELECTION Studies since 1992 were assessed using structured inclusion and quality-of-methods criteria. Studies scoring <4 on a 7-point global methodologic quality scale were excluded. In total, 124 studies were included. These studies had a mean quality score of 4.88 out of 7. SYNTHESIS Strong evidence of association with pesticide exposure was found for all neurologic outcomes, genotoxicity, and 4 of 6 reproductive effects: birth defects, fetal death, altered growth, and other outcomes. Exposure to pesticides generally doubled the level of genetic damage as measured by chromosome aberrations in lymphocytes. Only a few high-quality studies focused on the dermatologic effects of pesticides. In some of these studies, rates of dermatitis were higher among those who had had high exposure to pesticides on the job. CONCLUSION Evidence from research on humans consistently points to positive associations between pesticide exposure and 3 of the 4 non-cancer health outcomes studied. Physicians have a dual role in educating individual patients about the risks of exposure and in reducing exposure in the community by advocating for restrictions on use of pesticides. PMID:17934035

  13. Heat-modified citrus pectin induces apoptosis-like cell death and autophagy in HepG2 and A549 cancer cells.

    PubMed

    Leclere, Lionel; Fransolet, Maude; Cote, Francois; Cambier, Pierre; Arnould, Thierry; Van Cutsem, Pierre; Michiels, Carine

    2015-01-01

    Cancer is still one of the leading causes of death worldwide, and finding new treatments remains a major challenge. Previous studies showed that modified forms of pectin, a complex polysaccharide present in the primary plant cell wall, possess anticancer properties. Nevertheless, the mechanism of action of modified pectin and the pathways involved are unclear. Here, we show that citrus pectin modified by heat treatment induced cell death in HepG2 and A549 cells. The induced cell death differs from classical apoptosis because no DNA cleavage was observed. In addition, Z-VAD-fmk, a pan-caspase inhibitor, did not influence the observed cell death in HepG2 cells but appeared to be partly protective in A549 cells, indicating that heat-modified citrus pectin might induce caspase-independent cell death. An increase in the abundance of the phosphatidylethanolamine-conjugated Light Chain 3 (LC3) protein and a decrease in p62 protein abundance were observed in both cell types when incubated in the presence of heat-modified citrus pectin. These results indicate the activation of autophagy. To our knowledge, this is the first time that autophagy has been revealed in cells incubated in the presence of a modified form of pectin. This autophagy activation appears to be protective, at least for A549 cells, because its inhibition with 3-methyladenine increased the observed modified pectin-induced cytotoxicity. This study confirms the potential of modified pectin to improve chemotherapeutic cancer treatments. PMID:25794149

  14. Heat-Modified Citrus Pectin Induces Apoptosis-Like Cell Death and Autophagy in HepG2 and A549 Cancer Cells

    PubMed Central

    Leclere, Lionel; Fransolet, Maude; Cote, Francois; Cambier, Pierre; Arnould, Thierry; Van Cutsem, Pierre; Michiels, Carine

    2015-01-01

    Cancer is still one of the leading causes of death worldwide, and finding new treatments remains a major challenge. Previous studies showed that modified forms of pectin, a complex polysaccharide present in the primary plant cell wall, possess anticancer properties. Nevertheless, the mechanism of action of modified pectin and the pathways involved are unclear. Here, we show that citrus pectin modified by heat treatment induced cell death in HepG2 and A549 cells. The induced cell death differs from classical apoptosis because no DNA cleavage was observed. In addition, Z-VAD-fmk, a pan-caspase inhibitor, did not influence the observed cell death in HepG2 cells but appeared to be partly protective in A549 cells, indicating that heat-modified citrus pectin might induce caspase-independent cell death. An increase in the abundance of the phosphatidylethanolamine-conjugated Light Chain 3 (LC3) protein and a decrease in p62 protein abundance were observed in both cell types when incubated in the presence of heat-modified citrus pectin. These results indicate the activation of autophagy. To our knowledge, this is the first time that autophagy has been revealed in cells incubated in the presence of a modified form of pectin. This autophagy activation appears to be protective, at least for A549 cells, because its inhibition with 3-methyladenine increased the observed modified pectin-induced cytotoxicity. This study confirms the potential of modified pectin to improve chemotherapeutic cancer treatments. PMID:25794149

  15. Genetic polymorphisms in DNA repair and oxidative stress pathways may modify the association between body size and postmenopausal breast cancer

    PubMed Central

    McCullough, Lauren E.; Eng, Sybil M.; Bradshaw, Patrick T.; Cleveland, Rebecca J.; Steck, Susan E.; Terry, Mary Beth; Shen, Jing; Crew, Katherine D.; Rossner, Pavel; Ahn, Jiyoung; Ambrosone, Christine B.; Teitelbaum, Susan L.; Neugut, Alfred I.; Santella, Regina M.; Gammon, Marilie D.

    2015-01-01

    Purpose Obesity is associated with increased bioavailability of estrogen, hyperinsulemia and chronic inflammation, all of which may promote tumor growth. Given DNA repair and oxidative stress pathways may work together with these mechanisms to influence carcinogenesis, we hypothesized that genetic variation in these pathways may modify the obesity-postmenopausal breast cancer association. Methods Resources from a population-based case-control study (990 cases/970 controls) were used to construct logistic regression models. Body mass index (BMI, weight kg/height m2) was assessed 1-year prior to reference date. We characterized interactions between BMI and 29 genetic polymorphisms in oxidative stress and DNA repair pathways. Results Age-adjusted odds ratios (95% confidence intervals) for postmenopausal breast cancer were 1.24 (1.00–1.52) and 1.35 (1.09–1.71) for 25≥BMI<30 and BMI≥30, respectively. We observed multiplicative interactions (p≤0.05) for eight gene polymorphisms in DNA repair and oxidative stress pathways. For example, among MPO variant allele carriers, obesity was associated with a two-fold increased risk of postmenopausal breast cancer [2.13 (1.35–3.36)]; however in wild-type homozygotes, the relationship was less pronounced [1.33 (0.93–1.89)]. Our findings were no longer significant after Bonferroni correction. Conclusions Obesity may be particularly deleterious for postmenopausal breast cancer development in the presence of biologically plausible DNA repair or oxidative stress genotypes. PMID:25703993

  16. The 3' untranslated region C > T polymorphism of prohibitin is a breast cancer risk modifier in Polish women carrying a BRCA1 mutation.

    PubMed

    Jakubowska, Anna; Gronwald, Jacek; Górski, Bohdan; Huzarski, Tomasz; Byrski, Tomasz; Benner, Axel; Lubiński, Jan; Scott, Rodney J; Hamann, Ute

    2007-07-01

    The variable penetrance of breast cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. The C to T transition in the 3' untranslated region of the prohibitin (PHB) gene alters mRNA function and has been shown to be associated with an increased breast cancer risk among young North-American women who have one first-degree relative with breast cancer. To investigate whether the PHB 3'UTR polymorphism acts as a modifier of hereditary breast cancer risk we performed a case-control study among female BRCA1 mutation carriers, which included 258 cases and 258 controls who were unaffected by ovarian cancer, in situ breast carcinoma or any other type of cancer. Controls were matched to cases by year of birth and BRCA1 mutation (5382insC, 300 T > G, 4153delA). Genotyping analysis was performed using RFLP-PCR. Odds ratios (OR) were calculated using conditional and penalised univariable and multivariable logistic regression. Multivariable penalised logistic regression revealed CT (OR(adj), 2.03; 95% CI, 1.17-3.59) and combined CT + TT (OR(adj), 2.12; 95% CI, 1.23-3.70) genotypes as significant modifiers of breast cancer risk. Breast cancer risk did not differ between carriers of the 300 T > G and 5382insC mutation. Our results suggest that the PHB 3'UTR T allele increases the risk of breast cancer in patients who are already at increased risk of disease. PMID:17004108

  17. Effective field theory from modified gravity with massive modes

    NASA Astrophysics Data System (ADS)

    Capozziello, Salvatore; de Laurentis, Mariafelicia; Paolella, Mariacristina; Ricciardi, Giulia

    2015-10-01

    Massive gravitational modes in effective field theories can be recovered by extending General Relativity and taking into account generic functions of the curvature invariants, not necessarily linear in the Ricci scalar R. In particular, adopting the minimal extension of f(R) gravity, an effective field theory with massive modes is straightforwardly recovered. This approach allows to evade shortcomings like ghosts and discontinuities if a suitable choice of expansion parameters is performed.

  18. Unintended effects and their detection in genetically modified crops.

    PubMed

    Cellini, F; Chesson, A; Colquhoun, I; Constable, A; Davies, H V; Engel, K H; Gatehouse, A M R; Kärenlampi, S; Kok, E J; Leguay, J-J; Lehesranta, S; Noteborn, H P J M; Pedersen, J; Smith, M

    2004-07-01

    The commercialisation of GM crops in Europe is practically non-existent at the present time. The European Commission has instigated changes to the regulatory process to address the concerns of consumers and member states and to pave the way for removing the current moratorium. With regard to the safety of GM crops and products, the current risk assessment process pays particular attention to potential adverse effects on human and animal health and the environment. This document deals with the concept of unintended effects in GM crops and products, i.e. effects that go beyond that of the original modification and that might impact primarily on health. The document first deals with the potential for unintended effects caused by the processes of transgene insertion (DNA rearrangements) and makes comparisons with genetic recombination events and DNA rearrangements in traditional breeding. The document then focuses on the potential value of evolving "profiling" or "omics" technologies as non-targeted, unbiased approaches, to detect unintended effects. These technologies include metabolomics (parallel analysis of a range of primary and secondary metabolites), proteomics (analysis of polypeptide complement) and transcriptomics (parallel analysis of gene expression). The technologies are described, together with their current limitations. Importantly, the significance of unintended effects on consumer health are discussed and conclusions and recommendations presented on the various approaches outlined. PMID:15123383

  19. Effects of extrinsic curvature as modified Chaplygin gas and Lorentz violation

    NASA Astrophysics Data System (ADS)

    Ahmadi, F.

    2016-05-01

    The modified Chaplygin gas may be considered as a popular candidate for dark energy. We apply a gravitational explanation for the modified Chaplygin gas within the context of brane-world theory without using any junction condition or Z2 symmetry. Then, we study the behavior of the deceleration parameter and age of the universe in this framework. Also, we investigate the effect of the modified Chaplygin gas on the speed of the propagation of gravitational waves and explore local Lorentz violation in this model.

  20. Monitoring of environmental cancer initiators through hemoglobin adducts by a modified Edman degradation method

    SciTech Connect

    Toernqvist, M.M.; Mowrer, J.; Jensen, S.; Ehrenberg, L.

    1986-04-01

    Tissue doses of cancer initiators/mutagens are suitably monitored through hemoglobin adducts formed in vivo, but the use of this method has been hampered by a lack of sufficiently simple and fast procedures. It was previously observed that when the N-terminal amino acid in hemoglobin, valine, is alkylated it is cleaved off by the Edman sequencing reagent, phenyl isothiocyanate, in the neutral-alkaline coupling medium, as opposed to the acidic medium required by normal amino acids. Based on this principle, conditions for a functioning procedure for gas chromatography/mass spectrometry (GC/MS) determination of N-terminal alkylvalines in hemoglobin were worked out. Derivatizing the protein in formamide solution with pentafluorophenyl isothiocyanate, using a /sup 2/H-alkylated protein as internal standard, and applying on-column injection during analysis, permit reproducible determination of hydroxyethylvaline and other adducts down into the dose range where cancer risks may be considered acceptably low.

  1. Breast Cancer Preoperative Staging: Does Contrast-Enhanced Magnetic Resonance Mammography Modify Surgery?

    PubMed Central

    Perono Biacchiardi, Chiara; Brizzi, Davide; Genta, Franco; Zanon, Eugenio; Camanni, Marco; Deltetto, Francesco

    2011-01-01

    Women with newly diagnosed breast cancer may have lesions undetected by conventional imaging. Recently contrast-enhanced magnetic resonance mammography (CE-MRM) showed higher sensitivity in breast lesions detection. The present analysis was aimed at evaluating the benefit of preoperative CE-MRM in the surgical planning. From 2005 to 2009, 525 consecutive women (25–75 years) with breast cancer, newly diagnosed by mammography, ultrasound, and needle-biopsy, underwent CE-MRM. The median invasive tumour size was 19 mm. In 144 patients, CE-MRM identified additional lesions. After secondlook, 119 patients underwent additional biopsy. CE-MRM altered surgery in 118 patients: 57 received double lumpectomy or wider excision (41 beneficial), 41 required mastectomy (40 beneficial), and 20 underwent contra lateral surgery (18 beneficial). The overall false-positive rate was 27.1% (39/144). CE-MRM contributed significantly to the management of breast cancer, suggesting more extensive disease in 144/525 (27.4%) patients and changing the surgical plan in 118/525 (22.5%) patients (99/525, 18.8% beneficial). PMID:22295233

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

    PubMed

    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

  3. Antitumor effect of traditional Chinese herbal medicines against lung cancer.

    PubMed

    Chen, Yuezhou; Zhu, Jianping; Zhang, Wenpeng

    2014-10-01

    Traditional Chinese herbal medicine (TCHM) is used widely alone or in combination with chemotherapy to treat lung cancer in China. Meta-analysis of clinical trials of TCHM against lung cancer suggested the potential, but not confirmed therapeutic effect. To gain detailed insight into the antilung cancer effects of TCHM, we searched for preclinical studies of TCHM against lung cancer published from 1995 to 2012 and systematically analyzed published articles focusing on the antitumor effect of individual TCHM in lung cancer cell lines or animal models. Among 93 herbal components isolated from 73 Chinese herbs, we found 10 herbal compounds that showed the strongest cytotoxicity in lung cancer cell lines through apoptosis or cell cycle arrest, and agents isolated from seven Chinese herbs that inhibited the primary tumor growth more than 35% in A549 xenografted mice models. In addition, three herbal components suppressed lung cancer cell migration in vitro at the concentration without cytotoxicity. Polyphyllin I, tanshinone IIA, isochaihulactone, 25-OCH3-PPD, and andrographolide were the five TCHM compounds that showed strong antilung cancer effects both in cells and in animal models, and studies of their analogs showed their structure-activity relationships. This review summarizes and analyzes contemporary studies on the antitumor effect of individual TCHM against lung cancer and animal models, providing perspectives to better understand the TCHM effect in lung cancer treatment and develop new antilung cancer drugs from TCHM. PMID:24892722

  4. Coffee Polyphenols Change the Expression of STAT5B and ATF-2 Modifying Cyclin D1 Levels in Cancer Cells

    PubMed Central

    Oleaga, Carlota; Ciudad, Carlos J.; Noé, Véronique; Izquierdo-Pulido, Maria

    2012-01-01

    Background. Epidemiological studies suggest that coffee consumption reduces the risk of cancer, but the molecular mechanisms of its chemopreventive effects remain unknown. Objective. To identify differentially expressed genes upon incubation of HT29 colon cancer cells with instant caffeinated coffee (ICC) or caffeic acid (CA) using whole-genome microarrays. Results. ICC incubation of HT29 cells caused the overexpression of 57 genes and the underexpression of 161, while CA incubation induced the overexpression of 12 genes and the underexpression of 32. Using Venn-Diagrams, we built a list of five overexpressed genes and twelve underexpressed genes in common between the two experimental conditions. This list was used to generate a biological association network in which STAT5B and ATF-2 appeared as highly interconnected nodes. STAT5B overexpression was confirmed at the mRNA and protein levels. For ATF-2, the changes in mRNA levels were confirmed for both ICC and CA, whereas the decrease in protein levels was only observed in CA-treated cells. The levels of cyclin D1, a target gene for both STAT5B and ATF-2, were downregulated by CA in colon cancer cells and by ICC and CA in breast cancer cells. Conclusions. Coffee polyphenols are able to affect cyclin D1 expression in cancer cells through the modulation of STAT5B and ATF-2. PMID:22919439

  5. Intellectual Disability Modifies Gender Effects on Disruptive Behaviors

    ERIC Educational Resources Information Center

    Einfeld, Stewart L.; Gray, Kylie M.; Ellis, Louise A.; Taffe, John; Emerson, Eric; Tonge, Bruce J.; Horstead, Sian K.

    2010-01-01

    In typically developing children, boys are more commonly diagnosed than girls with disruptive behavior disorders, namely, attention-deficit/hyperactivity disorder, conduct disorder, and oppositional defiant disorder. For children with intellectual disability (ID), the evidence for this gender effect is less clear. In this report we examine gender…

  6. Effects of Yoga on Cancer-Related Fatigue and Global Side-Effect Burden in Older Cancer Survivors

    PubMed Central

    Sprod, Lisa K.; Fernandez, Isabel D.; Janelsins, Michelle C.; Peppone, Luke J.; Atkins, James N.; Giguere, Jeffrey; Block, Robert; Mustian, Karen M.

    2014-01-01

    Background Sixty percent of cancer survivors are 65 years of age or older. Cancer and its treatments lead to cancer-related fatigue and many other side effects, in turn, creating substantial global side-effect burden (total burden from all side effects) which, ultimately, compromises functional independence and quality of life. Various modes of exercise, such as yoga, reduce cancer-related fatigue and global side-effect burden in younger cancer survivors, but no studies have specifically examined the effects of yoga on older cancer survivors. Objectives The purpose of this study was to assess the effects of a 4-week yoga intervention (Yoga for Cancer Survivors: YOCAS©®) on overall cancer-related fatigue, and due to its multidimensional nature, the subdomains of cancer-related fatigue (general, physical, emotional, and mental) and global side-effect burden in older cancer survivors. Materials and Methods We conducted a secondary analysis on data from a multicenter phase III randomized controlled clinical trial with 2 arms (standard care and standard care plus a 4-week YOCAS©® intervention). The sample for this secondary analysis was 97 older cancer survivors (≥ 60 years of age), between 2 months and 2 years post-treatment, who participated in the original trial. Results Participants in the YOCAS©® intervention arm reported significantly lower cancer-related fatigue, physical fatigue, mental fatigue, and global side-effect burden than participants in the standard care arm following the 4-week intervention period (p<0.05). Conclusions YOCAS©® is an effective standardized yoga intervention for reducing cancer-related fatigue, physical fatigue, mental fatigue, and global side-effect burden among older cancer survivors. PMID:25449185

  7. Effect of modified aminosilane interfaces in glass/epoxy composites

    SciTech Connect

    Porter, C.E.; Blum, F.D.

    1996-10-01

    The effects of the interfacial modification of glass/epoxy composites have been studied using 3-point bending tests. Hydrolyzed {gamma}-aminopropyltriethyoxysilane APS and {gamma}-aminobutyltriethoxysilane (ABS) were separately adsorbed onto E-glass and the treated fibers were then used in composites that used both a diglycidyl ether of bisphenol A and a diglycidyl ether of polypropylene epoxy matrix. Mechanical tests were used to characterize the flexural strength of the composite as a function of the silane coupling agent and the flexibility of the epoxy used.

  8. Efficient CD44-targeted magnetic resonance imaging (MRI) of breast cancer cells using hyaluronic acid (HA)-modified MnFe2O4 nanocrystals

    PubMed Central

    2013-01-01

    Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA, is closely related to the growth of cancer including proliferation, metastasis, invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a few kinds of HA-modified MnFe2O4 nanocrystals (MNCs) to serve as specific magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs were efficiently phase-transferred using aminated polysorbate 80 (P80) synthesized by introducing spermine molecules on the hydroxyl groups of P80. Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different ratios of HA on the equal amount of phase-transferred MNCs. The optimized conjugation ratio of HA against magnetic content was identified to exhibit not only effective CD44 finding ability but also high cell viability through in vitro experiments. The results of this study demonstrate that the suggested HA-MRCA shows strong potential to be used for accurate tumor diagnosis. PMID:23547716

  9. Efficient CD44-targeted magnetic resonance imaging (MRI) of breast cancer cells using hyaluronic acid (HA)-modified MnFe2O4 nanocrystals

    NASA Astrophysics Data System (ADS)

    Lee, Taeksu; Lim, Eun-Kyung; Lee, Jaemin; Kang, Byunghoon; Choi, Jihye; Park, Hyo Seon; Suh, Jin-Suck; Huh, Yong-Min; Haam, Seungjoo

    2013-04-01

    Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA, is closely related to the growth of cancer including proliferation, metastasis, invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a few kinds of HA-modified MnFe2O4 nanocrystals (MNCs) to serve as specific magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs were efficiently phase-transferred using aminated polysorbate 80 (P80) synthesized by introducing spermine molecules on the hydroxyl groups of P80. Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different ratios of HA on the equal amount of phase-transferred MNCs. The optimized conjugation ratio of HA against magnetic content was identified to exhibit not only effective CD44 finding ability but also high cell viability through in vitro experiments. The results of this study demonstrate that the suggested HA-MRCA shows strong potential to be used for accurate tumor diagnosis.

  10. Properties of modified dry masonry mixtures for effective masonry units

    NASA Astrophysics Data System (ADS)

    Semenov, V.; Rozovskaya, T.

    2015-01-01

    The paper is devoted to the problem of the development of dry light-weight mixtures with hollow ceramics microspheres (CMS) for masonry works. For the one-layer fencing structures including effective masonry units, the use of "warm" masonry mortars is necessary. The used light-weight masonry mortars do not provide the brand strength and thermal uniformity of the fencing structures because of high average density. The CMS are effective light-weight aggregate for such mortars. The influence of the dosage of CMS on the physics- and-mechanics parameters and the technological properties of the masonry mortars has been studied. The optimal mixture compositions have been obtained and their main properties have been determined. The influence of an air-entraining admixture and redispersible polymer powders on the average density and physics-and-mechanics parameters of the masonry mortars have been studied. The optimal compositions of light-weight dry masonry mixtures with CMS have been suggested. It has been established that the mortars, obtained from such mixtures, have the requisite average density, the water retention capacity more than 95 %, high homogeneity and high strength characteristics. The application of the proposed mixtures enables to reduce the construction material costs and to improve the energy efficiency of the fencing structures.

  11. Biological effects of hexitol and altritol-modified siRNAs targeting B-Raf

    PubMed Central

    Fisher, Michael; Abramov, Mikhail; Van Aerschot, Arthur; Rozenski, Jef; Dixit, Vidula; Juliano, Rudy L.; Herdewijn, Piet

    2009-01-01

    Increasing the effectiveness of siRNAs through chemical modification is an important task. Here we describe altritol and hexitol modified oligonucleotides targeting the B-Raf oncogene that is critical for the growth and survival of melanoma cells. Using assays for apoptosis, DNA synthesis, colony formation and B-Raf protein and message levels, we demonstrate that certain hexitol modifications can improve the effectiveness of B-Raf siRNAs and also increase duration of action. Altritol modified siRNAs were similar to or slightly less effective than unmodified B-Raf siRNA. Modifications at the 3′ or 5′ end of the sense strand, at the 3′ end of the antisense strand, or within either strand were well tolerated. The basis for the increased effectiveness of the hexitol-modified siRNAs is not fully understood but may be partly due to increased stability to nucleases. PMID:19374843

  12. A modified evaluation method to reduce finite pulse time effects in flash diffusivity measurement

    NASA Astrophysics Data System (ADS)

    Tao, Ye; Yang, Liping; Zhong, Qiu; Xu, Zijun; Luo, Caiyun

    2015-12-01

    A modified evaluation method for laser flash is proposed. In this method, the moment of laser-heating cutoff time is considered as zero point. The penetration depth and formula equation of the sample temperature distribution are obtained with the approximate analytical solution before time zero (during laser heating) for the physical model of a continuously heated half-infinite, well-distributed sample. The weighted-average and approximate-equation methods are then used to quantitatively determine the laser effect depth, which leads to the formulation of a modified evaluation method in flash thermal diffusivity measurement. Results of the simulation calculations and experiments confirm the correctness of the modified method, which remarkably increases flash method applications. The modified method is applicable only to cases in which δ(x) does not exceed the sample thickness ( √{ 12 α τ 0 } ≤ L ) during laser heating.

  13. A modified evaluation method to reduce finite pulse time effects in flash diffusivity measurement.

    PubMed

    Tao, Ye; Yang, Liping; Zhong, Qiu; Xu, Zijun; Luo, Caiyun

    2015-12-01

    A modified evaluation method for laser flash is proposed. In this method, the moment of laser-heating cutoff time is considered as zero point. The penetration depth and formula equation of the sample temperature distribution are obtained with the approximate analytical solution before time zero (during laser heating) for the physical model of a continuously heated half-infinite, well-distributed sample. The weighted-average and approximate-equation methods are then used to quantitatively determine the laser effect depth, which leads to the formulation of a modified evaluation method in flash thermal diffusivity measurement. Results of the simulation calculations and experiments confirm the correctness of the modified method, which remarkably increases flash method applications. The modified method is applicable only to cases in which δ(x) does not exceed the sample thickness (√(12ατ0)≤L) during laser heating. PMID:26724057

  14. Morphological Effect of Non-targeted Biomolecule-Modified MNPs on Reticuloendothelial System.

    PubMed

    Li, Xiao; Hu, Yan; Xiao, Jie; Cheng, Dengfeng; Xiu, Yan; Shi, Hongcheng

    2015-12-01

    Magnetic nanoparticles (MNPs) with special morphology were commonly used as biomaterials, while morphological effects of non-targeted biomolecule-modified MNPs on biological behaviors were still unclear. In this research, spherical and rod-like Fe3O4 in a comparable size were synthesized and then surface-modified by bovine serum albumin (BSA) as a model of non-targeted biomolecule-modified MNPs. Morphological effects were featured by TEM and quantification of in vitro phagocytic uptake, as well as the in vivo quantification of particles in reticuloendothelial system (RES)-related organs of normal Kunming mice. For these non-targeted BSA-modified MNPs, intracellular distributions were the same, but the rod-like MNPs were more likely to be uptake by macrophages; furthermore, the BSA-modified MNPs gathered in RES-related organs soon after intravenous injection, but the rod-like ones were expelled from the lung more quickly and expelled from the spleen more slowly. These preliminary results may be referable if MNPs or other similar biomolecule-modified nanoparticles were used. PMID:26383542

  15. Morphological Effect of Non-targeted Biomolecule-Modified MNPs on Reticuloendothelial System

    NASA Astrophysics Data System (ADS)

    Li, Xiao; Hu, Yan; Xiao, Jie; Cheng, Dengfeng; Xiu, Yan; Shi, Hongcheng

    2015-09-01

    Magnetic nanoparticles (MNPs) with special morphology were commonly used as biomaterials, while morphological effects of non-targeted biomolecule-modified MNPs on biological behaviors were still unclear. In this research, spherical and rod-like Fe3O4 in a comparable size were synthesized and then surface-modified by bovine serum albumin (BSA) as a model of non-targeted biomolecule-modified MNPs. Morphological effects were featured by TEM and quantification of in vitro phagocytic uptake, as well as the in vivo quantification of particles in reticuloendothelial system (RES)-related organs of normal Kunming mice. For these non-targeted BSA-modified MNPs, intracellular distributions were the same, but the rod-like MNPs were more likely to be uptake by macrophages; furthermore, the BSA-modified MNPs gathered in RES-related organs soon after intravenous injection, but the rod-like ones were expelled from the lung more quickly and expelled from the spleen more slowly. These preliminary results may be referable if MNPs or other similar biomolecule-modified nanoparticles were used.

  16. Targeted PRINTRTM nanoparticles for effective cancer therapy

    NASA Astrophysics Data System (ADS)

    McGowan, Kelly Marie

    Conventional therapeutics for the treatment of cancer are often faced with challenges such as systemic biodistribution within the body, drug degradation in vivo, low bioavailability at the site of disease, and off-target toxicity. As such, particulate drug delivery systems have been developed with the aim of minimizing these limitations of current therapies. Through the PRINTRTM (Particle Replication in Non-wetting Templates) technology, hydrogel nanoparticles, prepared from biocompatible poly(ethylene glycol) and acid-sensitive silyl ether crosslinkers, were functionalized and conjugated with targeting ligands for the folate receptor (FR), HER2 receptor, and transferrin receptor (TfR). By conjugating specific ligands to nanoparticles to impart specificity, highly selective targeting and internalization (>80%) of nanoparticles were demonstrated in various cancer cell lines. The extent of cellular uptake of targeted nanoparticles was dependent on the surface characteristics of the nanoparticles, particle concentration, and kinetics. Because a negative surface charge reduces nonspecific cellular uptake, attaching monoclonal antibodies to the surface of negatively charged PRINT nanoparticles facilitated specific binding of the antibodies to cellular surface receptors that subsequently triggered receptor-mediated endocytosis. Additionally, the multivalent nature of nanoparticles influenced cellular uptake. Specifically, nanoparticles with a higher valence internalized more rapidly and efficiently than those with a lower valence. Nanoparticles that selectively target and accumulate within diseased cells have the potential of minimizing drug degradation under physiological conditions, enhancing bioavailability at the tumor, improving the efficacy of the drug, and reducing toxicity from systemic biodistribution. Drug delivery through targeted nanoparticles was achieved by loading nanoparticles with silyl ether-modified gemcitabine prodrugs. Covalently reacting the prodrug

  17. Effect of accelerated weathering on surface chemistry of modified wood

    NASA Astrophysics Data System (ADS)

    Temiz, Ali; Terziev, Nasko; Eikenes, Morten; Hafren, Jonas

    2007-04-01

    In this study, the effects of UV-light irradiation and water spray on colour and surface chemistry of scots pine sapwood samples were investigated. The specimens were treated with chromated copper arsenate (CCA), a metal-free propiconazol-based formulation, chitosan, furfuryl alcohol and linseed and tall oils. The weathering experiment was performed by cycles of 2 h UV-light irradiation followed by water spray for 18 min. The changes at the surface of the weathered samples were characterised by Fourier transform infrared spectroscopy (FT-IR); colour characterizations were performed by measuring CIELab parameters. The results show that all treatment methods except chitosan treatment provided lower colour changes than the control groups after 800 h exposure in weathering test cycle, but differences between chitosan and control were also small. The lowest colour changes were found on linseed oil (full cell process) and CCA treated wood. FT-IR results show that oil treatment (linseed and tall oil) decreased the intensities of a lignin specific peak (1500-1515 cm -1). Absorption band changes at 1630-1660 cm -1 were reduced by all treatments.

  18. Effects of a Modified Gravitation Law on the Perihelion Shift

    NASA Astrophysics Data System (ADS)

    McDonnell, Jordan

    2007-05-01

    The perihelion shift in a satellite's orbit has become an important measure of the effects of non- Newtonian contributions to the force of gravity. Historically important contributions have been ascribed to general relativity, and more recently there has been interest in using measurements of the perihelion to corntrain parameters for forces from darlc energy, as well as explaining anomalous motion of artificial satellites. The functional form of the perihelion shut seen in the cases of general relativity and dark energy, calculated in the literature, is seen in the present work to generalize to other forces. The present work h d s a generalized formula for the precession caused by any central force for small eccentricity, as well as an integral giving the precession for any force with any eccentricity that b not been encountered in previous literature. In the case of power law forces, this integral is performed analytically. These results are analyzed numerically, and the new formulas are applied to recent applications in dark energy, anomalous satellite motion, and gravitational contributions from higher-dimensional theories.

  19. Antioxidative effect of folate-modified chitosan nanoparticles

    PubMed Central

    Chakraborty, Subhankari Prasad; Mahapatra, Santanu Kar; Sahu, Sumanta Kumar; Pramanik, Panchanan; Roy, Somenath

    2011-01-01

    Objective To evaluate the potency of carboxymethyl chitosan-2, 2′ ethylenedioxy bis-ethylamine-folate (CMC-EDBE-FA) on tissue injury, antioxidant status and glutathione system in tissue mitochondria and serum against nicotine-induced oxidative stress in mice. Methods CMC-EDBE-FA was prepared on basis of carboxymethyl chitosan tagged with folic acid by covalently linkage through 2, 2′ ethylenedioxy bis-ethylamine. Animals were divided into four groups, i.e., control, nicotine (1 mg/kg bw/day), CMC-EDBE-FA (1 mg/kg bw/day) and nicotine (1 mg/kg bw/day) and CMC-EDBE-FA (1 mg/kg bw/day) for 7 days. Levels of lipid peroxidation, oxidized glutathione level, antioxidant enzyme status and DNA damage were observed and compared. Results The significantly increase of lipid peroxidation, oxidized glutathione levels and DNA damage was observed in nicotine treated group as compared with control group; those were significantly reduced in CMC-EDBE-FA supplemented group. Moreover, significantly reduced antioxidant status in nicotine treated group was effectively ameliorated by the supplementation of CMC-EDBE-FA. Only CMC-EDBE-FA treated groups showed no significant change as compared with control group; rather than it repairs the tissue damage of nicotine treated group. Conclusions These findings suggest that CMC-EDBE-FA is non-toxic and ameliorates nicotine-induced toxicity. PMID:23569721

  20. Effects of modified atmosphere packaging on quality of 'Alphonso' Mangoes.

    PubMed

    Ramayya, Nidhi; Niranjan, Keshavan; Duncan, Eric

    2012-12-01

    Postharvest quality of Alphonso mangoes (Mangifera indica L) is vital to ensure proper ripening and good quality. 500 g mature green mangoes, were subjected to three pre- packaging hot water dips (20, 30 & 40°C) for 40 min, two packaging films (OPP unperforated and perforated), using three levels of gas concentrations of 25,50 and 75% v/v CO2 treatments (balance N2) and stored at 10°C for 21 days. During the storage period headspace gas composition, weight loss, ascorbic acid, pulp firmness, external fruit colour and overall quality score were measured to determine optimum storage conditions. The most effective postharvest condition was found to be dipping in water maintained at 40°C for 40 min, followed by packaging under 50% CO2 in bags made of unperforated film when compared to mangoes packed under 25 and 75% CO2 which showed deteriorated quality including spoilage and mould. Good keeping quality of at least 21 days was achieved under these conditions, which was much superior to the control samples that showed deterioration after 12 days of storage. PMID:24293691

  1. Effect of selected modified atmosphere packaging on Campylobacter survival in raw poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most current research on Campylobacter has focused on preharvest or processing plant cross contamination. Little is known about the effect of storage environment on the survival of Campylobacter on raw poultry. We evaluated the effects of modified storage atmosphere on the survival of naturally-oc...

  2. Effectiveness of a Modified Rapid Toilet Training Workshop for Parents of Children with Developmental Disabilities

    ERIC Educational Resources Information Center

    Rinald, Katherine; Mirenda, Pat

    2012-01-01

    Individuals with developmental disabilities often experience challenges in acquiring toileting skills, which highlights a need for effective toilet training strategies that can be readily disseminated to caregivers. The purpose of this multiple baseline study was to evaluate the effectiveness of a modified rapid toilet training workshop provided…

  3. Assessing the Treatment Effects in Apraxia of Speech: Introduction and Evaluation of the Modified Diadochokinesis Test

    ERIC Educational Resources Information Center

    Hurkmans, Joost; Jonkers, Roel; Boonstra, Anne M.; Stewart, Roy E.; Reinders-Messelink, Heleen A.

    2012-01-01

    Background: The number of reliable and valid instruments to measure the effects of therapy in apraxia of speech (AoS) is limited. Aims: To evaluate the newly developed Modified Diadochokinesis Test (MDT), which is a task to assess the effects of rate and rhythm therapies for AoS in a multiple baseline across behaviours design. Methods: The…

  4. Effect of chitosan molecular weight on rheological behavious of chitosan modified nanoclay at highly hydrated state

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Effect of chitosan molecular weight (M(cs)) on the rheological properties of chitosan modified clay (CMCs) at highly hydrated state was investigated. With special emphasis on its effect on the thixotropy of CMCs, the structure recovery at rest after underwent a pre-shearing process was further perfo...

  5. Combinatorial-Designed Epidermal Growth Factor Receptor-Targeted Chitosan Nanoparticles for Encapsulation and Delivery of Lipid-Modified Platinum Derivatives in Wild-Type and Resistant Non-Small-Cell Lung Cancer Cells.

    PubMed

    Nascimento, Ana Vanessa; Singh, Amit; Bousbaa, Hassan; Ferreira, Domingos; Sarmento, Bruno; Amiji, Mansoor M

    2015-12-01

    Development of efficient and versatile drug delivery platforms to overcome the physical and biological challenges in cancer therapeutics is an area of great interest, and novel materials are actively sought for such applications. Recent strides in polymer science have led to a combinatorial approach for generating a library of materials with different functional identities that can be "mixed and matched" to attain desired characteristics of a delivery vector. We have applied the combinatorial design to chitosan (CS), where the polymer backbone has been modified with polyethylene glycol, epidermal growth factor receptor-binding peptide, and lipid derivatives of varying chain length to encapsulate hydrophobic drugs. Cisplatin, cis-([PtCl2(NH3)2]), is one of the most potent chemotherapy drugs broadly administered for cancer treatment. Cisplatin is a hydrophilic drug, and in order for it to be encapsulated in the developed nanosystems, it was modified with lipids of varying chain length. The library of four CS derivatives and six platinum derivatives was self-assembled in aqueous medium and evaluated for physicochemical characteristics and cytotoxic effects in platinum-sensitive and -resistant lung cancer cells. The results show that the lipid-modified platinate encapsulation into CS nanoparticles significantly improved cellular cytotoxicity of the drug. In this work, we have also reinforced the idea that CS is a multifaceted system that can be as successful in delivering small molecules as it has been as a nucleic acids carrier. PMID:26523837

  6. Effect of ultracapacitor-modified PHEV protocol on performance degradation in lithium-ion cells

    NASA Astrophysics Data System (ADS)

    Hochgraf, Clark G.; Basco, John K.; Bohn, Theodore P.; Bloom, Ira

    2014-01-01

    The cycle life of lithium-ion batteries was investigated using a modified USABC electric vehicle testing protocol designed to simulate the effect of a hybrid energy-storage system (ultracapacitor and battery) in a plug-in hybrid electric vehicle. A side-by-side comparison of battery capacity and impedance changes with and without the effect of the ultracapacitor was performed. Calendar-life degradation effects were corrected for using control cells. The battery's rate of cycle-related capacity degradation decreased by a factor of 2 and rate of cycle-related impedance degradation, by a factor of 5.9 when exposed to the ultracapacitor-modified profile. The modified profile avoids exposure to regeneration energy and reduces maximum voltage of the battery.

  7. Newton's second law versus modified-inertia MOND: A test using the high-latitude effect

    SciTech Connect

    Ignatiev, A. Yu.

    2008-05-15

    The modified-inertia MOND is an approach that proposes a change in Newton's second law at small accelerations as an alternative to dark matter. Recently it was suggested that this approach can be tested in terrestrial laboratory experiments. One way of doing the test is based on the static high-latitude equinox modified-inertia effect: around each equinox date, 2 spots emerge on the Earth where static bodies experience spontaneous displacement due to the violation of Newton's second law required by the modified-inertia MOND. Here, a detailed theory of this effect is developed and estimates of the magnitude of the signal due to the effect are obtained. The expected displacement of a mirror in a gravitational-wave interferometer is found to be about 10{sup -14} m. Some experimental aspects of the proposal are discussed.

  8. Dendritic cell vaccine modified by Ag85A gene enhances anti-tumor immunity against bladder cancer.

    PubMed

    Zhang, Pei; Wang, Jinyan; Wang, Danan; Wang, Huan; Shan, Fengping; Chen, Liudan; Hou, Ying; Wang, Enhua; Lu, Chang-Long

    2012-11-01

    The ability of dendritic cells to provide all the signals required for T-cell activation makes them an ideal cancer vaccine platform. With the use of established DC2.4 cell line, originated from C57BL/6 mice and developed by superinfecting GM-CSF transduced bone marrow cells with myc and raf oncogenes, we investigated whether the DC 2.4 cell line transfected with Ag85A gene could enhance immunity against bladder cancer. Both phenotypic and functional analyses of Ag85A-DCs were done with use of FCM and T cell proliferation test. The cytotoxicity of Ag85A-DCs loaded with tumor cell lysate was verified by LDH. Finally, the production of interferon gamma was assayed by both ELISA and FCM. The immunotherapeutic effect of DC vaccine on murine bladder cancer was assessed pharmacologically and pathologically. Our results showed that Ag85A gene transfected DCs expressed high levels of key surface markers such as CD80, CD86 and MHC-II. The CTL primed with MB49 lysate-pulsed Ag85A-DCs elicits higher activity against MB49 tumor cells and upregulated level of IFN-γ production. Furthermore, the significant inhibitive effect on tumor growth in mice was found in the group of Ag85A-DC vaccine. The infiltration of CD4(+) or CD8(+) T cell within established tumor treated by Ag85A-DC vaccine significantly increased as compared with control groups. It is therefore concluded that DCs engineered by Ag85A gene exerts enhanced anti-tumor immunity against bladder cancer and this study might provide a meaningful mode of action with the use of Ag85A engineered DC vaccination in anti-cancer immunotherapy. PMID:22884511

  9. [The Warburg effect: from theory to therapeutic applications in cancer].

    PubMed

    Razungles, Julie; Cavaillès, Vincent; Jalaguier, Stéphan; Teyssier, Catherine

    2013-11-01

    Cancer cell metabolism described by Otto Warburg in the thirties became a cancer specific hallmark, also called "Warburg effect". Cancer cells use essentially glucose as fuel, through glycolysis, in order to meet their energy and biomass needs to insure their cell proliferation. Recent advances describe Warburg effect regulation by oncogenes and tumor suppressor genes. Moreover, mutations in some glycolysis enzymes are found in various cancers, highlighting the role of cell metabolism in cancer. In this review, we describe the mechanisms responsible for the Warburg effect at the molecular and cellular level, the role of cell signalling along with the implication of different transcription factors. As a cause or a consequence of tumorigenesis, the Warburg effect is now considered as a promising therapeutic target in the fight against cancer. PMID:24280507

  10. Effectiveness of a modified administration protocol for the medical treatment of canine pyometra.

    PubMed

    Contri, Alberto; Gloria, Alessia; Carluccio, Augusto; Pantaleo, Stefania; Robbe, Domenico

    2015-03-01

    Pyometra is one of the most common diseases in intact bitches. The aim of this study was to evaluate the effectiveness of a modified aglepristone protocol for the medical treatment of pyometra in the bitch. Of these, 73 bitches affected by pyometra of different breeds and age (2-14 years old) were enrolled. They were randomly assigned to a control group (CTG - 26 bitches) treated with classical protocol (aglepristone at 0, 1 and 6 days - day 0 = day of the diagnosis) and a modified treated group (MTG - 47 bitches) treated with a different administration protocol (aglepristone at 0, 2, 5 and 8 days). The classical protocol with the anti-progestagen aglepristone was effective in 88.5 % (23/26) of CTG bitches while the modified protocol was effective in all (47/47) of MTG bitches. One of the 23 CTG bitches received a further administration on day 14, which resolved the pyometra, while in the three cases of CTG bitches, in which the treatment was ineffective, an ovariohysterectomy was carried out. The modified protocol showed a success rate of 100 %, compared with the classical protocol proposed in the literature, and no recurrence of the disease was recorded in the 24 months follow up. After treatment, the oestrus onset was earlier than expected (interoestrus of 128 ± 32 days). In this study, the modified treatment protocol showed high efficacy and lack of recurrence within 24 months, suggesting a complete recovery of reproductive function in the bitch, with a normal fertility. PMID:25323020

  11. Effect of Fluoride-Modified Titanium Surface on Early Adhesion of Irradiated Osteoblasts

    PubMed Central

    Li, Jun Yuan; Zheng, Li Wu; Ma, Li; Kwong, Dora Lai Wan; Cheung, Lim Kwong; Pow, Edmond Ho Nang

    2015-01-01

    Objective. The present study aimed to investigate the effect of fluoride-modified titanium surface on adhesion of irradiated osteoblasts. Materials and Methods. Fluoride-modified surface was obtained and the morphology, roughness, and chemical composition of the surface were evaluated by scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy, respectively. The adhesion of irradiated osteoblast-like cells, in terms of number, area, and fluorescence intensity on the titanium surface, was evaluated using immunofluorescence staining. Results. Numerous nanosize pits were seen only in the F-TiO surface. The pits were more remarkable and uniform on F-TiO surface than on TiO surface; however, the amplitude of peaks and bottoms on F-TiO surface appeared to be smaller than on TiO surface. The Sa value and Sdr percentage of TiO surfaces were significantly higher than those of F-TiO surface. The concentrations of main elements such as titanium, oxygen, and carbon were similar on both surfaces. The number of irradiated osteoblasts adhered on the control surface was larger than on fluoride-modified surface. Meanwhile, the cells on the fluoride-modified surface formed more actin filaments. Conclusions. The fluoride-modified titanium surface alters the adhesion of irradiated osteoblasts. Further studies are needed to investigate the proliferation, differentiation, maturation, gene expression, and cytokine production of irradiated osteoblasts on fluoride-modified titanium surface. PMID:26266253

  12. Effects of a Modified Hand Compression Bandage for Treatment of Post-Burn Hand Edemas

    PubMed Central

    Park, Won Yong; Joo, So Young; Jang, Ki Un; Seo, Cheong Hoon; Jun, Ah Young

    2016-01-01

    Objective To evaluate the effect of a modified hand compression bandage in patients with a post-burn hand edema. Methods Patients were recruited from burn centers. We classified the patients into two groups: the modified hand compression bandage group comprising of 22 patients who had a modified hand compression bandage and received conventional physical therapy and the conventionally treated group, comprising of 20 patients who received only conventional physical therapy during the 4-week period post-burn. Hand circumference, hand skin thickness, and hand function were evaluated by grip strength, active range of motion (ROM), Jebsen hand function test, and visual analogue scale (VAS). These assessments were used to evaluate treatment effectiveness prior to the first treatment, 2 weeks after the first treatment, 4 weeks after the first treatment, and 4 months after the first treatment. Results As a result of repeated-measures analysis of variance on hand circumference, skin thickness, VAS, and each metacarpophalangeal joint ROM, we found significant differences that corresponded to time effect (p<0.05) and time×group (reciprocal action) effect (p<0.05). The results of grasp power, Jebsen hand function test, and each proximal interphalangeal joint ROM, show significant differences in accordance with the time effect (p<0.05), however, there was no reciprocal action effect (p>0.05). Conclusion The modified hand compression bandage will be clinically useful for the treatment of patients with post-burn hand edemas. PMID:27152286

  13. Does the use of specialist palliative care services modify the effect of socioeconomic status on place of death? A systematic review

    PubMed Central

    Chen, Hong; Nicolson, Donald J; Macleod, Una; Allgar, Victoria; Dalgliesh, Christopher; Johnson, Miriam

    2015-01-01

    Background: Cancer patients in lower socioeconomic groups are significantly less likely to die at home and experience more barriers to access to palliative care. It is unclear whether receiving palliative care may mediate the effect of socioeconomic status on place of death. Aim: This review examines whether and how use of specialist palliative care may modify the effect of socioeconomic status on place of death. Design: A systematic review was conducted. Eligible papers were selected and the quality appraised by two independent reviewers. Data were synthesised using a narrative approach. Data sources: MEDLINE, Embase, CINAHL, PsycINFO and Web of Knowledge were searched (1997–2013). Bibliographies were scanned and experts contacted. Papers were included if they reported the effect of both socioeconomic status and use of specialist palliative care on place of death for adult cancer patients. Results: Nine studies were included. All study subjects had received specialist palliative care. With regard to place of death, socioeconomic status was found to have (1) no effect in seven studies and (2) an effect in one study. Furthermore, one study found that the effect of socioeconomic status on place of death was only significant when patients received standard specialist palliative care. When patients received more intense care adapted to their needs, the effect of socioeconomic status on place of death was no longer seen. Conclusion: There is some evidence to suggest that use of specialist palliative care may modify the effect of socioeconomic status on place of death. PMID:26330454

  14. Cancer

    MedlinePlus

    ... Leukemia Liver cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer ... have any symptoms. In certain cancers, such as pancreatic cancer, symptoms often do not start until the disease ...

  15. Effects of bone-targeted agents on cancer progression and mortality.

    PubMed

    Coleman, Robert; Gnant, Michael; Morgan, Gareth; Clezardin, Philippe

    2012-07-18

    Bone-targeted treatments with bisphosphonates and denosumab, which reduce bone resorption, are known to reduce the risk of skeletal complications and prevent treatment-induced bone loss in patients with malignant bone disease. Additionally, these drugs may modify the course of bone destruction via inhibitory effects on the "vicious cycle" of growth factor and cytokine signaling between tumor and bone cells within the bone marrow microenvironment. Effects of the drugs on the stem cell niche, direct effects on the cancer cells, and immune modulation may also contribute. In early-stage (stages I, II, and III) breast cancer, treatment with the bisphosphonate zoledronic acid has shown improvements in disease-free and overall survival. Improved survival was particularly notable in women with established menopause at diagnosis and in premenopausal women with endocrine-responsive disease who received treatment with goserelin, which suppresses ovarian function by inhibiting the production of ovarian hormones. Additionally, in castrate-resistant prostate cancer, treatment with denosumab delays the development of bone metastases. These results strongly support the adjuvant use of bone-targeted treatments but suggest that reproductive hormones are an important treatment modifier to take into account. In advanced-stage (stage IV, ie, metastatic) cancers, survival benefits have been observed in patients with multiple myeloma and in patients with other solid tumors with rapid rates of bone destruction who received treatment with zoledronic acid. Here, we have critically reviewed the increasing evidence to support a disease-modifying effect of bone-targeted treatment and discussed the impact on clinical management. PMID:22752060

  16. The biologic effects of cigarette smoke on cancer cells.

    PubMed

    Sobus, Samantha L; Warren, Graham W

    2014-12-01

    Smoking is one of the largest preventable risk factors for developing cancer, and continued smoking by cancer patients is associated with increased toxicity, recurrence, risk of second primary cancer, and mortality. Cigarette smoke (CS) contains thousands of chemicals, including many known carcinogens. The carcinogenic effects of CS are well established, but relatively little work has been done to evaluate the effects of CS on cancer cells. In this review of the literature, the authors demonstrate that CS induces a more malignant tumor phenotype by increasing proliferation, migration, invasion, and angiogenesis and by activating prosurvival cellular pathways. Significant work is needed to understand the biologic effect of CS on cancer biology, including the development of model systems and the identification of critical biologic mediators of CS-induced changes in cancer cell physiology. PMID:25043526

  17. Removal effects and mechanisms of Microcystic aeruginosa by Chitosan-modified Adsorbent

    NASA Astrophysics Data System (ADS)

    Yang, Xi; Wu, Cuirong; He, Yan; Zhang, Bingru; Li, Fengting

    2010-11-01

    The health of humans and other organisms is threatened by increasingly serious water contamination by algae in all the country's major lakes such as Taihu Lake. This experiment was conducted to investigate the removal effects and mechanism of Microcystic aeruginosa by Chitosan-modified adsorbent, with comparison of polyaluminium chloride (PAC) and poly ferric sulfate (PFS). Microcystic aeruginosa grown in the laboratory was used for this experiment. The results showed that the algae-removal efficiency of Chitosan-modified adsorbent presents a good performance. When the dosage of the adsorbent reached 20 ppm, the turbidity and the chlorophyll a of treated water dropped by 90% and 86%, respectively. Compared to conventional coagulation, the dosage was reduced. The adhesive bridge effect of Chitosan and adsorption of modified adsorbent provided an important complement to subsequent dehydrating treatment for algae.

  18. Cancer radioimmunotherapy: Development of an effective approach

    SciTech Connect

    DeNardo, S.J.

    1985-01-01

    The objective of this program is the development of effective approaches for delivering radiation therapy to patients with cancer using radiopharmaceuticals produced from monoclonal antibodies. One major achievement of this program has been the development of a new, Cu-67 chelator (Teta). This chelator firmly holds copper even in the presence of competitive serum proteins. Copper has proven to be labile with other chelators. Also, a single photon emission tomographic camera was purchased with University and philanthropic funds specifically for this program. This allows full-time developmental work on quantitative imaging approaches and in vivo kinetics of our various radiopharmaceutical antibody products. The pharmakinetics of I-123 antibody and antibody fragments have been obtained in patients utilizing quantitative imaging and have demonstrated significant differences as well as the need for long- term studies with I-131 and Cu-67.

  19. A safety-modified SV40 Tag developed for human cancer immunotherapy

    PubMed Central

    Tseng-Rogenski, Stephanie S; Arredouani, Mohamed S; Escara-Wilke, June F; Neeley, Yilin C; Imperiale, Michael J; Sanda, Martin G

    2008-01-01

    Simian virus 40 (SV40)-like DNA sequences have been found in a variety of human tumors, raising the possibility that strategies targeting SV40 may provide a potential avenue for immunotherapy directed against SV40 large T Antigen (Tag)-expressing tumors. We generated a recombinant vaccinia (vac-mTag) expressing mTag and herein assessed the ability of mTag to transform cells and to interact with anti-oncoproteins, as well as screened for the presence of potential HLA-A2.1-restricted epitopes within mTag. We found that transfection of cells with mTag did not lead to their transformation. Also, we demonstrated that mTag protein is degraded rapidly in cells. In addition, our work revealed that mTag did not physically interact with certain anti-oncoproteins. Finally, two potential HLA-A2.1-restricted functional epitopes within mTag sequence were identified. Our results show that mTag lacks the oncogenecity of full-length Tag and harbors potential HLA-A2.1-restricted immunogenic epitopes, hence suggesting the safety of vac-mTag for use in cancer immunotherapy. PMID:19920890

  20. Hyaluronic Acid Modified Tantalum Oxide Nanoparticles Conjugating Doxorubicin for Targeted Cancer Theranostics.

    PubMed

    Jin, Yushen; Ma, Xibo; Feng, Shanshan; Liang, Xiao; Dai, Zhifei; Tian, Jie; Yue, Xiuli

    2015-12-16

    Theranostic tantalum oxide nanoparticles (TaOxNPs) of about 40 nm were successfully developed by conjugating functional molecules including polyethylene glycol (PEG), near-infrared (NIR) fluorescent dye, doxorubicin (DOX), and hyaluronic acid (HA) onto the surface of the nanoparticles (TaOx@Cy7-DOX-PEG-HA NPs) for actively targeting delivery, pH-responsive drug release, and NIR fluorescence/X-ray CT bimodal imaging. The obtained nanoagent exhibits good biocompatibility, high cumulative release rate in the acidic microenvironments, long blood circulation time, and superior tumor-targeting ability. Both in vitro and in vivo experiments show that it can serve as an excellent contrast agent to simultaneously enhance fluorescence imaging and CT imaging greatly. Most importantly, such a nanoagent could enhance the therapeutic efficacy of the tumor greatly and the tumor growth inhibition was evaluated to be 87.5%. In a word, multifunctional TaOx@Cy7-DOX-PEG-HA NPs can serve as a theranostic nanomedicine for fluorescence/X-ray CT bimodal imaging, remote-controlled therapeutics, enabling personalized detection, and treatment of cancer with high efficacy. PMID:26554699

  1. Modifiable Factors and Genetic Predisposition Associated with Gallbladder Cancer. A Concise Review.

    PubMed

    Liebe, Roman; Milkiewicz, Piotr; Krawczyk, Marek; Bonfrate, Leonilde; Portincasa, Piero; Krawczyk, Marcin

    2015-09-01

    Gallbladder cancer (GbCa) is the most frequent malignancy of the biliary tract. It is also the 6th most common gastrointestinal tumor. It is associated with very high lethality, mainly due to the lack of symptoms up to a very late and thus incurable state. As many as 80% of patients are diagnosed at very late stages of disease, which allow only palliative therapy. As a result, most of the patients with GbCa will die within 6 months of the diagnosis, hence the average 5-year survival does not exceed 5%. Currently, surgical resection represents the only curative option in GbCa, but this approach is feasible only at an early stage of the disease. Other oncologic therapies are of limited use. The incidence of GbCa is remarkably increased in certain populations such as Native North Americans, South Indian females and, in Europe, in the Polish population. It is not clear to date if these enhanced risk populations are the result of common environmental exposure or of shared genetic risk factors. In this review we provide an overview of the state-of-art in GbCa research with the focus on the current knowledge concerning genetic and environmental triggers of this tumor. PMID:26405706

  2. Biological response modifiers

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Much of what used to be called immunotherapy is now included in the term biological response modifiers. Biological response modifiers (BRMs) are those agents or approaches that modify the relationship between the tumor and host by modifying the host's biological response to tumor cells with resultant therapeutic effects. Most of the early work with BRMs centered around observations of spontaneous tumor regression and the association of tumor regression with concurrent bacterial infections. The BRM can modify the host response by increasing the host's antitumor responses through augmentation and/or restoration of effector mechanisms or mediators of the host's defense or decrease the deleterious component by the host's reaction, increasing the host's defenses by the administration of natural biologics (or the synthetic derivatives thereof) as effectors or mediators of an antitumor response, augmenting the host's response to modified tumor cells or vaccines, which might stimulate a greater response by the host or increase tumor-cell sensitivity to an existing response, decreasing the transformation and/or increase differentiation (maturation) of tumor cells, or increasing the ability of the host to tolerate damage by cytotoxic modalities of cancer treatment.

  3. Biological response modifiers

    SciTech Connect

    Weller, R.E.

    1991-10-01

    Much of what used to be called immunotherapy is now included in the term biological response modifiers. Biological response modifiers (BRMs) are defined as those agents or approaches that modify the relationship between the tumor and host by modifying the host's biological response to tumor cells with resultant therapeutic effects.'' Most of the early work with BRMs centered around observations of spontaneous tumor regression and the association of tumor regression with concurrent bacterial infections. The BRM can modify the host response in the following ways: Increase the host's antitumor responses through augmentation and/or restoration of effector mechanisms or mediators of the host's defense or decrease the deleterious component by the host's reaction; Increase the host's defenses by the administration of natural biologics (or the synthetic derivatives thereof) as effectors or mediators of an antitumor response; Augment the host's response to modified tumor cells or vaccines, which might stimulate a greater response by the host or increase tumor-cell sensitivity to an existing response; Decrease the transformation and/or increase differentiation (maturation) of tumor cells; or Increase the ability of the host to tolerate damage by cytotoxic modalities of cancer treatment.

  4. Modified Volumetric Modulated Arc Therapy in Left Sided Breast Cancer After Radical Mastectomy With Flattening Filter Free Versus Flattened Beams.

    PubMed

    Lai, Youqun; Chen, Yanyan; Wu, Sangang; Shi, Liwan; Fu, Lirong; Ha, Huiming; Lin, Qin

    2016-04-01

    Conventional volumetric modulated arc therapy (C-VMAT) for breast cancer after radical mastectomy had its limitation that resulted in larger volumes of normal tissue receiving low doses. We explored whether there was a way to deal with this disadvantage and determined the potential benefit of flattening filter-free (FFF) beams.Twenty patients with breast cancer after radical mastectomy were subjected to 3D conformal radiotherapy (3DCRT) and VMAT treatment planning. For VMAT plans, 3 different designs were employed with RapidArc form: conventional-VMAT plan (C-VMAT), modified-VMAT plan (M-VMAT), and modified-VMAT plan using FFF beams (M-VMAT-F). Plan quality and efficiency were assessed for all plans.For each technique in homogeneity, there were no statistically significant differences. VMAT plans showed superiority compared with 3DCRT in conformity. C-VMAT plans were obviously not only superior to 3DCRT in the medium to high-dose regions (about 15-50 Gy) but also resulted in larger volumes in low-dose regions (about 0-10 Gy). M-VMAT plans were similar to M-VMAT-F. Both of them might significantly reduce the regions of low dose compared with C-VMAT (V5lung: ∼ 11.5%; V5heart: ∼ 23.8%, P < 0.05), even less than 3DCRT in heart irradiation (V2.5heart, 9.4%, P < 0.05). For liver, contralateral breast, and lung irradiation, M-VMAT-F plans were slightly superior to M-VMAT with a reduction of ∼0.08, 0.2, and 0.24 Gy in the respective mean doses (P < 0.05).C-VMAT plans showed superiority compared with 3DCRT, while also resulted in larger volumes of normal tissue receiving low doses. M-VMAT and M-VMAT-F plans might not only reduce the region in the medium to high doses but also have lower volumes in low-dose regions. M-VMAT-F plans were slightly superior compared with M-VMAT due to further contralateral organs sparing. PMID:27057896

  5. Modified Volumetric Modulated Arc Therapy in Left Sided Breast Cancer After Radical Mastectomy With Flattening Filter Free Versus Flattened Beams

    PubMed Central

    Lai, Youqun; Chen, Yanyan; Wu, Sangang; Shi, Liwan; Fu, Lirong; Ha, Huiming; Lin, Qin

    2016-01-01

    Abstract Conventional volumetric modulated arc therapy (C-VMAT) for breast cancer after radical mastectomy had its limitation that resulted in larger volumes of normal tissue receiving low doses. We explored whether there was a way to deal with this disadvantage and determined the potential benefit of flattening filter-free (FFF) beams. Twenty patients with breast cancer after radical mastectomy were subjected to 3D conformal radiotherapy (3DCRT) and VMAT treatment planning. For VMAT plans, 3 different designs were employed with RapidArc form: conventional-VMAT plan (C-VMAT), modified-VMAT plan (M-VMAT), and modified-VMAT plan using FFF beams (M-VMAT-F). Plan quality and efficiency were assessed for all plans. For each technique in homogeneity, there were no statistically significant differences. VMAT plans showed superiority compared with 3DCRT in conformity. C-VMAT plans were obviously not only superior to 3DCRT in the medium to high-dose regions (about 15–50 Gy) but also resulted in larger volumes in low-dose regions (about 0–10 Gy). M-VMAT plans were similar to M-VMAT-F. Both of them might significantly reduce the regions of low dose compared with C-VMAT (V5lung: ∼ 11.5%; V5heart: ∼ 23.8%, P < 0.05), even less than 3DCRT in heart irradiation (V2.5heart, 9.4%, P < 0.05). For liver, contralateral breast, and lung irradiation, M-VMAT-F plans were slightly superior to M-VMAT with a reduction of ∼0.08, 0.2, and 0.24 Gy in the respective mean doses (P < 0.05). C-VMAT plans showed superiority compared with 3DCRT, while also resulted in larger volumes of normal tissue receiving low doses. M-VMAT and M-VMAT-F plans might not only reduce the region in the medium to high doses but also have lower volumes in low-dose regions. M-VMAT-F plans were slightly superior compared with M-VMAT due to further contralateral organs sparing. PMID:27057896

  6. Anthracycline Drugs on Modified Surface of Quercetin-Loaded Polymer Nanoparticles: A Dual Drug Delivery Model for Cancer Treatment

    PubMed Central

    Saha, Chabita; Kaushik, Agrima; Das, Asmita; Pal, Sandip; Majumder, Debashis

    2016-01-01

    Polymer nanoparticles are vehicles used for delivery of hydrophobic anti-cancer drugs, like doxorubicin, paclitaxel or chemopreventors like quercetin (Q). The present study deals with the synthesis and characterisation of nano formulations (NFs) from Q loaded PLGA (poly lactic-co-glycolic acid) nano particles (NPs) by surface modification. The surface of Q-loaded (NPs) is modified by coating with biopolymers like bovine serum albumin (BSA) or histones (His). Conventional chemotherapeutic drugs adriamycin (ADR) and mitoxantrone (MTX) are bound to BSA and His respectively before being coated on Q-loaded NPs to nano formulate NF1 and NF2 respectively. The sizes of these NFs are in the range 400–500 nm as ascertained by SEM and DLS measurements. Encapsulation of Q in polymer NPs is confirmed from shifts in FT-IR, TGA and DSC traces of Q-loaded NPs compared to native PLGA and Q. Surface modification in NFs is evidenced by three distinct regions in their TEM images; the core, polymer capsule and the coated surface. Negative zeta potential of Q-loaded NPs shifted to positive potential on surface modification in NF1 and NF2. In vitro release of Q from the NFs lasted up to twenty days with an early burst release. NF2 is better formulation than NF1 as loading of MTX is 85% compared to 23% loading of ADR. Such NFs are expected to overcome multi-drug resistance (MDR) by reaching and treating the target cancerous cells by virtue of size, charge and retention. PMID:27196562

  7. Anthracycline Drugs on Modified Surface of Quercetin-Loaded Polymer Nanoparticles: A Dual Drug Delivery Model for Cancer Treatment.

    PubMed

    Saha, Chabita; Kaushik, Agrima; Das, Asmita; Pal, Sandip; Majumder, Debashis

    2016-01-01

    Polymer nanoparticles are vehicles used for delivery of hydrophobic anti-cancer drugs, like doxorubicin, paclitaxel or chemopreventors like quercetin (Q). The present study deals with the synthesis and characterisation of nano formulations (NFs) from Q loaded PLGA (poly lactic-co-glycolic acid) nano particles (NPs) by surface modification. The surface of Q-loaded (NPs) is modified by coating with biopolymers like bovine serum albumin (BSA) or histones (His). Conventional chemotherapeutic drugs adriamycin (ADR) and mitoxantrone (MTX) are bound to BSA and His respectively before being coated on Q-loaded NPs to nano formulate NF1 and NF2 respectively. The sizes of these NFs are in the range 400-500 nm as ascertained by SEM and DLS measurements. Encapsulation of Q in polymer NPs is confirmed from shifts in FT-IR, TGA and DSC traces of Q-loaded NPs compared to native PLGA and Q. Surface modification in NFs is evidenced by three distinct regions in their TEM images; the core, polymer capsule and the coated surface. Negative zeta potential of Q-loaded NPs shifted to positive potential on surface modification in NF1 and NF2. In vitro release of Q from the NFs lasted up to twenty days with an early burst release. NF2 is better formulation than NF1 as loading of MTX is 85% compared to 23% loading of ADR. Such NFs are expected to overcome multi-drug resistance (MDR) by reaching and treating the target cancerous cells by virtue of size, charge and retention. PMID:27196562

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

    PubMed Central

    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

  9. Application of a posteriori granddaughter and modified granddaughter designs to determine Holstein haplotype effects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A posteriori and modified granddaughter designs were applied to determine haplotype effects for Holstein bulls and cows with BovineSNP50 genotypes. The a posteriori granddaughter design was applied to 52 sire families, each with >100 genotyped sons with genetic evaluations based on progeny tests. Fo...

  10. Application of a posteriori granddaughter and modified granddaughter designs to determine Holstein haplotype effects

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A posteriori and modified granddaughter designs were applied to determine haplotype effects for Holstein bulls and cows with BovineSNP50 genotypes. The a posteriori granddaughter design was applied to 52 sire families, each with '100 genotyped sons with genetic evaluations based on progeny tests. Fo...

  11. Effect of modified atmosphere packaging (MAP) on quality of Sea Buckthorn during postharvest storage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Modified atmosphere packaging (MAP) has been used to retain the quality of postharvest produce. In the present study the effect of MAP on quality of berry fruit of Sea buckthorn (Hippophae rhamnoides L., a hardy, deciduous shrub, native to Asia) during refrigerated storage was investigated. Sea buck...

  12. Effectiveness of the Modified Intensive Toilet Training Method on Teaching Toilet Skills to Children with Autism

    ERIC Educational Resources Information Center

    Ardiç, Avsar; Cavkaytar, Atilla

    2014-01-01

    The purpose of this study was to determine effectiveness of a modified version of Azrin and Foxx's (1971) intensive toilet training method on teaching of toilet skills to children with autism. This method consists of administering extra fluids and a time schedule, but does not use overcorrection procedures. Implementation requires a study of…

  13. The Effectiveness of Parental Communication in Modifying the Relation between Food Advertising and Children's Consumption Behaviour

    ERIC Educational Resources Information Center

    Buijzen, Moniek

    2009-01-01

    The aim of this study was to examine the effectiveness of various types of parental communication in modifying children's responses to television food advertising. In a combined diary-survey study among 234 parents of 4- to 12-year-old children, I investigated how different styles of advertising mediation (active vs. restrictive) and consumer…

  14. Genetic basis and detection of unintended effects in genetically modified crop plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In January 2014, an international meeting sponsored by the International Life Sciences Institute/Health and Environmental Sciences Institute and the Canadian Food Inspection Agency titled “Genetic Basis of Unintended Effects in Modified Plants” was held in Ottawa, Canada, bringing together over 75 s...

  15. The Effect of a Modified Moore Method on Attitudes and Beliefs in Precalculus

    ERIC Educational Resources Information Center

    Bailey, Brad; Cooper, Thomas E.; Briggs, Karen S.

    2012-01-01

    As part of a study on the effects of teaching with a Modified Moore Method (MMM), a survey containing 20 items from Schoenfeld's (1989) investigation of attitudes and beliefs about mathematics was administered to students in undergraduate precalculus classes. The study included one section of precalculus taught with an MMM, a student-centered and…

  16. Establishing Mand Emergence: The Effects of Three Training Procedures and Modified Antecedent Conditions

    ERIC Educational Resources Information Center

    Egan, Claire E.; Barnes-Holmes, Dermot

    2010-01-01

    This study examined the effects of a modified antecedent during probes for emergent mands following listener versus tact training for children with autism. Eight students, aged 7 to 11, were trained to respond to 3 sets of relational responses (front/back, left/right, on/under), each assigned a nonsense label. Three training types were evaluated:…

  17. 75 FR 4877 - In the Matter of Beta Gamma Nuclear Radiology; Confirmatory Order Modifying License (Effective...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ... rule (72 FR 49139, August 28, 2007). The E-Filing process requires participants to submit and serve all... Gamma Nuclear Radiology; Confirmatory Order Modifying License (Effective Immediately) I Beta Gamma Nuclear Radiology (BGNR) (Licensee) is the holder of medical License No. 52-25542-01, issued by the...

  18. The Effects of Modified Melodic Intonation Therapy on Nonfluent Aphasia: A Pilot Study

    ERIC Educational Resources Information Center

    Conklyn, Dwyer; Novak, Eric; Boissy, Adrienne; Bethoux, Francois; Chemali, Kamal

    2012-01-01

    Objective: Positive results have been reported with melodic intonation therapy (MIT) in nonfluent aphasia patients with damage to their left-brain speech processes, using the patient's intact ability to sing to promote functional language. This pilot study sought to determine the immediate effects of introducing modified melodic intonation therapy…

  19. Evidence for thermal anisotropy effects on shear modified ion acoustic instabilities

    NASA Astrophysics Data System (ADS)

    Scime, E. E.; Keesee, A. M.; Spangler, R. S.; Koepke, M. E.; Teodorescu, C.; Reynolds, E. W.

    2002-10-01

    Inclusion of thermal anisotropy effects is shown to be required to describe recently reported experimental measurements as shear-modified, ion acoustic instabilities. For the reported experimental conditions, isotropic theory yields no instability growth that depends on the magnitude of the shear in the parallel flow.

  20. Effect of Fillers Prepared from Enzymatically Modified Proteins on Mechanical Properties of Leather

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In an environment where petroleum feedstuffs are becoming increasingly too expensive for a good cost-effective return, utilization of renewable resources makes economic sense, particularly when these substrates are waste proteins. We have thus proposed the application of enzymatically modified wast...

  1. Systematic Review of School-based Interventions to Modify Dietary Behavior: Does Intervention Intensity Impact Effectiveness?

    ERIC Educational Resources Information Center

    Racey, Megan; O'Brien, Charlene; Douglas, Sabrina; Marquez, Olivia; Hendrie, Gilly; Newton, Genevieve

    2016-01-01

    Background: Owing to the associations between diet and health, it is important that effective health promotion strategies establish healthful eating behaviors from an early age. We reviewed the intensity of school-based interventions aimed to modify dietary behavior in preadolescent and adolescents and related intervention characteristics to…

  2. Risk of Cancer in Diabetes: The Effect of Metformin

    PubMed Central

    Malek, Mojtaba; Emami, Zahra; Khamseh, Mohammad E.

    2013-01-01

    Cancer is the second cause of death. Association of diabetes as a growing and costly disease with cancer is a major health concern. Meanwhile, preexisting diabetes is associated with an increased risk of all-cause and cancer-specific mortalities. Presence of diabetes related comorbidities, poorer response to cancer treatment, and excess mortality related to diabetes are among the most important explanations. Although diabetes appear to be a risk factor for cancer and is associated with the mortality risk in cancer patients, several factors such as diabetes duration, multiple drug therapy, and the presence of diabetes comorbidities make the assessment of the effect of diabetes treatment on cancer risk and mortality difficult. Metformin is the drug of choice for the treatment of type 2 diabetes. The available evidence from basic science, clinical, and population-based research supports the anticancer effect of metformin. However, randomized controlled clinical trials do not provide enough evidence for a strong protective effect of metformin on cancer incidence or mortality. One of the most important limitations of these trials is the short duration of the followup. Further long-term randomized controlled clinical trials specifically designed to determine metformin effect on cancer risk are needed to provide the best answer to this challenge. PMID:24224094

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

    MedlinePlus

    ... gov/news/fullstory_159602.html Arthritis Possible Side Effect of Certain Cancer Drugs: Study Doctors should weigh ... research is needed to confirm a cause-and-effect relationship, the researchers said. Still, "I don't ...

  4. Evaluation of Thermal Oxidative Aging Effect on the Rheological Performance of Modified Asphalt Binders

    NASA Astrophysics Data System (ADS)

    Zhu, Cheng

    Modified asphalt binder, which is combined by base binder and additive modifier, has been implemented in pavement industry for more than 30 years. Recently, the oxidative aging mechanism of asphalt binder has been studied for several decades, and appreciable finding results of asphalt binder aging mechanism were achieved from the chemistry and rheological performance aspects. However, most of these studies were conducted with neat binders, the research of aging mechanism of modified asphalt binder was limited. Nowadays, it is still highly necessary to clarify how the asphalt binder aging happens with the modified asphalt binder, what is the effect of the different modifiers (additives) on the binder aging process, how the rheological performance changes under the thermal oxidative aging conditions and so on. The objective of this study was to investigate the effect of isothermal oxidative aging conditions on the rheological performance change of the modified and controlled asphalt binders. There were totally 14 different sorts of asphalt binders had been aged in the PAV pans in the air-force drafted ovens at 50°C, 60°C and 85°C for 0.5 day to 240 days. The Fourier-Transform Infrared Spectroscopy (FT-IR) and Dynamic Shear Rheometer (DSR) were used to perform the experiments. The analysis of rheological indices (Low shear viscosity-LSV, Crossover modulus-G*c, Glover-Rowe Parameter-G-R, DSR function-DSR Fn) as a function of carbonyl area (CA) was conducted. With the SBS modification, both of the hardening susceptibility of the rheological index-LSV and G-R decreases compared with the corresponding base binder. The TR increased the hardening susceptibility of all the rheological indexes. While for the G*c, SBS increases the slope of the most modified asphalt binders except A and B_TR_X series binders. The multiple linear regression statistical analysis results indicate that the oxidative aging conditions play an important role on the CA, and rheological performance

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

    PubMed

    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

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

    Cancer.gov

    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.

  7. Inhibitory Effect of Baicalin and Baicalein on Ovarian Cancer Cells

    PubMed Central

    Chen, Jianchu; Li, Zhaoliang; Chen, Allen Y.; Ye, Xingqian; Luo, Haitao; Rankin, Gary O.; Chen, Yi Charlie

    2013-01-01

    Ovarian cancer is one of the primary causes of death for women all through the Western world. Baicalin and baicalein are naturally occurring flavonoids that are found in the roots and leaves of some Chinese medicinal plants and are thought to have antioxidant activity and possible anti-angiogenic, anti-cancer, anxiolytic, anti-inflammatory and neuroprotective activities. Two kinds of ovarian cancer (OVCAR-3 and CP-70) cell lines and a normal ovarian cell line (IOSE-364) were selected to be investigated in the inhibitory effect of baicalin and baicalein on cancer cells. Largely, baicalin and baicalein inhibited ovarian cancer cell viability in both ovarian cancer cell lines with LD50 values in the range of 45–55 μM for baicalin and 25–40 μM for baicalein. On the other hand, both compounds had fewer inhibitory effects on normal ovarian cells viability with LD50 values of 177 μM for baicalin and 68 μM for baicalein. Baicalin decreased expression of VEGF (20 μM), cMyc (80 μM), and NFkB (20 μM); baicalein decreased expression of VEGF (10 μM), HIF-1α (20 μM), cMyc (20 μM), and NFkB (40 μM). Therefore baicalein is more effective in inhibiting cancer cell viability and expression of VEGF, HIF-1α, cMyc, and NFκB in both ovarian cancer cell lines. It seems that baicalein inhibited cancer cell viability through the inhibition of cancer promoting genes expression including VEGF, HIF-1α, cMyc, and NFκB. Overall, this study showed that baicalein and baicalin significantly inhibited the viability of ovarian cancer cells, while generally exerting less of an effect on normal cells. They have potential for chemoprevention and treatment of ovarian cancers. PMID:23502466

  8. Evaluation of chromosome 6p22 as a breast cancer risk modifier locus in a follow-up study of BRCA2 mutation carriers

    PubMed Central

    Stevens, Kristen N.; Wang, Xianshu; Fredericksen, Zachary; Pankratz, Vernon S.; Greene, Mark H.; Andrulis, Irene L.; Thomassen, Mads; Caligo, Maria; Nathanson, Katherine L.; Jakubowska, Anna; Osorio, Ana; Hamann, Ute; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Southey, Melissa; Buys, Saundra S.; Singer, Christian F.; Hansen, Thomas V.O.; Arason, Adalgeir; Offit, Kenneth; Piedmonte, Marion; Montagna, Marco; Imyanitov, Evgeny; Tihomirova, Laima; Sucheston, Lara; Beattie, Mary; Neuhausen, Susan L.; Szabo, Csilla I.; Simard, Jacques; Spurdle, Amanda B.; Healey, Sue; Chen, Xiaoqing; Rebbeck, Timothy R.; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C; Couch, Fergus J.

    2012-01-01

    Several common germline variants identified through genome-wide association studies of breast cancer risk in the general population have recently been shown to be associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. When combined, these variants can identify marked differences in the absolute risk of developing breast cancer for mutation carriers, suggesting that additional modifier loci may further enhance individual risk assessment for BRCA1 and BRCA2 mutation carriers. Recently, a common variant on 6p22 (rs9393597) was found to be associated with increased breast cancer risk for BRCA2 mutation carriers [Hazard ratio (HR)=1.55, 95% CI 1.25–1.92, p=6.0×10−5]. This observation was based on data from GWAS studies in which, despite statistical correction for multiple comparisons, the possibility of false discovery remains a concern. Here we report on an analysis of this variant in an additional 6,165 BRCA1 and 3,900 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). In this replication analysis, rs9393597 was not associated with breast cancer risk for BRCA2 mutation carriers [HR=1.09, 95% CI 0.96–1.24, p=0.18]. No association with ovarian cancer risk for BRCA1 or BRCA2 mutation carriers or with breast cancer risk for BRCA1 mutation carriers was observed. This follow-up study suggests that, contrary to our initial report, this variant is not associated with breast cancer risk among individuals with germline BRCA2 mutations. PMID:23011509

  9. Kinetic effects on Alfven wave nonlinearity. II - The modified nonlinear wave equation

    NASA Technical Reports Server (NTRS)

    Spangler, Steven R.

    1990-01-01

    A previously developed Vlasov theory is used here to study the role of resonant particle and other kinetic effects on Alfven wave nonlinearity. A hybrid fluid-Vlasov equation approach is used to obtain a modified version of the derivative nonlinear Schroedinger equation. The differences between a scalar model for the plasma pressure and a tensor model are discussed. The susceptibilty of the modified nonlinear wave equation to modulational instability is studied. The modulational instability normally associated with the derivative nonlinear Schroedinger equation will, under most circumstances, be restricted to left circularly polarized waves. The nonlocal term in the modified nonlinear wave equation engenders a new modulational instability that is independent of beta and the sense of circular polarization. This new instability may explain the occurrence of wave packet steepening for all values of the plasma beta in the vicinity of the earth's bow shock.

  10. Simultaneous effect of modified gravity and primordial non-Gaussianity in large scale structure observations

    SciTech Connect

    Mirzatuny, Nareg; Khosravi, Shahram; Baghram, Shant; Moshafi, Hossein E-mail: khosravi@mail.ipm.ir E-mail: hosseinmoshafi@iasbs.ac.ir

    2014-01-01

    In this work we study the simultaneous effect of primordial non-Gaussianity and the modification of the gravity in f(R) framework on large scale structure observations. We show that non-Gaussianity and modified gravity introduce a scale dependent bias and growth rate functions. The deviation from ΛCDM in the case of primordial non-Gaussian models is in large scales, while the growth rate deviates from ΛCDM in small scales for modified gravity theories. We show that the redshift space distortion can be used to distinguish positive and negative f{sub NL} in standard background, while in f(R) theories they are not easily distinguishable. The galaxy power spectrum is generally enhanced in presence of non-Gaussianity and modified gravity. We also obtain the scale dependence of this enhancement. Finally we define galaxy growth rate and galaxy growth rate bias as new observational parameters to constrain cosmology.

  11. Effect of aging on morphology of organo-montmorillonite modified bitumen by atomic force microscopy.

    PubMed

    Zhang, H L; Wang, H C; Yu, J Y

    2011-04-01

    The morphology of unmodified and organo-montmorillonite modified bitumens was investigated by atomic force microscopy. The influence of thin film oven test and ultraviolet aging on the morphology of the binders was also analysed. The atomic force microscopy results showed that bitumen displayed a 'bee-like' structure and the dimension of the 'bee-like' structures was decreased to some extent with the introduction of organo-montmorillonite. Organo-montmorillonite showed a better interaction with the dispersed domains in comparison with the matrix in bitumen, which led to an obvious increase in the contrast between the dispersed domains and the matrix in bitumen. Compared with the unmodified bitumen, the single-phase trend in the organo-montmorillonite modified bitumen could be effectively prevented during thin film oven test and ultraviolet aging, indicating its good aging resistance which was in accordance with changes in physical properties of the organo-montmorillonite modified bitumen before and after aging. PMID:21118229

  12. Effect of chemical heterogeneity on photoluminescence of graphite oxide treated with S-/N-containing modifiers

    NASA Astrophysics Data System (ADS)

    Ebrahim, Amani M.; Rodríguez-Castellón, Enrique; Montenegro, José María; Bandosz, Teresa J.

    2015-03-01

    Graphite oxide (GO) obtained using Hummers method was modified by hydrothermal treatment either with sulfanilic acid or polystyrene (3-ammonium) sulfonate at 100 °C or 85 °C, respectively. Both modifiers contain sulfur in the oxidized forms and nitrogen in the reduced forms. The materials were characterized using FTIR, XPS, thermal analysis, potentiometric titration and SEM. Their photoluminescent properties and their alteration with an addition of Ag+ were also measured. As a result of these modifications nitrogen was introduced to the graphene layers as amines, imides, amides, and sulfur as sulfones and sulfonic acids. Moreover, the presence of polyaniline was detected. This significantly affected the polarity, acid-base character, and conductivity of the materials. Apparently carboxylic groups of GO were involved in the surface reactions. The modified GOs lost their layered structure and the modifications resulted in the high degree of structural and chemical heterogeneity. Photoluminescence in visible light was recorded and linked to the presence of heteroatoms. For the polystyrene (3-ammonium) sulfonate modified sample addition of Ag+ quenched the photoluminescence at low wavelength showing sensitivity as a possible optical detector. No apparent effect was found for the sulfanilic acid modified sample.

  13. Knockdown of TAZ modifies triple-negative breast cancer cell sensitivity to EGFR inhibitors by regulating YAP expression.

    PubMed

    Guo, Liwen; Zheng, Jiaping; Zhang, Jing; Wang, Haohao; Shao, Guoliang; Teng, Lisong

    2016-08-01

    Triple-negative breast cancer (TNBC) constitutes ~10-15% of breast cancer patients and represents an aggressive subtype with poor overall prognosis. TNBC is an important clinical challenge because it does not respond well to endocrine therapy and have a higher rate of early recurrence and distant metastasis following chemotherapy. Although it has been reported that the epidermal growth factor receptor (EGFR) was overexpressed in ~80% of TNBC, anti-EGFR therapy showed limited clinical benefit according to phase II studies. In this study, we first observed that knockdown of the transcriptional coactivator with PDZ-binding domain (TAZ) gene can regulate the sensitivity of TNBC cell lines to EGFR inhibitors (EGFRI) in a cell context-depended manner. Furthermore, in certain breast cancer cell lines the YES-associated protein, paralog of TAZ (YAP) expression can be upregulated by TAZ inhibition which leads to EGFRI resistance. These results suggest a specific inhibitor to TAZ/YAP combined with anti-EGFR therapy may prove effective and provide a reason why targeting EGFR showed limited clinical benefit in TNBC treatment. PMID:27373987

  14. Effect of modified hold-relax stretching and static stretching on hamstring muscle flexibility

    PubMed Central

    Ahmed, Hashim; Iqbal, Amir; Anwer, Shahnawaz; Alghadir, Ahmad

    2015-01-01

    [Purpose] The aim of present study was to compare the effectiveness of modified hold-relax stretching and static stretching in improving the hamstring muscle flexibility. [Subjects and Methods] Forty-five male subjects with hamstring tightness were included in this study. The subjects were randomly placed into three groups: the modified hold-relax stretching, static stretching and control groups. The modified hold-relax stretching group performed 7 seconds of isometric contraction and then relaxed for 5 seconds, and this was repeated five times daily for five consecutive days. The static stretching group received 10 minutes of static stretching with the help of a pulley and weight system for five consecutive days. The control group received only moist heat for 20 minutes for five consecutive days. A baseline reading of passive knee extension (PKE) was taken prior to the intervention; rest measurements were taken immediate post intervention on day 1, day 3, day 5, and after a 1 week follow-up, i.e., at the 12th day. [Results] On comparing the baseline readings of passive knee extension (PKE), there was no difference noted between the three groups. On comparing the posttest readings on day 5 between the 3 groups, a significant difference was noted. However, post hoc analysis revealed an insignificant difference between the modified hold-relax stretching and static stretching groups. There was a significant difference between the static stretching and control groups and between the modified hold-relax stretching and control groups. [Conclusion] The results of this study indicate that both the modified hold-relax stretching technique and static stretching are equally effective, as there was no significant difference in improving the hamstring muscle flexibility between the two groups. PMID:25729210

  15. Effect of oleic acid modified polymeric bilayered nanoparticles on percutaneous delivery of spantide II and ketoprofen

    PubMed Central

    Shah, Punit; Desai, Pinaki; Singh, Mandip

    2011-01-01

    The objective of present study was to evaluate the effect of oleic acid modified polymeric bilayered nanoparticles (NPS) on combined delivery of two anti-inflammatory drugs, spantide II (SP) and ketoprofen (KP) on the skin permeation. NPS were prepared using poly(lactic-co-glycolic acid) (PLGA) and chitosan. SP and KP were encapsulated in different layers alone or/and in combination (KP-NPS, SP-NPS and SP+KP-NPS). The surface of NPS was modified with oleic acid (OA) (`Nanoease' technology) using an established procedure in the laboratory (KP-NPS-OA, SP-NPS-OA and SP+KP-NPS-OA). Fluorescent dyes (DiO and DID) containing surface modified (DiO-NPS-OA and DID-NPS-OA) and unmodified NPS (DiO-NPS and DID-NPS) were visualized in lateral rat skin sections using confocal microscopy and Raman confocal spectroscopy after skin permeation. In vitro skin permeation was performed in dermatomed human skin and HPLC was used to analyze the drug levels in different skin layers. Further, allergic contact dermatitis (ACD) model was used to evaluate the response of KP-NPS, SP-NPS, SP+KP-NPS, KP-NPS-OA, SP-NPS-OA and SP+KP-NPS-OA treatment in C57BL/6 mice. The fluorescence from OA modified NPS was observed upto depth of 240 μm and was significantly higher as compared to non-modified NPS. The amount of SP and KP retained in skin layers from OA modified NPS increased by several folds compare to unmodified NPS and control solution. In addition, the combination index value calculated from ACD response for solution suggested additive effect and moderate synergism for NPS-OA. Our results strongly suggest that surface modification of bilayered nanoparticles with oleic acid improved drug delivery to the deeper skin layers. PMID:22134117

  16. The effect of nursing consultation involving cancer survivors on newly diagnosed cancer patients’ quality of life

    PubMed Central

    Bahrami, Masoud; Parnian, Raziyeh; Samimi, Mozhgan Alam

    2012-01-01

    Introduction: Cancer and its treatments have a significant effect on the Quality of Life (QoL) of people who suffer from cancer. Nursing consultation involving cancer survivors might be beneficial for other patients as they successfully managed and lived with cancer. But controversies still exist in the research findings as how nursing consultation involving cancer survivors might influence other cancer patients’ QoL. Therefore, a research study was done to determine the effect of nursing consultation with the presence of cancer survivors on cancer patients’ QoL. Materials and Methods: The study was a quasi-experimental research using a pre-post test design, which was conducted in Sayyed- AL-Shohada Hospital affiliated to Isfahan University of Medical Sciences, Iran, in 2010. Twenty-two adult patients who suffered from acute leukemia who were receiving chemotherapy were selected. They participated in a nursing consultation group in which cancer survivors were actively engaged. The patients’ QoL was assessed before, 1 week, and 1 month after the nursing consultation using the European Organization for Research and Treatment of Cancer Quality of Life Core-30 Version 3 (EORTC QLQ-C30-V3) questionnaire. Results: Comparing QoL mean scores of patients in the symptom, performance, and the general health status scales showed that there was not any significant change in the QoL scores before, 1 week, and 1 month after the consultation. Conclusion: It seems that the nursing consultation with the presence of cancer survivors couldn’t enhance patients’ QoL, although it might prevent worsening the patients’ QoL. Cancer has deleterious impacts on patients’ QoL and nursing consultation may not improve QoL in a short period of time. It is recommended that the study be conducted with a larger sample, in a longer time and with a case-control design. PMID:23853645

  17. Late effects of treatment of cancer in infancy

    SciTech Connect

    Pastore, G.; Antonelli, R.; Fine, W.; Li, F.P.; Sallan, S.E.

    1982-01-01

    Eighty-six children were diagnosed with cancer in infancy, followed for at lest 5 years, and assessed for late effects of disease and therapy. One child subsequently died from respiratory failure and 3 died from second primary cancers. Another patient survived second primary cancers of the skin. The high frequency of new cancers (4 observed, 0.09 expected) was attributable to host susceptibility factors and treatment effects. Kyphoscoliosis was diagnosed in 44 patients, 40 of whom had received radiotherapy to the spine. Other patients had neurologic deficits, pulmonary fibrosis, hypoplastic breasts, bowel adhesions, thyroid nodules, musculoskeletal defects, and liver fibrosis associated with tumor therapy. Sequelae of cancer were more common after treatment in infancy than in later childhood. Improved treatments and knowledge of natural history can reduce adverse effects of therapy.

  18. Challenges to effective cancer control in China, India, and Russia.

    PubMed

    Goss, Paul E; Strasser-Weippl, Kathrin; Lee-Bychkovsky, Brittany L; Fan, Lei; Li, Junjie; Chavarri-Guerra, Yanin; Liedke, Pedro E R; Pramesh, C S; Badovinac-Crnjevic, Tanja; Sheikine, Yuri; Chen, Zhu; Qiao, You-lin; Shao, Zhiming; Wu, Yi-Long; Fan, Daiming; Chow, Louis W C; Wang, Jun; Zhang, Qiong; Yu, Shiying; Shen, Gordon; He, Jie; Purushotham, Arnie; Sullivan, Richard; Badwe, Rajendra; Banavali, Shripad D; Nair, Reena; Kumar, Lalit; Parikh, Purvish; Subramanian, Somasundarum; Chaturvedi, Pankaj; Iyer, Subramania; Shastri, Surendra Srinivas; Digumarti, Raghunadhrao; Soto-Perez-de-Celis, Enrique; Adilbay, Dauren; Semiglazov, Vladimir; Orlov, Sergey; Kaidarova, Dilyara; Tsimafeyeu, Ilya; Tatishchev, Sergei; Danishevskiy, Kirill D; Hurlbert, Marc; Vail, Caroline; St Louis, Jessica; Chan, Arlene

    2014-04-01

    Cancer is one of the major non-communicable diseases posing a threat to world health. Unfortunately, improvements in socioeconomic conditions are usually associated with increased cancer incidence. In this Commission, we focus on China, India, and Russia, which share rapidly rising cancer incidence and have cancer mortality rates that are nearly twice as high as in the UK or the USA, vast geographies, growing economies, ageing populations, increasingly westernised lifestyles, relatively disenfranchised subpopulations, serious contamination of the environment, and uncontrolled cancer-causing communicable infections. We describe the overall state of health and cancer control in each country and additional specific issues for consideration: for China, access to care, contamination of the environment, and cancer fatalism and traditional medicine; for India, affordability of care, provision of adequate health personnel, and sociocultural barriers to cancer control; and for Russia, monitoring of the burden of cancer, societal attitudes towards cancer prevention, effects of inequitable treatment and access to medicine, and a need for improved international engagement. PMID:24731404

  19. Students with Cancer: Presenting Issues and Effective Solutions

    ERIC Educational Resources Information Center

    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…

  20. Enhanced GMI effect in NiZn-ferrite-modified Fe-based amorphous ribbons

    NASA Astrophysics Data System (ADS)

    Sun, Xiaojun; Du, Jinlu; Zhu, Zengtai; Wang, Jianbo; Liu, Qingfang

    2015-06-01

    A thin NiZn-ferrite layer was fabricated on the free surface of a Fe-based amorphous ribbon by radio frequency magnetron sputtering, and the giant magnetoimpedance (GMI) effect was measured at different magnetic fields and frequencies. An enhanced GMI effect has been observed in the NiZn-ferrite-modified ribbon at all measured frequencies. The largest GMI ratio up to 80 % is about 2.6 times as large as that of the ribbon without any coating. This enhanced GMI effect is mainly explained in terms of induced stress, the transformation of the domain structure and the magnetic flux path in the modified ribbon. The results obtained are of significant importance in developing strong-signal magnetic sensors.

  1. Double targeting, controlled release and reversible delivery of daunorubicin to cancer cells by polyvalent aptamers-modified gold nanoparticles.

    PubMed

    Taghdisi, Seyed Mohammad; Danesh, Noor Mohammad; Lavaee, Parirokh; Emrani, Ahmad Sarreshtehdar; Hassanabad, Koroush Yousefi; Ramezani, Mohammad; Abnous, Khalil

    2016-04-01

    Clinical use of daunorubicin (Dau) in treatment of leukemia has been restricted because of its cardiotoxicity. Targeted delivery of anticancer drugs could decrease their off-target effects and enhance their efficacy. In this study a modified polyvalent aptamers (PA)-Daunorubicin (Dau)-Gold nanoparticles (AuNPs) complex was designed and its efficacy was assessed in Molt-4 cells (human acute lymphoblastic leukemia T-cell, target). Dau was efficiently loaded (10.5 μM) onto 1mL of PA-modified AuNPs. Dau was released from the PA-Dau-AuNPs complex in a pH-sensitive manner (faster release at pH5.5). The results of flow cytometry analysis indicated that the PA-Dau-AuNPs complex was efficiently internalized into target cells, but not into nontarget cells. The results of MTT assay were consistent with the internalization data. PA-Dau-AuNPs complex had less cytotoxicity in U266 cells compared to Dau alone and even Apt-Dau-AuNPs complex. The PA-Dau-AuNPs complex had more cytotoxicity in Molt-4 cells compared to Dau alone and even Apt-Dau-AuNPs complex. Cytotoxicity of PA-Dau-AuNPs complex was effectively antagonized using antisense of polyvalent aptamers. In conclusion, the designed drug delivery system inherited the properties of efficient drug loading, tumor targeting, pH-dependent drug release and controllable delivery of Dau to tumor cells. PMID:26838906

  2. Synthetic Lethality Screen Identifies RPS6KA2 as Modifier of Epidermal Growth Factor Receptor Activity in Pancreatic Cancer12

    PubMed Central

    Milosevic, Nada; Kühnemuth, Benjamin; Mühlberg, Leonie; Ripka, Stefanie; Griesmann, Heidi; Lölkes, Carolin; Buchholz, Malte; Aust, Daniela; Pilarsky, Christian; Krug, Sebastian; Gress, Thomas; Michl, Patrick

    2013-01-01

    Pancreatic cancer is characterized by a high degree of resistance to chemotherapy. Epidermal growth factor receptor (EGFR) inhibition using the small-molecule inhibitor erlotinib was shown to provide a small survival benefit in a subgroup of patients. To identify kinases whose inhibition acts synergistically with erlotinib, we employed a kinome-wide small-interfering RNA (siRNA)-based loss-of-function screen in the presence of erlotinib. Of 779 tested kinases, we identified several targets whose inhibition acted synergistically lethal with EGFR inhibition by erlotinib, among them the S6 kinase ribosomal protein S6 kinase 2 (RPS6KA2)/ribosomal S6 kinase 3. Activated RPS6KA2 was expressed in approximately 40% of 123 human pancreatic cancer tissues. RPS6KA2 was shown to act downstream of EGFR/RAS/mitogen-activated protein kinase kinase (MEK)/extracellular-signal regulated kinase (ERK) signaling and was activated by EGF independently of the presence of KRAS mutations. Knockdown of RPS6KA2 by siRNA led to increased apoptosis only in the presence of erlotinib, whereas RPS6KA2 activation or overexpression rescued from erlotinib- and gemcitabine-induced apoptosis. This effect was at least in part mediated by downstream activation of ribosomal protein S6. Genetic as well as pharmacological inhibition of RPS6KA2 by the inhibitor BI-D1870 acted synergistically with erlotinib. By applying this synergistic lethality screen using a kinome-wide RNA interference-library approach, we identified RPS6KA2 as potential drug target whose inhibition synergistically enhanced the effect of erlotinib on tumor cell survival. This kinase therefore represents a promising drug candidate suitable for the development of novel inhibitors for pancreatic cancer therapy. PMID:24403857

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

    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

  5. Direct electric current treatment modifies mitochondrial function and lipid body content in the A549 cancer cell line.

    PubMed

    Holandino, Carla; Teixeira, Cesar Augusto Antunes; de Oliveira, Felipe Alves Gomes; Barbosa, Gleyce Moreno; Siqueira, Camila Monteiro; Messeder, Douglas Jardim; de Aguiar, Fernanda Silva; da Veiga, Venicio Feo; Girard-Dias, Wendell; Miranda, Kildare; Galina, Antonio; Capella, Marcia Alves Marques; Morales, Marcelo Marcos

    2016-10-01

    Electrochemical therapy (EChT) entails treatment of solid tumors with direct electric current (DC). This work evaluated the specific effects of anodic flow generated by DC on biochemical and metabolic features of the A549 human lung cancer cell line. Apoptosis was evaluated on the basis of caspase-3 activity and mitochondrial transmembrane potential dissipation. Cell morphology was analyzed using transmission electron microscopy, and lipid droplets were studied through morphometric analysis and X-ray qualitative elemental microanalysis. High-resolution respirometry was used to assess mitochondrial respiratory parameters. Results indicated A549 viability decreased in a dose-dependent manner with a prominent drop between 18 and 24h after treatment (p<0.001), together with a two-fold increase in caspase-3 activity. AF-treatment induced a significantly increase (p<0.01) in the cell number with disrupted mitochondrial transmembrane potential. Furthermore, treated cells demonstrated important ultrastructural mitochondria damage and a three-fold increase in the cytoplasmic lipid bodies' number, quantified by morphometrical analyses. Conversely, 24h after treatment, the cells presented a two-fold increase of residual oxygen consumption, accounting for 45.3% of basal oxygen consumption. These results show remarkable alterations promoted by anodic flow on human lung cancer cells which are possibly involved with the antitumoral effects of EChT. PMID:27243447

  6. Anti-cancer activity of doxorubicin-loaded liposomes co-modified with transferrin and folic acid.

    PubMed

    Sriraman, Shravan Kumar; Salzano, Giusseppina; Sarisozen, Can; Torchilin, Vladimir

    2016-08-01

    Cancer-specific drug delivery represents an attractive approach to prevent undesirable side-effects and increase the accumulation of the drug in the tumor. Surface modification of nanoparticles such as liposomes with targeting moieties specific to the up-regulated receptors on the surface of tumor cells thus represents an effective strategy. Furthermore, since this receptor expression can be heterogeneous, using a dual-combination of targeting moieties may prove advantageous. With this in mind, the anti-cancer activity of PEGylated doxorubicin-loaded liposomes targeted with folic acid (F), transferrin (Tf) or both (F+Tf) was evaluated. The dual-targeted liposomes showed a 7-fold increase in cell association compared to either of the single-ligand targeted ones in human cervical carcinoma (HeLa) cell monolayers. The increased penetration and cell association of the dual-targeted liposomes were also demonstrated using HeLa cell spheroids. The in vitro cytotoxicity of the doxorubicin liposomes (LD) was then evaluated using HeLa and A2780-ADR ovarian carcinoma cell monolayers. In both these cell lines, the (F+Tf) LD showed significantly higher cytotoxic effects than the untargeted, or single-ligand targeted liposomes. In a HeLa xenograft model in nude mice, compared to the untreated group, though the untargeted LD showed 42% tumor growth inhibition, both the (F) LD and (F+Tf) LD showed 75% and 79% tumor growth inhibition respectively. These results thus highlight that though the dual-targeted liposomes represent an effective cytotoxic formulation in the in vitro setting, they were equally effective as the folic acid-targeted liposomes in reducing tumor burden in the more complex in vivo setting in this particular model. PMID:27264717

  7. Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.

    PubMed

    Asara, Yolande; Marchal, Juan A; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

    2013-01-01

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd. PMID:23941782

  8. Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

    PubMed Central

    Asara, Yolande; Marchal, Juan A.; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A.; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

    2013-01-01

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd. PMID:23941782

  9. Indoor Pollutant Exposures Modify the Effect of Airborne Endotoxin on Asthma in Urban Children

    PubMed Central

    Hansel, Nadia N.; Aloe, Charles; Schiltz, Allison M.; Peng, Roger D.; Rabinovitch, Nathan; Ong, Mary Jane; Williams, D’Ann L.; Breysse, Patrick N.; Diette, Gregory B.; Liu, Andrew H.

    2013-01-01

    Rationale: The effect of endotoxin on asthma morbidity in urban populations is unclear. Objectives: To determine if indoor pollutant exposure modifies the relationships between indoor airborne endotoxin and asthma health and morbidity. Methods: One hundred forty-six children and adolescents with persistent asthma underwent repeated clinical assessments at 0, 3, 6, 9, and 12 months. Home visits were conducted at the same time points for assessment of airborne nicotine, endotoxin, and nitrogen dioxide (NO2) concentrations. The effect of concomitant pollutant exposure on relationships between endotoxin and asthma outcomes were examined in stratified analyses and statistical models with interaction terms. Measurements and Main Results: Both air nicotine and NO2 concentrations modified the relationships between airborne endotoxin and asthma outcomes. Among children living in homes with no detectable air nicotine, higher endotoxin was inversely associated with acute visits and oral corticosteroid bursts, whereas among those in homes with detectable air nicotine, endotoxin was positively associated with these outcomes (interaction P value = 0.004 and 0.07, respectively). Among children living in homes with lower NO2 concentrations (<20 ppb), higher endotoxin was positively associated with acute visits, whereas among those living in homes with higher NO2 concentrations, endotoxin was negatively associated with acute visit (interaction P value = 0.05). NO2 also modified the effect of endotoxin on asthma symptom outcomes in a similar manner. Conclusions: The effects of household airborne endotoxin exposure on asthma are modified by coexposure to air nicotine and NO2, and these pollutants have opposite effects on the relationships between endotoxin and asthma-related outcomes. PMID:24066676

  10. Laryngeal cancer risk associated with smoking and alcohol consumption is modified by genetic polymorphisms in ERCC5, ERCC6 and RAD23B but not by polymorphisms in five other nucleotide excision repair genes.

    PubMed

    Abbasi, Rashda; Ramroth, Heribert; Becher, Heiko; Dietz, Andreas; Schmezer, Peter; Popanda, Odilia

    2009-09-15

    Laryngeal cancer is known to be associated with smoking and high alcohol consumption. Nucleotide excision repair (NER) plays a key role in repairing DNA damage induced by these exposures and might affect laryngeal cancer susceptibility. In a population-based case-control study including 248 cases and 647 controls, the association of laryngeal cancer with 14 single nucleotide polymorphisms (SNPs) in 8 NER genes (XPC, XPA, ERCC1, ERCC2, ERCC4, ERCC5, ERCC6 and RAD23B) was analyzed with respect to smoking and alcohol exposure. For genotyping, sequence specific hybridization probes were used. Data were evaluated by conditional logistic regression analysis, stratified for age and gender, and adjusted for smoking, alcohol consumption and education. Pro-carriers of ERCC6 Arg1230Pro showed a decreased risk for laryngeal cancer (OR = 0.53, 95% CI 0.34-0.85), strongest in heavy smokers and high alcohol consumers. ERCC5 Asp1104His was associated with risk in heavy smokers (OR = 1.70, 95% CI 1.1-2.5). Val-carriers of RAD23B Ala249Val had an increased cancer risk in heavy smokers (OR = 1.6, 95% CI 1.1-2.5) and high alcohol consumers (OR = 2.0, 95% CI 1.1-3.4). The combined effect of smoking and alcohol intake affected risk, at high exposure level, for ERCC6 1230Pro carriers (OR = 0.47, 95% CI 0.22-0.98) and RAD23B 249Val carriers (OR = 2.6, 95% CI 1.3-4.9). When tested for gene-gene interaction, presence of 3 risk alleles in the XPC-RAD23B complex increased the risk 2.1-fold. SNPs in the other genes did not show a significant association with laryngeal cancer risk. We conclude that common genetic variations in NER genes can significantly modify laryngeal cancer risk. PMID:19444904

  11. Multifunctional lactobionic acid-modified dendrimers for targeted drug delivery to liver cancer cells: investigating the role played by PEG spacer.

    PubMed

    Fu, Fanfan; Wu, Yilun; Zhu, Jingyi; Wen, Shihui; Shen, Mingwu; Shi, Xiangyang

    2014-09-24

    We report the development of a lactobionic acid (LA)-modified multifunctional dendrimer-based carrier system for targeted therapy of liver cancer cells overexpressing asialoglycoprotein receptors. In this study, generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers were sequentially modified with fluorescein isothiocyanate (FI) and LA (or polyethylene glycol (PEG)-linked LA, PEG-LA), followed by acetylation of the remaining dendrimer terminal amines. The synthesized G5.NHAc-FI-LA or G5.NHAc-FI-PEG-LA conjugates (NHAc denotes acetamide groups) were used to encapsulate a model anticancer drug doxorubicin (DOX). We show that both conjugates are able to encapsulate approximately 5.0 DOX molecules within each dendrimer and the formed dendrimer/DOX complexes are stable under different pH conditions and different aqueous media. The G5.NHAc-FI-PEG-LA conjugate appears to have a better cytocompatibility, enables a slightly faster DOX release rate, and displays better liver cancer cell targeting ability than the G5.NHAc-FI-LA conjugate without PEG under similar experimental conditions. Importantly, the developed G5.NHAc-FI-PEG-LA/DOX complexes are able to specifically inhibit the growth of the target cells with a better efficiency than the G5.NHAc-FI-LA/DOX complexes at a relatively high DOX concentration. Our results suggest a key role played by the PEG spacer that affords the dendrimer platform with enhanced targeting and therapeutic efficacy of cancer cells. The developed LA-modified multifunctional dendrimer conjugate with a PEG spacer may be used as a delivery system for targeted liver cancer therapy and offers new opportunities in the design of multifunctional drug carriers for targeted cancer therapy applications. PMID:25185074

  12. Liposomes, modified with PTD(HIV-1) peptide, containing epirubicin and celecoxib, to target vasculogenic mimicry channels in invasive breast cancer.

    PubMed

    Ju, Rui-Jun; Li, Xue-Tao; Shi, Ji-Feng; Li, Xiu-Ying; Sun, Meng-Ge; Zeng, Fan; Zhou, Jia; Liu, Lei; Zhang, Cheng-Xiang; Zhao, Wei-Yu; Lu, Wan-Liang

    2014-08-01

    Refractoriness of invasive breast cancer is closely related with the vasculogenic mimicry (VM) channels, which exhibit highly drug resistance to conventional chemotherapies. In the present study, the nanostructured targeting epirubicin plus celecoxib liposomes were developed by modifying a human immunodeficiency virus peptide lipid-derivative conjugate (DSPE-PEG2000-PTDHIV-1) for elimination of invasive breast cancer cells along with their VM channels. The studies were undertaken on invasive human breast cancer MDA-MB-435S cells and MDA-MB-435S xenografts in nude mice. The constructed targeting epirubicin plus celecoxib liposomes were approximately 100 nm in size. In vitro results showed that the targeting liposomes exhibited strong transport ability across cell and nuclei membranes of invasive breast cancer, were able to penetrate and destruct the invasive breast cancer spheroids, initiated apoptosis via activating apoptotic enzymes (caspase 8, 3), and destroyed the VM channels via down-regulating the protein indicators (MMP-9, VE-Cad, FAK, EphA2 and HIF-1α) in invasive breast cancer cells. In vivo results demonstrated that the targeting liposomes displayed a prolonged circulation time in blood system, accumulated more in tumor location, were able to eliminate the VM channels and angiogenesis in tumor tissues, and resulted in a robust overall anticancer efficacy in invasive breast cancer MDA-MB-435S xenografts in nude mice. In conclusion, the nanostructured targeting epirubicin plus celecoxib liposomes could eliminate invasive breast cancer along with the VM channels, hence providing a promising strategy for treatment of invasive breast cancer. PMID:24912818

  13. The adverse effects of sorafenib in patients with advanced cancers.

    PubMed

    Li, Ye; Gao, Zu-Hua; Qu, Xian-Jun

    2015-03-01

    Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in long-term efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers. PMID:25495944

  14. Tumor targetability and antitumor effect of docetaxel-loaded hydrophobically modified glycol chitosan nanoparticles.

    PubMed

    Hwang, Ho-Young; Kim, In-San; Kwon, Ick Chan; Kim, Yong-Hee

    2008-05-22

    Hydrophobically modified glycol chitosan (HGC) nanoparticles, a new nano-sized drug carrier, were prepared by introducing a hydrophobic molecule, cholanic acid, to water soluble glycol chitosan. The HGC nanoparticles were easily loaded with the anticancer drug docetaxel (DTX) using a dialysis method, and the resulting docetaxel-loaded HGC (DTX-HGC) nanoparticles formed spontaneously self-assembled aggregates with a mean diameter of 350 nm in aqueous condition. The DTX-HGC nanoparticles were well dispersed and stable for 2 weeks under physiological conditions (pH 7.4 and 37 degrees C) and a sustained drug release profile, in vitro. In addition, the DTX-HGC nanoparticles were reasonably stable in the presence of excess bovine serum albumin, which suggested that the DTX-HGC nanoparticles might also be stable in the blood stream. The DTX-HGC nanoparticles exhibited a distinctive deformability in aqueous conditions, in that they could easily pass through a filter membrane with 200 nm pores despite their mean diameter of 350 nm. We also evaluated the time-dependent excretion profile, in vivo biodistribution, prolonged circulation time, and tumor targeting ability of DTX-HGC nanoparticles by using a non-invasive live animal imaging technology. Finally, under optimal conditions for cancer therapy, the DTX-HGC nanoparticles showed higher antitumor efficacy such as reduced tumor volume and increased survival rate in A549 lung cancer cells-bearing mice and strongly reduced the anticancer drug toxicity compared to that of free DTX in tumor-bearing mice. Together our results showed that the anticancer loaded nano-sized drug carriers are a promising nano-sized drug formulation for cancer therapy. PMID:18374444

  15. Effect of β-cyclodextrin on Rheological Properties of some Viscosity Modifiers.

    PubMed

    Rao, G Chandra Sekhara; Ramadevi, K; Sirisha, K

    2014-01-01

    Cyclodextrins are a group of novel excipients, extensively used in the present pharmaceutical industry. Sometimes they show significant interactions with other conventional additives used in the formulation of dosage forms. The effect of β-cyclodextrin on the rheological properties of aqueous solutions of some selected viscosity modifiers was studied in the present work. β-cyclodextrin showed two different types of effects on the rheology of the selected polymers. In case of natural polymers like xanthan gum and guar gum, enhanced apparent viscosity was found and in case of semi-synthetic polymers like sodium carboxymethyl cellulose and methyl cellulose, reduction in apparent viscosity was found. β-cyclodextrin was included at 0.5, 1 and 2% w/v concentrations into the polymeric solutions. These findings are useful in the adjustment of concentrations of viscosity modifiers during the formulation of physically stable disperse systems. PMID:25593389

  16. Effect of Reprocessing and Accelerated Weathering on Impact-Modified Recycled Blend

    NASA Astrophysics Data System (ADS)

    Ramesh, V.; Mohanty, Smita; Biswal, Manoranjan; Nayak, Sanjay K.

    2015-12-01

    Recovery of recycled polycarbonate, acrylonitrile butadiene styrene, high-impact polystyrene, and its blends from waste electrical and electronic equipment plastics products properties were enhanced by the addition of virgin polycarbonate and impact modifier. The optimized blend formulation was processed through five cycles, at processing temperature, 220-240 °C and accelerated weathering up to 700 h. Moreover, the effect of reprocessing and accelerated weathering in the physical properties of the modified blends was investigated by mechanical, thermal, rheological, and morphological studies. The results show that in each reprocessing cycle, the tensile strength and impact strength decreased significantly and the similar behavior has been observed from accelerated weathering. Subsequently, the viscosity decreases and this decrease becomes the effect of thermal and photo-oxidative degradation. This can be correlated with FTIR analysis.

  17. Cancer-Promoting Effects of Microbial Dysbiosis

    PubMed Central

    Sheflin, Amy M.; Whitney, Alyssa K.; Weir, Tiffany L.

    2014-01-01

    Humans depend upon our commensal bacteria for nutritive, immune-modulating and metabolic contributions to maintenance of health. However, this commensal community exists in careful balance that, if disrupted, enters dysbiosis; which has been shown to contribute to the etiology of colon, gastric, esophageal, pancreatic, laryngeal, breast and gallbladder carcinomas. This etiology is closely tied to host inflammation, which causes and is aggravated by microbial dysbiosis while increasing vulnerability to pathogens. Advances in sequencing technology have increased our ability to catalog microbial species associated with various cancer types across the body. However, defining microbial biomarkers as cancer predictors presents multiple challenges and existing studies identifying cancer-associated bacteria have reported inconsistent outcomes. Combining metabolites and microbiome analyses can help elucidate interactions between gut microbiota, metabolism and the host. Ultimately, understanding how gut dysbiosis impacts host response and inflammation will be critical to creating an accurate picture of the role of the microbiome in cancer. PMID:25123079

  18. Effects of modified clay on cysts of Scrippsiella trochoidea for harmful algal bloom control

    NASA Astrophysics Data System (ADS)

    Wang, Zhifu; Yu, Zhiming; Song, Xiuxian; Cao, Xihua; Han, Xiaotian

    2014-11-01

    We present results on the effect of modified clay on cyst formation of Scrippsiella trochoidea in harmful algal bloom (HAB). Modified clay (in concentration of 0, 0.1, 0.5, and 1.0 g/L) were added to cultures, and observations were made on cysts of S. trochoidea under controlled laboratory conditions. Results indicate that the removal rate of algal cells reached 97.7% at the clay concentration of 1.0 g/L. The cyst formation rate increased from 4.6% to 24.6% when the concentration of clay was increased from 0 to 1.0 g/L. Two cyst metamorphs were observed: spinal calcareous cysts and smooth noncalcareous ones. The proportion of the spinal cysts decreased from 76.9% to 24.1% when clay concentration increased from 0 to 1.0 g/L. In addition, modified clay affected cyst germination. The germination rate decreased with the increases in the clay concentrations. Non-calcareous cysts had a lower germination rate with a longer germination time. We conclude that modified clay could depress algal cell multiplication and promote formation of temporal cysts of S. trochoidea, which may help in controlling HAB outbreaks.

  19. Exchange bias effect modified asymmetric magnetization reversal in Ni/YMnO3 multiferroic bilayers

    NASA Astrophysics Data System (ADS)

    Gong, Junlu; Zheng, Dongxing; Li, Dong; Jin, Chao; Li, Peng; Feng, Liefeng; Bai, Haili

    2016-04-01

    Exchange bias (EB) effect modified asymmetric magnetization reversal in Ni/YMnO3 multiferroic bilayers was investigated by combining anisotropic magnetoresistance (AMR) with free energy methods. The promotion and inhibition effects of EB field on magnetization rotation result in the asymmetry of magnetization reversal. The AMR curves exhibit shape transition from arc-like to sin2θH-dependence with increasing external fields due to the competition between Zeeman energy and interfacial coupling energy. The phase shift and asymmetric behaviors become weak as the EB field decreases. Our work suggests that controlling the EB effect can be an alternative way to manipulate the magnetization reversal in exchange biased systems.

  20. [Effects of modified Ganmai Dazao decoction on neuroendocrine system in patients with climacteric depression].

    PubMed

    Ma, Xiao-Juan; Zhao, Jie; Feng, Zhen-Yu; Chang, Jian-Min; Meng, Shuang; Liu, Hu-Ze; Fan, Kai-Fang

    2014-12-01

    Clinical study of modified Ganmai Dazao decoction in the treatment of yang deficiency climacteric depression and observe the effects of modified Ganmai Dazao decoction on neuroendocrine system in patients with yang deficiency climacteric depression. 86 cases were randomly divided into treatment group treated with modified Ganmai Dazao decoction and control group treated with Deanxit. The curative effect was evaluated with Hamilton's depressive scale (HAMD) and pittsburgh sleep quality scale (PSQI) before and at the end of the two and four weeks of the treatment, the serum levels of serotonin (5-HT), norepinephrine (NE), estradiol (E2), follicle stimulating hormone (FSH), luteotropic hormone (LH) were detected before and after the four weeks of the treatment The results showed that the total effective power of treatment group was 88.4% and the total effective power of control group was 81.4% after four weeks interference, with insignificant difference between the two groups. After two and four weeks of the treatment, the score of HAMD decreased remarkably in both groups (P < 0.01), with insignificant difference between the two groups in same phase. After two and four weeks of the treatment, the total score of PSQI decreased remarkably in both groups (P < 0.05), with significant difference between the two groups after four weeks (P < 0.01). After four weeks of treatment, the serum levels of 5-HT and NE increased (P < 0.01), with insignificant difference between the groups. After four weeks of treatment, the serum levels of E2 increased obviously (P < 0.05), the levels of FSH decreased obviously (P < 0.05), the levels of LH decreased insignificant, with insignificant difference between two groups. This study indicates that modified Ganmai Dazao decoction has obvious therapeutic effects in the treatment of climacteric depression, and showed equivalent efficacy with Deanxit, and modified Ganmai Dazao decoction has better effect on improving the sleep quality in patients

  1. The effect of modified trampoline training on balance, gait, and falls efficacy of stroke patients

    PubMed Central

    Hahn, Joohee; Shin, Seonhae; Lee, Wanhee

    2015-01-01

    [Purpose] This research was conducted to investigate the effects of modified trampoline training on the balance, gait, and falls efficacy of stroke patients. [Subjects] Twenty-four stroke patients participated in this study. The subjects were randomly allocated to one of two groups: the trampoline group (n=12) or the control group (n=12). [Methods] Both groups participated in conventional physical therapy for thirty minutes per day, three times a week for six weeks. The trampoline group also took part in trampoline training for thirty minutes per day, three times a week for six weeks. We evaluated balance (Berg balance scale, timed up and go test), gait (dynamic gait index), and falls efficacy (falls efficacy scale-K) to confirm the effects of the intervention. [Results] Both the trampoline and the control group showed significant improvements in balance, gait, and falls efficacy compared to before the intervention, and the improvements were significantly greater in the trampoline group than in the control group. [Conclusion] Modified trampoline training resulted in significantly improved balance, dynamic gait, and falls efficacy of stroke patients compared to the control group. These results suggest that modified trampoline training is feasible and effective at improving balance, dynamic gait, and falls efficacy after stroke. PMID:26696696

  2. Total, Direct and Indirect Effects of Paan on Oral Cancer

    PubMed Central

    Merchant, Anwar T; Pitiphat, Waranuch

    2014-01-01

    Purpose Paan (betel leaf and betel nut quid) used with or without tobacco has been positively associated with oral cancer. Oral submucous fibrosis (OSMF), a pre-cancerous condition caused by paan, lies on the causal pathway between paan use and oral cancer. The purpose of this analysis was to estimate the effect of paan consumption on oral cancer risk when it is mediated by OSMF. Methods We used mediation methods proposed by Vanderweele, which are based on causal inference principles, to characterize the total, direct and indirect effects of paan, consumed with and without tobacco, on oral cancer mediated by OSMF. We reanalyzed case-control data collected from three hospitals in Karachi, Pakistan between July 1996 and March 1998. Results For paan without tobacco the total effect on oral cancer was OR=7.39, 95% CI, 1.01, 38.11, natural indirect effect (due to OSMF among paan users) was OR=2.48, 95% CI, 0.99, 10.44, and the natural direct effect (due to paan with OSMF absent) was OR=3.32, 95% CI, 0.68, 10.07. For paan with tobacco the total direct effect was OR=15.68, 95% CI, 3.00, 54.90, natural indirect effect was OR=2.18, 95% CI,0.82, 5.52, and the natural direct effect was OR=7.27, 95% CI,2.15, 20.43. Conclusions Paan, whether or not it contained tobacco, raised oral cancer risk irrespective of OSMF. Oral cancer risk was higher among those who used paan with tobacco. PMID:25542140

  3. Ultraviolet photodetectors based on ZnO nanorods-seed layer effect and metal oxide modifying layer effect

    NASA Astrophysics Data System (ADS)

    Zhou, Hai; Fang, Guojia; Liu, Nishuang; Zhao, Xingzhong

    2011-12-01

    Pt/ZnO nanorod (NR) and Pt/modified ZnO NR Schottky barrier ultraviolet (UV) photodetectors (PDs) were prepared with different seed layers and metal oxide modifying layer materials. In this paper, we discussed the effect of metal oxide modifying layer on the performance of UV PDs pre- and post-deposition annealing at 300°C, respectively. For Schottky barrier UV PDs with different seed layers, the MgZnO seed layer-PDs without metal oxide coating showed bigger responsivity and larger detectivity ( D λ*) than those of PDs with ZnO seed layer, and the reason was illustrated through energy band theory and the electron transport mechanism. Also the ratio of D 254* to D 546* was calculated above 8 × 102 for all PDs, which demonstrated that our PDs showed high selectivity for detecting UV light with less influence of light with long wavelength.

  4. Hyaluronic Acid-Modified Multifunctional Q-Graphene for Targeted Killing of Drug-Resistant Lung Cancer Cells.

    PubMed

    Luo, Yanan; Cai, Xiaoli; Li, He; Lin, Yuehe; Du, Dan

    2016-02-17

    Considering the urgent need to explore multifunctional drug delivery system for overcoming multidrug resistance, we prepared a new nanocarbon material Q-Graphene as a nanocarrier for killing drug-resistant lung cancer cells. Attributing to the introduction of hyaluronic acid and rhodamine B isothiocyanate (RBITC), the Q-Graphene-based drug delivery system was endowed with dual function of targeted drug delivery and fluorescence imaging. Additionally, doxorubicin (DOX) as a model drug was loaded on the surface of Q-Graphene via π-π stacking. Interestingly, the fluorescence of DOX was quenched by Q-Graphene due to its strong electron-accepting capability, and a significant recovery of fluorescence was observed, while DOX was released from Q-Graphene. Because of the RBITC labeling and the effect of fluorescence quenching/restoring of Q-Graphene, the uptake of nanoparticles and intracellular DOX release can be tracked. Overall, a highly promising multifunctional nanoplatform was developed for tracking and monitoring targeted drug delivery for efficiently killing drug-resistant cancer cells. PMID:26785717

  5. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    ClinicalTrials.gov

    2016-05-02

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pleural Mesothelioma

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

    PubMed Central

    Chakrabarty, Jyothi; Vidyasagar, MS; Fernandes, Donald; Joisa, Ganapathi; Varghese, Prabha; Mayya, Sreemathi

    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 this study was to determine the effectiveness of pranayama on cancer-related fatigue among breast cancer patients undergoing radiation therapy as measured by cancer fatigue scale. Settings and Design: Shirdi Sai Baba Cancer Hospital and Research Center, Kasturba Hospital Manipal. Materials and Methods: Study was a randomized controlled trial done among breast cancer patients receiving radiation therapy. Statistical Analysis Used: Demographic characteristics of the participants are presented as frequency and percentage. Comparison of means of cancer-related fatigue between the two groups is done by Mann-Whitney U-test and comparison of pre- and pos t-test means of cancer-related fatigue among the experimental group is done by Wilcoxon sign rank test. Results: There was a significant difference between the two groups with regard to the scores of cancer-related fatigue. The experimental group of patients who performed pranayama along with radiation therapy experienced less fatigue. Conclusions: Pranayama can be used as a supportive therapy for breast cancer patients undergoing radiation therapy. PMID:25558133

  7. Modulatory effects and molecular mechanisms of olive oil and other dietary lipids in breast cancer.

    PubMed

    Escrich, Eduard; Solanas, Montserrat; Moral, Raquel; Escrich, Raquel

    2011-01-01

    Breast cancer is the most common cancer among women worldwide. In addition to genetic and endocrine factors, the environment, and specifically dietary habits, plays a key role in the aetiology of this malignancy. Epidemiological and, especially, experimental studies have shown a relationship between dietary lipids and breast cancer although there are conflicting results concerning their potential to modify cancer risk in humans. Abundant data have attributed a potential chemopreventive effect to extra-virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, which is associated with low incidence and mortality rates from cardiovascular disease and some cancers, including that of the breast. It is well-established that the healthy effects of EVOO can be attributed both to its particular fatty acid composition (a high content in oleic acid (OA), a suitable quantity of essential polyunsaturated fatty acids (PUFA) and a relatively low n-6 PUFA/n-3 PUFA ratio) and its richness in minor bioactive compounds such as squalene and phenolic antioxidants. The specific mechanisms by which EVOO and other dietary lipids may exert their modulatory effects on cancer are not fully understood although abundant research has proposed the following: They influence in the stages of the carcinogenesis process, oxidative stress, alteration of the hormonal status, modification of the structure and function of cell membranes, modulation of cell signalling transduction pathways, regulation of gene expression and influence in the immune system. This article will explore the current knowledge of these mechanisms, including our own results in the context of the international literature. PMID:21443482

  8. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

    PubMed

    Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A; Andrulis, Irene L; Arun, Banu K; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A; Campbell, Ian; Chan, Salina B; Claes, Kathleen B M; Cohn, David E; Cook, Jackie; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; Pauw, Antoine de; Delnatte, Capucine; Diez, Orland; Domchek, Susan M; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K; Goldgar, David E; Hake, Christopher R; Hansen, Thomas V O; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B L; Houdayer, Claude; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M; Vijai, Joseph; Karlan, Beth Y; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R; Montagna, Marco; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C; Rookus, Matti A; Ross, Eric A; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F; Slavin, Thomas P; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I; Tea, Muy-Kheng; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J; Greene, Mark H; Couch, Fergus J; Offit, Kenneth; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population. PMID:27463617

  9. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    PubMed Central

    Vigorito, Elena; Kuchenbaecker, Karoline B.; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A.; Andrulis, Irene L.; Arun, Banu K.; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A.; Campbell, Ian; Chan, Salina B.; Claes, Kathleen B. M.; Cohn, David E.; Cook, Jackie; Daly, Mary B.; Damiola, Francesca; Davidson, Rosemarie; de Pauw, Antoine; Delnatte, Capucine; Diez, Orland; Domchek, Susan M.; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F.; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D. Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D.; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A.; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K.; Goldgar, David E.; Hake, Christopher R.; Hansen, Thomas V. O.; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B. L.; Houdayer, Claude; Hulick, Peter J.; Imyanitov, Evgeny N.; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M.; Vijai, Joseph; Karlan, Beth Y.; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L.; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R.; Montagna, Marco; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I.; Ong, Kai-ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C.; Rookus, Matti A.; Ross, Eric A.; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F.; Slavin, Thomas P.; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I.; Tea, Muy-Kheng; Teixeira, Manuel R.; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J.; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N.; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J.; Greene, Mark H.; Couch, Fergus J.; Offit, Kenneth; Pharoah, Paul D. P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10−16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10−6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population. PMID:27463617

  10. Are Breast Cancer Navigation Programs Cost-Effective? Evidence from the Chicago Cancer Navigation Project

    PubMed Central

    Markossian, Talar W.; Calhoun, Elizabeth A.

    2010-01-01

    Objectives One of the aims of the Chicago Cancer Navigation Project (CCNP) is to reduce the interval of time between abnormal breast cancer screening and definitive diagnosis in patients who are navigated as compared to usual care. In this article, we investigate the extent to which total costs of breast cancer navigation can be off-set by survival benefits and savings in lifetime breast cancer-attributable costs. Methods Data sources for the cost-effectiveness analysis include data from published literature, secondary data from the NCI’s Surveillance Epidemiology and End Results program, and primary data from the CCNP. Results If women enrolled in CCNP receive breast cancer diagnosis earlier by 6-months as compared to usual care, then navigation is borderline cost-effective for $95,625 per life-year saved. Results from sensitivity analyses suggest that the cost-effectiveness of navigation is sensitive to: the interval of time between screening and diagnosis, percent increase in number of women who receive cancer diagnosis and treatment, women’s age, and the positive predictive value of a mammogram. Conclusions In planning cost-effective navigation programs, special considerations should be made regarding the characteristics of the disease, program participants, and the initial screening test that determines program eligibility. PMID:20685001

  11. Targeting human equilibrative nucleoside analog transporter (hENT1) expression through modified low glycemic index diet in pancreatic cancer.

    PubMed

    Pazienza, Valerio; Del Nobile Matteo, Alessandro

    2014-06-01

    Pancreatic cancer is a highly aggressive and chemotherapy-resistant cancer. Up to date, the primary goals of nutrition interventions for pancreatic cancer' patients are to prevent or reverse loss of weight and malnutrition in order to maintain dose and schedule of cancer treatments and/or to manage symptoms due to the lack of enzymes' production by the damaged pancreas. With this script, we sought to underline the potential link between dietary settings and the modulation of chemoresistance in pancreatic cancer. PMID:24874245

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

    PubMed Central

    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

    2014-01-01

    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. PMID:25493015

  13. Effect of penetration modifiers on the dermal and transdermal delivery of drugs and cosmetic active ingredients.

    PubMed

    Otto, A; Wiechers, J W; Kelly, C L; Hadgraft, J; du Plessis, J

    2008-01-01

    In this study the effect of 2 penetration modifiers, dimethyl isosorbide (DMI) and diethylene glycol monoethyl ether (DGME) on the skin delivery of hydroquinone (HQ), salicylic acid (SA) and octadecenedioic acid (DIOIC) was investigated. Ten percent DMI and DGME were separately formulated into oil-in-water emulsions containing 1.8% HQ, SA and DIOIC, respectively. Skin delivery and the flux across split-thickness human skin of the active ingredients were determined using Franz diffusion cells. An emulsion with 10% water incorporated instead of the water-soluble penetration modifiers served as a control. The study showed that neither 10% DMI nor 10% DGME significantly enhanced the skin permeation of the various lipophilic active ingredients or the uptake into the skin. It was hypothesized that the addition of the penetration modifiers to the emulsions not only enhanced the solubility of the various active ingredients in the skin but also in the formulation, resulting in a reduced thermodynamic activity and hence a weaker driving force for penetration. Therefore, the effect of DMI and DGME on the solubility of the active ingredients in the skin was counteracted by a simultaneous reduction in the thermodynamic activity in the formulation. PMID:18832865

  14. The Effectiveness of Modified Vertical Dome Division Technique in Reducing Nasal Tip Projection in Rhinoplasty

    PubMed Central

    Gandomi, Behrooz; Arzaghi, Mohammad Hossein; Rafatbakhsh, Mohammad

    2011-01-01

    Background: The technique of vertical dome division or tip defining, involves incising the lateral crura and vestibular skin at or lateral to the dome or tip defining point. The incision divides the lower lateral cartilage into a lateral segment and a medial segment, which are advanced anteriorly and sutured together to increase tip projection. The present study aimed at assessing a new vertical dome division, which is a modified version of vertical dome technique to decrease nasal tip projection, and increase or decrease nasal tip rotation and other tip deformities. Methods: The medical files of patients undergone rhinoplasty from 2003 to 2008 were retrospectively analyzed. The files were selected from a computerized rhinoplasty database of patients, who had been operated using a modified vertical dome technique and followed-up for one year or more after the surgery. Results: A total of 3756 patients were operated. Complications related to the nasal tip such as bossae, bifidity, persistent tip projection or tip asymmetry was seen in 81 patients (2.1%). Revisions for tip-related problems were performed in 42 patients (1.1%). Conclusions: The findings suggest that the modified vertical dome technique is an effective method for nasal tip deprojection and narrowing via an open approach. The length of follow-up and the large sample size support effectiveness of the technique. PMID:23359623

  15. Multi-mutational model for cancer based on age-time patterns of radiation effects: 2. Biological aspects

    SciTech Connect

    Mendelsohn, M.L.; Pierce, P.A.

    1997-09-04

    Biological properties of relevance when modeling cancers induced in the atom bomb survivors include the wide distribution of the induced cancers across all organs, their biological indistinguishability from background cancers, their rates being proportional to background cancer rates, their rates steadily increasing over at least 50 years as the survivors age, and their radiation dose response being linear. We have successfully described this array of properties with a modified Armitage-Doll model using 5 to 6 somatic mutations, no intermediate growth, and the dose-related replacement of any one of these time-driven mutations by a radiation-induced mutation. Such a model is contrasted to prevailing models that use fewer mutations combined with intervening growth. While the rationale and effectiveness of our model is compelling for carcinogenesis in the atom bomb survivors, the lack of a promotional component may limit the generality of the model for other types of human carcinogenesis.

  16. Effects of aging on repair bond strengths of a polyacid-modified composite resin.

    PubMed

    Yap, A U; Sau, C W; Lye, K W

    1999-01-01

    The effect of age of a poly-acid-modified composite resin on repair bond strength after different methods of surface conditioning was studied. Surface conditioning methods included the following: maleic acid with resin application; polyacrylic acid with resin application; sand-blasting with resin application. Shear bond testing between the aged and new material was carried out with an Instron Universal Testing Machine. Although repair bonds strengths after all surface conditioning methods were significantly higher than the control group at 1 week, no statistically significant differences in bond strengths were noted after aging the material for 6 months. After all aging periods, surface conditioning with sand-blasting and resin application resulted in the highest repair bond for poly-acid-modified composite resins. Specimens with cohesive failure in the material gave significantly higher repair bond strengths than specimens with adhesive failure at the repaired interface. PMID:10823087

  17. Comparison of Cancer-specific and General Health Literacy Assessments in an Educated Population: Correlations and Modifying Factors.

    PubMed

    Jenkins, Wiley D; Zahnd, Whitney E; Spenner, Allison; Wiley, Celeste; Roles, Rhonda; Potini, Yogitha; Jones, Linda S

    2016-06-01

    An information onslaught accompanies cancer diagnoses, but patient comprehension (health literacy; HL) is frequently low, impacting both immediate care and longer term follow-up. Knowledge and adoption of preventive measures is especially important for cancer survivors due to their increased risk of secondary malignant neoplasms. We sought to evaluate the Test of Functional Health Literacy Adult (S-TOFHLA) against the recently developed cancer-specific Cancer Message Literacy Test (CMLT-r) among an educated population of both cancer survivors and those cancer-free. Participants were recruited 2013 (May through December) from various units within a local hospital and from several local churches, and each completed the S-TOFHLA and CMLT-r and provided demographic information and cancer status. The 109 participants had a mean age of 58 years and were as follows: 65.1 % female; 92.7 % white, 50.4 % college graduates, and 41.3 % cancer survivors. S-TOFHLA scores ranged from 12-36 (mean 34.1) and non-significantly varied by gender, education, cancer status, and age. CMLT-r scores ranged from 28.6-100 % (mean 86.4 %) and significantly varied by education (p = 0.013), but not by gender, cancer status, or age. Overall, CMLT-r and S-TOFHLA significantly correlated (p < 0.001). Assessment scores were skewed towards the maximum with non-significant differences by cancer status. As cancer survivorship improves and as the population becomes more educated, more refined approaches to assess health literacy should be considered. Increased education does not imply increased health literacy, and cancer survivorship does not imply higher health or cancer literacy. Concerted efforts to improve patient understanding and implementation of preventive measures are imperative. PMID:25820603

  18. Effects of a novel telomerase inhibitor, GRN163L, in human breast cancer.

    PubMed

    Gellert, Ginelle C; Dikmen, Z Gunnur; Wright, Woodring E; Gryaznov, Sergei; Shay, Jerry W

    2006-03-01

    Telomerase activity is undetectable in most normal tissues but the vast majorities of cancers express active telomerase. Therefore, telomerase serves as an attractive target for the treatment of cancers. GRN163L is a lipid-modified oligonucleotide N3'-->P5' thio-phosphoramidate complementary to the RNA template region of human telomerase. The anti-telomerase activity of GRN163L was evaluated using MDA-MB-231 and MDA-MB-435 human breast adenocarcinoma cell lines. Twice weekly administration of GRN163L resulted in the inhibition of telomerase activity and progressive telomere shortening. Cells treated with GRN163L did not demonstrate decreased cell proliferation for up to 2 weeks. However, after additional treatment, cell proliferation gradually decreased in GRN163L-treated cells compared to untreated or mismatch control oligoncleotide treated cells. Furthermore, anti-tumorigenic effects were seen in cells treated with GRN163L, as cells lose their ability to form colonies in soft agar and were unable to form colonies in the clonal efficiency assay upon incubation with GRN163L. Moreover, breast cancer cells that were treated with GRN163L for only 1 week prior to plating in invasion chambers, and when bulk telomere are still long, exhibit significantly diminished invasive potential. These results reveal critical information regarding the effectiveness of GRN163L as a potential therapeutic agent for the treatment of human breast cancer. PMID:16319992

  19. Effects of psoralens as anti-tumoral agents in breast cancer cells

    PubMed Central

    Panno, Maria Luisa; Giordano, Francesca

    2014-01-01

    This review examines the biological properties of coumarins, widely distributed at the highest levels in the fruit, followed by the roots, stems and leaves, by considering their beneficial effects in the prevention of some diseases and as anti-cancer agents. These compounds are well known photosensitizing drugs which have been used as pharmaceuticals for a broad number of therapeutic applications requiring cell division inhibitors. Despite this, even in the absence of ultraviolet rays they are active. The current paper mainly focuses on the effects of psoralens on human breast cancer as they are able to influence many aspects of cell behavior, such as cell growth, survival and apoptosis. In addition, analytical and pharmacological data have demonstrated that psoralens antagonize some metabolizing enzymes, affect estrogen receptor stability and counteract cell invasiveness as well as cancer drug resistance. The scientific findings summarized highlight the pleiotropic functions of phytochemical drugs, given that recently their target signals and how these are modified in the cells have been identified. The encouraging results in this field suggest that multiple modulating strategies based on coumarin drugs in combination with canonical chemotherapeutic agents or radiotherapy could be a useful approach to address the treatment of many types of cancer. PMID:25114850

  20. Dosage-Dependent Modifiers of Position Effect Variegation in Drosophila and a Mass Action Model That Explains Their Effect

    PubMed Central

    Locke, J.; Kotarski, M. A.; Tartof, K. D.

    1988-01-01

    Twelve dominant enhancers of position effect variegation, representing four loci on the second and third chromosomes of Drosophila melanogaster, have been induced by P-element mutagenesis. Instead of simple transposon insertions, seven of these mutations are cytologically visible duplications and three are deficiencies. The duplications define two distinct regions, each coinciding with a locus that also behaves as a dominant haplo-dependent suppressor of variegation. Conversely, two of the deficiencies overlap with a region that contains a haplo-dependent enhancer of variegation while duplications of this same region act to suppress variegation. The third deficiency defines another haplo-dependent enhancer. These data indicate that loci capable of modifying variegation do so in an antipodal fashion through changes in the wild-type gene copy number and may be divided into two reciprocally acting classes. Class I modifiers enhance variegation when duplicated or suppress variegation when deficient. Class II modifiers enhance when deficient but suppress when duplicated. From our data, and those of others, we propose that in Drosophila there are about 20 to 30 dominant loci that modify variegation. Most appear to be of the class I type whereas only two class II modifiers have been identified so far. From these observations we put forth a model, based on the law of mass action, for understanding how such suppressor-enhancer loci function. We propose that each class I modifier codes for a structural protein component of heterochromatin and their effects on variegation are a consequence of their dosage dependent influence on the extent of the assembly of heterochromatin at the chromosomal site of the position effect. It is further proposed that class II modifiers may inhibit the class I products directly, bind to hypothetical termination sites that define heterochromatin boundaries or promote euchromatin formation. Consistent with our mass action model we find that

  1. [Symptoms of Cancer Patients and Kampo Formulas Effective for Them].

    PubMed

    Inoue, Miki; Hoshino, Etsuo

    2015-12-01

    Patients with cancer exhibit various symptoms induced by cancer itself and its therapy leadingto fatigue; however, their vital energy can be restored by administration of Kampo, which is a traditional Japanese herbal medicine. Restoration and maintenance of mental and physical energy are important for successful cancer treatment. For this purpose, appropriate use of Kampo formulas, such as"Ho-zai", formulas to vitalize fatigued patients (eg, Hochu-ekki-to, Juzen-taiho-to, Ninjin-yoeito), "Hojin-zai", formulas to restore energy (eg, Gosha-jinki-gan), and"Kuoketsu-zai ", formulas to resolve stagnant blood flow (eg, Keishi-bukuryo-gan, Tokaku-joki-to, Toki-shakuyaku-san) are administered in combination. Consequently, basic autonomic functions, such as appetite, sleep, defecation, and urination normalize and the nutritional and mental conditions are restored. These favorable changes in the patients' condition allow completion of the standard cancer therapy course, resultingin an improved outcome of cancer therapy and successful treatment. Kampo therapy can be administered as the final treatment option for patients with last-stage cancer who do not have any other effective therapy options. If patients with cancer are administered Kampo formulas, their vital energy is restored, and they develop a will to fight the cancer. As a result, communication becomes easier. PMID:26809299

  2. Genetic basis and detection of unintended effects in genetically modified crop plants.

    PubMed

    Ladics, Gregory S; Bartholomaeus, Andrew; Bregitzer, Phil; Doerrer, Nancy G; Gray, Alan; Holzhauser, Thomas; Jordan, Mark; Keese, Paul; Kok, Esther; Macdonald, Phil; Parrott, Wayne; Privalle, Laura; Raybould, Alan; Rhee, Seung Yon; Rice, Elena; Romeis, Jörg; Vaughn, Justin; Wal, Jean-Michel; Glenn, Kevin

    2015-08-01

    In January 2014, an international meeting sponsored by the International Life Sciences Institute/Health and Environmental Sciences Institute and the Canadian Food Inspection Agency titled "Genetic Basis of Unintended Effects in Modified Plants" was held in Ottawa, Canada, bringing together over 75 scientists from academia, government, and the agro-biotech industry. The objectives of the meeting were to explore current knowledge and identify areas requiring further study on unintended effects in plants and to discuss how this information can inform and improve genetically modified (GM) crop risk assessments. The meeting featured presentations on the molecular basis of plant genome variability in general, unintended changes at the molecular and phenotypic levels, and the development and use of hypothesis-driven evaluations of unintended effects in assessing conventional and GM crops. The development and role of emerging "omics" technologies in the assessment of unintended effects was also discussed. Several themes recurred in a number of talks; for example, a common observation was that no system for genetic modification, including conventional methods of plant breeding, is without unintended effects. Another common observation was that "unintended" does not necessarily mean "harmful". This paper summarizes key points from the information presented at the meeting to provide readers with current viewpoints on these topics. PMID:25716164

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

    ClinicalTrials.gov

    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

  4. Factors influencing the transfection efficiency and cellular uptake mechanisms of Pluronic P123-modified polypropyleneimine/pDNA polyplexes in multidrug resistant breast cancer cells.

    PubMed

    Gu, Jijin; Hao, Junguo; Fang, Xiaoling; Sha, Xianyi

    2016-04-01

    Generally, the major obstacles for efficient gene delivery are cellular internalization and endosomal escape of nucleic acid such as plasmid DNA (pDNA) or small interfering RNA (siRNA). We previously developed Pluronic P123 modified polypropyleneimine (PPI)/pDNA (P123-PPI/pDNA) polyplexes as a gene delivery system. The results showed that P123-PPI/pDNA polyplexes revealed higher transfection efficiency than PPI/pDNA polyplexes in multidrug resistant breast cancer cells. As a continued effort, the present investigation on the factors influencing the transfection efficiency, cellular uptake mechanisms, and intracellular fate of P123-PPI/pDNA polyplexes is reported. The presence of P123 was the main factor influencing the transfection efficiency of P123-PPI/pDNA polyplexes in MCF-7/ADR cells, but other parameters, such as N/P ratio, FBS concentration, incubation time and temperature were important as well. The endocytic inhibitors against clathrin-mediated endocytosis (CME), caveolae-mediated endocytosis (CvME), and macropinocytosis were involved in the internalization to investigate their effects on the cellular uptake and transfection efficiency of P123-PPI/pDNA polyplexes in vitro. The data showed that the internalization of P123-PPI/pDNA polyplexes was obtained from both CME and CvME. Colocalization experiments with TRITC-transferrin (CME indicator), Alexa Fluor 555-CTB (CvME indicator), monoclonal anti-α-tubulin (microtubule indicator), and LysoTracker Green (Endosome/lysosome indicator) were carried out to confirm the internalization routes. The results showed that both CME and CvME played vital roles in the effective transfection of P123-PPI/pDNA polyplexes. Endosome/lysosome system and skeleton, including actin filament and microtubule, were necessary for the transportation after internalization. PMID:26741268

  5. Suppressive Effects of Tea Catechins on Breast Cancer.

    PubMed

    Xiang, Li-Ping; Wang, Ao; Ye, Jian-Hui; Zheng, Xin-Qiang; Polito, Curt Anthony; Lu, Jian-Liang; Li, Qing-Sheng; Liang, Yue-Rong

    2016-01-01

    Tea leaf (Camellia sinensis) is rich in catechins, which endow tea with various health benefits. There are more than ten catechin compounds in tea, among which epigallocatechingallate (EGCG) is the most abundant. Epidemiological studies on the association between tea consumption and the risk of breast cancer were summarized, and the inhibitory effects of tea catechins on breast cancer, with EGCG as a representative compound, were reviewed in the present paper. The controversial results regarding the role of tea in breast cancer and areas for further study were discussed. PMID:27483305

  6. Long-Term Employment Effects of Surviving Cancer1

    PubMed Central

    Moran, John R.; Short, Pamela Farley; Hollenbeak, Christopher S.

    2011-01-01

    We compare employment and usual hours of work for prime-age cancer survivors from the Penn State Cancer Survivor Survey to a comparison group drawn from the Panel Study of Income Dynamics using cross-sectional and difference-in-differences regression and matching estimators. Because earlier research has emphasized workers diagnosed at older ages, we focus on employment effects for younger workers. We find that as long as two to six years after diagnosis, cancer survivors have lower employment rates and work fewer hours than other similarly-aged adults. PMID:21429606

  7. Suppressive Effects of Tea Catechins on Breast Cancer

    PubMed Central

    Xiang, Li-Ping; Wang, Ao; Ye, Jian-Hui; Zheng, Xin-Qiang; Polito, Curt Anthony; Lu, Jian-Liang; Li, Qing-Sheng; Liang, Yue-Rong

    2016-01-01

    Tea leaf (Camellia sinensis) is rich in catechins, which endow tea with various health benefits. There are more than ten catechin compounds in tea, among which epigallocatechingallate (EGCG) is the most abundant. Epidemiological studies on the association between tea consumption and the risk of breast cancer were summarized, and the inhibitory effects of tea catechins on breast cancer, with EGCG as a representative compound, were reviewed in the present paper. The controversial results regarding the role of tea in breast cancer and areas for further study were discussed. PMID:27483305

  8. Effect of modifying agents on the hydrophobicity and yield of zinc borate synthesized by zinc oxide

    NASA Astrophysics Data System (ADS)

    Acarali, Nil Baran; Bardakci, Melek; Tugrul, Nurcan; Derun, Emek Moroydor; Piskin, Sabriye

    2013-06-01

    The aim of this study was to synthesize zinc borate using zinc oxide, reference boric acid, and reference zinc borate (reference ZB) as the seed, and to investigate the effects of modifying agents and reaction parameters on the hydrophobicity and yield, respectively. The reaction parameters include reaction time (1-5 h), reactant ratio (H3BO3/ZnO by mass: 2-5), seed ratio (seed crystal/(H3BO3+ZnO) by mass: 0-2wt%), reaction temperature (50-120°C), cooling temperature (10-80°C), and stirring rate (400-700 r/min); the modifying agents involve propylene glycol (PG, 0-6wt%), kerosene (1wt%-6wt%), and oleic acid (OA, 1wt%-6wt%) with solvents (isopropyl alcohol (IPA), ethanol, and methanol). The results of reaction yield obtained from either magnetically or mechanically stirred systems were compared. Zinc borate produced was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and contact angle tests to identify the hydrophobicity. In conclusion, zinc borate is synthesized successfully under the optimized reaction conditions, and the different modifying agents with various solvents affect the hydrophobicity of zinc borate.

  9. Synergistic effects of amine and protein modified epoxy-support on immobilized lipase activity.

    PubMed

    Cui, Caixia; Tao, Yifeng; Ge, Chunling; Zhen, Yueju; Chen, Biqiang; Tan, Tianwei

    2015-09-01

    We have developed an improved and effective method to immobilize Yarrowia lipolytica lipase Lip2 (YLIP2) on an epoxy poly-(glycidylmethacrylate-triallyisocyanurate-ethyleneglycoldimethacrylate) (PGMA-TAIC-EGDMA) support structure with or without amine or/and protein modifications. Our results show that there is an increase in the activity of the immobilized lipase on n-butylamine (BA) modified support (420U/g support) and the biocompatible gelatin modified support (600U/g support) when compared to the support without modification (240U/g support). To further study the influences of BA and gelatin modification on the activity of the immobilized lipase, gelatin and BA were concurrently used to decorate the support structure. Lipase immobilized on 2% BA/gelatin (1:1) modified support obtained the highest activity (1180U/g support), which was five-fold higher than that on a native support structure. These results suggest that the activity of a support-immobilized lipase depends on the support surface properties and a moderate support surface micro-environment was crucial for elevated activity. Collectively, these data show that a combined gelatin and BA modification regulates the support surface more suitable for immobilizing YLIP2. PMID:26073154

  10. Effects of modified cellulose nanocrystals on the barrier and migration properties of PLA nano-biocomposites.

    PubMed

    Fortunati, E; Peltzer, M; Armentano, I; Torre, L; Jiménez, A; Kenny, J M

    2012-10-01

    The aim of this paper is to report the impact of the addition of cellulose nanocrystals on the barrier properties and on the migration behaviour of poly(lactic acid), PLA, based nano-biocomposites prepared by the solvent casting method. Their microstructure, crystallinity, barrier and overall migration properties were investigated. Pristine (CNC) and surfactant-modified cellulose nanocrystals (s-CNC) were used, and the effect of the cellulose modification and content in the nano-biocomposites was investigated. The presence of surfactant on the nanocrystal surface favours the dispersion of CNC in the PLA matrix. Electron microscopy analysis shows the good dispersion of s-CNC in the nanoscale with well-defined single crystals indicating that the surfactant allowed a better interaction between the cellulose structures and the PLA matrix. Reductions of 34% in water permeability were obtained for the cast films containing 1 wt.% of s-CNC while good oxygen barrier properties were detected for nano-biocomposites with both 1 wt.% and 5 wt.% of modified and un-modified cellulose nanocrystals, underlining the improvement provided by cellulose on the PLA films. Moreover, the migration level of the studied nano-biocomposites was below the overall migration limits required by the current normative for food packaging materials in both non-polar and polar simulants. PMID:22840025

  11. GSTM1 and GSTP1 Polymorphisms as Potential Factors for Modifying the Effect of Smoking on Inflammatory Response

    PubMed Central

    Kim, Jin-Hee; Park, Shin-Goo; Lee, Kwan-Hee; Choi, Ji-Ho; Ha, Eun-Hee; Myung, Seung-Kwon

    2006-01-01

    Inflammation has been known to be an important underlying condition for development of various diseases including cancer. The aims of this study were to investigate whether tobacco smoke exposure increases the level of inflammation biomarkers and the GSTM1 and GSTP1 gene polymorphisms are associated with inflammatory response due to tobacco smoke exposure. We measured urinary cotinine level in 300 healthy university students. Total serum TNF-α levels and blood WBC counts were determined to evaluate inflammatory response. Allelic loss of the GSTM1 and the GSTP1 (Ile105Val) polymorphism were determined by PCR and RFLP. Tobacco smoke exposure was found to be associated with increase of both TNF-α level and WBC count. Particularly, smokers with combination of GSTM1 null and GSTP1 AG or GG genotypes showed higher TNF-α level than those with the other genotype combinations (p=0.07). This result suggests that smoking may induce inflammation measured as TNF-α level or WBC count and combinations of the GSTM1 and GSTP1 polymorphisms may modify the effect of smoking on serum TNF-α level. PMID:17179680

  12. The effect of acupuncture on leukocyte levels in peripheral blood is modified by aspirin.

    PubMed

    Rivas-Vilchis, José Federico; Barrera-Escorcia, Eduardo; Fregoso-Padilla, Martha

    2009-01-01

    It has been shown that acupuncture can modify circulating levels of subpopulations of leukocytes. There have been few investigations on the effect of acupuncture on prostaglandins metabolism. Aspirin is capable of inhibiting the metabolism of prostaglandins and to produce several pharmacological effects. The objective of this study was to determine whether prior administration of aspirin could modify the action of acupuncture on levels of circulating leukocytes. Fourteen healthy males (age: 19-23 years) were recruited from a university student population. This study was a placebo-controlled, prospective, cross-over design. Subjects were randomly assigned into A or B groups. Group A received aspirin 500 mg and group B placebo, after 1 week of a washout period, group A received placebo and group B aspirin. Subjects were given acupuncture with manual needling in GV14 (Dazhui) acupoint 2 hr after receiving medication. The needle was stimulated for 10 sec and was kept in place for 5 min. Leukocytes and their subpopulations were quantified in blood samples taken immediately before and 2 hr after acupuncture treatment. In each subject pre-acupuncture values were compared to those post-acupuncture. The results showed that acupuncture significantly increased overall leukocytes (p=0.006) and neutrophils (p<0.001). Aspirin partially inhibited these effects. The data suggest that the effect of acupuncture on leukocytes may be related to levels of prostaglandins. PMID:22128425

  13. The accuracy of preoperative axillary nodal staging in primary breast cancer by ultrasound is modified by nodal metastatic load and tumor biology.

    PubMed

    Dihge, Looket; Grabau, Dorthe A; Rasmussen, Rogvi W; Bendahl, Pär-Ola; Rydén, Lisa

    2016-08-01

    Background The outcome of axillary ultrasound (AUS) with fine-needle aspiration biopsy (FNAB) in the diagnostic work-up of primary breast cancer has an impact on therapy decisions. We hypothesize that the accuracy of AUS is modified by nodal metastatic burden and clinico-pathological characteristics. Material and methods The performance of AUS and AUS-guided FNAB for predicting nodal metastases was assessed in a prospective breast cancer cohort subjected for surgery during 2009-2012. Predictors of accuracy were included in multivariate analysis. Results AUS had a sensitivity of 23% and a specificity of 95%, while AUS-guided FNAB obtained 73% and 100%, respectively. AUS-FNAB exclusively detected macro-metastases (median four metastases) and identified patients with more extensive nodal metastatic burden in comparison with sentinel node biopsy. The accuracy of AUS was affected by metastatic size (OR 1.11), obesity (OR 2.46), histological grade (OR 4.43), and HER2-status (OR 3.66); metastatic size and histological grade were significant in the multivariate analysis. Conclusions The clinical utility of AUS in low-risk breast cancer deserves further evaluation as the accuracy decreased with a low nodal metastatic burden. The diagnostic performance is modified by tumor and clinical characteristics. Patients with nodal disease detected by AUS-FNAB represent a group for whom neoadjuvant therapy should be considered. PMID:27050668

  14. Cancer

    MedlinePlus

    ... body. Cancerous cells are also called malignant cells. Causes Cancer grows out of cells in the body. Normal ... of many cancers remains unknown. The most common cause of cancer-related death is lung cancer. In the U.S., ...

  15. The Prognostic Effect of Statin Use on Urologic Cancers

    PubMed Central

    Luo, You; She, Dong-Li; Xiong, Hu; Fu, Sheng-Jun; Yang, Li

    2015-01-01

    Abstract Recent studies suggest that statin may benefit cancer prognosis, especially through its radiosensitization effect. But controversy exists in other studies. Hence, we performed a meta-analysis of results from 35 studies to evaluate the effect of statin use on urologic cancers. We conducted computerized search from PubMed, Embase, and ISI Web of Knowledge through May 2015, screened the retrieved references, and collected and evaluated relevant information. We extracted and synthesized corresponding hazard ratios (HR) and confidence interval (CI) by using Review Manager 5.3 and STATA 13. This review was registered at PROSPERO with registration No. CRD42015020171. We selected total 35 retrospective studies and conducted a meta-analysis of results from these studies. The pooled results suggested no benefit of statin use to bladder cancer and renal cell carcinoma, except overall survival [HR = 0.81, 95% CI: 0.69–0.96]. However, significant improvement of prostate cancer prognosis including overall survival [HR = 0.82, 95% CI: 0.70–0.97] and cancer-specific survival [HR = 0.70, 95% CI: 0.59–0.83] was indicated, but not including tumor progression [HR = 0.84, 95% CI: 0.62–1.14]. Statin use improved biochemical recurrence of prostate cancer in radiotherapy patients [HR = 0.68, 95% CI: 0.54–0.85] but not in radical prostatectomy patients [HR = 0.97, 95% CI: 0.82–1.15]. Current evidence suggests no benefit of statin use to bladder cancer and renal cell carcinoma, except in overall survival. While statin use benefited prostate cancer patients in overall survival, cancer-specific survival but not in tumor progression; it also improved biochemical recurrence in radiotherapy patients but not in radical patients. To verify these results, randomized controlled trials are necessary. PMID:26356727

  16. Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells

    PubMed Central

    Wang, Chong-Zhi; Luo, Xiaoji; Zhang, Bin; Song, Wen-Xin; Ni, Ming; Mehendale, Sangeeta; Xie, Jing-Tian; Aung, Han H.; He, Tong-Chuan

    2009-01-01

    Purpose Panax notoginseng is a commonly used Chinese herb. Although a few studies have found that notoginseng shows anti-tumor effects, the effect of this herb on colorectal cancer cells has not been investigated. 5-Fluorouracil (5-FU) is a chemotherapeutic agent for the treatment of colorectal cancer that interferes with the growth of cancer cells. However, this compound has serious side effects at high doses. In this study, using HCT-116 human colorectal cancer cell line, we investigated the possible synergistic anti-cancer effects between notoginseng flower extract (NGF) and 5-FU on colon cancer cells. Methods The anti-proliferation activity of these modes of treatment was evaluated by MTS cell proliferation assay. Apoptotic effects were analyzed by using Hoechst 33258 staining and Annexin-V/PI staining assays. The anti-proliferation effects of four major single compounds from NGF, ginsenosides Rb1, Rb3, Rc and Rg3 were also analyzed. Results Both 5-FU and NGF inhibited proliferation of HCT-116 cells. With increasing doses of 5-FU, the anti-proliferation effect was slowly increased. The combined usage of 5-FU 5 μM and NGF 0.25 mg/ml, significantly increased the anti-proliferation effect (59.4 ± 3.3%) compared with using the two medicines separately (5-FU 5 μM, 31.1 ± 0.4%; NGF 0.25 mg/ml, 25.3 ± 3.6%). Apoptotic analysis showed that at this concentration, 5-FU did not exert an apoptotic effect, while apoptotic cells induced by NGF were observed, suggesting that the anti-proliferation target(s) of NGF may be different from that of 5-FU, which is known to inhibit thymidilate synthase. Conclusions This study demonstrates that NGF can enhance the anti-proliferation effect of 5-FU on HCT-116 human colorectal cancer cells and may decrease the dosage of 5-FU needed for colorectal cancer treatment. PMID:17009031

  17. Therapeutic effect analysis on the treatment of congenital glaucoma through modified combined trabeculotomy-trabeculectomy

    PubMed Central

    Wu, Zhen-Kai; Wu, Jing; Tan, Qian; Jiang, Jian; Song, Wei-Tao; Xia, Xiao-Bo

    2016-01-01

    AIM To evaluate the therapeutic effect and the safety of the treatment of congenital glaucoma through modified combined trabeculotomy-trabeculectomy. METHODS The clinical data of 27 cases (altogether 42 eyes), which included 7 cases of infants (10 eyes) and 20 cases of teenagers (32 eyes), of congenital glaucoma undertook modified combined trabeculotomy-trabeculectomy were analyzed retrospectively. The parameters evaluated included the post operation visual acuity, the anterior chamber, the filtering bleb, the intraocular pressure, the C/D ratio, visual field, the retinal nerve fiber layer changes and the complications. RESULTS The follow-up period was 1 to 29mo, averaging 13.3±7.7mo. Upon the last visit after the operation, functional filtering blebs developed in all the involved eyes. The intraocular pressure was controlled under 21 mm Hg, which was decreased by 60% when compared with that before the operation, without using any medication. There were no significant changes in the post operation visual acuity and the retinal nerve fiber layer thickness before and after the operation in teenager group (P>0.05), and both the post operation C/D ratio and the visual field mean defect (MD) were reduced compared with those before the operation (P<0.05). There were no severe complications in any of the patients. CONCLUSION The modified combined trabeculotomy-trabeculectomy can effectively reduce the intraocular pressure and control the development of glaucoma in cases of congenital glaucoma. It is a safe and effective operative method for the treatment of congenital glaucoma. PMID:26949643

  18. Effects of modified Shu-Gan-Liang-Xue decoction combined with anastrozole on osteoblastic proliferation and differentiation of MC3T3-E1 cells

    PubMed Central

    ZHOU, FEI; HAN, SHUYAN; ZHOU, NING; ZHENG, WENXIAN; LI, PINGPING

    2015-01-01

    Aromatase inhibitors (AIs) are widely used in the treatment of hormone-dependent breast cancer and as a result, aromatase inhibitor-associated bone loss (AIBL) has become a major concern amongst patients receiving AI treatment. Modified Shu-Gan-Liang-Xue decoction (mSGLXD), a clinical prescription, has been used for ameliorating AIBL in patients with breast cancer for decades and has achieved good clinical efficacy. However, the mechanism underlying how mSGLXD influences bone homeostasis and alleviates AIBL has remained elusive. In the present study, mSGLXD was supplemented with Rhizoma Drynariae containing phytoestrogens, and the safety of mSGLXD was evaluated. mSGLXD did not possess estrogenic activity and significantly inhibited the proliferation of estrogen receptor-positive breast cancer cell line MCF-7, which suggested that mSGLXD was safe for postmenopausal patients with breast cancer. Subsequently, the effects of mSGLXD alone or in combination with anastrozole on osteoblastic MC3T3-E1 cell proliferation and differentiation were investigated. Cell counting kit-8, reverse transcription-polymerase chain reaction and biochemical methods, such as ELISA and alizarin red S staining, were used in the present study. It was revealed that mSGLXD not only stimulated MC3T3-E1 cell proliferation, but also upregulated alkaline phosphatase and osteocalcin gene and protein expression levels. High concentrations of anastrozole (10 or 100 μmol/l) markedly inhibited MC3T3-E1 cell proliferation, but this inhibitory effect was attenuated by mSGLXD. Furthermore, mSGLXD increased MC3T3-E1 cell mineralization following β-glycerophosphate and ascorbic acid induction. Therefore, the results of the present study suggested that mSGLXD may be a promising adjuvant therapy, with high safety and efficacy, for the prevention and treatment of AIBL in patients with breast cancer who receive AI treatment. PMID:25405542

  19. The effect of elastomer chain length on properties of silicone-modified polyimide adhesives

    NASA Technical Reports Server (NTRS)

    St.clair, A. K.; St.clair, T. L.; Ezzell, S.

    1981-01-01

    A series of polyimides containing silicone elastomers was synthesized in order to study the effects of the elastomer chain length on polymer properties. The elastomer with repeat units varying from n=10 to 105 was chemically reacted into the backbone of an addition polyimide oligomer via reactive aromatic amine groups. Glass transition temperatures of the elastomer and polyimide phases were observed by torsional braid analysis. The elastomer-modified polyimides were tested as adhesives for bonding titanium in order to determine their potential for aerospace applications. Adhesive lap shear tests were performed before and after aging bonded specimens at elevated temperatures.

  20. A modified suture placement technique to avoid suture drag or "cheese wire" effect.

    PubMed

    Cravy, T V

    1980-05-01

    A modified technique is described for microsurgical suture placement, irrespective of the closure technique, to prevent suture drag and loosening of the suture following postoperative wound edema. Fine, elastic, non-absorbable sutures which loosen as a result of suture drag or "cheese wiring" have no more reliability than do absorbable or silk sutures. Predictable and reproducible results of suture placement are necessary to allow the surgeon to effectively use the operating keratometer in the control and modification of corneal astigmatism following anterior segment surgery. PMID:6992018

  1. A modified and cost-effective method for hair cortisol analysis.

    PubMed

    Xiang, Lianbin; Sunesara, Imran; Rehm, Kristina E; Marshall, Gailen D

    2016-05-01

    Hair cortisol may hold potential as a biomarker for assessment of chronic psychological stress. We report a modified and cost-effective method to prepare hair samples for cortisol assay. Hair samples were ground using an inexpensive ball grinder - ULTRA-TURRAX tube drive. Cortisol was extracted from the powder under various defined conditions. The data showed that the optimal conditions for this method include cortisol extraction at room temperature and evaporation using a stream of room air. These findings should allow more widespread research using economical technology to validate the utility of hair cortisol as a biomarker for assessing chronic stress status. PMID:26767335

  2. Grafting Genetically Modified Cells to the Damaged Brain: Restorative Effects of NGF Expression

    NASA Astrophysics Data System (ADS)

    Rosenberg, Michael B.; Friedmann, Theodore; Robertson, Robin C.; Tuszynski, Mark; Wolff, Jon A.; Breakefield, Xandra O.; Gage, Fred H.

    1988-12-01

    Fibroblasts were genetically modified to secrete nerve growth factor (NGF) by infection with a retroviral vector and then implanted into the brains of rats that had surgical lesions of the fimbria-fornix. The grafted cells survived and produced sufficient NGF to prevent the degeneration of cholinergic neurons that would die without treatment. In addition, the protected cholinergic cells sprouted axons that projected in the direction of the cellular source of NGF. These results indicate that a combination of gene transfer and intracerebral grafting may provide an effective treatment for some disorders of the central nervous system.

  3. Effects of vascularization on cancer nanochemotherapy outcomes

    NASA Astrophysics Data System (ADS)

    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.

  4. Biologic effect of neurogenesis in pancreatic cancer.

    PubMed

    He, Dandan; Manzoni, Adriana; Florentin, Diego; Fisher, William; Ding, Yi; Lee, MinJae; Ayala, Gustavo

    2016-06-01

    Pancreatic cancer (PaCA) is a deadly disease with few systemic therapeutic options. The head of the pancreas is the most innervated part and most common location of cancer. However, little is known about the contribution of the nerve-cancer interaction to facilitate pancreatic progression. To quantify PaCA axonogenesis, we used a 3-dimensional in vitro neurogenesis model. In addition, neurogenesis in human PaCA was analyzed using PGP9.5 immunohistochemistry, deconvolution imaging, and image segmentation and analysis. There was a significant increase of the total area of neurites in the in vitro coculture with dorsal root ganglia group than control. The nerve density in PaCA tissue was significantly higher than normal pancreatic tissue. To study the functional role of nerves in PaCA, male athymic nude (Nu-Nu) mice were divided into 3 groups: (A) animals were coinjected with MIA PaCa-2 cells and 20U/kg weight units of Botulinum toxin (Botox) (n=10); (B) first injected with Botox and 6weeks later MIA PaCa-2 cancer cells (n=4); and (C) control animals were injected with equivalent amounts of saline fluid (n=9). Animals were sacrificed 6weeks later. Tumor size and apoptotic count (terminal deoxynucleotidyl transferase dUTP nick-end labeling) were measured. Tumor size was decreased and apoptotic rate increased in Botox-treated PaCA. Our data indicate that neural microenvironment may play an important role in the progression of PaCA. It may lead to novel nerve-targeted coadjuvant therapies for PaCA. PMID:26980040

  5. Application of a posteriori granddaughter and modified granddaughter designs to determine Holstein haplotype effects.

    PubMed

    Weller, J I; VanRaden, P M; Wiggans, G R

    2013-08-01

    A posteriori and modified granddaughter designs were applied to determine haplotype effects for Holstein bulls and cows with BovineSNP50 [~50,000 single nucleotide polymorphisms (SNP); Illumina Inc., San Diego, CA] genotypes. The a posteriori granddaughter design was applied to 52 sire families, each with ≥100 genotyped sons with genetic evaluations based on progeny tests. For 33 traits (milk, fat, and protein yields; fat and protein percentages; somatic cell score; productive life; daughter pregnancy rate; heifer and cow conception rates; service-sire and daughter calving ease; service-sire and daughter stillbirth; 18 conformation traits; and net merit), the analysis was applied to the autosomal segment with the SNP with the greatest effect in the genomic evaluation of each trait. All traits except 2 had a within-family haplotype effect. The same design was applied with the genetic evaluations of sons corrected for SNP effects associated with chromosomes besides the one under analysis. The number of within-family contrasts was 166 without adjustment and 211 with adjustment. Of the 52 bulls analyzed, 36 had BovineHD (high density; Illumina Inc.) genotypes that were used to test for concordance between sire quantitative trait loci and SNP genotypes; complete concordance was not obtained for any effects. Of the 31 traits with effects from the a posteriori granddaughter design, 21 were analyzed with the modified granddaughter design. Only sires with a contrast for the a posteriori granddaughter design and ≥200 granddaughters with a record usable for genetic evaluation were included. Calving traits could not be analyzed because individual cow evaluations were not computed. Eight traits had within-family haplotype effects. With respect to milk and fat yields and fat percentage, the results on Bos taurus autosome (BTA) 14 corresponded to the hypothesis that a missense mutation in the diacylglycerol O-acyltransferase 1 (DGAT1) gene is the main causative mutation

  6. Effects of thyroid hormones on human breast cancer cell proliferation.

    PubMed

    Hall, Linda C; Salazar, Eddie P; Kane, Staci R; Liu, Nan

    2008-03-01

    The involvement of estrogens in breast cancer development and growth has been well established. However, the effects of thyroid hormones and their combined effects with estrogens are not well studied. We investigated the response of human breast cancer cells to thyroid hormone, particularly the role of T3 in mediating cell proliferation and gene expression. We demonstrated that 17beta-estradiol (E2) or triiodothyronine (T3) promoted cell proliferation in a dose-dependent manner in both MCF-7 and T47-D cell lines. The E2- or T3-dependent cell proliferation was suppressed by co-administration of the ER antagonist ICI. We also demonstrated that T3 could enhance the effect of E2 on cell proliferation in T47-D cells. Using an estrogen response element (ERE)-mediated luciferase assay, we determined that T3 was able to induce the activation of ERE-mediated gene expression in MCF-7 cells, although the effects were much weaker than that induced by E2. These results suggest that T3 can promote breast cancer cell proliferation and increase the effect of E2 on cell proliferation in some breast cancer cell lines and thus that T3 may play a role in breast cancer development and progression. PMID:18328691

  7. Effectiveness of plasma treatment on pancreatic cancer cells

    PubMed Central

    HATTORI, NORIFUMI; YAMADA, SUGURU; TORII, KOJI; TAKEDA, SHIGEOMI; NAKAMURA, KAE; TANAKA, HIROMASA; KAJIYAMA, HIROAKI; KANDA, MITSURO; FUJII, TSUTOMU; NAKAYAMA, GORO; SUGIMOTO, HIROYUKI; KOIKE, MASAHIKO; NOMOTO, SHUJI; FUJIWARA, MICHITAKA; MIZUNO, MASAAKI; HORI, MASARU; KODERA, YASUHIRO

    2015-01-01

    Non-equilibrium atmospheric pressure plasma (NEAPP) has attracted attention in cancer therapy. We explored the indirect effect of NEAPP through plasma-activated medium (PAM) on pancreatic cancer cells in vitro and in vivo. In this study, four pancreatic cancer cell lines were used and the antitumor effects of PAM treatment were evaluated using a cell proliferation assay. To explore functional mechanisms, morphological change and caspase-3/7 activation in cells were also assessed. Furthermore, reactive oxygen species (ROS) generation in cells was examined and N-acetyl cysteine (NAC), an intracellular ROS scavenger, was tested. Finally, the antitumor effect of local injection of PAM was investigated in a mouse xenograft model. We found that PAM treatment had lethal effect on pancreatic cancer cells. Typical morphological findings suggestive of apoptosis such as vacuolization of cell membranes, small and round cells and aggregation of cell nuclei, were observed in the PAM treated cells. Caspase-3/7 activation was detected in accordance with the observed morphological changes. Additionally, ROS uptake was observed in all cell lines tested, while the antitumor effects of PAM were completely inhibited with NAC. In the mouse xenograft model, the calculated tumor volume on day 28 in the PAM treatment group was significantly smaller compared with the control group [28±22 vs. 89±38 (mm3 ± SD), p=0.0031]. These results show that PAM treatment of pancreatic cancer might be a promising therapeutic strategy. PMID:26351772

  8. Apoptotic effect of noscapine in breast cancer cell lines.

    PubMed

    Quisbert-Valenzuela, Edwin O; Calaf, Gloria M

    2016-06-01

    Cancer is a public health problem in the world and breast cancer is the most frequently cancer in women. Approximately 15% of the breast cancers are triple-negative. Apoptosis regulates normal growth, homeostasis, development, embryogenesis and appropriate strategy to treat cancer. Bax is a protein pro-apoptotic enhancer of apoptosis in contrast to Bcl-2 with antiapoptotic properties. Initiator caspase-9 and caspase-8 are features of intrinsic and extrinsic apoptosis pathway, respectively. NF-κB is a transcription factor known to be involved in the initiation and progression of breast cancer. Noscapine, an alkaloid derived from opium is used as antitussive and showed antitumor properties that induced apoptosis in cancer cell lines. The aim of the present study was to determine the apoptotic effect of noscapine in breast cancer cell lines compared to breast normal cell line. Three cell lines were used: i) a control breast cell line MCF-10F; ii) a luminal-like adenocarcinoma triple-positive breast cell line MCF-7; iii) breast cancer triple-negative cell line MDA-MB-231. Our results showed that noscapine had lower toxicity in normal cells and was an effective anticancer agent that induced apoptosis in breast cancer cells because it increases Bax gene and protein expression in three cell lines, while decreases Bcl-xL gene expression, and Bcl-2 protein expression decreased in breast cancer cell lines. Therefore, Bax/Bcl-2 ratio increased in the three cell lines. This drug increased caspase-9 gene expression in breast cancer cell lines and caspase-8 gene expression increased in MCF-10F and MDA-MB-231. Furthermore, it increased cleavage of caspase-8, suggesting that noscapine-induced apoptosis is probably due to the involvement of extrinsic and intrinsic apoptosis pathways. Antiapoptotic gene and protein expression diminished and proapoptotic gene and protein expression increased noscapine-induced expression, probably due to decrease in NF-κB gene and protein expression

  9. Combined effects of gamma irradiation and a modified atmospheric packaging on the physicochemical characteristics of sausage

    NASA Astrophysics Data System (ADS)

    Ahn, Hyun-Joo; Kim, Jae-Hyun; Jo, Cheorun; Lee, Ju-Woon; Yook, Hong-Sun; Kim, Hee-Yun; Byun, Myung-Woo

    2004-09-01

    This study is to investigate the combined effects of irradiation and a modified atmospheric packaging (MAP) on the color, nitrosoheme pigments (NO-Mb), residual nitrite and N-nitrosodimethylamine (NDMA) in sausage during storage. Sausage with air, vacuum, CO 2, N 2, or CO 2/N 2 packaging was irradiated at 5 kGy. Irradiation reduced the red color of sausage, and a vacuum or MAP was effective in minimizing the loss of redness. The reduction of NO-Mb was observed by irradiation, while the MAP was more effective in maintaining the NO-Mb than the aerobic ones. Residual nitrite was reduced by irradiation, and the contents were lower under vacuum or MAP than aerobic ones. NDMA was significantly reduced by irradiation.

  10. The effectiveness of parental communication in modifying the relation between food advertising and children's consumption behaviour.

    PubMed

    Buijzen, Moniek

    2009-03-01

    The aim of this study was to examine the effectiveness of various types of parental communication in modifying children's responses to television food advertising. In a combined diary-survey study among 234 parents of 4- to 12-year-old children, I investigated how different styles of advertising mediation (active vs. restrictive) and consumer communication (concept-oriented vs. socio-oriented) moderated the relation between children's advertising exposure and their consumption of advertised energy-dense food products. Interaction analysis in regression showed that active advertising mediation (i.e. explaining the purpose and nature of advertising), and socio-oriented consumer communication (i.e. emphasizing control and restrictions) significantly reduced the impact of advertising on children's food consumption. Parental restrictions of advertising exposure were only effective among younger children (<8). These results suggest that critical discussion about advertising and rule making about consumption are most effective in countering the impact of food advertising. PMID:19972665

  11. Effect of 2-aminoadamantane derivatives on behavior of mice in a modified light/dark test.

    PubMed

    Avgustinovich, D F; Fomina, M K; Suslov, E V; Tolstikova, T G; Volcho, K P; Salakhutdinov, N F

    2014-12-01

    The effects of two derivatives of 2-aminoadamantane, enantiomers J447H and J579, on the behavior of male and female C57Bl/6J mice were studied using a modified light/dark test. The substances differed by their effects on the behavior of male mice. J579 reduced the number of rearings. J447H in a dose of 1 mg/kg affected more parameters: it reduced exploratory activity 1 h after administration and stimulated exploratory and motor activity in 2 h. In female mice, J447H significantly reduced the number of peepings into holes in 2 h after administration. The results indicate that further analysis of the effects of J579 and especially J447H is required. PMID:25430650

  12. Targeted and ultrasound-triggered drug delivery using liposomes co-modified with cancer cell-targeting aptamers and a thermosensitive polymer.

    PubMed

    Ninomiya, Kazuaki; Yamashita, Takahiro; Kawabata, Shinya; Shimizu, Nobuaki

    2014-07-01

    In this study, we demonstrated the feasibility of targeted and ultrasound-triggered drug delivery using liposomes co-modified with single stranded DNA aptamers that recognized platelet-derived growth factor receptors (PDGFRs) as targeting ligands for breast cancer cells and poly(NIPMAM-co-NIPAM) as the thermosensitive polymer (TSP) to sensitize these liposomes to high temperature. TSP-modified liposomes (TSP liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation for 30 s at 0.5 W/cm(2) as well as the case under incubation for 5 min at 42 °C. Ultrasound-triggered calcein release from TSP liposomes was due to an increased local temperature, resulting from cavitation bubble collapse induced by ultrasound, and not due to an increase in the bulk medium temperature. Liposomes modified with PDGFR aptamers (APT liposomes) bound to MDA-MB-231 human breast cancer cells through PDGFR aptamers; however, they did not bind to primary human mammary epithelial cells (HMECs). The binding of APT liposomes was greatest for MDA-MB-231 cells, followed by MCF-7, WiDr, and HepG2 cancer cells. In a cell injury assay using doxorubicin (DOX)-loaded APT/TSP liposomes and ultrasound irradiation, cell viability of MDA-MB-231 at 24h after ultrasound irradiation (1 MHz for 30 s at 0.5 W/cm(2)) with DOX-loaded APT/TSP liposomes was 60%, which was lower than that with ultrasound irradiation and DOX-loaded TSP liposomes or with DOX-loaded APT/TSP liposomes alone. PMID:24418100

  13. RAD51 135G→C Modifies Breast Cancer Risk among BRCA2 Mutation Carriers: Results from a Combined Analysis of 19 Studies

    PubMed Central

    Antoniou, Antonis C. ; Sinilnikova, Olga M. ; Simard, Jacques ; Léoné, Mélanie ; Dumont, Martine ; Neuhausen, Susan L. ; Struewing, Jeffery P. ; Stoppa-Lyonnet, Dominique ; Barjhoux, Laure ; Hughes, David J. ; Coupier, Isabelle ; Belotti, Muriel ; Lasset, Christine ; Bonadona, Valérie ; Bignon, Yves-Jean ; Rebbeck, Timothy R. ; Wagner, Theresa ; Lynch, Henry T. ; Domchek, Susan M. ; Nathanson, Katherine L. ; Garber, Judy E. ; Weitzel, Jeffrey ; Narod, Steven A. ; Tomlinson, Gail ; Olopade, Olufunmilayo I. ; Godwin, Andrew ; Isaacs, Claudine ; Jakubowska, Anna ; Lubinski, Jan ; Gronwald, Jacek ; Górski, Bohdan ; Byrski, Tomasz ; Huzarski, Tomasz ; Peock, Susan ; Cook, Margaret ; Baynes, Caroline ; Murray, Alexandra ; Rogers, Mark ; Daly, Peter A. ; Dorkins, Huw ; Schmutzler, Rita K. ; Versmold, Beatrix ; Engel, Christoph ; Meindl, Alfons ; Arnold, Norbert ; Niederacher, Dieter ; Deissler, Helmut ; Spurdle, Amanda B. ; Chen, Xiaoqing ; Waddell, Nicola ; Cloonan, Nicole ; Kirchhoff, Tomas ; Offit, Kenneth ; Friedman, Eitan ; Kaufmann, Bella ; Laitman, Yael ; Galore, Gilli ; Rennert, Gad ; Lejbkowicz, Flavio ; Raskin, Leon ; Andrulis, Irene L. ; Ilyushik, Eduard ; Ozcelik, Hilmi ; Devilee, Peter ; Vreeswijk, Maaike P. G. ; Greene, Mark H. ; Prindiville, Sheila A. ; Osorio, Ana ; Benítez, Javier ; Zikan, Michal ; Szabo, Csilla I. ; Kilpivaara, Outi ; Nevanlinna, Heli ; Hamann, Ute ; Durocher, Francine ; Arason, Adalgeir ; Couch, Fergus J. ; Easton, Douglas F. ; Chenevix-Trench, Georgia 

    2007-01-01

    RAD51 is an important component of double-stranded DNA–repair mechanisms that interacts with both BRCA1 and BRCA2. A single-nucleotide polymorphism (SNP) in the 5′ untranslated region (UTR) of RAD51, 135G→C, has been suggested as a possible modifier of breast cancer risk in BRCA1 and BRCA2 mutation carriers. We pooled genotype data for 8,512 female mutation carriers from 19 studies for the RAD51 135G→C SNP. We found evidence of an increased breast cancer risk in CC homozygotes (hazard ratio [HR] 1.92 [95% confidence interval {CI} 1.25–2.94) but not in heterozygotes (HR 0.95 [95% CI 0.83–1.07]; P=.002, by heterogeneity test with 2 degrees of freedom [df]). When BRCA1 and BRCA2 mutation carriers were analyzed separately, the increased risk was statistically significant only among BRCA2 mutation carriers, in whom we observed HRs of 1.17 (95% CI 0.91–1.51) among heterozygotes and 3.18 (95% CI 1.39–7.27) among rare homozygotes (P=.0007, by heterogeneity test with 2 df). In addition, we determined that the 135G→C variant affects RAD51 splicing within the 5′ UTR. Thus, 135G→C may modify the risk of breast cancer in BRCA2 mutation carriers by altering the expression of RAD51. RAD51 is the first gene to be reliably identified as a modifier of risk among BRCA1/2 mutation carriers. PMID:17999359

  14. Penetrance of HNPCC-related cancers in a retrolective cohort of 12 large Newfoundland families carrying a MSH2 founder mutation: an evaluation using modified segregation models

    PubMed Central

    Kopciuk, Karen A; Choi, Yun-Hee; Parkhomenko, Elena; Parfrey, Patrick; McLaughlin, John; Green, Jane; Briollais, Laurent

    2009-01-01

    Background Accurate risk (penetrance) estimates for associated phenotypes in carriers of a major disease gene are important for genetic counselling of at-risk individuals. Population-specific estimates of penetrance are often needed as well. Families ascertained from high-risk disease clinics provide substantial data to estimate penetrance of a disease gene, but these estimates must be adjusted for possible specific sources of bias. Methods A cohort of 12 independently ascertained HNPCC families harbouring a founder MSH2 mutation was identified from a cancer genetics clinic in St. John's, Newfoundland, Canada. Carrier status was known for 247 family members but phenotype information on up to 85 additional relatives with unknown carrier status was available; using modified segregation models these additional individuals could be included in the analyses. Three HNPCC-related phenotypes were evaluated as age at diagnosis of: any HNPCC cancer (first cancer), colorectal cancer (CRC), and endometrial cancer (EC) for females. Results Lifetime (age 70) risk estimates for male and female carriers were similar for developing any HNPCC cancer (Males = 98.2%, 95% Confidence Interval (CI) = (93.8%, 99.9%); Females = 92.8%, 95% CI = (82.4%, 99.1%)) but female carriers experienced substantially reduced lifetime risk for developing CRC compared to male carriers (Females = 38.9%, 95% CI = (24.2%, 62.1%); Males = 84.5%, 95% CI = (67.3%, 91.3%)). Female non-carriers had very low lifetime risk for these two outcomes while male non-carriers had lifetime risks intermediate to the female carriers and non-carriers. Female carriers had a lifetime risk of developing EC of 82.4%. Relative risks for developing any HNPCC cancer (carriers relative to non-carriers) were substantially greater for females compared to their male counterparts (Females = 54.8, 95%CI = (4.4, 379.8); Males = 9.7, 95% CI = (0.3, 23.8)). Relative risks for developing CRC at age 70 were substantially greater for females

  15. Effect of selected modified atmosphere packaging on Campylobacter survival in raw poultry.

    PubMed

    Byrd, J A; Sams, A R; Hargis, B M; Caldwell, D J

    2011-06-01

    Most current research on Campylobacter has focused on preharvest or processing plant cross-contamination. Little is known about the effect of storage environment on the survival of Campylobacter on raw poultry. We evaluated the effects of modified storage atmosphere and freezing on the survival of naturally occurring Campylobacter on raw poultry. Broiler carcasses (n = 560) were collected as they exited the chiller in 2 commercial processing plants and were sampled for the detection of Campylobacter, Escherichia coli, psychrophiles, and total aerobes at 0 and 14 d of refrigerated (2°C) storage. Gases evaluated were air, 100% O(2), 100% CO(2), and a standard poultry modified atmosphere packaging mixture (5% O(2) + 10% CO(2) + 85% N). Freezing was included as a control group. All carcasses were sampled by the whole-carcass rinse method. The rinse fluid was recovered and pooled from 5 individual rinses, and serial dilutions were made for examination of Campylobacter (42°C, 48 h), E. coli (37°C, 24 h), psychrophiles (plate count agar, 4°C, 7 d), and total aerobic bacterial populations (plate count agar, 37°C, 24 h). Campylobacter counts for all treatments were reduced during the 14-d storage period but the 100% O(2) treatment caused a significantly (P < 0.05) greater reduction than the other gas treatments. For the psychrophiles, storage in air resulted in the greatest growth after 14 d, with reduced psychrophilic growth allowed by either O(2) or the modified atmosphere packaging mixture (not different from each other). Of the treatments evaluated, CO(2) allowed the least growth of psychrophiles. Proliferation of E. coli and aerobes was the greatest when packaged in air after 14 d, whereas CO(2) packaging resulted in the least growth. These data suggest that storage under O(2) may reduce Campylobacter recovery and slow psychrophile and aerobe recovery following storage. PMID:21597074

  16. Preclinical and Clinical Effects of Mistletoe against Breast Cancer

    PubMed Central

    Marvibaigi, Mohsen; Amini, Neda; Abdul Majid, Fadzilah Adibah; Jaganathan, Saravana Kumar

    2014-01-01

    Breast cancer is among the most frequent types of cancer in women worldwide. Current conventional treatment options are accompanied by side effects. Mistletoe is amongst the important herbal medicines traditionally used as complementary remedies. An increasing number of studies have reported anticancer activity of mistletoe extracts on breast cancer cells and animal models. Some recent evidence suggests that cytotoxic activity of mistletoe may be mediated through different mechanisms. These findings provide a good base for clinical trials. Various studies on mistletoe therapy for breast cancer patients revealed similar findings concerning possible benefits on survival time, health-related quality of life (HRQoL), remission rate, and alleviating adverse reactions to conventional therapy. This review provides an overview of the recent findings on preclinical experiments and clinical trials of mistletoe for its cytotoxic and antitumor activity and its effect on HRQoL in breast cancer patients. Moreover, studies investigating molecular and cellular mechanisms underlying antitumor activity of mistletoe are discussed in this paper. The analyzed trials provided evidence that there might be a combination of pharmacological and motivational aspects mediated by the mistletoe extract application which may contribute to the clinical benefit and positive outcome such as improved HRQoL and self-regulation in breast cancer patients. PMID:25136622

  17. Physical activity and its mechanistic effects on prostate cancer.

    PubMed

    Wekesa, A; Harrison, M; Watson, R W

    2015-09-01

    Beneficial effects of physical activity have been illustrated in numerous aspects of health. With the increasing incidence of prostate cancer and changes in physical activity of men, understanding the link between the two has important implications for changing this cancer burden. Both positive and negative associations between physical activity and prostate cancer have been previously demonstrated in observational epidemiological studies. Elucidating the biological mechanisms would lead to a better understanding of how physical activity influences the progression of prostate cancer. This review was undertaken to: (1) identify evidence in literature that demonstrates the effects of physical activity on skeletal muscle secretomes, (2) indicate the plausible signaling pathways these proteins might activate, and (3) identify evidence in literature that demonstrates the roles of the signaling pathways in prostate cancer progression and regression. We also discuss proposed biological mechanisms and signaling pathways by which physical activity may prevent the development and progression of prostate cancer. We discuss proteins involved in the normal and aberrant growth and development of the prostate gland that may be affected by physical activity. We further identify future directions for research, including a better understanding of the biological mechanisms, the need to standardize physical activity and identify mechanistic end points of physical activity that can then be correlated with outcomes. PMID:25800589

  18. Induction of apoptosis in cancer cells through N-acetyl-l-leucine-modified polyethylenimine-mediated p53 gene delivery.

    PubMed

    Li, Zhiyuan; Zhang, Liu; Li, Quanshun

    2015-11-01

    Herein, N-acetyl-L-leucine-modified polyethylenimine was successfully constructed through the EDC/NHS-mediated coupling reaction and employed as vectors to accomplish p53 gene delivery using HeLa (p53wt) and PC-3 cells (p53null) as models. Compared with PEI25K, the derivatives exhibited lower cytotoxicity, protein adsorption and hemolytic activity, together with satisfactory pDNA condensation capability and gene transfection efficiency. After p53 transfection, MTT analysis confirmed that the cell proliferation was inhibited. Flow cytometric analysis showed that the derivative-mediated p53 delivery could induce stronger early apoptosis than PEI25K and Lipofectamine(2000). Further, PC-3 cells showed higher sensitivity to the exogenous p53 transfection than HeLa cells. The mechanism for inducing apoptosis was determined to be up-regulation of p53 expression at both mRNA and protein levels using RT-PCR and western blotting analysis. Expression level and activity analysis of caspase-3, -8 and -9, and mitochondrial membrane potential measurement revealed that p53 transfection mediated by these derivatives facilitated early apoptosis of tumor cells via a mitochondria-dependent apoptosis pathway. Thus, the derivatives showed potential as biocompatible carriers for realizing effective tumor gene therapy. PMID:26322477

  19. Do tobacco and alcohol modify protective effects of diet on oral carcinogenesis?

    PubMed

    Toporcov, Tatiana Natasha; Tavares, Giovanna Emann; Rotundo, Ligia Drovandi Braga; Vaccarezza, Gabriela Fürst; Biazevic, Maria Gabriela Haye; Brasileiro, Rosana Sarmento; de Carvalho, Marcos Brasilino; JMichaluart unior, Pedro; Kowalski, Luiz Paulo; Antunes, José Leopoldo Ferreira

    2012-01-01

    Recent systematic reviews concluded that the frequent consumption of fruits and vegetables is inversely associated with the risk of oral cancer. We assessed this association, specifically comparing results obtained to nonsmokers and smokers, as well to nondrinkers and drinkers. We conducted a case-control study involving 296 patients with oral squamous cell carcinoma (cases) attended in 3 major hospitals of São Paulo, Brazil, paired with 296 controls, recruited from outpatient units of the same hospitals. Multivariate models assessed the effect of fruits and salads according to smoking and drinking. The intake of fruit was associated with the prevention of the disease in the specific assessment among light [odds ratio (OR) = 0.46; 95% confidence interval (CI) = 0.27-0.78) and heavy (OR = 0.30; 95% CI = 0.14-0.65) smokers. The same was observed for vegetables consumption. For nonsmokers, no fruit (OR = 50; 95% CI = 0.22-1.12) or vegetable (for tomato, OR = 0.53; 95% CI = 0.31-0.93) was associated with reduced risk of oral and oropharyngeal cancer. Similar results were found in the stratified analysis according to drinking status with OR = 0.51 (95% CI = 0.30-0.87) and 0.18 for fruits (95% CI = 0.07-0.45), respectively, for light and heavy drinkers. This observation suggests that the protective effect of fruit and salad intake may modulate the deleterious effects from tobacco and alcohol. PMID:23163847

  20. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor–negative breast cancer in the general population

    PubMed Central

    Antoniou, Antonis C; Wang, Xianshu; Fredericksen, Zachary S; McGuffog, Lesley; Tarrell, Robert; Sinilnikova, Olga M; Healey, Sue; Morrison, Jonathan; Kartsonaki, Christiana; Lesnick, Timothy; Ghoussaini, Maya; Barrowdale, Daniel; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Eccles, Diana; Evans, D Gareth; Eeles, Ros; Izatt, Louise; Chu, Carol; Douglas, Fiona; Paterson, Joan; Stoppa-Lyonnet, Dominique; Houdayer, Claude; Mazoyer, Sylvie; Giraud, Sophie; Lasset, Christine; Remenieras, Audrey; Caron, Olivier; Hardouin, Agnès; Berthet, Pascaline; Hogervorst, Frans B L; Rookus, Matti A; Jager, Agnes; van den Ouweland, Ans; Hoogerbrugge, Nicoline; van der Luijt, Rob B; Meijers-Heijboer, Hanne; García, Encarna B Gómez; Devilee, Peter; Vreeswijk, Maaike P G; Lubinski, Jan; Jakubowska, Anna; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Cybulski, Cezary; Spurdle, Amanda B; Holland, Helene; Goldgar, David E; John, Esther M; Hopper, John L; Southey, Melissa; Buys, Saundra S; Daly, Mary B; Terry, Mary-Beth; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Preisler-Adams, Sabine; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy; Blum, Joanne L; Piedmonte, Marion; Rodriguez, Gustavo C; Wakeley, Katie; Boggess, John F; Basil, Jack; Blank, Stephanie V; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Milgrom, Roni; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Kirchhoff, Tomas; Vijai, Joseph; Gaudet, Mia M; Altshuler, David; Guiducci, Candace; Loman, Niklas; Harbst, Katja; Rantala, Johanna; Ehrencrona, Hans; Gerdes, Anne-Marie; Thomassen, Mads; Sunde, Lone; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Viel, Alessandra; Radice, Paolo; Caldes, Trinidad; de la Hoya, Miguel; Singer, Christian F; Fink-Retter, Anneliese; Greene, Mark H; Mai, Phuong L; Loud, Jennifer T; Guidugli, Lucia; Lindor, Noralane M; Hansen, Thomas V O; Nielsen, Finn C; Blanco, Ignacio; Lazaro, Conxi; Garber, Judy; Ramus, Susan J; Gayther, Simon A; Phelan, Catherine; Narod, Stephen; Szabo, Csilla I; Benitez, Javier; Osorio, Ana; Nevanlinna, Heli; Heikkinen, Tuomas; Caligo, Maria A; Beattie, Mary S; Hamann, Ute; Godwin, Andrew K; Montagna, Marco; Casella, Cinzia; Neuhausen, Susan L; Karlan, Beth Y; Tung, Nadine; Toland, Amanda E; Weitzel, Jeffrey; Olopade, Olofunmilayo; Simard, Jacques; Soucy, Penny; Rubinstein, Wendy S; Arason, Adalgeir; Rennert, Gad; Martin, Nicholas G; Montgomery, Grant W; Chang-Claude, Jenny; Flesch-Janys, Dieter; Brauch, Hiltrud; Severi, Gianluca; Baglietto, Laura; Cox, Angela; Cross, Simon S; Miron, Penelope; Gerty, Sue M; Tapper, William; Yannoukakos, Drakoulis; Fountzilas, George; Fasching, Peter A; Beckmann, Matthias W; Silva, Isabel dos Santos; Peto, Julian; Lambrechts, Diether; Paridaens, Robert; Rüdiger, Thomas; Försti, Asta; Winqvist, Robert; Pylkäs, Katri; Diasio, Robert B; Lee, Adam M; Eckel-Passow, Jeanette; Vachon, Celine; Blows, Fiona; Driver, Kristy; Dunning, Alison; Pharoah, Paul P D; Offit, Kenneth; Pankratz, V Shane; Hakonarson, Hakon; Chenevix-Trench, Georgia; Easton, Douglas F; Couch, Fergus J

    2011-01-01

    Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (Ptrend = 2.3 × 10−9 to Ptrend = 3.9 × 10−7), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17–1.35; rs2363956 HR = 0.84, 95% CI 0.80–0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor–negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75–0.92, Ptrend = 0.0003) and an association with estrogen receptor–positive disease in the opposite direction (OR = 1.07, 95% CI 1.01–1.14, Ptrend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 × 10−7 to Ptrend = 8 × 10−5; rs2363956 per-allele OR = 0.80, 95% CI 0.74–0.87, Ptrend = 1.1 × 10−7). PMID:20852631

  1. Mutant p53-R273H mediates cancer cell survival and anoikis resistance through AKT-dependent suppression of BCL2-modifying factor (BMF)

    PubMed Central

    Tan, B S; Tiong, K H; Choo, H L; Fei-Lei Chung, F; Hii, L-W; Tan, S H; Yap, I KS; Pani, S; Khor, N TW; Wong, S F; Rosli, R; Cheong, S-K; Leong, C-O

    2015-01-01

    p53 is the most frequently mutated tumor-suppressor gene in human cancers. Unlike other tumor-suppressor genes, p53 mutations mainly occur as missense mutations within the DNA-binding domain, leading to the expression of full-length mutant p53 protein. Mutant p53 proteins not only lose their tumor-suppressor function, but may also gain new oncogenic functions and promote tumorigenesis. Here, we showed that silencing of endogenous p53-R273H contact mutant, but not p53-R175H conformational mutant, reduced AKT phosphorylation, induced BCL2-modifying factor (BMF) expression, sensitized BIM dissociation from BCL-XL and induced mitochondria-dependent apoptosis in cancer cells. Importantly, cancer cells harboring endogenous p53-R273H mutant were also found to be inherently resistant to anoikis and lack BMF induction following culture in suspension. Underlying these activities is the ability of p53-R273H mutant to suppress BMF expression that is dependent on constitutively active PI3K/AKT signaling. Collectively, these findings suggest that p53-R273H can specifically drive AKT signaling and suppress BMF expression, resulting in enhanced cell survivability and anoikis resistance. These findings open the possibility that blocking of PI3K/AKT will have therapeutic benefit in mutant p53-R273H expressing cancers. PMID:26181206

  2. Effects of Serum Triglycerides on Prostate Cancer and Breast Cancer Risk: A Meta-Analysis of Prospective Studies.

    PubMed

    Ma, Hong-Qun; Cui, Lian-Hua; Li, Cheng-Cheng; Yu, Zhuang; Piao, Jin-Mei

    2016-10-01

    Epidemiological studies show conflicting results regarding the link between serum triglyceride and the risk of prostate cancer and breast cancer. Therefore, we performed a meta-analysis of prospective studies to clarify this association. We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) database to identify relevant prospective studies of the relationship between serum triglyceride and prostate cancer and breast cancer risk. Study-specific estimates adjusting for potential confounders were combined to evaluate a summary relative risks (RRs) and 95% confidence intervals (95% CIs) using a fixed- or random-effects model. A total of 11 prospective studies (619,410 subjects and 15,691 incident prostate cancer patients) and 8 prospective studies (590,878 subjects and 12,177 incident breast cancer patients) were respectively included in our meta-analysis to assess the associations of serum triglyceride with prostate cancer and breast cancer risk. The pooled adjusted RR estimates for prostate cancer and breast cancer for the highest versus the lowest exposure levels of serum triglycerides were 0.95 (95% CI: 0.87-1.04) and 0.94 (95% CI: 0.87-1.00), respectively. Additionally, a dose-response analysis revealed that serum levels of triglycerides were not associated with the risk of prostate cancer and breast cancer. We found that serum triglyceride was not related to the risk of prostate cancer and breast cancer. PMID:27618148

  3. Effect of Fuel Fraction on Small Modified CANDLE Burn-up Based Gas Cooled Fast Reactors

    SciTech Connect

    Ariani, Menik; Su'ud, Zaki; Waris, Abdul; Asiah, Nur; Shafii, M. Ali; Khairurrijal

    2010-12-23

    A conceptual design study of Gas Cooled Fast Reactors with Modified CANDLE Burn-up has been performed. The objective of this research is to get optimal design parameters of such type reactors. The parameters of nuclear design including the critical condition, conversion ratio, and burn-up level were compared. These parameters are calculated by variation in the fuel fraction 47.5% up to 70%. Two dimensional full core multi groups diffusion calculations was performed by CITATION code. Group constant preparations are performed by using SRAC code system with JENDL-3.2 nuclear data library. In this design the reactor cores with cylindrical cell two dimensional R-Z core models are subdivided into several parts with the same volume in the axial directions. The placement of fuel in core arranged so that the result of plutonium from natural uranium can be utilized optimally for 10 years reactor operation. Modified CANDLE burn-up was established successfully in a core radial width 1.4 m. Total thermal power output for reference core is 550 MW. Study on the effect of fuel to coolant ratio shows that effective multiplication factor (k{sub eff}) is in almost linear relations with the change of the fuel volume to coolant ratio.

  4. Effect of Fuel Fraction on Small Modified CANDLE Burn-up Based Gas Cooled Fast Reactors

    NASA Astrophysics Data System (ADS)

    Ariani, Menik; Su'ud, Zaki; Waris, Abdul; Khairurrijal, Asiah, Nur; Shafii, M. Ali

    2010-12-01

    A conceptual design study of Gas Cooled Fast Reactors with Modified CANDLE Burn-up has been performed. The objective of this research is to get optimal design parameters of such type reactors. The parameters of nuclear design including the critical condition, conversion ratio, and burn-up level were compared. These parameters are calculated by variation in the fuel fraction 47.5% up to 70%. Two dimensional full core multi groups diffusion calculations was performed by CITATION code. Group constant preparations are performed by using SRAC code system with JENDL-3.2 nuclear data library. In this design the reactor cores with cylindrical cell two dimensional R-Z core models are subdivided into several parts with the same volume in the axial directions. The placement of fuel in core arranged so that the result of plutonium from natural uranium can be utilized optimally for 10 years reactor operation. Modified CANDLE burn-up was established successfully in a core radial width 1.4 m. Total thermal power output for reference core is 550 MW. Study on the effect of fuel to coolant ratio shows that effective multiplication factor (keff) is in almost linear relations with the change of the fuel volume to coolant ratio.

  5. Effect of H2O2 concentrations on copper removal using the modified hydrothermal biochar.

    PubMed

    Zuo, XiaoJun; Liu, Zhengang; Chen, MinDong

    2016-05-01

    This study investigated effect of H2O2 concentrations on copper removal using H2O2 modified hydrothermal carbonization Cymbopogon schoenanthus L. Spreng (HLG). Sorption behaviors of Cu (II) on the modified HLG by 20% H2O2 (mHLG2) could be the most desirable. Based on Langmuir isotherm, the maximum amount of Cu (II) uptake was in the sequence of mHLG2 (53.8mgg(-1))>mHLG1 (44.2mgg(-1))>mHLG3 (42.0mgg(-1))>mHLG0 (35.8mgg(-1)), which was higher than the results from majority of previous studies, suggesting that H2O2 modification advanced sorption capacity of hydrothermal biochars evidently. Effect mechanisms exploration indicated that the difference of Cu (II) removal by biochars before and after the modification was mainly related to functional groups. Carboxylic group was responsible for the best sorption property of Cu (II) by mHLG2, which was attributed to its significant relationships with H2O2 modification and Cu (II) removal. PMID:26894566

  6. Effects of breast and colorectal cancer on labour market outcomes-average effects and educational gradients.

    PubMed

    Heinesen, Eskil; Kolodziejczyk, Christophe

    2013-12-01

    We estimate causal effects of breast and colorectal cancer on labour market outcomes 1-3 years after the diagnosis. Based on Danish administrative data we estimate average treatment effects on the treated by propensity score weighting methods using persons with no cancer diagnosis as control group. We conduct robustness checks using matching, difference-in-differences methods and an alternative control group of later cancer patients. The different methods give approximately the same results. Cancer increases the risks of leaving the labour force and receiving disability pension, and the effects are larger for the less educated. Effects on income are small and mostly insignificant. We investigate some of the mechanisms which may be important in explaining the educational gradient in effects of cancer on labour market attachment. PMID:24096321

  7. The research priorities of patients attending UK cancer treatment centres: findings from a modified nominal group study

    PubMed Central

    Corner, J; Wright, D; Hopkinson, J; Gunaratnam, Y; McDonald, J W; Foster, C

    2007-01-01

    Members of the public are increasingly consulted over health care and research priorities. Patient involvement in determining cancer research priorities, however, has remained underdeveloped. This paper presents the findings of the first consultation to be conducted with UK cancer patients concerning research priorities. The study adopted a participatory approach using a collaborative model that sought joint ownership of the study with people affected by cancer. An exploratory, qualitative approach was used. Consultation groups were the main method, combining focus group and nominal group techniques. Seventeen groups were held with a total of 105 patients broadly representative of the UK cancer population. Fifteen areas for research were identified. Top priority areas included the impact cancer has on life, how to live with cancer and related support issues; risk factors and causes of cancer; early detection and prevention. Although biological and treatment related aspects of science were identified as important, patients rated the management of practical, social and emotional issues as a higher priority. There is a mismatch between the research priorities identified by participants and the current UK research portfolio. Current research activity should be broadened to reflect the priorities of people affected by the disease. PMID:17342090

  8. Modifying Effect of Heat Waves on the Relationship between Temperature and Mortality.

    PubMed

    Lee, Won Kyung; Lee, Hye Ah; Park, Hyesook

    2016-05-01

    Studies conducted to evaluate temporal trends of heat-related mortality have not considered the effects of heat waves; although it is known they can affect mortality and act as a modifying factor. After adjusting for long-term trends and seasonality, the effects of temperature on non-accidental deaths in Seoul and Busan (inland and coastal cities, respectively) were analyzed using a generalized additive model of Poisson distribution. We evaluated temporal trends of heat-related mortalities in four periods (1991-1995, 1996-2000, 2001-2005, and 2006-2012). The effects of temperature on mortality were evaluated according to the occurrence of a heat wave and results were compared in the two cities. The effect of temperature on mortality was the greatest in 1991-1995 in Seoul; no significant change was observed in Busan. When we stratified the study period by heat wave status, the risk increase in mortality was 15.9% per 1℃ during years with a heat wave in Seoul, which was much higher than 0.31% increase observed during years without a heat wave. On the other hand, Busan showed a linear relationship between temperature and mortality and no significant difference between years with or without a heat wave. Variations in the relationship between temperature and mortality could be misunderstood if heat waves are not considered. Furthermore, heterogeneity was found in the modifying effect of heat waves on heat-related mortality in inland and coastal cities. The findings of this study help understand relations between temperature and mortality. PMID:27134490

  9. Modifying Effect of Heat Waves on the Relationship between Temperature and Mortality

    PubMed Central

    2016-01-01

    Studies conducted to evaluate temporal trends of heat-related mortality have not considered the effects of heat waves; although it is known they can affect mortality and act as a modifying factor. After adjusting for long-term trends and seasonality, the effects of temperature on non-accidental deaths in Seoul and Busan (inland and coastal cities, respectively) were analyzed using a generalized additive model of Poisson distribution. We evaluated temporal trends of heat-related mortalities in four periods (1991-1995, 1996-2000, 2001-2005, and 2006-2012). The effects of temperature on mortality were evaluated according to the occurrence of a heat wave and results were compared in the two cities. The effect of temperature on mortality was the greatest in 1991-1995 in Seoul; no significant change was observed in Busan. When we stratified the study period by heat wave status, the risk increase in mortality was 15.9% per 1℃ during years with a heat wave in Seoul, which was much higher than 0.31% increase observed during years without a heat wave. On the other hand, Busan showed a linear relationship between temperature and mortality and no significant difference between years with or without a heat wave. Variations in the relationship between temperature and mortality could be misunderstood if heat waves are not considered. Furthermore, heterogeneity was found in the modifying effect of heat waves on heat-related mortality in inland and coastal cities. The findings of this study help understand relations between temperature and mortality. PMID:27134490

  10. Effects of Cancer-Associated EPHA3 Mutations on Lung Cancer

    PubMed Central

    2012-01-01

    Background Cancer genome sequencing efforts recently identified EPHA3, which encodes the EPHA3 receptor tyrosine kinase, as one of the most frequently mutated genes in lung cancer. Although receptor tyrosine kinase mutations often drive oncogenic conversion and tumorigenesis, the oncogenic potential of the EPHA3 mutations in lung cancer remains unknown. Methods We used immunoprecipitation, western blotting, and kinase assays to determine the activity and signaling of mutant EPHA3 receptors. A mutation-associated gene signature was generated from one large dataset, mapped to another training dataset with survival information, and tested in a third independent dataset. EPHA3 expression levels were determined by quantitative reverse transcription-polymerase chain reaction in paired normal-tumor clinical specimens and by immunohistochemistry in human lung cancer tissue microarrays. We assessed tumor growth in vivo using A549 and H1299 human lung carcinoma cell xenografts in mice (n = 7–8 mice per group). Tumor cell proliferation was measured by bromodeoxyuridine incorporation and apoptosis by multiple assays. All P values are from two-sided tests. Results At least two cancer-associated EPHA3 somatic mutations functioned as dominant inhibitors of the normal (wild type) EPHA3 protein. An EPHA3 mutation–associated gene signature that was associated with poor patient survival was identified. Moreover, EPHA3 gene copy numbers and/or expression levels were decreased in tumors from large cohorts of patients with lung cancer (eg, the gene was deleted in 157 of 371 [42%] primary lung adenocarcinomas). Reexpression of wild-type EPHA3 in human lung cancer lines increased apoptosis by suppression of AKT activation in vitro and inhibited the growth of tumor xenografts (eg, for H1299 cells, mean tumor volume with wild-type EPHA3 = 437.4mm3 vs control = 774.7mm3, P < .001). Tumor-suppressive effects of wild-type EPHA3 could be overridden in trans by dominant negative EPHA3

  11. Molecular pathways: Fumarate hydratase-deficient kidney cancer--targeting the Warburg effect in cancer.

    PubMed

    Linehan, W Marston; Rouault, Tracey A

    2013-07-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a hereditary cancer syndrome in which affected individuals are at risk for development of cutaneous and uterine leiomyomas and an aggressive form of type II papillary kidney cancer. HLRCC is characterized by germline mutation of the tricarboxylic acid (TCA) cycle enzyme, fumarate hydratase (FH). FH-deficient kidney cancer is characterized by impaired oxidative phosphorylation and a metabolic shift to aerobic glycolysis, a form of metabolic reprogramming referred to as the Warburg effect. Increased glycolysis generates ATP needed for increased cell proliferation. In FH-deficient kidney cancer, levels of AMP-activated protein kinase (AMPK), a cellular energy sensor, are decreased resulting in diminished p53 levels, decreased expression of the iron importer, DMT1, leading to low cellular iron levels, and to enhanced fatty acid synthesis by diminishing phosphorylation of acetyl CoA carboxylase, a rate-limiting step for fatty acid synthesis. Increased fumarate and decreased iron levels in FH-deficient kidney cancer cells inactivate prolyl hydroxylases, leading to stabilization of hypoxia-inducible factor (HIF)-1α and increased expression of genes such as VEGF and glucose transporter 1 (GLUT1) to provide fuel needed for rapid growth demands. Several therapeutic approaches for targeting the metabolic basis of FH-deficient kidney cancer are under development or are being evaluated in clinical trials, including the use of agents such as metformin, which would reverse the inactivation of AMPK, approaches to inhibit glucose transport, lactate dehydrogenase A (LDHA), the antioxidant response pathway, the heme oxygenase pathway, and approaches to target the tumor vasculature and glucose transport with agents such as bevacizumab and erlotinib. These same types of metabolic shifts, to aerobic glycolysis with decreased oxidative phosphorylation, have been found in a wide variety of other cancer types. Targeting the

  12. Effects of modifiers on the hydrophobicity of SiO2 films from nano-husk ash

    NASA Astrophysics Data System (ADS)

    Xu, Kejing; Sun, Qingwen; Guo, Yanqing; Dong, Shuhua

    2013-07-01

    Nano-husk ashes were prepared by burning rice-husk with self-propagating method. The super-hydrophobic SiO2 films from nano-husk ash were prepared by sol-gel method using hydroxy silicone oil (HSO), hexamethyldisilazane (HMS), or methyl triethoxysilane (MTS) as modifiers. The effects of modifiers on the hydrophobic property of SiO2 films were studied, and the performances were characterized by the XRD, UV-vis, BET, EDS, SEM, IR, and Contact Angle Analyzer. The results showed that the contact angle of SiO2 films was more than 160° when volume ratio of the modifiers to silicon-sodium solution (SSS) was 0.15. The mechanism of modifiers on SiO2 surfaces is a graft copolymerization. The hydrophobic groups in the modifiers replace the hydroxy groups on SiO2 surfaces and make SiO2 surfaces present super-hydrophobicity.

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

    PubMed

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

    2012-03-15

    Rosemary (Rosmarinus officinalis L.) is a popular culinary/medicinal herb. Recent studies have shown it has pharmacologic activities for cancer chemoprevention and therapy. This study evaluated the antiproliferation activity of rosemary extract (RE) against human ovarian cancer cells, and whether the extract and its three main active ingredients carnosol (CS), carnosic acid (CA) and rosmarinic acid (RA) can enhance the antiproliferation activity of cisplatin (CDDP). Our study showed that RE has significant antiproliferation activity on human ovarian cancer A2780 and its CDDP resistant daughter cell line A2780CP70, with IC(50) (50% inhibitory concentration) estimated at 1/1000 and 1/400 dilutions respectively. RE enhanced the antiproliferation effect with CDDP on both A2780 and A2780CP70 cells. A2780 cells were consistently more sensitive to CS, CA, and RA than A2780CP70 cells between 2.5 and 20μg/ml. CS and RA also showed synergistic antiproliferation effect with CDDP on A2780 cells at some concentrations. RE treated by ultrafiltration, dialysis, and removal of phenolics lost the antiproliferation activity suggested that the activity resides in phenolics with MW<1000Da. Apoptosis array study of A2780 cells treated with RE showed that the expression of a number of genes regulating apoptosis were modulated by the treatment. This study showed that RE inhibited the proliferation of ovarian cancer cell lines by affecting the cell cycle at multiple phases. It induced apoptosis by modifying the expression of multiple genes regulating apoptosis, and holds potential as an adjunct to cancer chemotherapy. PMID:22325591

  14. Effects of Dietary Factors and the NAT2 Acetylator Status on Gastric Cancer in Koreans

    PubMed Central

    Zhang, Yan Wei; Eom, Sang-Yong; Kim, Yong-Dae; Song, Young-Jin; Yun, Hyo-Yung; Park, Joo-Seung; Youn, Sei-Jin; Kim, Byung Sik; Kim, Heon; Hein, David W.

    2009-01-01

    Environmental dietary carcinogens and genetic polymorphisms in metabolic enzymes have been reported to be risk factors for gastric cancer. This study was undertaken to investigate the effects of the diet, the N-acetyltransferase (NAT) 2 acetylation status, and their interaction on gastric cancer risk. The study population consisted of 471 gastric cancer patients and 471 age- and sex-matched control subjects. NAT2 genotypes were identified using single-nucleotide primer extension reaction methods. Thirty-one alleles related to 12 polymorphism sites were assayed in this study. Significantly increased odds ratios were observed in former smokers (OR = 2.39, 95%CI = 1.57-3.62), heavy drinkers (OR = 1.28, 95%CI = 1.06-1.55), and individuals who eat well-done meat (OR = 1.24, 95%CI = 1.09-1.41). The odds ratios (95% CI) for high intake of kimchi, stews, and soybean paste were 3.27 (2.44-4.37), 1.96 (1.50-2.58), and 1.63 (1.24-2.14), respectively. The NAT2 genotype alone was not associated with gastric cancer risk. A significant gene-environment interaction was observed between environmental carcinogens and NAT2 genotypes. The odds ratios for kimchi, stews, and soybean paste were higher in slow/intermediate acetylators than in rapid acetylators. The odds ratios for slow/intermediate acetylators were 2.28 (95% CI: 1.29-4.04) for light smokers and 3.42 (95% CI: 2.06-5.68) for well-done meat intake. The NAT2 acetylator genotype may be an important modifier of the effects of environmental factors on gastric cancer risk. PMID:19350634

  15. Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement

    PubMed Central

    Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

    2013-01-01

    Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health. PMID:23752350

  16. Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement.

    PubMed

    Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

    2013-01-01

    Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health. PMID:23752350

  17. Development, Characterization and Validation of Trastuzumab-Modified Gold Nanoparticles for Molecularly Targeted Radiosensitization of Breast Cancer

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, Niladri

    The overexpression of the human epidermal growth factor receptor-2 (HER-2) in 20--25% of human breast cancers was investigated as a target for development of a gold nanoparticle (AuNP) based radiosensitizer for improving the efficacy of neoadjuvant X-radiation therapy of the disease. HER-2 targeted AuNPs were developed by covalently conjugating trastuzumab, a Health Canada approved monoclonal antibody for the treatment of HER-2-overexpressing breast cancer, to 30 nm AuNPs. Trastuzumab conjugated AuNPs were efficiently internalized by HER-2-overexpressing breast cancer cells (as assessed by darkfield microscopy and transmission electron microscopy) and increased DNA damage from X-radiation in these cells by more than 5-fold. To optimize delivery of AuNPs to HER-2-overexpressing tumors, high resolution microSPECT/CT imaging was used to track the in vivo fate of 111In-labelled non-targeted and HER-2 targeted AuNPs following intravenous (i.v.) or intratumoral (i.t.) injection. For i.v. injection, the effects of GdCl3 (for deactivation of macrophages) and non-specific (anti-CD20) antibody rituximab (for blocking of Fc mediated liver and spleen uptake) were studied. It was found that HER-2 targeting via attachment of trastuzumab paradoxically decreased tumor uptake as a result of faster elimination of the targeted AuNPs from the blood while improving internalization in HER-2-positive tumor cells as compared to non-targeted AuNPs. This phenomenon could be attributed to Fc-mediated recognition and subsequent sequestration of trastuzumab conjugated AuNP by the reticuloendothelial system (RES). Blocking of the RES did not increase tumor uptake of either HER-2 targeted or non-targeted AuNPs. Following i.t. injection, our results suggest that Au-NTs redistribute over time and traffick to the liver via the ipsilateral axillary lymph node leading to comparable exposure as seen with i.v. administration. In contrast, targeted AuNPs are bound and internalized by HER-2

  18. Modified Fletcher's 3-channel brachytherapy system with vaginal line source loading versus uterine tandem and vaginal cylinder system in Stage IIIA cervical cancer

    PubMed Central

    Low, JSH; Ng, KB

    2006-01-01

    Purpose The uterine tandem with open-ended vaginal cylinder is the most commonly used brachytherapy system for Federation Internationale de Gynecologie et d'Obstetrique (FIGO) Stage IIIA cervix cancer at the National Cancer Centre, Singapore. Without the 3-channel ovoid system, the dose to the parametrium is often compromised. In this study, a vaginal cylinder that could potentially be incorporated with the 3-channel system was developed, hence addressing the problem of treating both the vaginal disease extension and the parametrium. Methods and materials A hollow cylinder of 3 cm in diameter was incorporated with the Fletcher's 3-channel tandem and ovoid system. Treatment plans were generated with the single tandem line source with a vaginal cylinder applicator and the modified Fletcher's system using the Abacus version 3 brachytherapy treatment planning software. A nominal dose of 5 Gy was prescribed to point H for both plans. The perpendicular distance of the 5 Gy isodose line from the uterine tandem plane at the centre of the ovoid and the vaginal cylinder plane 1 cm below the os guard were then compared. Results The 5 Gy isodose line was 1.7 cm from the uterine tandem source at the location lateral through the centre of the ovoids on the plan with the uterine tandem and vaginal cylinder system as compared to a distance of 3.3 cm using the modified 3-channel Fletcher system. The 5 Gy isodose line was 2 cm lateral to the central source at the vaginal cylinder plane 1 cm below the os guard on the uterine tandem and vaginal cylinder system as compared to a distance of 2.5 cm on the Modified-Fletcher system. This corresponds to an increase of 1.6 cm and 0.5 cm depth of treated parametrium on the uterine tandem plane and vaginal cylinder plane respectively with the modified Fletcher's applicator as compared with the single line source cylinder system. Conclusion As compared with the single uterine tandem and open-ended vaginal cylinder system, an addition of 1.6 cm

  19. A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication

    PubMed Central

    Dahmen, Norbert; Beckmann, Lars; Lindström, Sara; Schoof, Nils; Czene, Kamila; Mittelstraß, Kirstin; Illig, Thomas; Seibold, Petra; Behrens, Sabine; Humphreys, Keith; Li, Jingmei; Liu, Jianjun; Olson, Janet E.; Wang, Xianshu; Hankinson, Susan E.; Truong, Thérèse; Menegaux, Florence; dos Santos Silva, Isabel; Johnson, Nichola; Chen, Shou-Tung; Yu, Jyh-Cherng; Ziogas, Argyrios; Kataja, Vesa; Kosma, Veli-Matti; Mannermaa, Arto; Anton-Culver, Hoda; Shen, Chen-Yang; Brauch, Hiltrud; Peto, Julian; Guénel, Pascal; Kraft, Peter; Couch, Fergus J.; Easton, Douglas F.; Hall, Per; Chang-Claude, Jenny

    2013-01-01

    Menopausal hormone therapy (MHT) is associated with an elevated risk of breast cancer in postmenopausal women. To identify genetic loci that modify breast cancer risk related to MHT use in postmenopausal women, we conducted a two-stage genome-wide association study (GWAS) with replication. In stage I, we performed a case-only GWAS in 731 invasive breast cancer cases from the German case-control study Mammary Carcinoma Risk Factor Investigation (MARIE). The 1,200 single nucleotide polymorphisms (SNPs) showing the lowest P values for interaction with current MHT use (within 6 months prior to breast cancer diagnosis), were carried forward to stage II, involving pooled case-control analyses including additional MARIE subjects (1,375 cases, 1,974 controls) as well as 795 cases and 764 controls of a Swedish case-control study. A joint P value was calculated for a combined analysis of stages I and II. Replication of the most significant interaction of the combined stage I and II was performed using 5,795 cases and 5,390 controls from nine studies of the Breast Cancer Association Consortium (BCAC). The combined stage I and II yielded five SNPs on chromosomes 2, 7, and 18 with joint P values <6 × 10−6 for effect modification of current MHT use. The most significant interaction was observed for rs6707272 (P = 3 × 10−7) on chromosome 2 but was not replicated in the BCAC studies (P = 0.21). The potentially modifying SNPs are in strong linkage disequilibrium with SNPs in TRIP12 and DNER on chromosome 2 and SETBP1 on chromosome 18, previously linked to carcinogenesis. However, none of the interaction effects reached genome-wide significance. The inability to replicate the top SNP × MHT interaction may be due to limited power of the replication phase. Our study, however, suggests that there are unlikely to be SNPs that interact strongly enough with MHT use to be clinically significant in European women. PMID:23423446

  20. A Gompertzian model with random effects to cervical cancer growth

    NASA Astrophysics Data System (ADS)

    Mazlan, Mazma Syahidatul Ayuni; Rosli, Norhayati

    2015-05-01

    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.

  1. A Gompertzian model with random effects to cervical cancer growth

    SciTech Connect

    Mazlan, Mazma Syahidatul Ayuni; Rosli, Norhayati

    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. Towards electron transport measurements in chemically modified graphene: effect of a solvent

    NASA Astrophysics Data System (ADS)

    Jacobsen, Arnhild; Koehler, Fabian M.; Stark, Wendelin J.; Ensslin, Klaus

    2010-12-01

    The chemical functionalization of graphene modifies the local electron density of carbon atoms and hence electron transport. Measuring these changes allows for a closer understanding of the chemical interaction and the influence of functionalization on the graphene lattice. However, not only chemistry, in this case diazonium chemistry, has an effect on electron transport. The latter is also influenced by defects and dopants resulting from different processing steps. Here, we show that the solvents used in the chemical reaction process change the transport properties. In more detail, the investigated combination of isopropanol and heating treatment reduces the doping concentration and significantly increases the mobility of graphene. Furthermore, isopropanol treatment alone increases the concentration of dopants and introduces an asymmetry between electron and hole transport, which might be difficult to distinguish from the effect of functionalization. The results shown in this work demand a closer look at the influence of solvents used for chemical modification in order to understand their influence.

  3. Pretreatment effects on the sorption of Cr(VI) onto surfactant-modified zeolite: Mechanism analysis.

    PubMed

    Song, Wenzhe; Shi, Taihong; Yang, Di; Ye, Jinpeng; Zhou, Yi; Feng, Yuxiang

    2015-10-01

    Adsorption of Cr(VI) onto different pretreated zeolites modified with cetylpyridinium chloride (CPC) is investigated using batch studies, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) measurements and scanning electron microscopy (SEM). The results indicate that acidification after alkalization is the most effective pretreatment method, and only alkalization would significantly reduce the sorption capability. This behavior is due to the precipitates, such as CaCO3 and MgCO3, generated after alkalization on zeolite surface interfere the formation of the CPC bilayer, which provides active sites for sorbing Cr(VI). The schematic of the adsorption mechanism is presented. The results indicate that developing a better understanding of the influence of different pretreatments is quite helpful and suggest that the content of Ca/Mg/Fe could be a good indication of the effectiveness of preprocessing. PMID:26232569

  4. Effects of information on young consumers' willingness to pay for genetically modified food: experimental auction analysis.

    PubMed

    Kajale, Dilip B; Becker, T C

    2014-01-01

    This study examines the effects of information on consumers' willingness to pay (WTP) for genetically modified food (GMF). We used Vickrey second price experimental auction method for elicitation of consumer WTP for GM potato chips and GM soya-chocolate bar. The sample used in this study was university students from Delhi, India. Four information formats (positive, negative, no information, and combined information about GM technology) were used for the examination. The results show that, when students received the combine information they were willing to pay around 17%-20% premium for GMF and when received the negative information they demanded around 22% discount for GMF. While the positive- and the no-information formats alone have no considerable effect on consumers' WTP for GMF. Overall, our findings suggest that while doing marketing of GMF in India, the best strategy is to provide combined information about GM technology. PMID:24735210

  5. The effects of internal radiation exposure on cancer mortality in nuclear workers at Rocketdyne/Atomics International.

    PubMed Central

    Ritz, B; Morgenstern, H; Crawford-Brown, D; Young, B

    2000-01-01

    We examined the effects of chronic exposure to radionuclides, primarily uranium and mixed-fission products, on cancer mortality in a retrospective cohort study of workers enrolled in the radiation-monitoring program of a nuclear research and development facility. Between 1950 and 1994, 2,297 workers were monitored for internal radiation exposures, and 441 workers died, 134 (30.4%) of them from cancer as the underlying cause. We calculated internal lung-dose estimates based on urinalysis and whole-body and lung counts reported for individual workers. We examined cancer mortality of workers exposed at different cumulative lung-dose levels using complete risk-set analysis for cohort data, adjusting for age, pay type, time since first radiation monitored, and external radiation. In addition, we examined the potential for confounding due to chemical exposures and smoking, explored whether external radiation exposure modifies the effects of internal exposure, and estimated effects after excluding exposures likely to have been unrelated to disease onset. Dose-response relations were observed for death from hemato- and lymphopoietic cancers and from upper aerodigestive tract cancers, adjusting for age, time since first monitored, pay type, and external (gamma) radiation dose. No association was found for other cancers, including cancers of the lung. Despite the small number of exposed deaths from specific cancer types and possible bias due to measurement error and confounding, the positive findings and strong dose-response gradients observed suggest carcinogenic effects of internal radiation to the upper aerodigestive tract and the blood and lymph system in this occupational cohort. However, causal inferences require replication of our results in other populations or confirmation with an extended follow-up of this cohort. PMID:10964795

  6. Effective Electrochemistry of Human Sulfite Oxidase Immobilized on Quantum-Dots-Modified Indium Tin Oxide Electrode.

    PubMed

    Zeng, Ting; Leimkühler, Silke; Koetz, Joachim; Wollenberger, Ulla

    2015-09-30

    The bioelectrocatalytic sulfite oxidation by human sulfite oxidase (hSO) on indium tin oxide (ITO) is reported, which is facilitated by functionalizing of the electrode surface with polyethylenimine (PEI)-entrapped CdS nanoparticles and enzyme. hSO was assembled onto the electrode with a high surface loading of electroactive enzyme. In the presence of sulfite but without additional mediators, a high bioelectrocatalytic current was generated. Reference experiments with only PEI showed direct electron transfer and catalytic activity of hSO, but these were less pronounced. The application of the polyelectrolyte-entrapped quantum dots (QDs) on ITO electrodes provides a compatible surface for enzyme binding with promotion of electron transfer. Variations of the buffer solution conditions, e.g., ionic strength, pH, viscosity, and the effect of oxygen, were studied in order to understand intramolecular and heterogeneous electron transfer from hSO to the electrode. The results are consistent with a model derived for the enzyme by using flash photolysis in solution and spectroelectrochemistry and molecular dynamic simulations of hSO on monolayer-modified gold electrodes. Moreover, for the first time a photoelectrochemical electrode involving immobilized hSO is demonstrated where photoexcitation of the CdS/hSO-modified electrode lead to an enhanced generation of bioelectrocatalytic currents upon sulfite addition. Oxidation starts already at the redox potential of the electron transfer domain of hSO and is greatly increased by application of a small overpotential to the CdS/hSO-modified ITO. PMID:26357959

  7. Antioxidant intake and risk of osteoporotic hip fracture in Utah: an effect modified by smoking status.

    PubMed

    Zhang, Jianjun; Munger, Ronald G; West, Nancy A; Cutler, D Richard; Wengreen, Heidi J; Corcoran, Christopher D

    2006-01-01

    The role of antioxidant intake in osteoporotic hip fracture risk is uncertain and may be modified by smoking. In the Utah Study of Nutrition and Bone Health, a statewide, population-based case-control study, the authors investigated whether antioxidant intake was associated with risk of osteoporotic hip fracture and whether this association was modified by smoking status. The analyses included data on 1,215 male and female cases aged > or = 50 years who incurred a hip fracture during 1997-2001 and 1,349 age- and sex-matched controls. Diet was assessed by food frequency questionnaire. Among ever smokers, participants in the highest quintile of vitamin E intake (vs. the lowest) had a lower risk of hip fracture after adjustment for confounders (odds ratio = 0.29, 95% confidence interval (CI): 0.16, 0.52; p-trend < 0.0001). The corresponding odds ratio for beta-carotene intake was 0.39 (95% CI: 0.23, 0.68; p-trend = 0.0004), and for selenium intake it was 0.27 (95% CI: 0.12, 0.58; p-trend = 0.0003). Vitamin C intake did not have a significant graded association with hip fracture risk among ever smokers. Similar findings were obtained when an overall antioxidant intake score was used (odds ratio = 0.19, 95% CI: 0.10, 0.37; p-trend < 0.0001). No similar associations were found in never smokers. Antioxidant intake was associated with reduced risk of osteoporotic hip fracture in these elderly subjects, and the effect was strongly modified by smoking status. PMID:16306312

  8. Framingham risk score modifies the effect of PM10 on heart rate variability.

    PubMed

    Feng, Yingying; Huang, Xiji; Sun, Huizhen; Liu, Chuanyao; Zhang, Bing; Zhang, Zhihong; Sharma Tengur, Vashish; Chen, Weihong; Wu, Tangchun; Yuan, Jing; Zhang, Xiaomin

    2015-08-01

    Health conditions may greatly modify the association between particulate matter (PM) and heart rate variability (HRV), but whether the modification of PM effect by coronary artery disease (CAD) risk status depends on the PM levels remains unknown. We investigated the associations between personal exposures to PM with aerodynamic diameter of ≤10μm (PM10) and ≤2.5μm (PM2.5) and concurrent HRV, and whether the effect of PM on HRV was modified by Framingham risk score (FRS) in healthy subjects with different PM exposure levels. Personal exposures to PM10 and PM2.5 were measured for 24h in 152 volunteers of community residents who were free of cardiovascular disease in two cities (Zhuhai and Wuhan) that differ in air quality. Simultaneously, 24h HRV indices were obtained from 3-channel Holter monitor. FRS was calculated based on age, sex, lipid profiles, blood pressure, diabetes, and smoking status. Linear regression models were constructed after adjusting for potential confounders. We found significant decrease in total power (TP) and low power (LF) with increased PM10 concentrations (P for trend<0.05) in the high PM levels city (Wuhan) and total population, but not in the low PM levels city (Zhuhai). We also observed significant modification of FRS on PM10 effect in Wuhan. Interestingly, elevated PM10 was associated in a greater decreased HRV in the low FRS subgroup, but not in the high FRS subgroup. However, we did not find any significant main effects of PM2.5 or PM2.5-FRS interactions on HRV in city-specified or city-combined analyses. Overall, the findings indicate that individual coronary risk profiles may modulate the association between particulate air pollution and HRV in high PM exposure levels. PMID:25863505

  9. Gender and Crime Victimization Modify Neighborhood Effects on Adolescent Mental Health

    PubMed Central

    Schmidt, Nicole M.; Bates, Lisa M.; Tchetgen-Tchetgen, Eric J.; Earls, Felton J.; Glymour, M. Maria

    2012-01-01

    OBJECTIVE: Leverage an experimental study to determine whether gender or recent crime victimization modify the mental health effects of moving to low-poverty neighborhoods. METHODS: The Moving to Opportunity (MTO) study randomized low-income families in public housing to an intervention arm receiving vouchers to subsidize rental housing in lower-poverty neighborhoods or to controls receiving no voucher. We examined 3 outcomes 4 to 7 years after randomization, among youth aged 5 to 16 years at baseline (n = 2829): lifetime major depressive disorder (MDD), psychological distress (K6), and Behavior Problems Index (BPI). Treatment effect modification by gender and family’s baseline report of recent violent crime victimization was tested via interactions in covariate-adjusted intent-to-treat and instrumental variable adherence-adjusted regression models. RESULTS: Gender and crime victimization significantly modified treatment effects on distress and BPI (P < .10). Female adolescents in families without crime victimization benefited from MTO treatment, for all outcomes (Distress B = –0.19, P = .008; BPI B = –0.13, P = .06; MDD B = –0.036, P = .03). Male adolescents in intervention families experiencing crime victimization had worse distress (B = 0.24, P = .004), more behavior problems (B = 0.30, P < .001), and nonsignificantly higher MDD (B = 0.022, P = .16) versus controls. Other subgroups experienced no effect of MTO treatment. Instrumental variable estimates were similar but larger. CONCLUSIONS: Girls from families experiencing recent violent crime victimization were significantly less likely to achieve mental health benefits, and boys were harmed, by MTO, suggesting need for cross-sectoral program supports to offset multiple stressors. PMID:22908105

  10. The effects of tricyclic antidepressants on breast cancer risk

    PubMed Central

    Sharpe, C R; Collet, J-P; Belzile, E; Hanley, J A; Boivin, J-F

    2002-01-01

    To test the hypothesis that tricyclic antidepressant use increases invasive female breast cancer incidence, we carried out a case–control study within the population of female beneficiaries of the Saskatchewan Prescription Drug Plan aged ⩾35 years from 1981–1995 with no history of cancer since 1970. This agency has provided full or partial coverage for outpatient prescriptions to Saskatchewan residents since 1975. We accrued 5882 histologically proven cases and 23 517 controls, randomly selected from the source population and individually matched on age and sampling time. Heavy exposure to any tricyclic antidepressants was associated with an elevated rate ratio for breast cancer 11–15 years later (2.02, 95% confidence interval: 1.34–3.04). Post hoc analyses based on the results of genotoxicity studies carried out using Drosophila melanogaster suggested that the increased risk could be attributed to the use of the six genotoxic tricyclic antidepressants, and not to the use of the four nongenotoxic tricyclic antidepressants. However, our results may have been confounded by the effects of other determinants of breast cancer associated with tricyclic antidepressant use. British Journal of Cancer (2002) 86, 92–97. DOI: 10.1038/sj/bjc/6600013 www.bjcancer.com © 2002 The Cancer Research Campaign PMID:11857018

  11. Growth inhibitory effect of Cucurbitacin E on breast cancer cells

    PubMed Central

    Lan, Tian; Wang, Linling; Xu, Qian; Liu, Weiguo; Jin, Hongchuan; Mao, Weimin; Wang, Xian; Wang, Xiaojia

    2013-01-01

    Objective: Due its inhibitory effects on chemical carcinogenesis and inflammation, Cucurbitacins have been proposed as an effective agent for the prevention or treatment of human cancers. In this study, we aimed to explore the effect of Cucurbitacin E (CuE) on human breast cancer cells. Methods: The inhibitory effect of CuE on proliferation of Bcap37 and MDA-MB-231 cells was assessed by MTT assay. The cell cycle distribution and cell apoptosis were determined by flow cytometry (FCM). The expression of pro-caspase 3, cleaved caspase 3, p21, p27 and the phosphorylation of signaling proteins was detected by Western Blotting. Results: CuE inhibited the growth of human breast cancer cells in a dose and time-dependent manner. FCM analysis showed that CuE induced G2/M phase arrest and cell apoptosis. CuE treatment promoted the cleavage of caspase 3 and upregulated p21 and p27. In addition, the phosphorylation of STAT3 but not ERK-1/2 was abrogated upon CuE treatment. Interestingly, losedose CuE significantly enhanced the growth inhibition induced by cisplatin. Conclusions Cucurbitacin E (CuE) could inhibit the growth of human breast cancer cells in vitro. CuE induced both apoptosis and cell cycle arrest probably through the inhibition of STAT3 function. Lose-dose CuE significantly enhanced the growth inhibitory effect of cisplatin on breast cancer cells, further indicating the potential clinical values of CuE for the prevention or treatment of human breast cancer PMID:24040444

  12. Japanese Cancer Association Meeting UICC International session--what is cost-effectiveness in cancer treatment?

    PubMed

    Akaza, Hideyuki; Kawahara, Norie; Roh, Jae Kyung; Inoue, Hajime; Park, Eun-Cheol; Lee, Kwang-Sig; Kim, Sukyeong; Hayre, Jasdeep; Naidoo, Bhash; Wilkinson, Thomas; Fukuda, Takashi; Jang, Woo Ick; Nogimori, Masafumi

    2014-01-01

    The Japan National Committee for the Union for International Cancer Control (UICC) and UICC-Asia Regional Office (ARO) organized an international session as part of the official program of the 72nd Annual Meeting of the Japanese Cancer Association to discuss the topic "What is cost-effectiveness in cancer treatment? " Healthcare economics are an international concern and a key issue for the UICC. The presenters and participants discussed the question of how limited medical resources can be best used to support life, which is a question that applies to both developing and industrialized countries, given that cancer treatment is putting medical systems under increasing strain. The emergence of advanced yet hugely expensive drugs has prompted discussion on methodologies for Health Technology Assessment (HTA) that seek to quantify cost and effect. The session benefited from the participation of various stakeholders, including representatives of industry, government and academia and three speakers from the Republic of Korea, an Asian country where discussion on HTA methodologies is already advanced. In addition, the session was joined by a representative of National Institute for Health and Care Excellence (NICE) of the United Kingdom, which has pioneered the concept of cost-effectiveness in a medical context. The aim of the session was to advance and deepen understanding of the issue of cost-effectiveness as viewed from medical care systems in different regions. PMID:24528045

  13. Effect of a six-month yoga exercise intervention on fitness outcomes for breast cancer survivors.

    PubMed

    Hughes, Daniel C; Darby, Nydia; Gonzalez, Krystle; Boggess, Terri; Morris, Ruth M; Ramirez, Amelie G

    2015-01-01

    Yoga-based exercise has proven to be beneficial for practitioners, including cancer survivors. This study reports on the improvements in physical fitness for 20 breast cancer survivors who participated in a six-month yoga-based exercise program (YE). Results are compared to a comprehensive exercise (CE) program group and a comparison (C) exercise group who chose their own exercises. "Pre" and "post" fitness assessments included measures of anthropometrics, cardiorespiratory capacity, strength and flexibility. Descriptive statistics, effect size (d), dependent sample 't' tests for all outcome measures were calculated for the YE group. Significant improvements included: decreased % body fat (-3.00%, d = -0.44, p < 0.001); increased sit to stand leg strength repetitions (2.05, d = 0.48, p = 0.003); forward reach (3.59 cm, d = 0.61, p = 0.01); and right arm sagittal range of motion (6.50°, d = 0.92, p = 0.05). To compare YE outcomes with the other two groups, a one-way analysis of variance (ANOVA) was used. YE participants significantly outperformed C participants on "forward reach" (3.59 cm gained versus -2.44 cm lost), (p = 0.009) and outperformed CE participants (3.59 cm gained versus 1.35 cm gained), but not statistically significant. Our results support yoga-based exercise modified for breast cancer survivors as safe and effective. PMID:26395825

  14. Pooled analysis indicates that the GSTT1 deletion, GSTM1 deletion, and GSTP1 Ile105Val polymorphisms do not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers

    PubMed Central

    Spurdle, Amanda B.; Fahey, Paul; Chen, Xiaoqing; McGuffog, Lesley; Easton, Douglas; Peock, Susan; Cook, Margaret; Simard, Jacques; Rebbeck, Tim R.; Antoniou, Antonis C.

    2011-01-01

    The GSTP1, GSTM1, and GSTT1 detoxification genes all have functional polymorphisms that are common in the general population. A single study of 320 BRCA1/2 carriers previously assessed their effect in BRCA1 or BRCA2 mutation carriers. This study showed no evidence for altered risk of breast cancer for individuals with the GSTT1 and GSTM1 deletion variants, but did report that the GSTP1 Ile105Val (rs1695) variant was associated with increased breast cancer risk in carriers. We investigated the association between these three GST polymorphisms and breast cancer risk using existing data from 718 women BRCA1 and BRCA2 mutation carriers from Australia, the UK, Canada, and the USA. Data were analyzed within a proportional hazards framework using Cox regression. There was no evidence to show that any of the polymorphisms modified disease risk for BRCA1 or BRCA2 carriers, and there was no evidence for heterogeneity between sites. These results support the need for replication studies to confirm or refute hypothesis-generating studies. PMID:19921428

  15. Characterizing Corrosion Effects of Weak Organic Acids Using a Modified Bono Test

    NASA Astrophysics Data System (ADS)

    Zhou, Yuqin; Turbini, Laura J.; Ramjattan, Deepchand; Christian, Bev; Pritzker, Mark

    2013-12-01

    To meet environmental requirements and achieve benefits of cost-effective manufacturing, no-clean fluxes (NCFs) or low-solids fluxes have become popular in present electronic manufacturing processes. Weak organic acids (WOAs) as the activation ingredients in NCFs play an important role, especially in the current lead-free and halogen-free soldering technology era. However, no standard or uniform method exists to characterize the corrosion effects of WOAs on actual metallic circuits of printed wiring boards (PWBs). Hence, the development of an effective quantitative test method for evaluating the corrosion effects of WOAs on the PWB's metallic circuits is imperative. In this paper, the modified Bono test, which was developed to quantitatively examine the corrosion properties of flux residues, is used to characterize the corrosion effects of five WOAs (i.e., abietic acid, succinic acid, glutaric acid, adipic acid, and malic acid) on PWB metallic circuits. Experiments were performed under three temperature/humidity conditions (85°C/85% RH, 60°C/93% RH, and 40°C/93% RH) using two WOA solution concentrations. The different corrosion effects among the various WOAs were best reflected in the testing results at 40°C and 60°C. Optical microscopy was used to observe the morphology of the corroded copper tracks, and scanning electron microscopy (SEM) energy-dispersive x-ray (EDX) characterization was performed to determine the dendrite composition.

  16. Modified Whole Effluent Toxicity Test to Assess and Decouple Wastewater Effects from Environmental Gradients

    PubMed Central

    Sauco, Sebastián; Gómez, Julio; Barboza, Francisco R.; Lercari, Diego; Defeo, Omar

    2013-01-01

    Environmental gradients and wastewater discharges produce aggregated effects on marine populations, obscuring the detection of human impact. Classical assessment methods do not include environmental effects in toxicity tests designs, which could lead to incorrect conclusions. We proposed a modified Whole Effluent Toxicity test (mWET) that includes environmental gradients in addition to effluent dilutions, together with the application of Generalized Linear Mixed Models (GLMM) to assess and decouple those effects. We tested this approach, analyzing the lethal effects of wastewater on a marine sandy beach bivalve affected by an artificial canal freshwater discharge used for rice crops irrigation. To this end, we compared bivalve mortality between canal water dilutions (CWd) and salinity controls (SC: without canal water). CWd were prepared by diluting the water effluent (sampled during the pesticide application period) with artificial marine water. The salinity gradient was included in the design by achieving the same final salinities in both CWd and SC, allowing us to account for the effects of salinity by including this variable as a random factor in the GLMM. Our approach detected significantly higher mortalities in CWd, indicating potential toxic effects of the effluent discharge. mWET represents an improvement over the internationally standardized WET tests, since it considers environmental variability and uses appropriate statistical analyses. PMID:23755304

  17. Antacid effects of Chinese herbal prescriptions assessed by a modified artificial stomach model

    PubMed Central

    Wu, Tsung-Hsiu; Chen, I-Chin; Chen, Lih-Chi

    2010-01-01

    AIM: To assess the antacid effects of the tonic Chinese herbal prescriptions, Si-Jun-Zi-Tang (SJZT) and Shen-Ling-Bai-Zhu-San (SLBZS). METHODS: Decoctions of the tonic Chinese herbal prescriptions, SJZT and SLBZS, were prepared according to Chinese original documents. The pH of the prescription decoctions and their neutralizing effects on artificial gastric acids were determined and compared with water and the active controls, sodium bicarbonate and colloidal aluminum phosphate. A modified model of Vatier’s artificial stomach was used to determine the duration of consistent neutralization effect on artificial gastric acids. The neutralization capacity in vitro was determined with the titration method of Fordtran’s model. RESULTS: The results showed that both SJZT and SLBZS have antacid effects in vitro. Compared with the water group, SJZT and SLBZS were found to possess significant gastric acid neutralizing effects. The duration for consistent neutralization of SLBZS was significantly longer than that of water. Also, SLBZS and SJZT exhibited significant antacid capacities compared to water. CONCLUSION: SJZT and SLBZS were consistently active in the artificial stomach model and are suggested to have antacid effects similar to the active control drugs. PMID:20845514

  18. Effects of modified multistage field test on performance and physiological responses in wheelchair basketball players.

    PubMed

    Weissland, Thierry; Faupin, Arnaud; Borel, Benoit; Berthoin, Serge; Leprêtre, Pierre-Marie

    2015-01-01

    A bioenergetical analysis of manoeuvrability and agility performance for wheelchair players is inexistent. It was aimed at comparing the physiological responses and performance obtained from the octagon multistage field test (MFT) and the modified condition in "8 form" (MFT-8). Sixteen trained wheelchair basketball players performed both tests in randomized condition. The levels performed (end-test score), peak values of oxygen uptake (VO2peak), minute ventilation (VEpeak), heart rate (HRpeak), peak and relative blood lactate (Δ[Lact(-)] = peak--rest values), and the perceived rating exertion (RPE) were measured. MFT-8 induced higher VO2peak and VEpeak values compared to MFT (VO2peak: 2.5 ± 0.6 versus 2.3 ± 0.6 L · min(-1) and VEpeak: 96.3 ± 29.1 versus 86.6 ± 23.4 L · min(-1); P < 0.05) with no difference in other parameters. Significant relations between VEpeak and end-test score were correlated for both field tests (P < 0.05). At exhaustion, MFT attained incompletely VO2peak and VEpeak. Among experienced wheelchair players, MFT-8 had no effect on test performance but generates higher physiological responses than MFT. It could be explained by demands of wheelchair skills occurring in 8 form during the modified condition. PMID:25802841

  19. An effective modified water extraction method for Landsat-8 OLI imagery of mountainous plateau regions

    NASA Astrophysics Data System (ADS)

    Gao, H.; Wang, L.; Jing, L.; Xu, J.

    2016-04-01

    Water body extraction from remote sensing imagery is an efficient way to investigate and monitor water resources. In the study area of this research, a mountainous plateau near Kashgar, China, sparse vegetation and seasonal rivers affect water body extraction. In order to extract water bodies, a modified water body extraction method is proposed in this paper and tested using Landsat-8 OLI imagery. Following this method, binary images are first generated using a classification, a Tasseled Cap transform, and a normalized difference water index, respectively, and then combined to yield a mask. Next, water bodies are delineated by masking the Landsat-8 OLI imagery and then refined by eliminating false areas using a supervised classification. It is demonstrated from the resulting water body maps that terrain related shadows in imagery were effectively eliminated and river tributaries and artificial ditches were precisely delineated, with accuracy up to 94%. Compared with several current water body extraction methods, the modified method yielded water body maps with better visualization and slightly improved accuracy.

  20. Void effect analysis of Pb-208 of fast reactors with modified CANDLE burn-up scheme

    NASA Astrophysics Data System (ADS)

    Widiawati, Nina; Su'ud, Zaki

    2015-09-01

    Void effect analysis of Pb-208 as coolant of fast reactors with modified candle burn-up scheme has been conducted. Lead cooled fast reactor (LFR) is one of the fourth-generation reactor designs. The reactor is designed with a thermal power output of 500 MWt. Modified CANDLE burn-up scheme allows the reactor to have long life operation by supplying only natural uranium as fuel cycle input. This scheme introducing discrete region, the fuel is initially put in region 1, after one cycle of 10 years of burn up it is shifted to region 2 and region 1 is filled by fresh natural uranium fuel. The reactor is designed for 100 years with 10 regions arranged axially. The results of neutronic calculation showed that the void coefficients ranged from -0.6695443 % at BOC to -0.5273626 % at EOC for 500 MWt reactor. The void coefficients of Pb-208 more negative than Pb-nat. The results showed that the reactors with Pb-208 coolant have better level of safety than Pb-nat.

  1. Effects of Modified Multistage Field Test on Performance and Physiological Responses in Wheelchair Basketball Players

    PubMed Central

    Weissland, Thierry; Faupin, Arnaud; Borel, Benoit; Berthoin, Serge; Leprêtre, Pierre-Marie

    2015-01-01

    A bioenergetical analysis of manoeuvrability and agility performance for wheelchair players is inexistent. It was aimed at comparing the physiological responses and performance obtained from the octagon multistage field test (MFT) and the modified condition in “8 form” (MFT-8). Sixteen trained wheelchair basketball players performed both tests in randomized condition. The levels performed (end-test score), peak values of oxygen uptake (VO2peak), minute ventilation (VEpeak), heart rate (HRpeak), peak and relative blood lactate (Δ[Lact−] = peak – rest values), and the perceived rating exertion (RPE) were measured. MFT-8 induced higher VO2peak and VEpeak values compared to MFT (VO2peak: 2.5 ± 0.6 versus 2.3 ± 0.6 L·min−1 and VEpeak: 96.3 ± 29.1 versus 86.6 ± 23.4 L·min−1; P < 0.05) with no difference in other parameters. Significant relations between VEpeak and end-test score were correlated for both field tests (P < 0.05). At exhaustion, MFT attained incompletely VO2peak and VEpeak. Among experienced wheelchair players, MFT-8 had no effect on test performance but generates higher physiological responses than MFT. It could be explained by demands of wheelchair skills occurring in 8 form during the modified condition. PMID:25802841

  2. Effect of prior cold work on creep properties of a titanium modified austenitic stainless steel

    NASA Astrophysics Data System (ADS)

    Vijayanand, V. D.; Parameswaran, P.; Nandagopal, M.; Panneer Selvi, S.; Laha, K.; Mathew, M. D.

    2013-07-01

    Prior cold worked (PCW) titanium-modified 14Cr-15Ni austenitic stainless steel (SS) is used as a core-structural material in fast breeder reactor because of its superior creep strength and resistance to void swelling. In this study, the influence of PCW in the range of 16-24% on creep properties of IFAC-1 SS, a titanium modified 14Cr-15Ni austenitic SS, at 923 K and 973 K has been investigated. It was found that PCW has no appreciable effect on the creep deformation rate of the steel at both the test temperatures; creep rupture life increased with PCW at 923 K and remained rather unaffected at 973 K. The dislocation structure along with precipitation in the PCW steel was found to change appreciably depending on creep testing conditions. A well-defined dislocation substructure was observed on creep testing at 923 K; a well-annealed microstructure with evidences of recrystallization was observed on creep testing at 973 K. Creep rupture life of the steel increased with the increase in PCW at 923 K. This has been attributed to the partial retention of prior cold work induced dislocations which facilitated the extensive precipitation of secondary Ti(C,N) particles on the stable dislocation substructure. Creep rupture life of the steel did not vary with PCW at 973 K due to softening by recrystallization and absence of secondary Ti(C,N).

  3. Void effect analysis of Pb-208 of fast reactors with modified CANDLE burn-up scheme

    SciTech Connect

    Widiawati, Nina Su’ud, Zaki

    2015-09-30

    Void effect analysis of Pb-208 as coolant of fast reactors with modified candle burn-up scheme has been conducted. Lead cooled fast reactor (LFR) is one of the fourth-generation reactor designs. The reactor is designed with a thermal power output of 500 MWt. Modified CANDLE burn-up scheme allows the reactor to have long life operation by supplying only natural uranium as fuel cycle input. This scheme introducing discrete region, the fuel is initially put in region 1, after one cycle of 10 years of burn up it is shifted to region 2 and region 1 is filled by fresh natural uranium fuel. The reactor is designed for 100 years with 10 regions arranged axially. The results of neutronic calculation showed that the void coefficients ranged from −0.6695443 % at BOC to −0.5273626 % at EOC for 500 MWt reactor. The void coefficients of Pb-208 more negative than Pb-nat. The results showed that the reactors with Pb-208 coolant have better level of safety than Pb-nat.

  4. Decreased expression of TLR7 in gastric cancer tissues and the effects of TLR7 activation on gastric cancer cells

    PubMed Central

    JIANG, JIONG; DONG, LEI; QIN, BIN; SHI, HAITAO; GUO, XIAOYAN; WANG, YAN

    2016-01-01

    The present study aimed to determine the expression of Toll-like receptor 7 (TLR7) in gastric cancer tissues and investigate the effects of its activation on gastric cancer cells. Patients with gastric cancer (n=30) and patients without gastric cancer (control; n=14) who underwent gastroscopy were enrolled in the study. Gastric cancer and cancer-adjacent tissues were obtained from the patients with gastric cancer, and normal gastric epithelial tissues were obtained from the control patients. The TLR7 mRNA and protein expressions in different tissues were investigated by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The present study also determined the effects of TLR7 activation by the agonist imiquimod on TLR7 protein expression, proinflammatory cytokine secretion and viability in SGC-7901 gastric cancer cells. The mRNA and protein expression levels of TLR7 were significantly downregulated in gastric cancer tissues compared with cancer-adjacent and normal gastric epithelial tissues (P<0.01). Imiquimod significantly increased TLR7 protein expression levels, and promoted the secretion of proinflammatory cytokines tumor necrosis factor-α and interleukin-6 in SGC-7901 cells. Furthermore, imiquimod inhibited the proliferation of SGC-7901 cells in a dose- and time-dependent manner. Thus, the present study identified that the expression of TLR7 was decreased in gastric cancer tissues, and TLR7 activation enhanced TLR7 expression, promoted the production of proinflammatory cytokines and inhibited the growth of gastric cancer cells. PMID:27347192

  5. Effectiveness of liposomal paclitaxel against MCF-7 breast cancer cells.

    PubMed

    Heney, Melanie; Alipour, Misagh; Vergidis, Dimitrios; Omri, Abdelwahab; Mugabe, Clement; Th'ng, John; Suntres, Zacharias

    2010-12-01

    Paclitaxel is an effective chemotherapeutic agent that is widely used for the treatment of several cancers, including breast, ovarian, and non-small-cell lung cancer. Due to its high lipophilicity, paclitaxel is difficult to administer and requires solubilization with Cremophor EL (polyethoxylated castor oil) and ethanol, which often lead to adverse side effects, including life-threatening anaphylaxis. Incorporation of paclitaxel in dimyristoylphosphatidylcholine:dimyristoylphosphatidylglycerol (DPPC:DMPG) liposomes can facilitate its delivery to cancer cells and eliminate the adverse reactions associated with the Cremophor EL vehicle. Accordingly, the effectiveness of liposomal paclitaxel on MCF-7 breast cancer cells was examined. The results from this study showed that (i) the lipid components of the liposomal formulation were nontoxic, (ii) the cytotoxic effects of liposomal paclitaxel were improved when compared with those seen with conventional paclitaxel, and (iii) the intracellular paclitaxel levels were higher in MCF-7 cells treated with the liposomal paclitaxel formulation. The results of these studies showed that delivery of paclitaxel as a liposomal formulation could be a promising strategy for enhancing its chemotherapeutic effects. PMID:21164564

  6. Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data

    PubMed Central

    Li, Donghui

    2014-01-01

    Cigarette smoking is the best established modifiable risk factor for pancreatic cancer. Genetic factors that underlie smoking-related pancreatic cancer have previously not been examined at the genome-wide level. Taking advantage of the existing Genome-wide association study (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study in 2028 cases and 2109 controls to examine gene–smoking interactions at pathway/gene/single nucleotide polymorphism (SNP) level. Using the likelihood ratio test nested in logistic regression models and ingenuity pathway analysis (IPA), we examined 172 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, 3 manually curated gene sets, 3 nicotine dependency gene ontology pathways, 17 912 genes and 468 114 SNPs. None of the individual pathway/gene/SNP showed significant interaction with smoking after adjusting for multiple comparisons. Six KEGG pathways showed nominal interactions (P < 0.05) with smoking, and the top two are the pancreatic secretion and salivary secretion pathways (major contributing genes: RAB8A, PLCB and CTRB1). Nine genes, i.e. ZBED2, EXO1, PSG2, SLC36A1, CLSTN1, MTHFSD, FAT2, IL10RB and ATXN2 had P interaction < 0.0005. Five intergenic region SNPs and two SNPs of the EVC and KCNIP4 genes had P interaction < 0.00003. In IPA analysis of genes with nominal interactions with smoking, axonal guidance signaling (P=2.12×10−7) and α-adrenergic signaling (P=2.52×10−5) genes were significantly overrepresented canonical pathways. Genes contributing to the axon guidance signaling pathway included the SLIT/ROBO signaling genes that were frequently altered in pancreatic cancer. These observations need to be confirmed in additional data set. Once confirmed, it will open a new avenue to unveiling the etiology of smoking-associated pancreatic cancer. PMID:24419231

  7. Histone deacetylase inhibitor-induced cell death in bladder cancer is associated with chromatin modification and modifying protein expression: A proteomic approach.

    PubMed

    Li, Qingdi Quentin; Hao, Jian-Jiang; Zhang, Zheng; Hsu, Iawen; Liu, Yi; Tao, Zhen; Lewi, Keidren; Metwalli, Adam R; Agarwal, Piyush K

    2016-06-01

    The Cancer Genome Atlas (TCGA) project recently identified the importance of mutations in chromatin remodeling genes in human carcinomas. These findings imply that epigenetic modulators might have a therapeutic role in urothelial cancers. To exploit histone deacetylases (HDACs) as targets for cancer therapy, we investigated the HDAC inhibitors (HDACIs) romidepsin, trichostatin A, and vorinostat as potential chemotherapeutic agents for bladder cancer. We demonstrate that the three HDACIs suppressed cell growth and induced cell death in the bladder cancer cell line 5637. To identify potential mechanisms associated with the anti-proliferative and cytotoxic effects of the HDACIs, we used quantitative proteomics to determine the proteins potentially involved in these processes. Our proteome studies identified a total of 6003 unique proteins. Of these, 2472 proteins were upregulated and 2049 proteins were downregulated in response to HDACI exposure compared to the untreated controls (P<0.05). Bioinformatic analysis further revealed that those differentially expressed proteins were involved in multiple biological functions and enzyme-regulated pathways, including cell cycle progression, apoptosis, autophagy, free radical generation and DNA damage repair. HDACIs also altered the acetylation status of histones and non-histone proteins, as well as the levels of chromatin modification proteins, suggesting that HDACIs exert multiple cytotoxic actions in bladder cancer cells by inhibiting HDAC activity or altering the structure of chromatin. We conclude that HDACIs are effective in the inhibition of cell proliferation and the induction of apoptosis in the 5637 bladder cancer cells through multiple cell death-associated pathways. These observations support the notion that HDACIs provide new therapeutic options for bladder cancer treatment and thus warrant further preclinical exploration. PMID:27082124

  8. Histone deacetylase inhibitor-induced cell death in bladder cancer is associated with chromatin modification and modifying protein expression: A proteomic approach

    PubMed Central

    LI, QINGDI QUENTIN; HAO, JIAN-JIANG; ZHANG, ZHENG; HSU, IAWEN; LIU, YI; TAO, ZHEN; LEWI, KEIDREN; METWALLI, ADAM R.; AGARWAL, PIYUSH K.

    2016-01-01

    The Cancer Genome Atlas (TCGA) project recently identified the importance of mutations in chromatin remodeling genes in human carcinomas. These findings imply that epigenetic modulators might have a therapeutic role in urothelial cancers. To exploit histone deacetylases (HDACs) as targets for cancer therapy, we investigated the HDAC inhibitors (HDACIs) romidepsin, trichostatin A, and vorinostat as potential chemotherapeutic agents for bladder cancer. We demonstrate that the three HDACIs suppressed cell growth and induced cell death in the bladder cancer cell line 5637. To identify potential mechanisms associated with the anti-proliferative and cytotoxic effects of the HDACIs, we used quantitative proteomics to determine the proteins potentially involved in these processes. Our proteome studies identified a total of 6003 unique proteins. Of these, 2472 proteins were upregulated and 2049 proteins were downregulated in response to HDACI exposure compared to the untreated controls (P<0.05). Bioinformatic analysis further revealed that those differentially expressed proteins were involved in multiple biological functions and enzyme-regulated pathways, including cell cycle progression, apoptosis, autophagy, free radical generation and DNA damage repair. HDACIs also altered the acetylation status of histones and non-histone proteins, as well as the levels of chromatin modification proteins, suggesting that HDACIs exert multiple cytotoxic actions in bladder cancer cells by inhibiting HDAC activity or altering the structure of chromatin. We conclude that HDACIs are effective in the inhibition of cell proliferation and the induction of apoptosis in the 5637 bladder cancer cells through multiple cell death-associated pathways. These observations support the notion that HDACIs provide new therapeutic options for bladder cancer treatment and thus warrant further preclinical exploration. PMID:27082124

  9. Effects of curcumin on cancer cell mitochondrial function and potential monitoring with ¹⁸F-FDG uptake.

    PubMed

    Jung, Kyung-Ho; Lee, Jin Hee; Park, Jin Won; Moon, Seung-Hwan; Cho, Young Seok; Choe, Yearn Seong; Lee, Kyung-Han

    2016-02-01

    A better understanding of how curcumin influences cancer cell biology could help devise new strategies to enhance its antitumor effect. Many curcumin actions are proposed to occur by targeting mitochondrial function, among which glucose metabolism and reactive oxygen species (ROS) production are pivotal. However, little is known of how curcumin influences cancer cell glucose metabolism. We thus evaluated the effect of curcumin on cancer cell glucose metabolism and mitochondrial function, and further investigated whether these responses could be modified to enhance the anticancer potency of the compound. MCF-7 breast cancer cells treated with curcumin were measured for 18F-fluorodeoxyglucose (18F‑FDG) uptake, lactate production, hexokinase activity, oxygen consumption rate (OCR), ROS production and mitochondrial membrane potential (MMP). Activation of signaling pathways was evaluated by western blots, and cell survival was assessed with sulforhodamine B assays. Curcumin stimulated a 3.6-fold increase of 18F-FDG uptake in MCF-7 cells, along with augmented hexokinase activity and lactate efflux. This was accompanied by significantly suppressed cellular OCR, consistent with a metabolic shift to glycolytic flux. Inhibiting this metabolic response with 2-deoxyglucose (2-DG) blocked curcumin-induced mTOR activation and resulted in a greater anti-proliferative effect. Curcumin-induced MMP depolarization led to reduced ROS production, which may hinder the anticancer effect of the compound. Intracellular ROS was completely restored by adding Cu2+, which can bind and modify the curcumin's physico-chemical property, and this resulted in a marked potentiation of its anti-proliferative effect. Thus, curcumin suppresses cancer cell MMP and ROS generation, and this response is accompanied by stimulated 18F-FDG uptake via shifting of metabolism from mitochondrial respiration to glycolytic flux. These mitochondrial and metabolic responses may provide potential targets that can

  10. Pipeline materials modify the effectiveness of disinfectants in drinking water distribution systems.

    PubMed

    Lehtola, Markku J; Miettinen, Ilkka T; Lampola, Tiia; Hirvonen, Arja; Vartiainen, Terttu; Martikainen, Pertti J

    2005-05-01

    We studied how pipe material can modify the effectiveness of UV- and chlorine disinfection in drinking water and biofilms. This study was done with two pipe materials: copper and composite plastic (polyethylene, PE) in a pilot scale water distribution network. UV-disinfection decreased viable bacterial numbers in the pilot waterworks and outlet water of pipes on average by 79%, but in biofilms its disinfecting effect was minor. Chlorine decreased effectively the microbial numbers in water and biofilms of PE pipes. In outlet water from copper pipes, the effect of chlorination was weaker; microbial numbers increased back to the level before chlorination within a few days. In the biofilms present in the copper pipes, chlorine decreased microbial numbers only in front of the pipeline. One reason for weaker efficiency of chlorine in copper pipes was that its concentration declined more rapidly in the copper pipes than in the PE pipes. These results means that copper pipes may require a higher chlorine dosage than plastic pipes to achieve effective disinfection of the pipes. PMID:15869778

  11. Wave action modifies the effects of consumer diversity and warming on algal assemblages.

    PubMed

    Mrowicki, Robert J; O'Connor, Nessa E

    2015-04-01

    To understand the consequences of biodiversity loss, it is necessary to test how biodiversity-ecosystem functioning relationships may vary with predicted environmental change. In particular, our understanding will be advanced by studies addressing the interactive effects of multiple stressors on the role of biodiversity across trophic levels. Predicted increases in wave disturbance and ocean warming, together with climate-driven range shifts of key consumer species, are likely to have profound impacts on the dynamics of coastal marine communities. We tested whether wave action and temperature modified the effects of gastropod grazer diversity (Patella vulgata, Littorina littorea, and Gibbula umbilicalis) on algal assemblages in experimental rock pools. The presence or absence of L. littorea appeared to drive changes in microalgal and macroalgal biomass and macroalgal assemblage structure. Macroalgal biomass also decreased with increasing grazer species richness, but only when wave action was enhanced. Further, independently of grazer diversity, wave action and temperature had interactive effects on macroalgal assemblage structure. Warming also led to a reversal of grazer-macroalgal interaction strengths from negative to positive, but only when there was no wave action. Our results show that hydrodynamic disturbance can exacerbate the effects of changing consumer diversity, and may also disrupt the influence of other environmental stressors on key consumer-resource interactions. These findings suggest that the combined effects of anticipated abiotic and biotic change on the functioning of coastal marine ecosystems, although difficult to predict, may be substantial. PMID:26230022

  12. The effectiveness of different approaches to media literacy in modifying adolescents' responses to alcohol.

    PubMed

    Chen, Yi-Chun Yvonnes

    2013-01-01

    Fearing the negative effect that alcohol advertising might have on adolescents' receptiveness to the consumption of alcohol, health educators have used media literacy as an effective strategy to mitigate the effect of these messages in the media. The present study applied parental mediation to the design and evaluations of a media literacy curriculum that targets alcohol decision-making processes illustrated in the message interpretation process model. The authors conducted a pretest-posttest quasi-experiment of 171 adolescents to examine the effect of a negative evaluative approach and a balanced evaluative approach (a combination of negative and positive evaluative strategies) to media literacy on modifying adolescents' responses to alcohol messages. Results showed that different media literacy approaches had varying degrees of effectiveness on adolescent boys and girls. After receiving a negative media literacy lesson, adolescent boys regarded television characters as less realistic and believed that drinking alcohol had negative consequences. In contrast, adolescent girls benefited more from a balanced evaluative approach as their media skepticism attitude was enhanced. Results suggest that health educators should choose tailored pedagogical approaches that are based on gender to improve decision making regarding alcohol consumption. PMID:23496333

  13. Differential Effects of Estradiol and Bisphenol A on SET8 and SIRT1 Expression in Ovarian Cancer Cells

    PubMed Central

    Hayes, Laura; Weening, Allison

    2016-01-01

    Exposure to estrogenic compounds has been shown to epigenetically reprogram the female reproductive tract and may contribute to ovarian cancer. The goal of this study was to compare the effect of estradiol or bisphenol A (BPA) on the expression of histone-modifying enzymes (HMEs) in ovarian cancer cells. Using 2 human ovarian cancer cell lines, we examined the expression of SET8, a histone methyltransferase, and SIRT1, a histone deacetylase, after exposure to estrogen or BPA. These experiments were carried out in complete media (fetal bovine serum) that contain natural hormones to understand the impact of additional exposure to estrogen or BPA on HME expression. We found differential expression of the HMEs in the different models examined and between the different compounds. Further, we determined that the changes in gene expression occurred via estrogen receptor signaling using the estrogen receptor antagonist, ICI 182,780 (fulvestrant). PMID:27114721

  14. Modeling cancer immunotherapy: Assessing the effects of lymphocytes on cancer cell growth and motility

    NASA Astrophysics Data System (ADS)

    Ramos, R. A.; Zapata, Jair; Condat, C. A.; Deisboeck, Thomas S.

    2013-05-01

    A mesoscopic model is used to describe the effects of lymphocyte activity on a growing tumor. The model yields novel insights into the tumor-immune system interaction. In particular, we found that the presence of a putative chemotactic messenger that helps guide the lymphocytes towards the tumor is not critical to elicit the anti-tumor effects of the immune system, while lymphocytes that block tumor cell migration contribute to limit cancer expansion and thus have a more significant therapeutic impact.

  15. Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells

    PubMed Central

    Mouhieddine, Tarek H.; Nokkari, Amaly; Itani, Muhieddine M.; Chamaa, Farah; Bahmad, Hisham; Monzer, Alissar; El-Merahbi, Rabih; Daoud, Georges; Eid, Assaad; Kobeissy, Firas H.; Abou-Kheir, Wassim

    2015-01-01

    Background: Gliomas and neuroblastomas pose a great health burden worldwide with a poor and moderate prognosis, respectively. Many studies have tried to find effective treatments for these primary malignant brain tumors. Of interest, the AMP-activated protein kinase (AMPK) pathway was found to be associated with tumorigenesis and tumor survival, leading to many studies on AMPK drugs, especially Metformin, and their potential role as anti-cancer treatments. Cancer stem cells (CSCs) are a small population of slowly-dividing, treatment-resistant, undifferentiated cancer cells that are being discovered in a multitude of cancers. They are thought to be responsible for replenishing the tumor with highly proliferative cells and increasing the risk of recurrence. Methods: Metformin and 9-β-d-Arabinofuranosyl Adenine (Ara-a) were used to study the role of the AMPK pathway in vitro on U251 (glioblastoma) and SH-SY5Y (neuroblastoma) cell lines. Results: We found that both drugs are able to decrease the survival of U251 and SH-SY5Y cell lines in a 2D as well as a 3D culture model. Metformin and Ara-a significantly decreased the invasive ability of these cancer cell lines. Treatment with these drugs decreased the sphere-forming units (SFU) of U251 cells, with Ara-a being more efficient, signifying the extinction of the CSC population. However, if treatment is withdrawn before all SFUs are extinguished, the CSCs regain some of their sphere-forming capabilities in the case of Metformin but not Ara-a treatment. Conclusion: Metformin and Ara-a have proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem/progenitor cell population, which prevents recurrence. PMID:26635517

  16. Effect of Modified Alkaline Supplementation on Syngenic Melanoma Growth in CB57/BL Mice

    PubMed Central

    Spugnini, Enrico Pierluigi; Canese, Rossella; Gugliotta, Alessio; Fidanza, Stefano; Fais, Stefano

    2016-01-01

    Tumor extracellular acidity is a hallmark of malignant cancers. Thus, in this study we evaluated the effects of the oral administration of a commercially available water alkalizer (Basenpulver®) (BP) on tumor growth in a syngenic melanoma mouse model. The alkalizer was administered daily by oral gavage starting one week after tumor implantation in CB57/BL mice. Tumors were calipered and their acidity measured by in vivo MRI guided 31P MRS. Furthermore, urine pH was monitored for potential metabolic alkalosis. BP administration significantly reduced melanoma growth in mice; the optimal dose in terms of tolerability and efficacy was 8 g/l (p< 0.05). The in vivo results were supported by in vitro experiments, wherein BP-treated human and murine melanoma cell cultures exhibited a dose-dependent inhibition of tumor cell growth. This investigation provides the first proof of concept that systemic buffering can improve tumor control by itself and that this approach may represent a new strategy in prevention and/or treatment of cancers. PMID:27447181

  17. Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs.

    PubMed

    Gissberg, Olof; Zaghloul, Eman M; Lundin, Karin E; Nguyen, Chi-Hung; Landras-Guetta, Corinne; Wengel, Jesper; Zain, Rula; Smith, C I Edvard

    2016-06-01

    AS1411 is a g-quadruplex-forming aptamer capable of selectively entering cancer cells by nucleolin receptor-mediated uptake. In this study, we investigated the cell internalization properties and plasticity of AS1411 carrying different locked nucleic acid-containing cargo oligonucleotides (ONs) for delivery into A549 and U2OS cells. We found that internalization efficiency is highly governed by ON cargo chemistry and composition since the inherent antitumor properties of AS1411 were lost when attached to a nontoxic ON, noTox. However, a toxic ON, Tox, demonstrated potent cytotoxicity after aptamer-mediated uptake in A549 cells. We also examined the effect of unlocked nucleic acid (UNA) modifications in the loop region of the aptamer, and how the cargo ONs and UNA incorporation affect the secondary structure of AS1411, in the presence or absence of two novel ellipticine derivatives. These findings add new insights to the design and future applications of aptamer-guided delivery of ON cargo to cancer cells. PMID:26859550

  18. Diverse effect of WWOX overexpression in HT29 and SW480 colon cancer cell lines.

    PubMed

    Nowakowska, Magdalena; Pospiech, Karolina; Lewandowska, Urszula; Piastowska-Ciesielska, Agnieszka W; Bednarek, Andrzej Kazimierz

    2014-09-01

    WW-domain-containing oxidoreductase (WWOX) is the tumour suppressor gene from the common fragile site FRA16D, whose altered expression has been observed in tumours of various origins. Its suppressive role and influence on basic cellular processes such as proliferation and apoptosis have been confirmed in many in vitro and in vivo studies. Moreover, its protein is thought to take part in the regulation of tissue morphogenesis and cell differentiation. However, its role in colon cancer formation remains unclear. The aim of this study was to characterize the influence of WWOX on the process of colon cancerogenesis, the basic features of the cancer cell and its expression profiles. Multiple biological tests, microarray experiments and quantitative reverse transcriptase (RT)-PCR were performed on two colon cancer cell lines, HT29 and SW480, which differ in morphology, expression of differentiation markers, migratory characteristics and metastasis potential and which represent negative (HT29) and low (SW480) WWOX expression levels. The cell lines were subjected to retroviral transfection, inducting WWOX overexpression. WWOX was found to have diverse effects on proliferation, apoptosis and the adhesion potential of modified cell lines. Our observations suggest that in the HT29 colon cancer cell line, increased expression of WWOX may result in the transition of cancer cells into a more normal colon epithelium phenotype, while in SW480, WWOX demonstrated well-known tumour suppressor properties. Our results also suggest that WWOX does not behave as classical tumour suppressor gene, and its influence on cell functioning is more global and complicated. PMID:24938873

  19. The Effect of Cancer on Suicide among Elderly Holocaust Survivors

    ERIC Educational Resources Information Center

    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…

  20. The Effect of Cancer Warning Statements on Alcohol Consumption Intentions

    ERIC Educational Resources Information Center

    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…

  1. EFFECT OF CIGARETTE SMOKING IN EPIDEMIOLOGICAL STUDIES OF LUNG CANCER

    EPA Science Inventory

    This paper describes a method for adjusting the analysis of occupational-environmental lung cancer risks for the effects of cigarette smoking in cohort and case control studies. he method uses a function that relates an individual's death rate to his age and cigarette smoking his...