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Sample records for cancer effects modified

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer

    PubMed Central

    Garcia-Closas, Montserrat; Rothman, Nathaniel; Figueroa, Jonine D.; Prokunina-Olsson, Ludmila; Han, Summer S.; Baris, Dalsu; Jacobs, Eric J; Malats, Nuria; De Vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P; Sharma, Sapna; Fu, Yi-Ping; Kogevinas, Manolis; Wang, Zhaoming; Tang, Wei; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R; Schned, Alan; Andriole, Gerald; Grubb, Robert; Black, Amanda; Gapstur, Susan M; Thun, Michael; Diver, W Ryan; Weinstein, Stephanie J; Virtamo, Jarmo; Hunter, David J; Caporaso, Neil; Landi, Maria Teresa; Hutchinson, Amy; Burdett, Laurie; Jacobs, Kevin B; Yeager, Meredith; Fraumeni, Joseph F; Chanock, Stephen J; Silverman, Debra T; Chatterjee, Nilanjan

    2013-01-01

    Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to evaluate the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually and combined as a polygenic risk score (PRS). Thirty-year absolute risks and risk differences by levels of the PRS were estimated for US-males aged 50-years. Six out of 12 variants showed significant additive gene-environment interactions, most notably NAT2 (P=7×10-4) and UGT1A6 (P=8×10-4). The 30-year absolute risk of bladder cancer in US males was 6.2% for all current smokers. This risk ranged from 2.9% for current smokers in the lowest quartile of the PRS to 9.9% for current smokers in the upper quartile. Risk difference estimates indicated that 8,200 cases would be prevented if elimination of smoking occurred in 100,000 men in the upper PRS quartile, compared to 2,000 cases prevented by a similar effort in the lowest PRS quartile (P-additive =1×10-4). The impact of eliminating smoking the on number of bladder cancer cases prevented is larger for individuals at higher than lower genetic risk. Our findings could have implications for targeted prevention strategies. However, other smoking-related diseases, as well as practical and ethical considerations, need to be considered before any recommendations could be made. PMID:23536561

  6. Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer.

    PubMed

    Garcia-Closas, Montserrat; Rothman, Nathaniel; Figueroa, Jonine D; Prokunina-Olsson, Ludmila; Han, Summer S; Baris, Dalsu; Jacobs, Eric J; Malats, Nuria; De Vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P; Sharma, Sapna; Fu, Yi-Ping; Kogevinas, Manolis; Wang, Zhaoming; Tang, Wei; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R; Schned, Alan; Andriole, Gerald; Grubb, Robert; Black, Amanda; Gapstur, Susan M; Thun, Michael; Diver, William Ryan; Weinstein, Stephanie J; Virtamo, Jarmo; Hunter, David J; Caporaso, Neil; Landi, Maria Teresa; Hutchinson, Amy; Burdett, Laurie; Jacobs, Kevin B; Yeager, Meredith; Fraumeni, Joseph F; Chanock, Stephen J; Silverman, Debra T; Chatterjee, Nilanjan

    2013-04-01

    Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to assess the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually and combined as a polygenic risk score (PRS). Thirty-year absolute risks and risk differences by levels of the PRS were estimated for U.S. males aged 50 years. Six of 12 variants showed significant additive gene-environment interactions, most notably NAT2 (P = 7 × 10(-4)) and UGT1A6 (P = 8 × 10(-4)). The 30-year absolute risk of bladder cancer in U.S. males was 6.2% for all current smokers. This risk ranged from 2.9% for current smokers in the lowest quartile of the PRS to 9.9% for current smokers in the upper quartile. Risk difference estimates indicated that 8,200 cases would be prevented if elimination of smoking occurred in 100,000 men in the upper PRS quartile compared with 2,000 cases prevented by a similar effort in the lowest PRS quartile (P(additive) = 1 × 10(-4)). Thus, the potential impact of eliminating smoking on the number of bladder cancer cases prevented is larger for individuals at higher than lower genetic risk. Our findings could have implications for targeted prevention strategies. However, other smoking-related diseases, as well as practical and ethical considerations, need to be considered before any recommendations could be made.

  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. Biological Response Modifier in Cancer Immunotherapy.

    PubMed

    Liu, Ronghua; Luo, Feifei; Liu, Xiaoming; Wang, Luman; Yang, Jiao; Deng, Yuting; Huang, Enyu; Qian, Jiawen; Lu, Zhou; Jiang, Xuechao; Zhang, Dan; Chu, Yiwei

    2016-01-01

    Biological response modifiers (BRMs) emerge as a lay of new compounds or approaches used in improving cancer immunotherapy. Evidences highlight that cytokines, Toll-like receptor (TLR) signaling, and noncoding RNAs are of crucial roles in modulating antitumor immune response and cancer-related chronic inflammation, and BRMs based on them have been explored. In particular, besides some cytokines like IFN-α and IL-2, several Toll-like receptor (TLR) agonists like BCG, MPL, and imiquimod are also licensed to be used in patients with several malignancies nowadays, and the first artificial small noncoding RNA (microRNA) mimic, MXR34, has entered phase I clinical study against liver cancer, implying their potential application in cancer therapy. According to amounts of original data, this chapter will review the regulatory roles of TLR signaling, some noncoding RNAs, and several key cytokines in cancer and cancer-related immune response, as well as the clinical cases in cancer therapy based on them.

  9. Biologic response modifiers in pediatric cancer.

    PubMed

    Worth, L L; Jeha, S S; Kleinerman, E S

    2001-08-01

    Biologic response modifiers are becoming an important addition to surgery, chemotherapy, and radiotherapy in the management of cancer. As this field of research grows and expands, more biologic response modifiers will be incorporated into therapeutic regimens. By stimulating the immune system to eradicate minimal residual disease, these agents may improve the disease-free and long-term survival rates of patients with a variety of malignancies. The challenge is to incorporate biologic response modifiers into the treatment armamentarium in ways that will maximize their tumorigenicity.

  10. Modifiable and non-modifiable risk factors for pancreatic cancer: A review.

    PubMed

    Midha, Shallu; Chawla, Saurabh; Garg, Pramod Kumar

    2016-10-10

    Pancreatic ductal adenocarcinoma is associated with a poor prognosis and a high case-fatality rate. The reasons for poor prognosis are low rates of curative resection due to local infiltration and distant metastasis. To increase survival rates of patients with pancreatic cancer, early detection through surveillance and screening is important. However, screening could only be cost-effective in high-risk populations. Identification of significant risk factors therefore assumes significance. Risk factors could be non-modifiable or modifiable. Non-modifiable risk factors include increasing age, familial cancer syndromes, Afro-American race, hereditary and other forms of chronic pancreatitis, diabetes, and non-O blood group. Important modifiable risk factors include smoking, obesity, dietary factors such as non-vegetarian diet, and toxins. Preventive strategies at the population level and an effective screening program targeted at high-risk people may help in prevention and early detection of pancreatic ductal adenocarcinoma. PMID:27461582

  11. Magnetic-composite-modified polycrystalline silicon nanowire field-effect transistor for vascular endothelial growth factor detection and cancer diagnosis.

    PubMed

    Chen, Hsiao-Chien; Qiu, Jian-Tai; Yang, Fu-Liang; Liu, Yin-Chih; Chen, Min-Cheng; Tsai, Rung-Ywan; Yang, Hung-Wei; Lin, Chia-Yi; Lin, Chu-Chi; Wu, Tzong-Shoon; Tu, Yi-Ming; Xiao, Min-Cong; Ho, Chia-Hua; Huang, Chien-Chao; Lai, Chao-Sung; Hua, Mu-Yi

    2014-10-01

    This study proposes a vascular endothelial growth factor (VEGF) biosensor for diagnosing various stages of cervical carcinoma. In addition, VEGF concentrations at various stages of cancer therapy are determined and compared to data obtained by computed tomography (CT) and cancer antigen 125 (CA-125). The increase in VEGF concentrations during operations offers useful insight into dosage timing during cancer therapy. This biosensor uses Avastin as the biorecognition element for the potential cancer biomarker VEGF and is based on a n-type polycrystalline silicon nanowire field-effect transistor (poly-SiNW-FET). Magnetic nanoparticles with poly[aniline-co-N-(1-one-butyric acid) aniline]-Fe3O4 (SPAnH-Fe3O4) shell-core structures are used as carriers for Avastin loading and provide rapid purification due to their magnetic properties, which prevent the loss of bioactivity; furthermore, the high surface area of these structures increases the quantity of Avastin immobilized. Average concentrations in human blood for species that interfere with detection specificity are also evaluated. The detection range of the biosensor for serum samples covers the results expected from both healthy individuals and cancer patients.

  12. Octa-Arginine-Modified Pegylated Liposomal Doxorubicin: An Effective Treatment Strategy for Non-Small Cell Lung Cancer

    PubMed Central

    Biswas, Swati; Deshpande, Pranali P.; Perche, Federico; Dodwadkar, Namita S.; Sane, Shailendra D.; Torchilin, Vladimir P.

    2013-01-01

    The present study aims to evaluate the efficacy of octa-arginine (R8)-modified PEGylated liposomal doxorubicin (R8-PLD) for the treatment of non-small cell lung cancer, for which the primary treatment modality currently consists of surgery and radiotherapy. Cell-penetrating peptide R8 modification of Doxorubicin-(Dox)-loaded liposomes was performed by post-insertion of an R8-conjugated amphiphilic PEG-PE copolymer (R8-PEG-DOPE) into the liposomal lipid bilayer. In vitro analysis with the non-small cell lung cancer cell line, A549 confirmed the efficient cellular accumulation of Dox, delivered by R8-PLD compared to PLD. It led to the early initiation of apoptosis and a 9-fold higher level of the apoptotic regulator, caspase 3/7 (9.24±0.34) compared to PLD (1.07±0.19) at Dox concentration of 100 µg/mL. The treatment of A549 monolayers with R8-PLD increased the level of cell death marker lactate dehydrogenase (LDH) secretion (1.2 ± 0.1 for PLD and 2.3 ± 0.1 for R8-PLD at Dox concentration of 100 µg/mL) confirming higher cytotoxicity of R8-PLD than PLD, which was ineffective under the same treatment regimen (cell viability 90 ± 6 % in PLD vs. 45 ± 2 % in R8-PLD after 24 h). R8-PLD had significantly higher penetration into the hypoxic A549 tumor spheroids compared to PLD. R8-PLD induced greater level of apoptosis to A549 tumor xenograft and dramatic inhibition of tumor volume and tumor weight reduction. The R8-PLD treated tumor lysate had a elevated caspase3/7 expression than with R8-PLD treatment. This suggested system improved the delivery efficiency of Dox in selected model of cancer which supports the potential usefulness of R8-PLD in cancer treatment, lung cancer in particular. PMID:23419527

  13. Octa-arginine-modified pegylated liposomal doxorubicin: an effective treatment strategy for non-small cell lung cancer.

    PubMed

    Biswas, Swati; Deshpande, Pranali P; Perche, Federico; Dodwadkar, Namita S; Sane, Shailendra D; Torchilin, Vladimir P

    2013-07-10

    The present study aims to evaluate the efficacy of octa-arginine (R8)-modified pegylated liposomal doxorubicin (R8-PLD) for the treatment of non-small cell lung cancer, for which the primary treatment modality currently consists of surgery and radiotherapy. Cell-penetrating peptide R8 modification of Doxorubicin-(Dox)-loaded liposomes was performed by post-insertion of an R8-conjugated amphiphilic PEG-PE copolymer (R8-PEG-DOPE) into the liposomal lipid bilayer. In vitro analysis with the non-small cell lung cancer cell line, A549 confirmed the efficient cellular accumulation of Dox, delivered by R8-PLD compared to PLD. It led to the early initiation of apoptosis and a 9-fold higher level of the apoptotic regulator, caspase 3/7 (9.24±0.34) compared to PLD (1.07±0.19) at Dox concentration of 100 μg/mL. The treatment of A549 monolayers with R8-PLD increased the level of cell death marker lactate dehydrogenase (LDH) secretion (1.2±0.1 for PLD and 2.3±0.1 for R8-PLD at Dox concentration of 100 μg/mL) confirming higher cytotoxicity of R8-PLD than PLD, which was ineffective under the same treatment regimen (cell viability 90±6% in PLD vs. 45±2% in R8-PLD after 24h). R8-PLD had significantly higher penetration into the hypoxic A549 tumor spheroids compared to PLD. R8-PLD induced greater level of apoptosis to A549 tumor xenograft and dramatic inhibition of tumor volume and tumor weight reduction. The R8-PLD treated tumor lysate had a elevated caspase 3/7 expression than with R8-PLD treatment. This suggested system improved the delivery efficiency of Dox in selected model of cancer which supports the potential usefulness of R8-PLD in cancer treatment, lung cancer in particular. PMID:23419527

  14. 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

  15. Chromatin-modifying agents in anti-cancer therapy.

    PubMed

    Seidel, Carole; Florean, Cristina; Schnekenburger, Michael; Dicato, Mario; Diederich, Marc

    2012-11-01

    Epigenetic alterations are involved in every step of carcinogenesis. The development of chromatin-modifying agents (CMAs) has provided the ability to fight cancer by reversing these alterations. Currently, four CMAs have been approved for cancer treatment; two DNA demethylating agents and two deacetylase inhibitors. A number of promising CMAs are undergoing clinical trials in several cancer types. Moreover, already approved CMAs are still under clinical investigation to improve their efficacy and to extend their use to a broader panel of cancers. Combinatorial treatments with CMAs are already considered a promising strategy to improve clinical benefits and to limit side effects. The real mechanisms by which these CMAs allow the improvement and remission of patients are still obscure. A deeper analysis of the molecular features expressed by responding patients should be performed to reveal this information. In this review, we focus on clinical trials with CMAs, discussing the success and the pitfalls of this new class of anti-cancer drugs.

  16. 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

  17. 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

  18. 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

  19. 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…

  20. 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

  1. 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

  2. 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).

  3. 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

  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. 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…

  6. 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.

  7. A sensitive and selective magnetic graphene composite-modified polycrystalline-silicon nanowire field-effect transistor for bladder cancer diagnosis.

    PubMed

    Chen, Hsiao-Chien; Chen, Yi-Ting; Tsai, Rung-Ywan; Chen, Min-Cheng; Chen, Shi-Liang; Xiao, Min-Cong; Chen, Chien-Lun; Hua, Mu-Yi

    2015-04-15

    In this study, we describe the urinary quantification of apolipoprotein A II protein (APOA2 protein), a biomarker for the diagnosis of bladder cancer, using an n-type polycrystalline silicon nanowire field-effect transistor (poly-SiNW-FET). The modification of poly-SiNW-FET by magnetic graphene with long-chain acid groups (MGLA) synthesized via Friedel-Crafts acylation was compared with that obtained using short-chain acid groups (MGSA). Compared with MGSA, the MGLA showed a higher immobilization degree and bioactivity to the anti-APOA2 antibody (Ab) due to its lower steric hindrance. In addition, the magnetic properties enabled rapid separation and purification during Ab immobilization, ultimately preserving its bioactivity. The Ab-MGLA/poly-SiNW-FET exhibited a linear dependence of relative response to the logarithmical concentration in a range between 19.5pgmL(-1) and 1.95µgmL(-1), with a limit of detection (LOD) of 6.7pgmL(-1). An additional washing step before measurement aimed at excluding the interfering biocomponents ensured the reliability of the assay. We conclude that our biosensor efficiently distinguishes mean values of urinary APOA2 protein concentrations between patients with bladder cancer (29-344ngmL(-1)) and those with hernia (0.425-9.47ngmL(-1)).

  8. 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

  9. Impact of modifiable lifestyle factors on outcomes after breast cancer diagnosis: the Setouchi Breast Cancer Cohort Study.

    PubMed

    Taira, Naruto; Akiyama, Ichiro; Ishihara, Setsuko; Ishibe, Youichi; Kawasaki, Kensuke; Saito, Makoto; Shien, Tadahiko; Nomura, Tsunehisa; Hara, Fumikata; Mizoo, Taeko; Mizota, Yuri; Yamamoto, Seiichiro; Ohsumi, Shozo; Doihara, Hiroyoshi

    2015-06-01

    The primary purpose of this large cohort study is to investigate the effects on breast cancer outcomes of modifiable lifestyle factors after breast cancer diagnosis. These factors include physical activity, smoking, alcohol consumption, obesity and weight gain after diagnosis, alternative medicine and dietary factors. Women diagnosed with Stage 0 to III breast cancer are eligible for participation to this study. Lifestyle, use of alternative medicine, psychosocial factors, reproductive factors and health-related quality of life will be assessed using a questionnaire at the time of breast cancer diagnosis (baseline), and 1, 2, 3 and 5 years after diagnosis. Clinical information and breast cancer outcomes will be obtained from a breast cancer database. The primary endpoint will be disease-free survival. Secondary endpoints are overall survival, health-related quality of life, breast cancer-related symptoms and adverse events. Patient recruitment commenced in February 2013. Enrollment of 2000 breast cancer patients is planned during the 5-year recruitment period. The concept of the study is described in this article.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. Hyaluronic acid-modified multiwalled carbon nanotubes for targeted delivery of doxorubicin into cancer cells.

    PubMed

    Cao, Xueyan; Tao, Lei; Wen, Shihui; Hou, Wenxiu; Shi, Xiangyang

    2015-03-20

    Development of novel drug carriers for targeted cancer therapy with high efficiency and specificity is of paramount importance and has been one of the major topics in current nanomedicine. Here we report a general approach to using multifunctional multiwalled carbon nanotubes (MWCNTs) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for targeted cancer therapy. In this approach, polyethyleneimine (PEI)-modified MWCNTs were covalently conjugated with fluorescein isothiocyanate (FI) and hyaluronic acid (HA). The formed MWCNT/PEI-FI-HA conjugates were characterized via different techniques and were used as a new carrier system to encapsulate the anticancer drug doxorubicin for targeted delivery to cancer cells overexpressing CD44 receptors. We show that the formed MWCNT/PEI-FI-HA/DOX complexes with a drug loading percentage of 72% are water soluble and stable. In vitro release studies show that the drug release rate under an acidic condition (pH 5.8, tumor cell microenvironment) is higher than that under physiological condition (pH 7.4). Cell viability assay demonstrates that the carrier material has good biocompatibility in the tested concentration range, and the MWCNT/PEI-FI-HA/DOX complexes can specifically target cancer cells overexpressing CD44 receptors and exert growth inhibition effect to the cancer cells. The developed HA-modified MWCNTs hold a great promise to be used as an efficient anticancer drug carrier for tumor-targeted chemotherapy.

  18. 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.

  19. 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…

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Genome-wide DNA methylation modified by soy phytoestrogens: role for epigenetic therapeutics in prostate cancer?

    PubMed

    Karsli-Ceppioglu, Seher; Ngollo, Marjolaine; Adjakly, Mawussi; Dagdemir, Aslihan; Judes, Gaëlle; Lebert, André; Boiteux, Jean-Paul; Penault-LLorca, Frédérique; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

    2015-04-01

    In prostate cancer, DNA methylation is significantly associated with tumor initiation, progression, and metastasis. Previous studies have suggested that soy phytoestrogens might regulate DNA methylation at individual candidate gene loci and that they play a crucial role as potential therapeutic agents for prostate cancer. The purpose of our study was to examine the modulation effects of phytoestrogens on a genome-wide scale in regards to DNA methylation in prostate cancer. Prostate cancer cell lines DU-145 and LNCaP were treated with 40 μM of genistein and 110 μM of daidzein. DNMT inhibitor 5-azacytidine (2 μM) and the methylating agent budesonide (2 μM) were used to compare their demethylation/methylation effects with phytoestrogens. The regulatory effects of phytoestrogens on DNA methylation were analyzed by using a methyl-DNA immunoprecipitation method coupled with Human DNA Methylation Microarrays (MeDIP-chip). We observed that the methylation profiles of 58 genes were altered by genistein and daidzein treatments in DU-145 and LNCaP prostate cancer cells. In addition, the methylation frequencies of the MAD1L1, TRAF7, KDM4B, and hTERT genes were remarkably modified by genistein treatment. Our results suggest that the modulation effects of phytoestrogens on DNA methylation essentially lead to inhibition of cell growth and induction of apoptosis. Genome-wide methylation profiling reported here suggests that epigenetic regulation mechanisms and, by extension, epigenetics-driven novel therapeutic candidates warrant further consideration in future "omics" studies of prostate cancer.

  5. Transferrin surface-modified PLGA nanoparticles-mediated delivery of a proteasome inhibitor to human pancreatic cancer cells.

    PubMed

    Frasco, Manuela F; Almeida, Gabriela M; Santos-Silva, Filipe; Pereira, Maria do Carmo; Coelho, Manuel A N

    2015-04-01

    The aim of this study was to develop a drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles for an efficient and targeted action of the proteasome inhibitor bortezomib against pancreatic cancer cells. The PLGA nanoparticles were formulated with a poloxamer, and further surface-modified with transferrin for tumor targeting. The nanoparticles were characterized as polymer carriers of bortezomib, and the cellular uptake and growth inhibitory effects were evaluated in pancreatic cells. Cellular internalization of nanoparticles was observed in normal and cancer cells, but with higher uptake by cancer cells. The sustained release of the loaded bortezomib from PLGA nanoparticles showed cytotoxic effects against pancreatic normal and cancer cells. Noteworthy differential cytotoxicity was attained by transferrin surface-modified PLGA nanoparticles since significant cell growth inhibition by delivered bortezomib was only observed in cancer cells. These findings demonstrate that the ligand transferrin enhanced the targeted delivery of bortezomib-loaded PLGA nanoparticles to pancreatic cancer cells. These in vitro results highlight the transferrin surface-modified PLGA nanoparticles as a promising system for targeted delivery of anticancer drugs. PMID:25046528

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

    SciTech Connect

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

    1995-03-01

    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. 24 refs., 3 figs., 4 tabs.

  7. 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

  8. 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...

  9. Care of the cancer survivor: metabolic syndrome after hormone-modifying therapy.

    PubMed

    Redig, Amanda J; Munshi, Hidayatullah G

    2010-01-01

    Emerging evidence implicates metabolic syndrome as a long-term cancer risk factor but also suggests that certain cancer therapies might increase patients' risk of developing metabolic syndrome secondary to cancer therapy. In particular, breast cancer and prostate cancer are driven in part by sex hormones; thus, treatment for both diseases is often based on hormone-modifying therapy. Androgen suppression therapy in men with prostate cancer is associated with dyslipidemia, increasing risk of cardiovascular disease, and insulin resistance. Anti-estrogen therapy in women with breast cancer can affect lipid profiles, cardiovascular risk, and liver function. As the number of cancer survivors continues to grow, treating physicians must be aware of the potential risks facing patients who have been treated with either androgen suppression therapy or anti-estrogen therapy so that early diagnosis and intervention can be achieved.

  10. 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

  11. Endoscopic optical coherence tomography with a modified microelectromechanical systems mirror for detection of bladder cancers

    NASA Astrophysics Data System (ADS)

    Xie, Tuqiang; Xie, Huikai; Fedder, Gary K.; Pan, Yingtian

    2003-11-01

    Experimental results of a modified micromachined microelectromechanical systems (MEMS) mirror for substantial enhancement of the transverse laser scanning performance of endoscopic optical coherence tomography (EOCT) are presented. Image distortion due to buckling of MEMS mirror in our previous designs was analyzed and found to be attributed to excessive internal stress of the transverse bimorph meshes. The modified MEMS mirror completely eliminates bimorph stress and the resultant buckling effect, which increases the wobbling-free angular optical actuation to greater than 37°, exceeding the transverse laser scanning requirements for EOCT and confocal endoscopy. The new optical coherence tomography (OCT) endoscope allows for two-dimensional cross-sectional imaging that covers an area of 4.2 mm × 2.8 mm (limited by scope size) and at roughly 5 frames/s instead of the previous area size of 2.9 mm × 2.8 mm and is highly suitable for noninvasive and high-resolution imaging diagnosis of epithelial lesions in vivo. EOCT images of normal rat bladders and rat bladder cancers are compared with the same cross sections acquired with conventional bench-top OCT. The results clearly demonstrate the potential of EOCT for in vivo imaging diagnosis and precise guidance for excisional biopsy of early bladder cancers.

  12. 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

  13. 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

  14. A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer

    PubMed Central

    Kershaw, Michael H.; Westwood, Jennifer A.; Parker, Linda L.; Wang, Gang; Eshhar, Zelig; Mavroukakis, Sharon A.; White, Donald E.; Wunderlich, John R.; Canevari, Silvana; Rogers-Freezer, Linda; Chen, Clara C.; Yang, James C.; Rosenberg, Steven A.; Hwu, Patrick

    2007-01-01

    Purpose A phase I study was conducted to assess the safety of adoptive immunotherapy using gene-modified autologous T cells for the treatment of metastatic ovarian cancer. Experimental Design T cells with reactivity against the ovarian cancer – associated antigen α-folate receptor (FR) were generated by genetic modification of autologous T cells with a chimeric gene incorporating an anti-FR single-chain antibody linked to the signaling domain of the Fc receptor γ chain. Patients were assigned to one of two cohorts in the study. Eight patients in cohort 1received a dose escalation of T cells in combination with high-dose interleukin-2, and six patients in cohort 2 received dual-specific T cells (reactive with both FR and allogeneic cells) followed by immunization with allogeneic peripheral blood mononuclear cells. Results Five patients in cohort 1 experienced some grade 3 to 4 treatment-related toxicity that was probably due to interleukin-2 administration, which could be managed using standard measures. Patients in cohort 2 experienced relatively mild side effects with grade 1to 2 symptoms. No reduction in tumor burden was seen in any patient. Tracking 111In-labeled adoptively transferred T cells in cohort 1revealed a lack of specific localization of T cells to tumor except in one patient where some signal was detected in a peritoneal deposit. PCR analysis showed that gene-modified T cells were present in the circulation in large numbers for the first 2 days after transfer, but these quickly declined to be barely detectable 1month later in most patients. An inhibitory factor developed in the serum of three of six patients tested over the period of treatment, which significantly reduced the ability of gene-modified T cells to respond against FR+ tumor cells. Conclusions Large numbers of gene-modified tumor-reactive T cells can be safely given to patients, but these cells do not persist in large numbers long term. Future studies need to employ strategies to

  15. Elimination of progressive mammary cancer by repeated administrations of chimeric antigen receptor-modified T cells.

    PubMed

    Globerson-Levin, Anat; Waks, Tova; Eshhar, Zelig

    2014-05-01

    Continuous oncogenic processes that generate cancer require an on-going treatment approach to eliminate the transformed cells, and prevent their further development. Here, we studied the ability of T cells expressing a chimeric antibody-based receptor (CAR) to offer a therapeutic benefit for breast cancer induced by erbB-2. We tested CAR-modified T cells (T-bodies) specific to erbB-2 for their antitumor potential in a mouse model overexpressing a human erbB-2 transgene that develops mammary tumors. Comparing the antitumor reactivity of CAR-modified T cells under various therapeutic settings, either prophylactic, prior to tumor development, or therapeutically. We found that repeated administration of CAR-modified T cells is required to eliminate spontaneously developing mammary cancer. Systemic, as well as intratumoral administered CAR-modified T cells accumulated at tumor sites and eventually eliminated the malignant cells. Interestingly, within a few weeks after a single CAR T cells' administration, and rejection of primary lesion, tumors usually relapsed both in treated mammary gland and at remote sites; however, repeated injections of CAR-modified T cells were able to control the secondary tumors. Since spontaneous tumors can arise repeatedly, especially in the case of syndromes characterized by specific susceptibility to cancer, multiple administrations of CAR-modified T cells can serve to control relapsing disease.

  16. Classification of lung cancer patients and controls by chromatography of modified nucleosides in serum

    USGS Publications Warehouse

    McEntire, John E.; Kuo, Kenneth C.; Smith, Mark E.; Stalling, David L.; Richens, Jack W.; Zumwalt, Robert W.; Gehrke, Charles W.; Papermaster, Ben W.

    1989-01-01

    A wide spectrum of modified nucleosides has been quantified by high-performance liquid chromatography in serum of 49 male lung cancer patients, 35 patients with other cancers, and 48 patients hospitalized for nonneoplastic diseases. Data for 29 modified nucleoside peaks were normalized to an internal standard and analyzed by discriminant analysis and stepwise discriminant analysis. A model based on peaks selected by a stepwise discriminant procedure correctly classified 79% of the cancer and 75% of the noncancer subjects. It also demonstrated 84% sensitivity and 79% specificity when comparing lung cancer to noncancer subjects, and 80% sensitivity and 55% specificity in comparing lung cancer to other cancers. The nucleoside peaks having the greatest influence on the models varied dependent on the subgroups compared, confirming the importance of quantifying a wide array of nucleosides. These data support and expand previous studies which reported the utility of measuring modified nucleoside levels in serum and show that precise measurement of an array of 29 modified nucleosides in serum by high-performance liquid chromatography with UV scanning with subsequent data modeling may provide a clinically useful approach to patient classification in diagnosis and subsequent therapeutic monitoring.

  17. Modified recalcification time (MRT): a sensitive cancer test? Review of the evidence.

    PubMed Central

    Spillert, C. R.; Lazaro, E. J.

    1995-01-01

    In the past, hypercoagulability causing cancer-related thrombosis (Trousseau phenomenon) remained unproven for lack of an appropriate coagulation test. This review proves that a modified recalcification time (MRT) test can detect cancer-related hypercoagulability. The hallmark of this test involves incorporating tissue factor (TF) in accurately assessing coagulability. Blood from controls and cancer patients was incubated with saline and endotoxin (to enhance clotting ability by monocyte-generated TF). The MRT with saline incubation (MRTS) and the MRT with endotoxin incubation (MRTE) were determined instrumentally. The MRTE is a more inclusive measure of total TF activity than the MRTS in nonadvanced cancer. The MRTE values (minutes +/- standard deviation) were: controls-5.69 +/- 0.8; miscellaneous cancers-3.17 +/- 1.1; head, neck, and colon cancers-3.9 +/- 0.6; breast cancers-3.6 +/- 0.6; gynecological cancers-4.1 +/- 0.9; and prostate cancers-3.4 +/- 1.1. The MRTE, by demonstrating hypercoagulability in nonadvanced (including occult) cancer, qualifies as a more sensitive marker for cancer than the Trousseau phenomenon. The data suggest that this test may be the most sensitive blood test to detect early cancer. PMID:9583965

  18. 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

  19. 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.

  20. 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

  1. 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

  2. Development of a folate-modified curcumin loaded micelle delivery system for cancer targeting.

    PubMed

    Yang, Chunfen; Chen, Hao; Zhao, Jie; Pang, Xin; Xi, Yanwei; Zhai, Guangxi

    2014-09-01

    Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, the encapsulating efficiency and drug-loading were 80.73±0.16% and 4.84±0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur.

  3. Gender effects in familial cancer.

    PubMed

    Hemminki, Kari; Li, Xinjun

    2002-11-10

    Very limited data are available on sex ratios in familial cancer. Such data would be valuable in the assessment of sex chromosome effects and of interactions between background and familial rates. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and over 1 million neoplasms to analyze familial risks for male and female offspring by paternal and maternal concordant cancer. Sex ratios for familial cancer were derived for cancer at 15 sites shared by men and women. At 14 sites the sex ratio (male/female) for familial relative risk ranged between 0.78 and 1.41, with no evidence of sex preference, suggesting that sex chromosomes do not contribute to a noticeable extent to familial risks. Furthermore, in cancers where the background incidence varied extensively by sex, such as bladder cancer (sex ratio 2.82) and nonthyroid endocrine tumors (0.65), the familial effect was proportionate to the background incidence and the familial sex ratio was close to unity. In thyroid cancer, the familial sex ratio was 2.48 (1.54-3.98) and the background incidence ratio was 0.31. This was the first evidence of an inverse sex ratio in primary cancer, i.e., higher familial risk in the gender of low background risk. The high familial ratio, 2.85 (95% CI: 1.35-6.03), was due to thyroid adenocarcinoma, encompassing both papillary and follicular types.

  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. 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

  6. 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.

  7. SLC gene-modified dendritic cells mediate T cell-dependent anti-gastric cancer immune responses in vitro.

    PubMed

    Xue, Gang; Cheng, Ying; Ran, Feng; Li, Xianhui; Huang, Tao; Yang, Yong; Zhang, Yanbiao

    2013-02-01

    Dendritic cells (DCs) are potent professional antigen-presenting cells (APCs) with the ability to prime naïve T cells, and play an important role in the initiation and regulation of immune responses. In this study, we constructed a recombinant adenovirus carrying the SLC gene (Ad-SLC), and detected the biological effects of Ad-SLC-modified DCs as an adjuvant for the initiation of gastric cancer immune responses. Human DCs were transfected with Ad-SLC and the recombinant adenovirus carrying the β-galactosidase gene, Ad-LacZ, respectively. Modified DCs were pulsed with the cell lysate antigen of SGC-7901 cells (a type of gastric cancer cell line) and co-cultured with autologous T cells. The T cells were harvested and incubated with SGC-7901 cells and the cytotoxic function of the T cells was detected. Based on the data, the expression of mature DC phenotypes CD83 and CCR7 was upregulated after transfection with Ad-SLC and the chemotaxis function of DCs was augmented after transfection with Ad-SLC. Moreover, the expression of RANTES in DCs was upregulated by Ad-SLC transfection, while expression levels of IL-12p70 and IL-10 were not significantly altered. When co-cultured with autologous T cells, DCs modified with the SLC gene and pulsed with SGC-7901 cell lysates significantly promoted the proliferation of autologous T cells and induced Th1 differentiation, and displayed a strong cytotoxicity to SGC-7901 cells. In conclusion, Ad-SLC promoted DC maturation, enhancing the ability of DCs for T-cell chemotaxis and T-cell stimulation, and induced specific anti-gastric cancer cellular immunity. Recombinant Ad-SLC-modified DCs may be used as an adjuvant to induce an effective anti-gastric cancer immune response.

  8. Gene-modified hematopoietic stem cells for cancer immunotherapy.

    PubMed

    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.

  9. 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.

  10. 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...

  11. 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

  12. Potential adverse health effects of genetically modified crops.

    PubMed

    Bakshi, Anita

    2003-01-01

    Genetically modified crops have the potential to eliminate hunger and starvation in millions of people, especially in developing countries because the genetic modification can produce large amounts of foods that are more nutritious. Large quantities are produced because genetically modified crops are more resistant to pests and drought. They also contain greater amounts of nutrients, such as proteins and vitamins. However, there are concerns about the safety of genetically modified crops. The concerns are that they may contain allergenic substances due to introduction of new genes into crops. Another concern is that genetic engineering often involves the use of antibiotic-resistance genes as "selectable markers" and this could lead to production of antibiotic-resistant bacterial strains that are resistant to available antibiotics. This would create a serious public health problem. The genetically modified crops might contain other toxic substances (such as enhanced amounts of heavy metals) and the crops might not be "substantially equivalent" in genome, proteome, and metabolome compared with unmodified crops. Another concern is that genetically modified crops may be less nutritious; for example, they might contain lower amounts of phytoestrogens, which protect against heart disease and cancer. The review of available literature indicates that the genetically modified crops available in the market that are intended for human consumption are generally safe; their consumption is not associated with serious health problems. However, because of potential for exposure of a large segment of human population to genetically modified foods, more research is needed to ensure that the genetically modified foods are safe for human consumption.

  13. 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

  14. Does calcium in drinking water modify the association between nitrate in drinking water and risk of death from colon cancer?

    PubMed

    Chiu, Hui-Fen; Tsai, Shang-Shyue; Chen, Pei-Shih; Wu, Trong-Neng; Yang, Chun-Yuh

    2011-09-01

    The objective of this study was to explore whether calcium (Ca) levels in drinking water modified the effects of nitrate on colon cancer risk. A matched case-control study was used to investigate the relationship between the risk of death from colon cancer and exposure to nitrate in drinking water in Taiwan. All colon cancer deaths of Taiwan residents from 2003 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth and year of death. Information on the levels of nitrate-nitrogen (NO(3)-N) and Ca in drinking water have been collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cases and controls was assumed to be the source of the subject's NO(3)-N and Ca exposure via drinking water. We observed evidence of an interaction between drinking water NO(3)-N and Ca intake via drinking water. This is the first study to report effect modification by Ca intake from drinking water on the association between NO(3)-N exposure and risk of colon cancer mortality.

  15. Modified Transverse Thoracosternotomy and Cost-Effective Reinforced Sternal Closure.

    PubMed

    Costa, Joseph; Sonett, Joshua R; D'Ovidio, Frank

    2015-12-01

    The bilateral transverse thoracosternotomy clamshell incision provides excellent exposure to the mediastinal structures in double lung transplantation. The use of a modified transverse sternotomy and a figure of 8 configuration with one monofilament metal wire, along with two longitudinal wires across the sternal division, results in greater stability and equally distributed oblique tension. Our described technique was more cost effective and resulted in no incidence of dehiscence. We present our experience using a modified transverse sternotomy and reinforced sternal closure method.

  16. 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.

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

    PubMed

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

    2013-02-09

    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.

  18. 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

  19. 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

  20. 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

  1. Effective fermion kinematics from modified quantum gravity

    NASA Astrophysics Data System (ADS)

    Alexandre, J.; Leite, J.

    2016-10-01

    We consider a classical fermion and a classical scalar, propagating on two different kinds of four-dimensional diffeomorphism breaking gravity backgrounds, and we derive the one-loop effective dispersion relation for matter, after integrating out gravitons. One gravity model involves quadratic divergences at one-loop, as in Einstein gravity, and the other model is the z = 3 non-projectable Horava-Lifshitz gravity, which involves logarithmic divergences only. Although these two models behave differently in the ultraviolet, the IR phenomenology for matter fields is comparable: (i) for generic values for the parameters, both models identify 1010 GeV as the characteristic scale above which they are not consistent with current upper bounds on Lorentz symmetry violation; (ii) for both models, there is always a fine-tuning of parameters which allows the cancellation of the indicator for Lorentz symmetry violation.

  2. 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.

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

    PubMed

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

    2014-09-01

    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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Increased apoptosis in cancer cells in vitro and in vivo by ceramides in transferrin-modified liposomes

    PubMed Central

    Koshkaryev, Alexander; Piroyan, Aleksandr

    2012-01-01

    Lysosomes are a promising therapeutic target for induction apoptosis in cancer cells due to lysosomal membrane permeabilization (LMP) leading to leakage of hydrolytic enzymes, especially the cathepsins, into the cytoplasm. We hypothesized that with the modification of the ceramide-loaded liposomes with transferrin (Tf), we would achieve both tumor targeting and increased delivery of lysosome-destabilizing agents, such as ceramides to lysosomes, to initiate LMP-induced apoptosis. We prepared Tf-modified (TL) and plain (PL) liposomes loaded with short (C6) or long (C16) N-acyl chain ceramides. Uptake, intracellular localization of liposomes, stability of the lysosomal membrane and release of cathepsin D were investigated on Hela cells by fluorescence microscopy and flow cytometry. Apoptosis was evaluated by binding of fluorescently-labeled Annexin V. Antitumor and pro-apoptotic effects of C6Cer-loaded Tf-liposomes were demonstrated in vivo in an A2780-ovarian carcinoma xenograft mouse model. TL were internalized specifically via the TfR-dependent endocytic pathway and localized within the endosomelysosomal compartment. Ceramide-loaded Tf-liposomes significantly increased apoptosis compared with ceramide-free and ceramide-loaded non-modified liposomes. The treatment of cancer cells with TL led to increased LMP and cytoplasmic relocation of the intralysosomal cathepsin D. A strong antitumor and pro-apoptotic effect of C6Cer-loaded TL was also demonstrated in vivo in an A2780-ovarian carcinoma xenograft mouse model. The lysosomal accumulation of ceramides delivered by Tf-liposomes initiates the permeabilization of the lysosomal membranes required for the release of lysosomal cathepsins into the cytoplasm and initiation of the cancer cell apoptosis both in vitro and in vivo. PMID:22336588

  11. Former poison gas workers and cancer: incidence and inhibition of tumor formation by treatment with biological response modifier N-CWS.

    PubMed

    Yamakido, M; Ishioka, S; Hiyama, K; Maeda, A

    1996-05-01

    Mustard gas is known to have mutagenic and carcinogenic effects on animal and human cells. In this report, 1,632 male Japanese who worked in poison gas factories at some time between the years 1927 and 1945 were studied to determine comparative risk for development of cancer, the reference population being data on Japanese males overall. The standardized mortality ratio (SMR) for lung cancer in workers directly and indirectly involved in the production of mustard gas was significantly elevated. In addition, SMR for lung cancer in worker who had worked for more than 5 years was also significantly elevated. Thus, poison gas workers who had engaged in the production of mustard gas or related work for more than 5 years are a high-risk group for lung cancer. Under the cancer preventive program, Nocardia rubra cell-wall skeleton (N-CWS) was administered to 146 former poison gas workers. During a 4.5 year observation period, development of cancers was found in 7 treated workers and 17 untreated controls. After elimination of the influence of smoking level, a significant suppression of development of cancers was noted in the N-CWS-treated workers as compared to the untreated controls. Although the molecular mechanisms of carcinogenesis in former poison gas workers remains unclear, our study proposes the possible effect of biological response modifiers in the prevention of cancer development in high-risk human subjects.

  12. 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

  13. 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

  14. 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

  15. Development of effective modified cellulase for cellulose hydrolysis process

    SciTech Connect

    Park, J.W.; Kajiuchi, Toshio . Dept. of Chemical Engineering)

    1995-02-20

    Cellulase was modified with amphilic copolymers made of [alpha]-allyl-[omega]-methoxy polyoxyalkylene (POA) and maleic acid anhydride (MAA) to improve the cellulose hydrolytic reactivity and cellulase separation. Amino groups of the cellulase molecule are covalently coupled with the MAA functional groups of the copolymer. At the maximum degree of modification (DM) of 55%, the modified cellulase activity retained more than 80% of the unmodified native cellulase activity. The modified cellulase shows greater stability against temperature, pH, and organic solvents, and demonstrated greater conversion of substrate than native cellulase does. Cellulase modification is also useful for controlling strong adsorption of cellulase onto substrate. Moreover, cellulase modified with the amphiphilic copolymer displays different separation characteristics which are new. One is a reactive two-phase partition and another is solubility in organic solvents. It appears that these characteristics of modified cellulase work very effectively in the hydrolysis of cellulose as a total system, which constitutes the purification of cellulase from culture broth, hydrolysis of cellulose, and recovery of cellulase from the reaction mixture.

  16. Genetic Variation in Myeloperoxidase Modifies the Association of Serum α-Tocopherol with Aggressive Prostate Cancer among Current Smokers12

    PubMed Central

    Cheng, Ting-Yuan David; Barnett, Matt J.; Kristal, Alan R.; Ambrosone, Christine B.; King, Irena B.; Thornquist, Mark D.; Goodman, Gary E.; Neuhouser, Marian L.

    2011-01-01

    We investigated associations of serum α- and γ-tocopherols and their effect modification by polymorphisms in oxidative stress regulatory enzymes in relation to prostate cancer risk. In a nested case-control study in the Carotene and Retinol Efficacy Trial, prerandomized serum α- and γ-tocopherol were assayed among 684 men with incident prostate cancer [375 nonaggressive and 284 aggressive cancer (stage III/IV or Gleason score ≥7)] and 1441 controls. Manganese superoxide dismutase Ala-16Val (rs4880), glutathione peroxidase 1 Pro200Leu (rs1050450), catalase −262 C > T (rs1001179), and myeloperoxidase (MPO) G–463A (rs2333227) were genotyped. A multivariate-adjusted inverse association of serum α-tocopherol with total prostate cancer risk was observed in current smokers (OR = 0.62, 95% CI = 0.40–0.96, 4th vs. 1st quartiles). High (≥median) compared to low serum concentrations of α- and γ-tocopherol were inversely associated with aggressive prostate cancer in current smokers (OR = 0.50, 95% CI = 0.32–0.78 and OR = 0.64, 95% CI = 0.43–0.95, respectively). The association was stronger among those with MPO G/A+A/A genotypes. Among current smokers with low serum α-tocopherol concentrations, MPO G/A+A/A, the genotypes downregulating oxidative stress, were associated with an increased risk for aggressive prostate cancer (OR = 2.06, 95% CI = 1.22–3.46). Conversely, current smokers with these genotypes who had high α-tocopherol concentrations had a reduced risk for aggressive prostate cancer (OR = 0.34, 95% CI = 0.15–0.80; P-interaction = 0.001). In conclusion, among current smokers, both high serum α- and γ-tocopherol concentrations were associated with reduced risks of aggressive prostate cancer. The α-tocopherol–associated risks are modified by polymorphism in MPO G–463A. PMID:21795425

  17. 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

  18. Can selenium be a modifier of cancer risk in CHEK2 mutation carriers?

    PubMed

    Gupta, Satish; Jaworska-Bieniek, Katarzyna; Lubinski, Jan; Jakubowska, Anna

    2013-11-01

    Selenium is an essential trace element for humans, playing an important role in various major metabolic pathways. Selenium helps to protect the body from the poisonous effects of heavy metals and other harmful substances. Medical studies have provided evidence of selenium supplementation in preventing certain cancers. Low and too high selenium (Se) status correlates with increased risk of e.g. lung, larynx, colorectal and prostate cancers. A higher level of selenium and supplementation with selenium has been shown to be associated with substantially reduced cancer mortality. Selenium exerts its biological roles through selenoproteins, which are involved in oxidoreductions, redox signalling, antioxidant defence, thyroid hormone metabolism and immune responses. Checkpoint kinase 2 (CHEK2) is an important signal transducer of cellular responses to DNA damage and acts as a tumour suppressor gene. Mutations in the CHEK2 gene have been shown to be associated with increased risks of several cancers. Four common mutations in CHEK2 gene (1100delC, IVS2+1G>A, del5395 and I157T) have been identified in the Polish population. Studies have provided evidence that CHEK2-truncating and/or missense mutations are associated with increased risk of breast, prostate, thyroid, colon and kidney cancers. The variability in penetrance and cancer expression in CHEK2 mutation carriers can probably be explained by the influence of other genetic or environmental factors. One of the possible candidates is Se, which together with genetic variations in selenoprotein genes may influence susceptibility to cancer risk.

  19. 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.

  20. Oral complications of cancer therapies. Pretherapy interventions to modify salivary dysfunction

    SciTech Connect

    Wolff, A.; Atkinson, J.C.; Macynski, A.A.; Fox, P.C. )

    1990-01-01

    Salivary gland dysfunction is a common side effect of cancer therapies. Salivary secretions are reduced rapidly after starting head and neck radiotherapy. Salivary gland dysfunction has also been linked to bone marrow transplantation and to cytotoxic chemotherapy. Salivary gland stimulation during radiation has been suggested as a means of reducing radiation damage. Results of an ongoing study investigating the effects of pilocarpine on radiation-induced salivary gland dysfunction suggest that parotid function was preserved, but not submandibular/sublingual function. Also, patients receiving pilocarpine had less frequent oral complaints. Further research is necessary to develop means of preventing or alleviating the salivary side effects of cancer therapies. 37 references.

  1. 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

  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. Clinical Relevance of the Tumor Location-Modified Lauren Classification System of Gastric Cancer

    PubMed Central

    Choi, Jang Kyu; Park, Young Suk; Jung, Do Hyun; Son, Sang Yong; Ahn, Sang Hoon; Kim, Hyung Ho

    2015-01-01

    Purpose The Lauren classification system is a very commonly used pathological classification system of gastric adenocarcinoma. A recent study proposed that the Lauren classification should be modified to include the anatomical location of the tumor. The resulting three types were found to differ significantly in terms of genomic expression profiles. This retrospective cohort study aimed to evaluate the clinical significance of the modified Lauren classification (MLC). Materials and Methods A total of 677 consecutive patients who underwent curative gastrectomy from January 2005 to December 2007 for histologically confirmed gastric cancer were included. The patients were divided according to the MLC into proximal non-diffuse (PND), diffuse (D), and distal non-diffuse (DND) type. The groups were compared in terms of clinical features and overall survival. Multivariate analysis served to assess the association between MLC and prognosis. Results Of the 677 patients, 48, 358, and 271 had PND, D, and DND, respectively. Their 5-year overall survival rates were 77.1%, 77.7%, and 90.4%. Compared to D and PND, DND was associated with significantly better overall survival (both P<0.01). Multivariate analysis showed that age, differentiation, lympho-vascular invasion, T and N stage, but not MLC, were independent prognostic factors for overall survival. Multivariate analysis of early gastric cancer patients showed that MLC was an independent prognostic factor for overall survival (odds ratio, 5.946; 95% confidence intervals, 1.524~23.197; P=0.010). Conclusions MLC is prognostic for survival in patients with gastric adenocarcinoma, in early gastric cancer. DND was associated with an improved prognosis compared to PND or D. PMID:26468416

  4. 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...

  5. Autophagy, Warburg, and Warburg Reverse Effects in Human Cancer

    PubMed Central

    Gonzalez, Claudio D.; Alvarez, Silvia; Ropolo, Alejandro; Rosenzvit, Carla; Gonzalez Bagnes, Maria F.; Vaccaro, Maria I.

    2014-01-01

    Autophagy is a highly regulated-cell pathway for degrading long-lived proteins as well as for clearing cytoplasmic organelles. Autophagy is a key contributor to cellular homeostasis and metabolism. Warburg hypothesized that cancer growth is frequently associated with a deviation of a set of energy generation mechanisms to a nonoxidative breakdown of glucose. This cellular phenomenon seems to rely on a respiratory impairment, linked to mitochondrial dysfunction. This mitochondrial dysfunction results in a switch to anaerobic glycolysis. It has been recently suggested that epithelial cancer cells may induce the Warburg effect in neighboring stromal fibroblasts in which autophagy was activated. These series of observations drove to the proposal of a putative reverse Warburg effect of pathophysiological relevance for, at least, some tumor phenotypes. In this review we introduce the autophagy process and its regulation and its selective pathways and role in cancer cell metabolism. We define and describe the Warburg effect and the newly suggested “reverse” hypothesis. We also discuss the potential value of modulating autophagy with several pharmacological agents able to modify the Warburg effect. The association of the Warburg effect in cancer and stromal cells to tumor-related autophagy may be of relevance for further development of experimental therapeutics as well as for cancer prevention. PMID:25197670

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. Unintended effects in genetically modified crops: revealed by metabolomics?

    PubMed

    Rischer, Heiko; Oksman-Caldentey, Kirsi-Marja

    2006-03-01

    In Europe the commercialization of food derived from genetically modified plants has been slow because of the complex regulatory process and the concerns of consumers. Risk assessment is focused on potential adverse effects on humans and the environment, which could result from unintended effects of genetic modifications: unintended effects are connected to changes in metabolite levels in the plants. One of the major challenges is how to analyze the overall metabolite composition of GM plants in comparison to conventional cultivars, and one possible solution is offered by metabolomics. The ultimate aim of metabolomics is the identification and quantification of all small molecules in an organism; however, a single method enabling complete metabolome analysis does not exist. Given a comprehensive extraction method, a hierarchical strategy--starting with global fingerprinting and followed by complementary profiling attempts--is the most logical and economic approach to detect unintended effects in GM crops.

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

    PubMed

    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

    2013-12-01

    Women using menopausal hormone therapy (MHT) are at increased risk of developing 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 11 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 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showing P values for interaction (Pint) <3.0 × 10(-3) were selected for replication using pooled case-control data from 11 studies of the Breast Cancer Association Consortium, including 7689 cases (676 lobular) and 9266 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(-6)), two SNPs in SLC25A21 (combined Pint≤4.8 × 10(-5)), and three SNPs in PLCG2 (combined Pint≤4.5 × 10(-5)). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7 × 10(-5)), one SNP in CD80 (combined Pint≤8.2 × 10(-6)), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10(-6)), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6 × 10(-5)). 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.

  14. [Unintended effects assessment of genetically modified crops using omics techniques].

    PubMed

    Zhao, Yan; Li, Yan-Yan

    2013-12-01

    Safety assessment is the essential process for commercial application of genetically modified (GM) crops. Omics techniques can be used to evaluate the safety of GM crops unbiasedly at different biological levels, such as transcripts, proteins and metabolites. In the present review, the researches on unintended effects assessment of GM crops using transcriptomic, proteomic and metabolomic techniques in recent ten years have been summarized. The facts show that the environmental factors (growing area and season) and genotype difference play greater roles than gene insertion does for most unintended variations in GM crops.

  15. 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

  16. 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

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

    PubMed Central

    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

  18. Modified Habitats Influence Kelp Epibiota via Direct and Indirect Effects

    PubMed Central

    Marzinelli, Ezequiel M.; Underwood, Antony J.; Coleman, Ross A.

    2011-01-01

    Addition of man-made structures alters abiotic and biotic characteristics of natural habitats, which can influence abundances of biota directly and/or indirectly, by altering the ecology of competitors or predators. Marine epibiota in modified habitats were used to test hypotheses to distinguish between direct and indirect processes. In Sydney Harbour, kelps on pier-pilings supported greater covers of bryozoans, particularly of the non-indigenous species Membranipora membranacea, than found on natural reefs. Pilings influenced these patterns and processes directly due to the provision of shade and indirectly by altering abundances of sea-urchins which, in turn, affected covers of bryozoans. Indirect effects were more important than direct effects. This indicates that artificial structures affect organisms living on secondary substrata in complex ways, altering the biodiversity and indirectly affecting abundances of epibiota. Understanding how these components of habitats affect ecological processes is necessary to allow sensible prediction of the effects of modifying habitats on the ecology of organisms. PMID:21755011

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Effects of Modifier Type on Properties of in Situ Organo-Montmorillonite Modified Wood Flour/Poly(lactic acid) Composites.

    PubMed

    Liu, Ru; Chen, Yu; Cao, Jinzhen

    2016-01-13

    Wood flour (WF) was modified with sodium-montmorillonite (Na-MMT) and two types of surfactant modifiers, namely, didecyl dimethylammonium chloride (DDAC) and sodium dodecyl sulfonate (SDS) though a two-step process inside WF. The thus-modified WFs were characterized, and the effects of MMT type on physical, mechanical, and thermal properties of their composites with poly(lactic acid) (PLA) were investigated. The results showed: (1) either DDAC or SDS could modified Na-MMT into OMMT, and then uniformly distributed in WF cell walls; (2) OMMT improved the physical properties, most mechanical properties, and thermal properties of the composites except for the impact strength; and (3) compared with SDS, DDAC seemed to perform better in properties of composites. However, DDAC showed some negative effect on the early stage of composite thermal decomposition. PMID:26671464

  4. 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.

  5. A Modified In vitro Invasion Assay to Determine the Potential Role of Hormones, Cytokines and/or Growth Factors in Mediating Cancer Cell Invasion.

    PubMed

    Bagati, Archis; Koch, Zethan; Bofinger, Diane; Goli, Haneesha; Weiss, Laura S; Dau, Rosie; Thomas, Megha; Zucker, Shoshanna N

    2015-04-24

    Blood serum serves as a chemoattractant towards which cancer cells migrate and invade, facilitating their intravasation into microvessels. However, the actual molecules towards which the cells migrate remain elusive. This modified invasion assay has been developed to identify targets which drive cell migration and invasion. This technique compares the invasion index under three conditions to determine whether a specific hormone, growth factor, or cytokine plays a role in mediating the invasive potential of a cancer cell. These conditions include i) normal fetal bovine serum (FBS), ii) charcoal-stripped FBS (CS-FBS), which removes hormones, growth factors, and cytokines and iii) CS-FBS + molecule (denoted "X"). A significant change in cell invasion with CS-FBS as compared to FBS, indicates the involvement of hormones, cytokines or growth factors in mediating the change. Individual molecules can then be added back to CS-FBS to assay their ability to reverse or rescue the invasion phenotype. Furthermore, two or more factors can be combined to evaluate the additive or synergistic effects of multiple molecules in driving or inhibiting invasion. Overall, this method enables the investigator to determine whether hormones, cytokines, and/or growth factors play a role in cell invasion by serving as chemoattractants or inhibitors of invasion for a particular type of cancer cell or a specific mutant. By identifying specific chemoattractants and inhibitors, this modified invasion assay may help to elucidate signaling pathways that direct cancer cell invasion.

  6. Immunoregulatory biological response modifiers: effect of cytokines on septic shock

    PubMed Central

    De Simone, Claudio

    1993-01-01

    Whole bacteria or bacterial components or their extracts were employed to restore or augment the immune system. Beneficial effects were attained with these agents in treating various diseases. These agents were named biological response modifiers (BRMs) because they regulated certain cellular components of the immune system. The cellular regulation induced by these BRMs was found to be due to cytokines. The cytokines were shown to act directly on the various cellular components and to provide therapeutic benefit in various autoimmune and immune deficiency diseases. Overproduction of specific cytokines however leads to a deleterious effect on the host. Overproduction of tumour necrosis factor (endotoxin, lipopolysaccharide) leads to septic shock. Bacteraemia is the leading cause of overproduction of tumour necrosis factor (TNF). Septic shock in many cases leads to death. Several monoclonal antibodies to lipopolysaccharide (LPS) and anticytokines have demonstrated protection against septic shock. PMID:18475571

  7. Comparative effectiveness in esophagogastric cancer.

    PubMed

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

    2015-01-01

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

  8. 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

  9. Late effects of cancer treatment in breast cancer survivors.

    PubMed

    Agrawal, Sushma

    2014-04-01

    Postoperative radiation therapy (RT) and chemotherapy,both reduces the risk of local recurrence and extends overall survival in patients with breast cancer (BC). Concerns have, however, been raised about the risk of acute and chronic side effects in breast cancer survivors as the number of treated individuals is large and their expected survival is long compared to most patients with other malignant diseases. Cardiac toxicity, reproductive dysfunction, pneumonitis (RP),arm lymph edema, neuropathy, skin changes are examples of the wide range of complications that has been associated with adjuvant treatment.

  10. 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

  11. 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

  12. 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

  13. 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...

  14. [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

  15. L-2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer

    PubMed Central

    Shim, Eun-Hee; Livi, Carolina B.; Rakheja, Dinesh; Tan, Jubilee; Benson, Daniel; Parekh, Vishwas; Kho, Eun-Young; Ghosh, Arindam P.; Kirkman, Richard; Velu, Sadanan; Dutta, Shilpa; Chenna, Balachandra; Rea, Shane L; Mishur, Robert J; Li, Qiuhua; Johnson-Pais, Teresa L.; Guo, Lining; Bae, Sejong; Wei, Shi; Block, Karen; Sudarshan, Sunil

    2014-01-01

    Through unbiased metabolomics, we identified elevations of the metabolite 2-hydroxyglutarate (2HG) in renal cell carcinoma (RCC). 2HG can inhibit 2-oxoglutaratre (2-OG) dependent dioxygenases which mediate epigenetic events including DNA and histone demethylation. 2HG accumulation, specifically the D- enantiomer, can result from gain of function mutations of isocitrate dehydrogenase (IDH1, IDH2) found in several different tumors. In contrast, kidney tumors demonstrate elevations of the L enantiomer of 2HG (L-2HG). High 2HG tumors demonstrate reduced DNA levels of 5-hydroxymethylcytosine (5hmC) consistent with 2-HG mediated inhibition of TET (Ten Eleven Translocation) enzymes which convert 5-methylcystoine (5mC) to 5hmC. L-2HG elevation is mediated in part by reduced expression of L-2HG dehydrogenase (L2HGDH). L2HGDH reconstitution in RCC cells lowers L-2HG and promotes 5hmC accumulation. Additionally, L2HGDH expression in RCC cells reduces histone methylation and suppresses in vitro tumor phenotypes. Our report identifies L-2HG as an epigenetic modifier and putative oncometabolite in kidney cancer. PMID:25182153

  16. 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.

  17. 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

  18. 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

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

    PubMed

    Lowe, Frazer J; Luettich, Karsta; Gregg, Evan O

    2013-05-01

    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.

  20. Doxorubicin in TAT peptide-modified multifunctional immunoliposomes demonstrates increased activity against both drug-sensitive and drug-resistant ovarian cancer models.

    PubMed

    Apte, Anjali; Koren, Erez; Koshkaryev, Alexander; Torchilin, Vladimir P

    2014-01-01

    Multidrug resistance (MDR) is a hallmark of cancer cells and a crucial factor in chemotherapy failure, cancer reappearance, and patient deterioration. We have previously described the physicochemical characteristics and the in vitro anticancer properties of a multifunctional doxorubicin-loaded liposomal formulation. Lipodox(®), a commercially available PEGylated liposomal doxorubicin, was made multifunctional by surface-decorating with a cell-penetrating peptide, TATp, conjugated to PEG 1000-PE, to enhance liposomal cell uptake. A pH-sensitive polymer, PEG 2000-Hz-PE, with a pH-sensitive hydrazone (Hz) bond to shield the peptide in the body and expose it only at the acidic tumor cell surface, was used as well. In addition, an anti-nucleosome monoclonal antibody 2C5 attached to a long-chain polymer to target nucleosomes overexpressed on the tumor cell surface was also present. Here, we report the in vitro cell uptake and cytotoxicity of the modified multifunctional immunoliposomes as well as the in vivo studies on tumor xenografts developed subcutaneously in nude mice with MDR and drug-sensitive human ovarian cancer cells (SKOV-3). Our results show the ability of multifunctional immunoliposomes to overcome MDR by enhancing cytotoxicity in drug-resistant cells, compared with non-modified liposomes. Furthermore, in comparison with the non-modified liposomes, upon intravenous injection of these multifunctional immunoliposomes into mice with tumor xenografts, a significant reduction in tumor growth and enhanced therapeutic efficacy of the drug in both drug-resistant and drug-sensitive mice was obtained. The use of "smart" multifunctional delivery systems may provide the basis for an effective strategy to develop, improve, and overcome MDR cancers in the future. PMID:24145298

  1. Doxorubicin in TAT peptide-modified multifunctional immunoliposomes demonstrates increased activity against both drug-sensitive and drug-resistant ovarian cancer models

    PubMed Central

    Apte, Anjali; Koren, Erez; Koshkaryev, Alexander; Torchilin, Vladimir P

    2014-01-01

    Multidrug resistance (MDR) is a hallmark of cancer cells and a crucial factor in chemotherapy failure, cancer reappearance, and patient deterioration. We have previously described the physicochemical characteristics and the in vitro anticancer properties of a multifunctional doxorubicin-loaded liposomal formulation. Lipodox®, a commercially available PEGylated liposomal doxorubicin, was made multifunctional by surface-decorating with a cell-penetrating peptide, TATp, conjugated to PEG1000-PE, to enhance liposomal cell uptake. A pH-sensitive polymer, PEG2000-Hz-PE, with a pH-sensitive hydrazone (Hz) bond to shield the peptide in the body and expose it only at the acidic tumor cell surface, was used as well. In addition, an anti-nucleosome monoclonal antibody 2C5 attached to a long-chain polymer to target nucleosomes overexpressed on the tumor cell surface was also present. Here, we report the in vitro cell uptake and cytotoxicity of the modified multifunctional immunoliposomes as well as the in vivo studies on tumor xenografts developed subcutaneously in nude mice with MDR and drug-sensitive human ovarian cancer cells (SKOV-3). Our results show the ability of multifunctional immunoliposomes to overcome MDR by enhancing cytotoxicity in drug-resistant cells, compared with non-modified liposomes. Furthermore, in comparison with the non-modified liposomes, upon intravenous injection of these multifunctional immunoliposomes into mice with tumor xenografts, a significant reduction in tumor growth and enhanced therapeutic efficacy of the drug in both drug-resistant and drug-sensitive mice was obtained. The use of “smart” multifunctional delivery systems may provide the basis for an effective strategy to develop, improve, and overcome MDR cancers in the future. PMID:24145298

  2. 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

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

    PubMed

    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.

  4. 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

  5. How can I help myself? A critical review of modifiable behaviors, medications, and complementary alternative medicine for men receiving radiotherapy for prostate cancer.

    PubMed

    Tseng, Yolanda D; Martin, Neil E

    2013-07-01

    Men receiving radiation for prostate cancer frequently want to know what steps they can take to optimize their chance of cure and reduce their risk of side effects. A variety of modifiable behaviors, medications, and complementary alternative medicine interventions have been investigated in this regard. In this review, we summarize data on tobacco use, exercise, statins and aspirin, and vitamins. There is limited randomized data supporting any of the interventions and additional studies are needed before clinicians can confidently inform their patients regarding what steps to take to improve their outcomes.

  6. Dual function of RGD-modified VEGI-192 for breast cancer treatment.

    PubMed

    Wu, Jueheng; Jiang, Yi; Yang, Wan; He, Zhenjian; Meng, Shiyu; Zhang, Qianhui; Lin, Min; Zhang, Henan; Li, Weifeng; Yang, Yaochao; Jia, Yiqun; Qian, Liang; Lu, Dihan; Cai, Wenjia; Luo, Guotian; Wang, Yesong; Zhu, Xun; Li, Mengfeng

    2012-04-18

    Identification of endogenous angiogenesis inhibitors has led to development of an increasingly attractive strategy for cancer therapy and other angiogenesis-driven diseases. Vascular endothelial growth inhibitor (VEGI), a potent and relatively nontoxic endogenous angiogenesis inhibitor, has been intensively studied, and this work shed new light on developing promising anti-angiogenic strategies. It is well-documented that the RGD (Arg-Gly-Asp) motif exhibits high binding affinity to integrin α(v)β(3), which is abundantly expressed in cancer cells and specifically associated with angiogenesis on tumors. Here, we designed a fusion protein containing the special RGD-4C motif sequence and VEGI-192, aimed at offering more effective multiple targeting to tumor cells and tumor vasculature, and higher anti-angiogenic and antitumor efficacy. Functional tests demonstrated that the purified recombinant human RGD-VEGI-192 protein (rhRGD-VEGI-192) potently inhibited endothelial growth in vitro and suppressed neovascularization in chicken chorioallantoic membrane in vivo, to a higher degree as compared with rhVEGI-192 protein. More importantly, rhRGD-VEGI-192, but not rhVEGI-192 protein, could potentially target MDA-MB-435 breast tumor cells, significantly inhibiting growth of MDA-MB-435 cells in vitro, triggered apoptosis in MDA-MB-435 cells by activation of caspase-8 as well as caspase-3, which was mediated by activating the JNK signaling associated with upregulation of pro-apoptotic protein Puma, and consequently led to the observed significant antitumor effect in vivo against a human breast cancer xenograft. Our study indicated that the RGD-VEGI-192 fusion protein might represent a novel anti-angiogenic and antitumor strategy.

  7. Synthesis and in vitro study of cisplatin-loaded Fe3O4 nanoparticles modified with PLGA-PEG6000 copolymers in treatment of lung cancer.

    PubMed

    Nejati-Koshki, Kazem; Mesgari, Mehran; Ebrahimi, Eommolbanin; Abbasalizadeh, Farhad; Fekri Aval, Sedigeh; Khandaghi, Amir Ahmad; Abasi, Mozhgan; Akbarzadeh, Abolfazl

    2014-01-01

    In the field of cancer therapy, magnetic nanoparticles modified with biocompatible copolymers are promising vehicles for the delivery of hydrophobic drugs such as Cisplatin. The major aim of this effort was to evaluate whether Cisplatin-Encapsulated magnetic nanoparticles improved the anti-tumour effect of free Cisplatin in lung cancer cells. The PLGA-PEG triblock copolymer was synthesised by ring-opening polymerisation of d,l-lactide and glycolide with polyethylene glycol (PEG6000) as an initiator. The bulk properties of these copolymers were characterised using Fourier transform infrared spectroscopy. Cisplatin-loaded nanoparticles (NPs) were prepared by double emulsion solvent evaporation technique and were characterised for size, drug entrapment efficiency (%), drug content (% w/w), and surface morphology. In vitro release profile of cisplatin-loaded NP formulations was determined. Cytotoxic assays were evaluated in lung carcinoma (A549)-treated cells by the MTT assay technique. In addition, the particles were characterised by X-ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. The anti-proliferative effect of Cisplatin appeared much earlier when the drug was encapsulated in magnetic nanoparticles than when it was free. Cisplatin-Encapsulated magnetic nanoparticles significantly enhanced the decrease in IC50 rate. The in vitro cytotoxicity test showed that the Fe3O4-PLGA-PEG6000 magnetic nanoparticles had no cytotoxicity and were biocompatible. The chemotherapeutic effect of free Cisplatin on lung cancer cells is improved by its encapsulation in modified magnetic nanoparticles. This approach has the prospective to overcome some major limitations of conventional chemotherapy and may be a promising strategy for future applications in lung cancer therapy. PMID:25090589

  8. Cancer treatment: fertility and sexual side effects in women

    MedlinePlus

    Different types of cancer treatment can affect your sexuality and fertility in different ways. Surgery for cancer: ... Effects: What Women Can Do About Changes in Sexuality and Fertility. April 2007. www.cancer.gov/cancertopics/ ...

  9. The Effect of Random Voids in the Modified Gurson Model

    NASA Astrophysics Data System (ADS)

    Fei, Huiyang; Yazzie, Kyle; Chawla, Nikhilesh; Jiang, Hanqing

    2012-02-01

    The porous plasticity model (usually referred to as the Gurson-Tvergaard-Needleman model or modified Gurson model) has been widely used in the study of microvoid-induced ductile fracture. In this paper, we studied the effects of random voids on the porous plasticity model. Finite-element simulations were conducted to study a copper/tin/copper joint bar under uniaxial tension using the commercial finite-element package ABAQUS. A randomly distributed initial void volume fraction with different types of distribution was introduced, and the effects of this randomness on the crack path and macroscopic stress-strain behavior were studied. It was found that consideration of the random voids is able to capture more detailed and localized deformation features, such as different crack paths and different ultimate tensile strengths, and meanwhile does not change the macroscopic stress-strain behavior. It seems that the random voids are able to qualitatively explain the scattered observations in experiments while keeping the macroscopic measurements consistent.

  10. 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.

  11. 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.

  12. 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

  13. Effects of a modified maxillary orthopaedic splint: a cephalometric evaluation.

    PubMed

    Uner, O; Yücel-Eroğlu, E

    1996-06-01

    Taking the presence of an interplay between the vertical and sagittal components of craniofacial development into consideration, the beneficial therapeutic potential impacts of controlling vertical development on the correction of Class II discrepancies has been previously investigated. In the present study, a modified maxillary orthopaedic splint combined with an anterior high-pull headgear was used for early correction of the vertical and consequently sagittal dentoskeletal discrepancy as the initial stage of treatment. The aim was to evaluate its effects on the maxillary and mandibular dentoskeletal development, as well as rotational growth pattern. In order to compare with and distinguish from the uninterrupted growth changes, a control group was formed by matching each one of the control subjects to a subject in the treatment group according to certain criteria. The initial and second standardized lateral cephalograms of each subject was evaluated by means of an adopted and biologically more substantial cephalometric analysis. Evaluation of the changes induced by the splint in comparison with the uninterrupted growth changes revealed that the splint had both orthopaedic and orthodontic effects on the growth pattern of the dentoskeletal structures. There seemed to exist a relationship between the direction of total mandibular and maxillary rotations. In addition, it was believed that in order to cause a forward mandibular rotation, i.e. to change the rotational mandibular growth pattern from a backward into a forward direction, the posterior vertical maxillary development should be restrained, but anterior vertical maxillary development should be relatively more restrained or reversed and, thereby, the rotational growth pattern of the maxilla should be changed from a backward into a forward direction. Moreover, the bite block effect of the splint seemed to cause a favourable change in the condylar growth direction from a backward to an upward direction.

  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. Modifier Genes and their effect on Duchenne Muscular Dystrophy

    PubMed Central

    Vo, Andy H.; McNally, Elizabeth M.

    2015-01-01

    Purpose of Review Recently, genetic pathways that modify the clinical severity of Duchenne Muscular Dystrophy have been identified. The pathways uncovered as modifiers are useful to predict prognosis and also elucidate molecular signatures that can be manipulated therapeutically. Recent Findings Modifiers have been identified using combinations of transcriptome and genome profiling. Osteopontin, encoded by the SPP1 gene, was found using gene expression profiling. LTBP4, encoding latent transforming growth factor β binding protein 4 was initially discovered using a genomewide screen in mice and then validated in cohorts of Duchenne Muscular Dystrophy patients. These two pathways converge in that they both regulate TGFβ. A third modifier, Anxa6 that specifies annexin A6, is a calcium binding protein has been identified using mouse models, and regulates the injury pathway and sarcolemmal resealing. Summary Genetic modifiers can serve as biomarkers for outcomes in Duchenne Muscular Dystrophy. Modifiers can alter strength and ambulation in muscular dystrophy, and these same features can be used as endpoints used in clinical trials. Moreover, because genetic modifiers can influence outcomes, these genetic markers should be considered when stratifying results in muscular dystrophy. PMID:26263473

  16. The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms

    PubMed Central

    Abdal Dayem, Ahmed; Choi, Hye Yeon; Yang, Gwang-Mo; Kim, Kyeongseok; Saha, Subbroto Kumar; Cho, Ssang-Goo

    2016-01-01

    The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The interplay between autophagy and apoptosis in the anti-cancer activity of polyphenols will also be highlighted. In addition, the potential of polyphenols to target cancer stem cells (CSCs) via various mechanisms will be explained. Recently, the use of natural products as chemotherapeutics and chemopreventive drugs to overcome the side effects and resistance that arise from using chemical-based agents has garnered the attention of the scientific community. Polyphenol research is considered a promising field in the treatment and prevention of breast cancer. PMID:27657126

  17. Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer.

    PubMed

    Gao, Zhiguang; Guo, Bomin; Gao, Renyuan; Zhu, Qingchao; Wu, Wen; Qin, Huanlong

    2015-10-01

    Studies using animal models have demonstrated that probiotics may have a beneficial role in the prevention of colorectal cancer (CRC); however, the underlying mechanism of the beneficial effects of interventional probiotic treatment on gut microbiota has remained elusive. In the present study, pyrosequencing of the V3 region of the 16S rRNA genes was conducted in order to determine the extent to which probiotics alter the microbiota. The observations of the present study indicated that the microbial structure of cancerous tissue differed significantly from that of healthy individuals and that the CRC microbiota exhibited lower diversity. It was indicated that interventional treatment with probiotics increased the density and diversity of mucosal microbes, and altered the mucosa‑associated microbiota. Pyrosequencing demonstrated that probiotics significantly reduced (5‑fold) the abundance of a bacterial taxon assigned to the genus Fusobacterium, which had been previously suggested to be a contributing factor to increase tumorigenesis. Accordingly, interventional probiotic therapy is suggested to be able to improve the composition of the mucosal microbial flora and significantly reduce the abundance of mucosa-associated pathogens in patients with CRC.

  18. Improving supportive care for women with breast cancer in Australia: the challenge of modifying health systems.

    PubMed

    Redman, Sally; Turner, Jane; Davis, Cindy

    2003-09-01

    Although the benefits of many psychosocial support strategies in improving well being in women with breast cancer have been demonstrated, few women receive these programs as part of routine care. This paper provides some recommendations, based on experience in Australia, about how access to evidence-based supportive care strategies might be improved through modification of health systems. It demonstrates the paucity of research about the costs and health service implications of psychosocial support strategies, which is vital to health planning and service delivery change. It outlines the systematic approach taken in Australia to improving psychosocial support nationally by: the development of research reviews; preparation of guidelines about supportive care; implementation of programs to foster the adoption of guidelines through modification of policy, health service delivery and clinician training; and monitoring programs. Coalitions of government, health care professionals and consumers are key to effective lobbying for change. If all women with breast cancer are to receive better supportive care, there is a need for approaches which: refocus the research effort in psycho-oncology; develop more strategic approaches to generating change in health systems and health policy and foster partnerships to advocate for improved resources.

  19. 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

  20. 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

  1. 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; Mousavi, 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.

  2. 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.

  3. 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.

  4. 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%.

  5. 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.

  6. Magnetic-nanoparticle-modified paclitaxel for targeted therapy for prostate cancer.

    PubMed

    Hua, Mu-Yi; Yang, Hung-Wei; Chuang, Cheng-Keng; Tsai, Rung-Ywan; Chen, Wen-Jauh; Chuang, Kun-Lung; Chang, Ying-Hsu; Chuang, Heng-Chang; Pang, See-Tong

    2010-10-01

    A nontoxic drug nanocarrier containing carboxyl groups was successfully developed by mixing magnetic nanoparticles (MNPs) of Fe(3)O(4) with the water-soluble polyaniline derivative poly[aniline-co-sodium N-(1-one-butyric acid) aniline] (SPAnNa) and doping with HCl aqueous solution to form SPAnH/MNPs shell/core. SPAnH/MNPs could be used to effectively immobilize the hydrophobic drug paclitaxel (PTX), thus enhancing the drug's thermal stability and water solubility. Up to 302.75 mug of PTX could be immobilized per mg of SPAnH/MNPs. SPAnH/MNPs-bound-PTX (bound-PTX) was more stable than free-PTX at both 25 degrees C and 37 degrees C. Furthermore, bound-PTX was more cytotoxic to human prostate carcinoma cells (PC3 and CWR22R) than free-PTX at 37 degrees C, and the inhibition of cellular growth was even more pronounced when magnetic targeting was applied to the bound-PTX. These data indicate that this magnetically targeted drug delivery system provides more effective treatment of prostate cancer cells using lower therapeutic doses and thus with potentially fewer side-effects.

  7. 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

  8. A reusable magnetic graphene oxide-modified biosensor for vascular endothelial growth factor detection in cancer diagnosis.

    PubMed

    Lin, Chih-Wen; Wei, Kuo-Chen; Liao, Shih-sheng; Huang, Chiung-Yin; Sun, Chia-Liang; Wu, Pei-Jung; Lu, Yu-Jen; Yang, Hung-Wei; Ma, Chen-Chi M

    2015-05-15

    Early cancer diagnosis is critical for the prevention of metastasis. However, simple and efficient methods are needed to improve the diagnosis and evaluation of cancer. Here, we propose a reusable biosensor based on a magnetic graphene oxide (MGO)-modified Au electrode to detect vascular endothelial growth factor (VEGF) in human plasma for cancer diagnosis. In this biosensor, Avastin is used as the specific biorecognition element, and MGO is used as the carrier for Avastin loading. The use of MGO enables rapid purification due to its magnetic properties, which prevents the loss of bioactivity. Moreover, the biosensor can be constructed quickly, without requiring a drying process, which is convenient for proceeding to detection. Our reusable biosensor provides the appropriate sensitivity for clinical diagnostics and has a wide range of linear detection, from 31.25-2000 pg mL(-1), compared to ELISA analysis. In addition, in experiments with 100% serum from clinical samples, readouts from the sensor and an ELISA for VEGF showed good correlation within the limits of the ELISA kit. The relative standard deviation (RSD) of the change in current (ΔC) for reproducibility of the Au biosensor was 2.36% (n=50), indicating that it can be reused with high reproducibility. Furthermore, the advantages of the Avastin-MGO-modified biosensor for VEGF detection are that it provides an efficient detection strategy that not only improves the detection ability but also reduces the cost and decreases the response time by 10-fold, indicating its potential as a diagnosis product.

  9. Genetic Variation as a Modifier of Association between Therapeutic Exposure and Subsequent Malignant Neoplasms in Cancer Survivors

    PubMed Central

    Bhatia, Smita

    2014-01-01

    Subsequent malignant neoplasms (SMNs) are associated with significant morbidity and are a major cause of premature mortality among cancer survivors. Several large studies have demonstrated a strong association between the radiation and/or chemotherapy used to treat the primary cancer and the risk of developing SMNs. However, for any given therapeutic exposure, the risk of developing an SMN varies between individuals. Genomic variation can potentially modify the association between therapeutic exposures and SMN risk, and can possibly explain the observed inter-individual variability. This article provides a brief overview of the current knowledge regarding the role of genomic variation in the development of therapy-related SMNs. This article also discusses the methodological challenges in undertaking an endeavor to develop a deeper understanding of the molecular underpinnings of therapy-related SMNs, such as, an appropriate study design, identification of an adequately sized study population together with a reliable plan for collecting and maintaining high quality DNA, clinical validation of the phenotype, and selection of an appropriate approach or platform for genotyping. Understanding the modifiers of risk of treatment-related SMNs is critical to developing targeted intervention strategies and optimizing risk-based health care of cancer survivors. PMID:25355167

  10. Genetic variation as a modifier of association between therapeutic exposure and subsequent malignant neoplasms in cancer survivors.

    PubMed

    Bhatia, Smita

    2015-03-01

    Subsequent malignant neoplasms (SMNs) are associated with significant morbidity and are a major cause of premature mortality among cancer survivors. Several large studies have demonstrated a strong association between the radiation and/or chemotherapy used to treat primary cancer and the risk of developing SMNs. However, for any given therapeutic exposure, the risk of developing an SMN varies between individuals. Genomic variation can potentially modify the association between therapeutic exposures and SMN risk and may explain the observed interindividual variability. In this review, the author provides a brief overview of the current knowledge regarding the role of genomic variation in the development of therapy-related SMNs and discusses the methodological challenges in undertaking an endeavor to develop a deeper understanding of the molecular underpinnings of therapy-related SMNs, such as an appropriate study design, the identification of an adequately sized study population together with a reliable plan for collecting and maintaining high-quality DNA, clinical validation of the phenotype, and the selection of an appropriate approach or platform for genotyping. Understanding the factors that can modify the risk of treatment-related SMNs is critical to developing targeted intervention strategies and optimizing risk-based health care for cancer survivors.

  11. 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

  12. 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

  13. Effect of ageing on rheological properties of storage-stable SBS/sulfur-modified asphalts.

    PubMed

    Zhang, Feng; Yu, Jianying; Wu, Shaopeng

    2010-10-15

    Oxidative ageing as an inevitable process in practical road paving has a great effect on the properties of polymer-modified asphalts (PMAs). In this article, the effect of short-term and long-term oxidative ageing on the rheological, physical properties and the morphology of the styrene-butadiene-styrene (SBS)- and storage-stable SBS/sulfur-modified asphalts was studied, respectively. The analysis on the rheological and physical properties of the PMAs before and after ageing showed the two major effects of ageing. On one hand, ageing prompted the degradation of polymer and increased the viscous behaviour of the modified binders, on the other, ageing changed the asphalt compositions and improved the elastic behaviour of the modified binders. The final performance of the aged binders depended on the combined effect. After ageing, the storage-stable SBS/sulfur-modified asphalts showed an obvious viscous behaviour compare with the SBS-modified asphalts and this led to an improved low-temperature creep property. The rutting resistance of the SBS-modified asphalts declined by the addition of sulfur due to the structural instability of the SBS/sulfur-modified asphalts. The rheological properties of the modified binders before and after ageing also depended strongly on the structural characteristics of SBS. The observation by using optical microscopy showed the compatibility between asphalt and SBS was improved with further ageing, especially for the storage-stable SBS/sulfur-modified asphalts.

  14. Effect of ageing on rheological properties of storage-stable SBS/sulfur-modified asphalts.

    PubMed

    Zhang, Feng; Yu, Jianying; Wu, Shaopeng

    2010-10-15

    Oxidative ageing as an inevitable process in practical road paving has a great effect on the properties of polymer-modified asphalts (PMAs). In this article, the effect of short-term and long-term oxidative ageing on the rheological, physical properties and the morphology of the styrene-butadiene-styrene (SBS)- and storage-stable SBS/sulfur-modified asphalts was studied, respectively. The analysis on the rheological and physical properties of the PMAs before and after ageing showed the two major effects of ageing. On one hand, ageing prompted the degradation of polymer and increased the viscous behaviour of the modified binders, on the other, ageing changed the asphalt compositions and improved the elastic behaviour of the modified binders. The final performance of the aged binders depended on the combined effect. After ageing, the storage-stable SBS/sulfur-modified asphalts showed an obvious viscous behaviour compare with the SBS-modified asphalts and this led to an improved low-temperature creep property. The rutting resistance of the SBS-modified asphalts declined by the addition of sulfur due to the structural instability of the SBS/sulfur-modified asphalts. The rheological properties of the modified binders before and after ageing also depended strongly on the structural characteristics of SBS. The observation by using optical microscopy showed the compatibility between asphalt and SBS was improved with further ageing, especially for the storage-stable SBS/sulfur-modified asphalts. PMID:20637542

  15. 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

  16. 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…

  17. Positive selection of gene-modified cells increases the efficacy of pancreatic cancer suicide gene therapy.

    PubMed

    Martinez-Quintanilla, Jordi; Cascallo, Manel; Gros, Alena; Fillat, Cristina; Alemany, Ramon

    2009-11-01

    Thymidine kinase (TK)-mediated suicide gene therapy has been considered for the treatment of pancreatic cancer. However, despite a bystander effect, the proportion of transduced tumor cells has proven too low to result in efficacy. We propose the use of a drug-selectable marker (MDR1) to enrich TK-expressing cells using chemotherapy. This enrichment or positive selection phase may increase the efficacy of suicide gene therapy. To test this strategy, we generated stable NP18MDR/TK-GFP transfectants and showed docetaxel resistance in vivo. Mixed tumors of MDR/TK-expressing cells and parental NP18 cells were established and docetaxel was used to increase the proportion of TK-expressing cells. After this positive selection phase, suicide gene therapy with ganciclovir was applied. Upon positive selection, the proportion of TK-expressing cells increased from 4% to 22%. Subsequent suicide gene therapy was more effective compared with a control group without positive selection. Starting with 10% of TK-expressing cells the positive-negative selection strategy completely inhibited tumor growth. Taken together, these results suggest that a positive-negative selection strategy based on MDR and TK genes represents an efficient way to increase the proportion of TK-expressing cells in the tumor and the efficacy of TK-mediated suicide gene therapy.

  18. Proteins modified by the lipid peroxidation aldehyde DODE in MCF7 breast cancer cells

    PubMed Central

    Slade, Peter G.; Williams, Michelle V.; Brahmbatt, Viral; Dash, Ajit; Wishnok, John S.; Tannenbaum, Steven R.

    2010-01-01

    The hydroperoxide of linoleic acid (13-HPODE) degrades to 9,12-dioxo-10(E)-dodecenoic acid (DODE) which readily modifies proteins. This study identified the major proteins in MCF7 cells modified by DODE. To reduce false positives, three methods were use to identify DODE-modified proteins. First, cells were treated with a synthetically biotinylated 13-HPODE (13-HPODE-biotin). Modified proteins were enriched by neutravidin affinity and identified by 2D-LC-MS/MS. Second, cells were treated with native 13-HPODE. Protein-carbonyls were biotinylated with an aldehyde reactive probe (ARP) and modified proteins enriched by neutravidin affinity and identified by 2D-LC-MS/MS. Third, using a newly developed DODE antibody, DODE modified proteins were located by 2D-SDS-PAGE and Western blot and identified by in-gel digestion and LC-MS/MS. Analysis of the proteins characterized by all three methods revealed a significant overlap and identified 32 primary proteins modified by DODE in MCF7 cells. These results demonstrated the feasibility for the cellular formation of DODE protein-carbonyl adducts that may be future indicators of oxidative stress. PMID:20131800

  19. 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.

  20. Effect of modified calm conditions on nuclear dispersion estimates.

    PubMed

    Hu, S J; Katagiri, H; Kobayashi, H

    1995-01-01

    When the definition of calm in atmospheric diffusion analyses is changed from 0.5 m s-1 to 0.1 m s-1, actual and more accurate low wind speeds and wind directions can be used to calculate the average air concentrations due to continuous releases of radionuclides at 10-m stack height more realistically and accurately. However, this modified calm condition has little affect on the calculated adult thyroid exposure for a postulated accident.

  1. Effect of modified calm conditions on nuclear dispersion estimates.

    PubMed

    Hu, S J; Katagiri, H; Kobayashi, H

    1995-01-01

    When the definition of calm in atmospheric diffusion analyses is changed from 0.5 m s-1 to 0.1 m s-1, actual and more accurate low wind speeds and wind directions can be used to calculate the average air concentrations due to continuous releases of radionuclides at 10-m stack height more realistically and accurately. However, this modified calm condition has little affect on the calculated adult thyroid exposure for a postulated accident. PMID:7989197

  2. [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

  3. [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.

  4. Detection of circulating tumor cells in prostate cancer based on carboxylated graphene oxide modified light addressable potentiometric sensor.

    PubMed

    Gu, Yajun; Ju, Cheng; Li, Yanjun; Shang, Zhiqun; Wu, Yudong; Jia, Yunfang; Niu, Yuanjie

    2015-04-15

    Circulating tumor cells (CTCs) are a group of rare cancer cells that have detached from a primary tumor and circulate in the bloodstream. Herein, light addressable potentiometric sensor (LAPS) was exploited in the label-free detection of CTCs in the prostate cancer. To this end, the mouse anti-human epithelial cell adhesion molecule (anti-EpCAM) monoclonal antibody was selected as the probe to capture CTCs according to our western blot experiments, and therefore the anti-EpCAM was immobilized on the surface of carboxylated graphene oxide (GO-COOH) modified LAPS. Spiking experiments confirmed that LAPS' voltage decreased with the increasing of CTCs' concentration both in phosphate buffer (PBS) and blood, and as few as 10 CTCs in 1ml of blood could be detected, illustrating the high sensitivity of the proposed strategy. The analysis of healthy blood samples revealed no change in electrical signal, confirming the specificity of the system. Ultraviolet-visible (UV-vis) spectroscopy, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and immunofluorescent assay (IFA) were conducted to characterize GO-COOH, testify its existence on LAPS and validate CTCs' capturing by anti-EpCAM grafted on GO-COOH modified substrates. It is indicated that LAPS could be a potential platform for CTCs detection and may provide a powerful tool for downstream analysis.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. [Antifibrosis effect of modified forms of catalase and superoxide dismutase in experimental silicosis].

    PubMed

    Maksimenko, A V; Bezrukavnikova, L M; Grigor'eva, E L; Tishchenko, E G; Arkhipova, O G; Iaglov, V V; Torchilin, V P

    1992-01-01

    The forms of catalase modified by treatment with dextran aldehyde were obtained and studied. Efficacy of the preparations containing native and modified forms of catalase and superoxide dismutase as well as their covalent bienzyme conjugate containing catalase-dextran aldehyde-superoxide dismutase was studied in rats with simulated silicosis. The preparations were administered into rats by means of inhalation and intraperitoneal injection. Positive protective effect exhibited a mixture of native enzymes and their covalent conjugate. The most pronounced additional effect was caused by the mixture of native catalase and superoxide dismutase as compared with modified preparation of superoxide dismutase. The preparation of bienzyme containing conjugate was less effective. PMID:1384235

  10. 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

  11. 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.

  12. 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

  13. Videos to influence: a systematic review of effectiveness of video-based education in modifying health behaviors.

    PubMed

    Tuong, William; Larsen, Elizabeth R; Armstrong, April W

    2014-04-01

    This systematic review examines the effectiveness of videos in modifying health behaviors. We searched PubMed (1975-2012), PsycINFO (1975-2012), EMBASE (1975-2012), and CINAHL (1983-2012) for controlled clinical trials that examined the effectiveness of video interventions in changing health behaviors. Twenty-eight studies comprised of 12,703 subjects were included in the systematic review. Video interventions were variably effective for modifying health behaviors depending on the target behaviors to be influenced. Video interventions appear to be effective in breast self-examination, prostate cancer screening, sunscreen adherence, self-care in patients with heart failure, HIV testing, treatment adherence, and female condom use. However, videos have not shown to be effective in influencing addiction behaviors when they are not tailored. Compared to loss-framing, gain-framed messages may be more effective in promoting certain types of health behavior change. Also, video modeling may facilitate learning of new behaviors and can be an important consideration in future video interventions.

  14. Selective adsorption of modified nucleoside cancer biomarkers by hybrid molecularly imprinted adsorbents.

    PubMed

    Iwanowska, Agnieszka; Yusa, Shin-Ichi; Nowakowska, Maria; Szczubiałka, Krzysztof

    2016-08-01

    Modified adenosine nucleosides have been proposed to be potential DNA-based biomarkers for early diagnosis of tumor and a promising tool for the development of noninvasive prediction systems. However, the low concentration of modified adenosine nucleosides in physiological fluids makes them challenging for both quantitative and qualitative determination. Therefore, materials, which are potentially useful for selective adsorption of nucleobase-containing compounds, were obtained. To obtain the adsorbents, the silica gel particles were coated layer-by-layer with films of the polymers with different combinations of polymers containing thymine groups. Next, the microspheres were irradiated with UV light in the presence of 2'-deoxyadenosine or 5'-deoxy-5'-(methylthio)adenosine, as template molecules, which resulted in the photodimerization of thymine moieties and molecular imprinting of adsorbed modified adenosine compounds. The selectivity of the adsorption was significantly enhanced by the photoimprinting process. Eventually, the imprinted particles have shown an improved ability to recognize mainly 2'-deoxyadenosine and 5'-deoxy-5'-(methylthio)adenosine molecules. The best performing adsorbent was obtained using modified natural polysaccharides. The studied materials could serve as promising adsorbents of biomarkers for tumor diagnostics. PMID:27296785

  15. 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.

  16. OA01.13. An evaluation on mutra taila bindu pariksha with a modified device in LAS01 (a herbo-mineral compound) treated cancer patients

    PubMed Central

    Sharma, Vinamra; Tiwari, Anoop; Tripathi, Rajesh; Srivastava, Ashok; Saxena, R C; Trivedi, V. P.

    2012-01-01

    Purpose: Ashtavidh rogi pariksha one of the main diagnostic methods described in Ayurveda includes Mutra Taila Bindu Pariksha (MTBP), which is simple and cost effective. Modern diagnostic investigations of tumor markers and radiological procedures are costly and usual tests for recording different stages of cancer. MTBP is also used at Lavanya Ayurvedic Hospital in Cancer patients as diagnostic and prognostic parameters. Test depends on pattern of spreading of oil drop over surface of patient's urine. Method: This procedure was modified keeping all parameters fixed like distance at which sesame oil falls and procedure of collection of urine sample. This equipment was attached with a photographic device. 50 randomly selected cases were divided into two groups. Group I consisted of 10 healthy volunteers and group II consisted of 40 pre diagnosed cases of different types of cancer. Patients were made to sleep at 9 PM. On next morning (5 AM) mid stream urine of the first urination was collected in a standard sized beaker of 250 ml. Sample beaker was kept in a specifically designed glass and fibre cabinet, which was devoid of air. A 10 ml glass burette filled with Tila taila (Sesame oil) was fixed over beaker containing urine. One drop of sesame oil was dropped over the stable surface of urine from a distance of 2 cm. The oil drop dispersal pattern on the surface of collected urine sample was recorded photographically. It was analysed periodically at monthly intervals for three times. Result: The results of oil spreading nature, direction and shape over urine surface were compared with modern biochemical, haematological and radiological parameters in different stages of cancer. Conclusion: The pattern of dispersal of sesame oil was progressively changed in relation to the improvement in subjective and bjective parameters in LAS01 treated cases.

  17. Selective effects of a fiber chimeric conditionally replicative adenovirus armed with hep27 gene on renal cancer cell.

    PubMed

    Fang, Lin; Cheng, Qian; Liu, Wenshun; Zhang, Jie; Ge, Yan; Zhang, Qi; Li, Liantao; Liu, Junjie; Zheng, Junnian

    2016-06-01

    ASBTARCT Adenoviruses mediated cancer gene therapies are widely investigated and show a promising effect on cancer treatment. However, efficient gene transfer varies among different cancer cell lines based on the expression of coxsakie adenovirus receptor (CAR). Hep27, a member of dehydrogenase/reductase (SDR) family, can bind to Mdm2, resulting in the attenuation of Mdm2-mediated p53 degradation. Here we constructed a fiber chimeric adenovirus carrying hep27 gene (F5/35-ZD55-Hep27), in which the fiber protein of 5-serotype adenovirus (Ad5) was substituted by that of 35-serotype adenovirus (Ad35), aiming to facilitate the infection for renal cancer cells and develop the role of hep27 in cancer therapy. We evaluated the CAR and CD46 (a membrane cofactor protein for Ad35) expression in four kinds of renal cancer cells and assessed the relationship between receptors and infection efficiency. 5/35 fiber-modified adenovirus had a much promising infectivity compared with Ad5-based vector in renal cancer cells. F5/35-ZD55-Hep27 had enhanced antitumor activity against human renal cancer cells compared to the other groups. Further, hep27 mediated p53 and cleaved-PARP upregulation and mdm2 downregulation was involved and caused increased apoptosis. Moreover, F5/35-ZD55-Hep27 significantly suppressed tumor growth in subcutaneous renal cancer cell xenograft models. Our data demonstrated that 5/35 fiber-modified adenovirus F5/35-ZD55-Hep27 transferred into renal cancers efficiently and increased p53 to induce cancer cell apoptosis. Thus 5/35 fiber-modified adenoviral vector F5/35-ZD55-Hep27 might a promising vector and antitumor reagent for renal cancer gene therapy. PMID:27195521

  18. Selective effects of a fiber chimeric conditionally replicative adenovirus armed with hep27 gene on renal cancer cell.

    PubMed

    Fang, Lin; Cheng, Qian; Liu, Wenshun; Zhang, Jie; Ge, Yan; Zhang, Qi; Li, Liantao; Liu, Junjie; Zheng, Junnian

    2016-06-01

    ASBTARCT Adenoviruses mediated cancer gene therapies are widely investigated and show a promising effect on cancer treatment. However, efficient gene transfer varies among different cancer cell lines based on the expression of coxsakie adenovirus receptor (CAR). Hep27, a member of dehydrogenase/reductase (SDR) family, can bind to Mdm2, resulting in the attenuation of Mdm2-mediated p53 degradation. Here we constructed a fiber chimeric adenovirus carrying hep27 gene (F5/35-ZD55-Hep27), in which the fiber protein of 5-serotype adenovirus (Ad5) was substituted by that of 35-serotype adenovirus (Ad35), aiming to facilitate the infection for renal cancer cells and develop the role of hep27 in cancer therapy. We evaluated the CAR and CD46 (a membrane cofactor protein for Ad35) expression in four kinds of renal cancer cells and assessed the relationship between receptors and infection efficiency. 5/35 fiber-modified adenovirus had a much promising infectivity compared with Ad5-based vector in renal cancer cells. F5/35-ZD55-Hep27 had enhanced antitumor activity against human renal cancer cells compared to the other groups. Further, hep27 mediated p53 and cleaved-PARP upregulation and mdm2 downregulation was involved and caused increased apoptosis. Moreover, F5/35-ZD55-Hep27 significantly suppressed tumor growth in subcutaneous renal cancer cell xenograft models. Our data demonstrated that 5/35 fiber-modified adenovirus F5/35-ZD55-Hep27 transferred into renal cancers efficiently and increased p53 to induce cancer cell apoptosis. Thus 5/35 fiber-modified adenoviral vector F5/35-ZD55-Hep27 might a promising vector and antitumor reagent for renal cancer gene therapy.

  19. A novel class of mitochondria-targeted soft electrophiles modifies mitochondrial proteins and inhibits mitochondrial metabolism in breast cancer cells through redox mechanisms.

    PubMed

    Vayalil, Praveen K; Oh, Joo-Yeun; Zhou, Fen; Diers, Anne R; Smith, M Ryan; Golzarian, Hafez; Oliver, Patsy G; Smith, Robin A J; Murphy, Michael P; Velu, Sadanandan E; Landar, Aimee

    2015-01-01

    Despite advances in screening and treatment over the past several years, breast cancer remains a leading cause of cancer-related death among women in the United States. A major goal in breast cancer treatment is to develop safe and clinically useful therapeutic agents that will prevent the recurrence of breast cancers after front-line therapeutics have failed. Ideally, these agents would have relatively low toxicity against normal cells, and will specifically inhibit the growth and proliferation of cancer cells. Our group and others have previously demonstrated that breast cancer cells exhibit increased mitochondrial oxygen consumption compared with non-tumorigenic breast epithelial cells. This suggests that it may be possible to deliver redox active compounds to the mitochondria to selectively inhibit cancer cell metabolism. To demonstrate proof-of-principle, a series of mitochondria-targeted soft electrophiles (MTSEs) has been designed which selectively accumulate within the mitochondria of highly energetic breast cancer cells and modify mitochondrial proteins. A prototype MTSE, IBTP, significantly inhibits mitochondrial oxidative phosphorylation, resulting in decreased breast cancer cell proliferation, cell attachment, and migration in vitro. These results suggest MTSEs may represent a novel class of anti-cancer agents that prevent cancer cell growth by modification of specific mitochondrial proteins.

  20. 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

  1. [Effect of SDS on the adsorption of Cd2+ onto amphoteric modified bentonites].

    PubMed

    Wang, Jian-Tao; Meng, Zhao-Fu; Yang, Ya-Ti; Yang, Shu-Ying; Li, Bin; Xu, Shao-e

    2014-07-01

    Under different modified ratios, temperatures, pH and ionic strengths, the effect of sodium dodecyl sulfonate (SDS) on the adsorption of Cd2+ onto bentonites which modified with amphoteric modifier dodecyl dimethyl betaine (BS-12) was studied by batch experiments, and the adsorption mechanism was also discussed. Results showed that the adsorption of Cd2+ on amphoteric bentonites can be enhanced significantly by SDS combined modification, Cd2+ adsorption decreases in the order: BS + 150SDS (BS-12 + 150% SDS) > BS + 100SDS (BS-12 + 100% SDS) > BS +50SDS(BS-12 + 50% SDS) > BS + 25SDS (BS-12 + 25% SDS) > BS (BS-12) > CK (unmodified soil). The adsorption isotherm can be described by the Langmuir equation. The change of temperature effect from positive on CK and amphoteric bentonites to negative on BS + 150SDS bentonites is observed with an increase of SDS modified ratio. The pH has little influence on Cd2+ adsorption on bentonites. The adsorption of Cd2+ on bentonites decreases with ionic strength rise, but the effect of ionic strength can be reduced with an increase of SDS modified ratio also. The adsorption thermodynamic parameters demonstrated that the adsorption of Cd2+ on modified bentonites was spontaneously controlled by entropy increment. When the SDS modified ratio is lower than 100% CEC, the adsorption of Cd2+ on modified bentonites is a process with characteristics of both enthalpy increment and entropy increment, while the SDS modified ratio is equal to or higher than 100% CEC, the adsorption of Cd2+ on modified bentonites becomes a process of enthalpy decrement and entropy increment. PMID:25244843

  2. 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

  3. 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

  4. Modifying metabolically sensitive histone marks by inhibiting glutamine metabolism affects gene expression and alters cancer cell phenotype.

    PubMed

    Simpson, Natalie E; Tryndyak, Volodymyr P; Pogribna, Marta; Beland, Frederick A; Pogribny, Igor P

    2012-12-01

    The interplay of metabolism and epigenetic regulatory mechanisms has become a focal point for a better understanding of cancer development and progression. In this study, we have acquired data supporting previous observations that demonstrate glutamine metabolism affects histone modifications in human breast cancer cell lines. Treatment of non-invasive epithelial (T-47D and MDA-MB-361) and invasive mesenchymal (MDA-MB-231 and Hs-578T) breast cancer cell lines with the glutaminase inhibitor, Compound 968, resulted in cytotoxicity in all cell lines, with the greatest effect being observed in MDA-MB-231 breast cancer cells. Compound 968-treatment induced significant downregulation of 20 critical cancer-related genes, the majority of which are anti-apoptotic and/or promote metastasis, including AKT, BCL2, BCL2L1, CCND1, CDKN3, ERBB2, ETS1, E2F1, JUN, KITLG, MYB, and MYC. Histone H3K4me3, a mark of transcriptional activation, was reduced at the promoters of all but one of these critical cancer genes. The decrease in histone H3K4me3 at global and gene-specific levels correlated with reduced expression of SETD1 and ASH2L, genes encoding the histone H3K4 methyltransferase complex. Further, the expression of other epigenetic regulatory genes, known to be downregulated during apoptosis (e.g., DNMT1, DNMT3B, SETD1 and SIRT1), was also downregulated by Compound 968. These changes in gene expression and histone modifications were accompanied by the activation of apoptosis, and decreased invasiveness and resistance of MDA-MB-231 cells to chemotherapeutic drug doxorubicin. The results of this study provide evidence to a link between cytotoxicity caused by inhibiting glutamine metabolism with alterations of the epigenome of breast cancer cells and suggest that modification of intracellular metabolism may enhance the efficiency of epigenetic therapy. PMID:23117580

  5. 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.

  6. 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

  7. 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

  8. Synthesis and evaluation of perfluorooctylbromide nanoparticles modified with a folate receptor for targeting ovarian cancer: in vitro and in vivo experiments

    PubMed Central

    Liu, Xinjie; Zhao, Jiannong; Guo, Dajing; Wang, Zhigang; Song, Weixiang; Chen, Weijuan; Zhou, Jun

    2015-01-01

    Background: Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. However, detecting ovarian cancer at an early stage remains challenging. In this work, we aimed to synthesize a folate-receptor-targeting perfluorooctylbromide nanoparticle (FR-TPNP) as a targeted computed tomography (CT) contrast agent for the early detection of ovarian cancer. Methods: Perfluorooctylbromide (PFOB) was encapsulated in Poly (lactic-co-glycolic acid) (PLGA) by a two-step emulsion technique to construct the nanoparticles. Folate-poly (ethylene glycol)-carboxylic acid (Fol-PEG-COOH) was introduced to modify the surface of the nanoparticles through attachment to the PLGA. The effects of different volume ratios of PFOB to PLGA on the characteristics of the FR-TPNP emulsions were compared. The size distribution and potential of the FR-TPNPs were assessed with a laser particle size analyzer system. The in vitro targeting ability of the FR-TPNPs was observed with a confocal laser scanning microscope (CLSM), and the in vivo transportation of the FR-TPNPs was evaluated with CT. Results: The sizes of the FR-TPNP emulsion with different volume ratios varied from 302.67 ± 27.83 nm to 563.68 ± 47.29 nm, and the mean CT value ranged from 233 ± 20.59 HU to 587.66 ± 159.51 HU. Both the size and mean CT value increased with the volume ratio. The FR-TPNPs showed greater cell affinity and targeting efficiency to SKOV3 cells than the control group and folic acid interference group in vitro, as observed by CLSM. A significant CT enhancement of ovarian cancer xenografts in the targeted group of a nude mice model was observed 2 h post-injection; it increased to a peak at 12 h and had a duration of 48 h. The mean CT value of the tumor in the targeted group was considerably higher than those in the non-targeted and other groups 6 h post-injection. Conclusion: The synthesized FR-TPNP emulsion was an effective CT contrast agent with highly efficient targeting ability and a

  9. 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

  10. 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.

  11. The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.

    PubMed

    Ferreyra Solari, Nazarena E; Belforte, Fiorella S; Canedo, Lucía; Videla-Richardson, Guillermo A; Espinosa, Joaquín M; Rossi, Mario; Serna, Eva; Riudavets, Miguel A; Martinetto, Horacio; Sevlever, Gustavo; Perez-Castro, Carolina

    2016-09-15

    KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. Mechanistic investigations showed that KANSL2 regulates cell self-renewal, which correlates with effects on expression of the stemness transcription factor POU5F1. RNAi-mediated silencing of POU5F1 reduced KANSL2 levels, linking these two genes to stemness control in GBM cells. Together, our findings indicate that KANSL2 acts to regulate the stem cell population in GBM, defining it as a candidate GBM biomarker for clinical use. Cancer Res; 76(18); 5383-94. ©2016 AACR.

  12. 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.

  13. Successful Treatment with Modified FOLFOX6 and Panitumumab in a Cecal Cancer Patient Undergoing Hemodialysis.

    PubMed

    Kobayashi, Mariko; Endo, Shinji; Hamano, Yukako; Imanishi, Mamiko; Akutsu, Daisuke; Sugaya, Akinori; Ochi, Daisuke; Moriwaki, Toshikazu; Hyodo, Ichinosuke

    2016-01-01

    Combination chemotherapy of mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) plus panitumumab, a fully human monoclonal antibody against epidermal growth factor receptor (EGFR), is one of the standard treatments for metastatic colorectal cancer (mCRC) without KRAS mutation. A few reports suggested no need of dose adjustment of cetuximab, a similar chimeric anti-EGFR antibody, in patients with renal impairment. However, panitumumab combined with cytotoxic drugs for hemodialysis patients has not been reported. We herein report a case of a hemodialysis mCRC patient successfully treated with mFOLFOX6 and panitumumab combination therapy. PMID:26781010

  14. Optimization of Landscape Phage Fusion Protein-Modified Polymeric PEG-PE Micelles for Improved Breast Cancer Cell Targeting

    PubMed Central

    Wang, Tao; Petrenko, Valery A.; Torchilin, Vladimir P.

    2015-01-01

    Amphiphilic landscape phage fusion proteins with high affinity and selectivity towards breast cancer MCF-7 (Michigan Cancer Foundation-7) cells self-assemble with polymeric PEG-PE conjugates to form mixed micelles (phage-micelles) capable of cancer cell-targeted delivery of poorly-soluble drugs. While the PEG corona provides the stability and longevity to the micelles, its presence is a potential steric difficulties for the interaction of phage fusion protein with cell surface targets. We attempted to address this problem by controlling the length of the PEG block and the phage fusion protein quantity, selecting the optimal ones to produce a reasonable retention of the targeting affinity and selectivity of the MCF-7-specific phage fusion protein. Three PEG-PE conjugates with different PEG lengths were used to construct phage- and plain-micelles, followed by FACS analysis of the effect of the PEG length on their binding affinity and selectivity towards target MCF-7 cells using either a MCF-7 cell monoculture or a cell co-culture model composed of target cancer MCF-7 cells and non-target, non-cancer C166 cells expressing GFP (Green Fluorescent Protein). Both, the length of PEG and quantity of phage fusion protein had a profound impact on the targetability of the phage-micelles. Phage-micelles prepared with PEG2k-PE achieved a desirable binding affinity and selectivity. Incorporation of a minimal concentration of phage protein, up to 0.5%, produced maximal targeting efficiency towards MCF-7 cells. Overall, phage-micelles with PEG2k-PE and 0.5% of phage protein represent the optimal formulation for targeting towards breast cancer cells. PMID:26451274

  15. Potentiation of pH-sensitive polymer-modified liposomes with cationic lipid inclusion as antigen delivery carriers for cancer immunotherapy.

    PubMed

    Yoshizaki, Yuta; Yuba, Eiji; Sakaguchi, Naoki; Koiwai, Kazunori; Harada, Atsushi; Kono, Kenji

    2014-09-01

    Cationic lipid-incorporated liposomes modified with pH-sensitive polymers were prepared by introducing 3, 5-didodecyloxybenzamidine as a cationic lipid to egg yolk phosphatidylcholine liposomes modified with 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG) as a pH-sensitive polymer. These liposomes were stable at neutral pH, but were destabilized below pH 6.0 because MGlu-HPG changed its characteristics from hydrophilic to hydrophobic in response to the pH decrease. Cationic lipid inclusion improved their pH sensitivity at weakly acidic pH and association of liposomes with murine dendritic cell (DC) lines. Cationic lipid-incorporated liposomes delivered entrapped ovalbumin (OVA) molecules not only to cytosol but also to endosome/lysosome. Treatment with cationic lipid-incorporated liposomes induced up-regulation of antigen presentation-involved molecules on DCs, the promotion of cytokine production, and antigen presentation via both major histocompatibility complex (MHC) class I and II molecules. Especially, antigen presentation via MHC class II was promoted by cationic lipid inclusion, which might correspond to efficient endosome/lysosome delivery of OVA. Subcutaneous administration of OVA-loaded cationic lipid-incorporated liposomes induced antigen-specific antibody production in serum and Th1-dominant immune responses in the spleen. Furthermore, administration of the cationic lipid-incorporated liposomes to mice bearing E.G7-OVA tumor more significantly reduced the tumor volume than liposomes without cationic lipids. Therefore, cationic lipid inclusion into pH-sensitive polymer-modified liposomes, which can achieve both efficient antigen intracellular delivery and activation of antigen presenting cell, is an effective approach to develop antigen carriers for efficient cancer immunotherapy.

  16. 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…

  17. 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.

  18. 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

  19. Effects on electrochemical performances for host material caused by structure change of modifying material.

    PubMed

    Zhang, Yantao; Zhou, Enlou; Song, Dawei; Shi, Xixi; Wang, Xiaoqing; Guo, Jian; Zhang, Lianqi

    2014-09-01

    High ionic conductive lithium niobium oxides were selected as the modifying material to investigate the effects on the electrochemical performances for host material LiNi1/3Co1/3Mn1/3O2 caused by the structure change of the modifying material at various calcination temperatures and modifying amounts. X-ray diffraction (XRD) studies revealed that the structure of the modifying material was single LiNbO3 phase after being calcined at 500 °C and changed to LiNbO3-Li3NbO4 mixture phases at 600 and 700 °C, and further changed to single Li3NbO4 phase at 800 °C. Electrochemical tests displayed that both LiNbO3 and Li3NbO4 phases of modifying material could contribute to the improvement of the cycle performances for the host material, but the improvement degree of Li3NbO4 phase was more evident. The cycle performances and high rate performances of the modified host material (calcined at 700 °C) electrodes were improved with the right modifying amount.

  20. Modifiers of epigenetic reprogramming show paternal effects in the mouse

    PubMed Central

    Chong, Suyinn; Vickaryous, Nicola; Ashe, Alyson; Zamudio, Natasha; Youngson, Neil; Hemley, Sarah; Stopka, Tomas; Skoultchi, Arthur; Matthews, Jacqui; Scott, Hamish S; de Kretser, David; O’Bryan, Moira; Blewitt, Marnie; Whitelaw, Emma

    2011-01-01

    There is increasing evidence that epigenetic information can be inherited across generations in mammals, despite extensive reprogramming both in the gametes and in the early developing embryo. One corollary to this is that disrupting the establishment of epigenetic state in the gametes of a parent, as a result of heterozygosity for mutations in genes involved in reprogramming, could affect the phenotype of offspring that do not inherit the mutant allele. Here we show that such effects do occur following paternal inheritance in the mouse. We detected changes to transcription and chromosome ploidy in adult animals. Paternal effects of this type have not been reported previously in mammals and suggest that the untransmitted genotype of male parents can influence the phenotype of their offspring. PMID:17450140

  1. 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

  2. Mammary renin-angiotensin system-regulating aminopeptidase activities are modified in rats with breast cancer.

    PubMed

    del Pilar Carrera, Maria; Ramírez-Expósito, Maria Jesus; Mayas, Maria Dolores; García, Maria Jesus; Martínez-Martos, Jose Manuel

    2010-12-01

    Angiotensin II in particular and/or the local renin-angiotensin system in general could have an important role in epithelial tissue growth and modelling; therefore, it is possible that it may be involved in breast cancer. In this sense, previous works of our group showed a predominating role of angiotensin II in tumoral tissue obtained from women with breast cancer. However, although classically angiotensin II has been considered the main effector peptide of the renin-angiotensin system cascade, several of its catabolism products such as angiotensin III and angiotensin IV also possess biological functions. These peptides are formed through the activity of several proteolytic regulatory enzymes of the aminopeptidase type, also called angiotensinases. The aim of this work was to analyse several specific angiotensinase activities involved in the renin-angiotensin system cascade in mammary tissue from control rats and from rats with mammary tumours induced by N-methyl-nitrosourea (NMU), which may reflect the functional status of their target peptides under the specific conditions brought about by the tumoural process. The results show that soluble and membrane-bound specific aspartyl aminopeptidase activities and membrane-bound glutamyl aminopeptidase activity increased in mammary tissue from NMU-treated animals and soluble aminopeptidase N and aminopeptidase B activities significantly decreased in mammary tissue from NMU-treated rats. These changes support the existence of a local mammary renin-angiotensin system and that this system and its putative functions in breast tissue could be altered by the tumour process, in which we suggest a predominant role of angiotensin III. All described data about the renin-angiotensin system in mammary tissue support the idea that it must be involved in normal breast tissue functions, and its disruption could be involved in one or more steps of the carcinogenesis process.

  3. Effects of Standard and Modified Gravity on Interplanetary Ranges

    NASA Astrophysics Data System (ADS)

    Iorio, L.

    We numerically investigate the impact on the two-body range of several Newtonian and non-Newtonian dynamical effects for some Earth-planet (Mercury, Venus, Mars, Jupiter, Saturn) pairs, in view of the expected cm-level accuracy in some future planned or proposed interplanetary ranging operations. The general relativistic gravitomagnetic Lense-Thirring effect should be modeled and solved for in future accurate ranging tests of Newtonian and post-Newtonian gravity, because it falls within their measurability domain. It could a priori "imprint" the determination of some of the target parameters of the tests considered. Moreover, the ring of the minor asteroids, Ceres, Pallas, Vesta (and also many other asteroids if Mars is considered) and the trans-Neptunian objects (TNOs) act as sources of nonnegligible systematic uncertainty on the larger gravitoelectric post-Newtonian signals from which it is intended to determine the parameters γ and β of the parametrized post-Newtonian (PPN) formalism with very high precision (several orders of magnitude better than the current 10-4-10-5 levels). Also, other putative, nonconventional gravitational effects, like a violation of the strong equivalence principle (SEP), a secular variation of the Newtonian constant of gravitation G, and the Pioneer anomaly, are considered. The presence of a hypothetical, distant planetary-sized body X could be detectable with future high-accuracy planetary ranging. Our analysis can, in principle, be extended to future interplanetary ranging scenarios in which one or more spacecrafts in heliocentric orbits are involved. The impact of fitting the initial conditions, and of the noise in the observations, on the actual detectability of the dynamical signatures investigated, which may be partly absorbed in the estimation process, should be quantitatively addressed in further studies.

  4. 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.

  5. New Strategies in Engineering T-cell Receptor Gene-Modified T cells to More Effectively Target Malignancies.

    PubMed

    Schmitt, Thomas M; Stromnes, Ingunn M; Chapuis, Aude G; Greenberg, Philip D

    2015-12-01

    The immune system, T cells in particular, have the ability to target and destroy malignant cells. However, antitumor immune responses induced from the endogenous T-cell repertoire are often insufficient for the eradication of established tumors, as illustrated by the failure of cancer vaccination strategies or checkpoint blockade for most tumors. Genetic modification of T cells to express a defined T-cell receptor (TCR) can provide the means to rapidly generate large numbers of tumor-reactive T cells capable of targeting tumor cells in vivo. However, cell-intrinsic factors as well as immunosuppressive factors in the tumor microenvironment can limit the function of such gene-modified T cells. New strategies currently being developed are refining and enhancing this approach, resulting in cellular therapies that more effectively target tumors and that are less susceptible to tumor immune evasion.

  6. Effect of citalopram in the modified forced swim test in rats.

    PubMed

    Kuśmider, Maciej; Solich, Joanna; Pałach, Paulina; Dziedzicka-Wasylewska, Marta

    2007-01-01

    The present study examined the effect of citalopram (7.5 and 15 mg/kg) in the modified forced swim test (FST) in Wistar rats, in comparison to the effect of desipramine at the same doses. The citalopram at both doses increased swimming behavior, at the cost of climbing and immobility. The administration of desipramine increased climbing behavior while immobility counts were decreased. The modified FST is indeed more sensitive than the conventional FST in describing precisely the behavioral effects of antidepressant drugs, allowing to roughly estimate the contribution of individual neurotransmitter system to the mechanism of action of the studied drug.

  7. 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.

  8. 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.

  9. Modifying anti-inflammatory effect of Diclofenac with Murraya koenigii.

    PubMed

    Kaur, Ginpreet; Daftardar, Saloni; Barve, Kalyani H

    2014-01-01

    Murraya koenigii (Curry leaves) has been widely used in Asian countries for the treatment of some ailments such as diabetes and hypertension. In the present study, leaves of Murraya koenigii were extracted with ethanol and evaluated for anti-inflammatory activity in rats using carrageenan induced paw edema method. Ethanolic extract showed a potent anti-inflammatory activity at third hour after carrageenan administration when compared with the standard drug, Diclofenac. The percent inhibition of paw volume was found to be 84.75% for 50 mg/kg of extract whereas it was found to be 80.86% for 50 mg/kg extract in combination with Diclofenac 10 mg/kg. Thus, the present study suggests that the combination therapy potentiates the anti-inflammatory effect of diclofenac and may help in reducing the dose of the synthetic drug. Some relevant patents are also outlined in this article.

  10. Molecular insights into the OGG1 gene, a cancer risk modifier in BRCA1 and BRCA2 mutations carriers

    PubMed Central

    Benitez-Buelga, Carlos; Vaclová, Tereza; Ferreira, Sofia; Urioste, Miguel; Inglada-Perez, Lucia; Soberón, Nora; Blasco, Maria A.; Osorio, Ana; Benitez, Javier

    2016-01-01

    We have recently shown that rs2304277 variant in the OGG1 glycosidase gene of the Base Excision Repair pathway can increase ovarian cancer risk in BRCA1 mutation carriers. In the present study, we aimed to explore the role of this genetic variant on different genome instability hallmarks to explain its association with cancer risk. We have evaluated the effect of this polymorphism on OGG1 transcriptional regulation and its contribution to telomere shortening and DNA damage accumulation. For that, we have used a series of 89 BRCA1 and BRCA2 mutation carriers, 74 BRCAX cases, 60 non-carrier controls and 23 lymphoblastoid cell lines (LCL) derived from BRCA1 mutation carriers and non-carriers. We have identified that this SNP is associated to a significant OGG1 transcriptional down regulation independently of the BRCA mutational status and that the variant may exert a synergistic effect together with BRCA1 or BRCA2 mutations on DNA damage and telomere shortening. These results suggest that this variant, could be associated to a higher cancer risk in BRCA1 mutation carriers, due to an OGG1 transcriptional down regulation and its effect on genome instability. PMID:27015555

  11. Ultrasensitive Bisphenol A Field-Effect Transistor Sensor Using an Aptamer-Modified Multichannel Carbon Nanofiber Transducer.

    PubMed

    Kim, Sung Gun; Lee, Jun Seop; Jun, Jaemoon; Shin, Dong Hoon; Jang, Jyongsik

    2016-03-01

    Bisphenol A (BPA) is a known endocrine-disrupting compound (EDC) that has a structure similar to that of the hormone estrogen. Even low concentrations of BPA are able to bind estrogen receptors, thereby inducing severe diseases such as reproductive disorders, chronic diseases, and various types of cancer. Despite such serious effects, the use of BPA remains widespread. Therefore, monitoring of both dietary and nondietary exposure to BPA is important for human healthcare. Herein, we present a field-effect transistor (FET) sensor using aptamer-modified multichannel carbon nanofibers (MCNFs) to detect BPA. The MCNFs are fabricated via single-nozzle electrospinning of two immiscible polymer solutions followed by thermal treatment in an inert atmosphere. The MCNFs are then oxidized using a solution of HNO3 and H2SO4 to introduce carboxyl groups on the surface of the fibers. The carboxyl-functionalized MCNFs (CMCNFs) are immobilized on an amine-functionalized electrode substrate by forming a covalent bond, and amine-functionalized BPA-binding aptamers are modified in the same manner on the CMCNFs. The resulting FET sensors exhibit a high sensitivity, as well as specificity toward BPA at an unprecedentedly low concentration of 1 fM. Furthermore, these sensors are stable and could be reused for repeated assays. PMID:26883578

  12. 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…

  13. 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…

  14. 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...

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  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.

  2. 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.

  3. 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

  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. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  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. 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

  14. Differential effects of bisphosphonates on breast cancer cell lines.

    PubMed

    Verdijk, R; Franke, H R; Wolbers, F; Vermes, I

    2007-02-01

    Bisphosphonates may induce direct anti-tumor effects in breast cancer cells in vitro. In this study, six bisphosphonates were administered to three breast cancer cell lines. Cell proliferation was measured by quantification of the expression of Cyclin D1 mRNA. Apoptosis was determined by flow cytometry of a DNA fragmentation assay. We demonstrated that bisphosphonates have direct effects on cell proliferation and apoptosis in different breast cancer cell lines. However, not all bisphosphonates act equally on breast cancer cells in vitro. Zoledronate seems to be the most potent of the six bisphosphonates. This in vitro study showed that bisphosphonates possess promising anti-tumor potential.

  15. Synthesis and characterization of a glycine-modified heptamethine indocyanine dye for in vivo cancer-targeted near-infrared imaging.

    PubMed

    Liu, Tao; Luo, Shenglin; Wang, Yang; Tan, Xu; Qi, Qingrong; Shi, Chunmeng

    2014-01-01

    Near-infrared (NIR) fluorescent sensors have emerged as promising molecular tools for cancer imaging and detection in living systems. However, cancer NIR fluorescent sensors are very challenging to develop because they are required to exhibit good specificity and low toxicity as an eligible contrast agent. Here, we describe the synthesis of a new heptamethine indocyanine dye (NIR-27) modified with a glycine at the end of each N-alkyl side chain, and its biological characterization for in vivo cancer-targeted NIR imaging. In addition to its high specificity, NIR-27 also shows lower cytotoxicity than indocyanine green, a nonspecific NIR probe widely used in clinic. These characteristics suggest that NIR-27 is a promising prospect as a new NIR fluorescent sensor for sensitive cancer detection.

  16. 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.

  17. 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

  18. 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

  19. Genetic variation: effect on prostate cancer

    PubMed Central

    Sissung, Tristan M.; Price, Douglas K.; Del Re, Marzia; Ley, Ariel M.; Giovannetti, Elisa; Danesi, Romano

    2014-01-01

    Summary The crucial role of androgens in the development of prostate cancer is well established. The aim of this review is to examine the role of constitutional (germline) and tumor-specific (somatic) polymorphisms within important regulatory genes of prostate cancer. These include genes encoding enzymes of the androgen biosynthetic pathway, the androgen receptor gene, genes that encode proteins of the signal transduction pathways that may have a role in disease progression and survival, and genes involved in prostate cancer angiogenesis. Characterization of deregulated pathways critical to cancer cell growth have lead to the development of new treatments, including the CYP17 inhibitor abiraterone and clinical trials using novel drugs that are ongoing or recently completed [1]. The pharmacogenetics of the drugs used to treat prostate cancer will also be addressed. This review will define how germline polymorphisms are known affect a multitude of pathways, and therefore phenotypes, in prostate cancer etiology, progression, and treatment. PMID:25199985

  20. Effect of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine.

    PubMed

    Ewen, S W; Pusztai, A

    1999-10-16

    Diets containing genetically modified (GM) potatoes expressing the lectin Galanthus nivalis agglutinin (GNA) had variable effects on different parts of the rat gastrointestinal tract. Some effects, such as the proliferation of the gastric mucosa, were mainly due to the expression of the GNA transgene. However, other parts of the construct or the genetic transformation (or both) could also have contributed to the overall biological effects of the GNA-GM potatoes, particularly on the small intestine and caecum.

  1. Human cancer xenografts in outbred nude mice can be confounded by polymorphisms in a modifier of tumorigenesis.

    PubMed

    Zeineldin, Maged; Jensen, Derek; Paranjape, Smita R; Parelkar, Nikhil K; Jokar, Iman; Vielhauer, George A; Neufeld, Kristi L

    2014-08-01

    Tumorigenicity studies often employ outbred nude mice, in the absence of direct evidence that this mixed genetic background will negatively affect experimental outcome. Here we show that outbred nude mice carry two different alleles of Pla2g2a, a genetic modifier of intestinal tumorigenesis in mice. Here, we identify previous unreported linked polymorphisms in the promoter, noncoding and coding sequences of Pla2g2a and show that outbred nude mice from different commercial providers are heterogeneous for this polymorphic Pla2g2a allele. This heterogeneity even extends to mice obtained from a single commercial provider, which display mixed Pla2g2a genotypes. Notably, we demonstrated that the polymorphic Pla2g2a allele affects orthotopic xenograft establishment of human colon cancer cells in outbred nude mice. This finding establishes a non-cell-autonomous role for Pla2g2a in suppressing intestinal tumorigenesis. Using in vitro reporter assays and pharmacological inhibitors, we show promoter polymorphisms and nonsense-mediated RNA decay (NMD) as underlying mechanisms that lead to low Pla2g2a mRNA levels in tumor-sensitive mice. Together, this study provides mechanistic insight regarding Pla2g2a polymorphisms and demonstrates a non-cell-autonomous role for Pla2g2a in suppressing tumors. Moreover, our direct demonstration that mixed genetic backgrounds of outbred nude mice can significantly affect baseline tumorigenicity cautions against future use of outbred mice for tumor xenograft studies.

  2. Discovery of sialyl Lewis A and Lewis X modified protein cancer biomarkers using high density antibody arrays

    PubMed Central

    Rho, Jung-hyun; Mead, Judson R.; Wright, W. Shea; Brenner, Dean E.; James, W. Stave; Gildersleeve, Jeffrey C.; Lampe, Paul D.

    2013-01-01

    We report on a high-dimensional method to globally profile glycoproteins that are modified with sialyl Lewis A or Lewis X glycans. Specifically, glycoproteins in serum or plasma are fractionated on a high-density antibody microarray (i.e., each are localized to their specific antibody spot) and are specifically detected via fluorescently labeled anti-sialyl Lewis A or anti- Lewis X antibodies with quantification in a microarray scanner. Non-glycosylated proteins or glycoproteins with other glycan motifs do not interfere with this assay. The whole process is very rapid and applicable for high-throughput screening without the need for purification of glycoproteins from the samples. Using these methods, sialyl Lewis A or Lewis X moieties were found to be expressed on many previously unreported secreted or membrane associated proteins. Furthermore, the combination of sialyl Lewis A or Lewis X content with protein level increased the ability of certain glycoproteins to distinguish 30 patients with stage III and IV colon cancer from 60 control samples. Thus, this highly sensitive method is capable of discovering novel specific glycan modifications on proteins, many of which will likely be useful for disease detection and monitoring. PMID:24185138

  3. 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.

  4. Modified weak measurements for the detection of the photonic spin Hall effect

    NASA Astrophysics Data System (ADS)

    Chen, Shizhen; Zhou, Xinxing; Mi, Chengquan; Luo, Hailu; Wen, Shuangchun

    2015-06-01

    Weak measurement is an important technique for the detection of the tiny spin-dependent splitting in photonic spin Hall effect. The weak measurement is only valid when the probe wave function remains almost undisturbed during the procedure of measurements. However, it does not always satisfy such condition in some practical situations, such as in the strong-coupling regime or when the preselected and postselected states are nearly orthogonal. In this paper, we develop a modified weak measurement for the detection of the photonic spin Hall effect when the probe wave function is distorted. We find that the measuring procedure with preselected and postselected ensembles is still effective. This scheme is important for us to detect the photonic spin Hall effect in the case where neither weak nor strong measurements can detect the spin-dependent splitting. The modified theory is valid not only in the weak-coupling regime but also in the strong-coupling regime, and especially in the intermediate regime. The theoretical models of conventional weak measurements and modified weak measurements are established and compared. We show that the experimental results coincide well with the predictions of the modified theory.

  5. 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…

  6. 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…

  7. 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...

  8. 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…

  9. 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...

  10. 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…

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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…

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

    PubMed

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

    2015-02-01

    [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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. Effects of modified-implement training on fast bowling in cricket.

    PubMed

    Petersen, Carl J; Wilson, Barry D; Hopkins, Will G

    2004-01-01

    The effects of training with overweight and underweight cricket balls on fast-bowling speed and accuracy were investigated in senior club cricket bowlers randomly assigned to either a traditional (n = 9) or modified-implement training (n = 7) group. Both groups performed bowling training three times a week for 10 weeks. The traditional training group bowled only regulation cricket balls (156 g), whereas the modified-implement training group bowled a combination of overweight (161-181 g), underweight (151-131 g) and regulation cricket balls. A radar gun measured the speed of 18 consecutive deliveries for each bowler before, during and after the training period. Video recordings of the deliveries were also analysed to determine bowling accuracy in terms of first-bounce distance from the stumps. Bowling speed, which was initially 108 +/- 5 km h(-1) (mean +/- standard deviation), increased in the modified-implement training group by 4.0 km x h(-1) and in the traditional training group by 1.3 km x h(-1) (difference, 2.7 km x h(-1); 90% confidence limits, 1.2 to 4.2 km x h(-1)). For a minimum worthwhile change of 5 km x h(-1), the chances that the true effect on bowling speed was practically beneficial/trivial/harmful were 1.0/99/< 0.1%. For bowling accuracy, the chances were 1/48/51%. This modified-implement training programme is not a useful training strategy for club cricketers.

  8. Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI) in Patients with Small Cell Lung Cancer_ Comparison with Original ALI

    PubMed Central

    Kim, Young Saing; Seo, Ja-Young; Park, Inkeun; Ahn, Hee Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI) using CT-determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI. Methods L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable. Results Patients with low ALI (cut-off, 31.1, n = 94) had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p < 0.001), and patients with low mALI (cut-off 67.7, n = 94) had shorter OS than patients with high mALI (median, 6.8 months vs. 16.5 months; p < 0.001). There was no significant difference in estimates of median survival time between low ALI and low mALI (z = 0.000, p = 1.000) and between high ALI and high mALI (z = 0.330, p = 0.740). Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004), along with advanced age (HR, 1.49, p = 0.045), extensive disease (HR, 2.27, p < 0.001), supportive care only (HR, 7.86, p < 0.001), and elevated LDH (HR, 1.45, p = 0.037). Furthermore, goodness of fit of this prognostic model was not significantly increased by adding mALI as an extra variable (LR difference = 2.220, p = 0.136). Conclusion The present study confirms mALI using CT-determined L3MI has no additional prognostic

  9. 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

  10. Effects of Scheduled Exercise on Cancer-Related Fatigue in Women with Early Breast Cancer

    PubMed Central

    Husebø, Anne Marie Lunde; Dyrstad, Sindre Mikal; Mjaaland, Ingvil; Søreide, Jon Arne

    2014-01-01

    While physical activity during cancer treatment is found beneficial for breast cancer patients, evidence indicates ambiguous findings concerning effects of scheduled exercise programs on treatment-related symptoms. This study investigated effects of a scheduled home-based exercise intervention in breast cancer patients during adjuvant chemotherapy, on cancer-related fatigue, physical fitness, and activity level. Sixty-seven women were randomized to an exercise intervention group (n = 33, performed strength training 3x/week and 30 minutes brisk walking/day) and a control group (n = 34, performed their regular physical activity level). Data collection was performed at baseline, at completion of chemotherapy (Post1), and 6-month postchemotherapy (Post2). Exercise levels were slightly higher in the scheduled exercise group than in the control group. In both groups, cancer-related fatigue increased at Post1 but returned to baseline at Post2. Physical fitness and activity levels decreased at Post1 but were significantly improved at Post2. Significant differences between intervention and control groups were not found. The findings suggest that generally recommended physical activity levels are enough to relief cancer-related fatigue and restore physical capacity in breast cancer patients during adjuvant chemotherapy, although one cannot rule out that results reflect diminishing treatment side effects over time. PMID:24563628

  11. Cancer-promoting effects of microbial dysbiosis.

    PubMed

    Sheflin, Amy M; Whitney, Alyssa K; Weir, Tiffany L

    2014-10-01

    Humans depend on 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; this has been shown to contribute to the pathogenesis of colon, gastric, esophageal, pancreatic, laryngeal, breast, and gallbladder carcinomas. This development is closely tied to host inflammation, which causes and is aggravated by microbial dysbiosis and increases 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

  12. KAT6A, a chromatin modifier from the 8p11-p12 amplicon is a candidate oncogene in luminal breast cancer.

    PubMed

    Turner-Ivey, Brittany; Guest, Stephen T; Irish, Jonathan C; Kappler, Christiana S; Garrett-Mayer, Elizabeth; Wilson, Robert C; Ethier, Stephen P

    2014-08-01

    The chromosome 8p11-p12 amplicon is present in 12% to 15% of breast cancers, resulting in an increase in copy number and expression of several chromatin modifiers in these tumors, including KAT6A. Previous analyses in SUM-52 breast cancer cells showed amplification and overexpression of KAT6A, and subsequent RNAi screening identified KAT6A as a potential driving oncogene. KAT6A is a histone acetyltransferase previously identified as a fusion partner with CREB binding protein in acute myeloid leukemia. Knockdown of KAT6A in SUM-52 cells, a luminal breast cancer cell line harboring the amplicon, resulted in reduced growth rate compared to non-silencing controls and profound loss of clonogenic capacity both in mono-layer and in soft agar. The normal cell line MCF10A, however, did not exhibit slower growth with knockdown of KAT6A. SUM-52 cells with KAT6A knockdown formed fewer mammospheres in culture compared to controls, suggesting a possible role for KAT6A in self-renewal. Previous data from our laboratory identified FGFR2 as a driving oncogene in SUM-52 cells. The colony forming efficiency of SUM-52 KAT6A knockdown cells in the presence of FGFR inhibition was significantly reduced compared to cells with KAT6A knockdown only. These data suggest that KAT6A may be a novel oncogene in breast cancers bearing the 8p11-p12 amplicon. While there are other putative oncogenes in the amplicon, the identification of KAT6A as a driving oncogene suggests that chromatin-modifying enzymes are a key class of oncogenes in these cancers, and play an important role in the selection of this amplicon in luminal B breast cancers. PMID:25220592

  13. KAT6A, a Chromatin Modifier from the 8p11-p12 Amplicon is a Candidate Oncogene in Luminal Breast Cancer

    PubMed Central

    Turner-Ivey, Brittany; Guest, Stephen T.; Irish, Jonathan C.; Kappler, Christiana S.; Garrett-Mayer, Elizabeth; Wilson, Robert C.; Ethier, Stephen P.

    2014-01-01

    The chromosome 8p11-p12 amplicon is present in 12% to 15% of breast cancers, resulting in an increase in copy number and expression of several chromatin modifiers in these tumors, including KAT6A. Previous analyses in SUM-52 breast cancer cells showed amplification and overexpression of KAT6A, and subsequent RNAi screening identified KAT6A as a potential driving oncogene. KAT6A is a histone acetyltransferase previously identified as a fusion partner with CREB binding protein in acute myeloid leukemia. Knockdown of KAT6A in SUM-52 cells, a luminal breast cancer cell line harboring the amplicon, resulted in reduced growth rate compared to non-silencing controls and profound loss of clonogenic capacity both in mono-layer and in soft agar. The normal cell line MCF10A, however, did not exhibit slower growth with knockdown of KAT6A. SUM-52 cells with KAT6A knockdown formed fewer mammospheres in culture compared to controls, suggesting a possible role for KAT6A in self-renewal. Previous data from our laboratory identified FGFR2 as a driving oncogene in SUM-52 cells. The colony forming efficiency of SUM-52 KAT6A knockdown cells in the presence of FGFR inhibition was significantly reduced compared to cells with KAT6A knockdown only. These data suggest that KAT6A may be a novel oncogene in breast cancers bearing the 8p11-p12 amplicon. While there are other putative oncogenes in the amplicon, the identification of KAT6A as a driving oncogene suggests that chromatin-modifying enzymes are a key class of oncogenes in these cancers, and play an important role in the selection of this amplicon in luminal B breast cancers. PMID:25220592

  14. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    ClinicalTrials.gov

    2016-11-01

    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

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

    MedlinePlus

    ... Arthritis Possible Side Effect of Certain Cancer Drugs: Study Doctors should weigh the risk-benefit ratio, researcher ... of drugs that boost the immune system," said study author Dr. Laura Cappelli. She is a rheumatologist ...

  16. 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

  17. 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

  18. Effects of sunscreen on skin cancer and photoaging.

    PubMed

    Iannacone, Michelle R; Hughes, Maria Celia B; Green, Adèle C

    2014-01-01

    Application of sunscreen to the skin is widely used as an adjunct strategy, along with wearing protective clothing and seeking shade, to protect against skin cancer and photoaging that result from excessive sun exposure. Many epidemiological studies of case-control and cohort study design have studied the effects of sunscreen use on skin cancer, and more recently photoaging, but their findings have been mostly uninformative. This review of results of randomized controlled trials shows that the evidence, though limited, supports beneficial effects of sunscreen application on the occurrence of skin cancers and skin photoaging.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. [The effect of modified nano-diamonds of detonation synthesis on the protein fractions of human blood].

    PubMed

    Botvich, Iu A; Olkhovskiĭ, I A; Baron, I I; Puzyr', A P; Baron, A V; Bondar', V S

    2013-11-01

    It is established that the modified nano-diamonds of detonation synthesis are able to bind serum proteins of human blood. The relative selectivity is established concerning the effect of modified nano-diamonds of detonation synthesis on beta2- and gamma-globulin fractions of serum. The evidence of concentration dependence of effect of modified nano-diamonds of detonation synthesis from serum proteins is established. The study results make it possible to consider modified nano-diamonds of detonation synthesis as a potential sorbent in technologies of hemodialysis, plasmapheresis, isolation of blood proteins and as a foundation for development of new systems of laboratory diagnostic.

  5. 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.

  6. 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.

  7. [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

  8. A Modified Spontaneously Closed Defunctioning Tube Ileostomy After Anterior Resection of the Rectum for Rectal Cancer with a Low Colorectal Anastomosis.

    PubMed

    Sheng, Qin-Song; Hua, Han-Ju; Cheng, Xiao-Bin; Wang, Wei-Bing; Chen, Wen-Bin; Xu, Jia-He; Lin, Jian-Jiang

    2016-04-01

    The aim of this study is to introduce a new technique of modified spontaneously closed defunctioning tube ileostomy after anterior resection of the rectum for rectal cancer with a low colorectal anastomosis. Patients with rectal cancer who underwent anterior resection of rectum with a low colorectal anastomosis and chose a modified defunctioning tube ileostomy between March 2012 and August 2013 were retrospectively reviewed. Data on the success of the operation procedures, post-operative hospital stay, and post-operative tube ileostomy-related complications were analyzed. One hundred fifty-two patients (87 males and 65 females; 57.1 ± 17.4 years) undergoing the modified defunctioning tube ileostomy after anterior resection for rectal cancer were included. The post-operative hospital stay was 11.9 ± 3.2 days. The tube was removed on days 22.6 ± 4.1 after operation and the ileostomy wound closed spontaneously within 13.1 ± 1.9 days. Twenty-five patients felt tube-associated pain or discomfort, which was relieved after a period of adaptation and appropriate tube adjustment. Nine patients suffered from tube blockage and were treated successfully with saline irrigation. Two patients had intestinal obstruction, which was resolved with conservative treatment. Three patients developed leakage of the distal anastomosis: two were successfully treated with conservative measures and the other completely recovered after reoperation. The modified spontaneously closed defunctioning tube ileostomy appears efficacious and safe. This technique may be used to protect the distal anastomosis and simultaneously decrease the ileostomy complications, and minimize the morbidity and mortality associated with stoma takedown.

  9. 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

  10. The Fascinating Effects of Baicalein on Cancer: A Review

    PubMed Central

    Liu, Hui; Dong, Yonghui; Gao, Yutong; Du, Zhipeng; Wang, Yuting; Cheng, Peng; Chen, Anmin; Huang, Hui

    2016-01-01

    Cancer is one of the leading causes of death worldwide and a major global health problem. In recent decades, the rates of both mortality and morbidity of cancer have rapidly increased for a variety of reasons. Despite treatment options, there are serious side effects associated with chemotherapy drugs and multiple forms of drug resistance that significantly reduce their effects. There is an accumulating amount of evidence on the pharmacological activities of baicalein (e.g., anti-inflammatory, antioxidant, antiviral, and antitumor effects). Furthermore, there has been great progress in elucidating the target mechanisms and signaling pathways of baicalein’s anti-cancer potential. The anti-tumor functions of baicalein are mainly due to its capacities to inhibit complexes of cyclins to regulate the cell cycle, to scavenge oxidative radicals, to attenuate mitogen activated protein kinase (MAPK), protein kinase B (Akt) or mammalian target of rapamycin (mTOR) activities, to induce apoptosis by activating caspase-9/-3 and to inhibit tumorinvasion and metastasis by reducing the expression of matrix metalloproteinase-2/-9 (MMP-2/-9). In this review, we focused on the relevant biological mechanisms of baicalein involved in inhibiting various cancers, such as bladder cancer, breast cancer, and ovarian cancer. Moreover, we also summarized the specific mechanisms by which baicalein inhibited the growth of various tumors in vivo. Taken together, baicalein may be developed as a potential, novel anticancer drug to treat tumors. PMID:27735841

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

    PubMed

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

    2014-12-01

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

  12. 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.

  13. 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

  14. 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.

  15. Effect of thioperamide on modified forced swimming test-induced oxidative stress in mice.

    PubMed

    Akhtar, Mohd; Pillai, K K; Vohora, Divya

    2005-10-01

    This study was designed i) to investigate the role of histamine H3-receptor ligands on mouse modified forced swimming test, a method that distinguishes the catecholaminergic behaviour with that of serotonergic compounds and ii) to evaluate the role of free radicals in mediation of such effects. Swiss strain albino mice were treated with different doses of histamine H3-receptor antagonist thioperamide (3.75, 7.5 and 15 mg/kg intraperitoneally) and agonist (R)-alpha-methylhistamine (5 microg intracerebroventricularly). The climbing, swimming and immobility times were recorded for 6 min. Immediately after modified forced swimming test, the animals were sacrificed and parameters of oxidative stress were assessed in the brain by measuring the thiobarbituric acid reactive substance (TBARS), glutathione (GSH) and catalase levels. Thioperamide (7.5 and 15 mg/kg intraperitoneally) dose-dependently decreased immobility time and increased swimming time but not climbing time. The behaviour of mice treated with (R)-alpha-methylhistamine was similar to that of control mice. A significant reduction in GSH and an increase in catalase levels were observed in brains of mice exposed to modified forced swimming test. Thioperamide pretreatment dose-dependently reversed such an alteration in oxidative stress parameters. (R)-alpha-methylhistamine caused a reversal of altered catalase but not GSH levels. Thioperamide shows antidepressant effects in the modified forced swimming test and causes a reversal of the test-induced oxidative stress indicating its antioxidant potential. The antidepressant effect of thioperamide appears to be mediated via serotonergic and/or antioxidant mechanisms.

  16. 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

  17. 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

  18. 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

  19. Use of genetically modified viruses and genetically engineered virus-vector vaccines: environmental effects.

    PubMed

    Chan, Vivian S W

    2006-11-01

    Despite major therapeutic advances, infectious diseases remain highly problematic. Recent advancements in technology in producing DNA-based vaccines, together with the growing knowledge of the immune system, have provided new insights into the identification of the epitopes needed to target the development of highly targeted vaccines. Genetically modified (GM) viruses and genetically engineered virus-vector vaccines possess significant unpredictability and a number of inherent harmful potential hazards. For all these vaccines, safety assessment concerning unintended and unwanted side effects with regard to targeted vaccinees has always been the main focus. Important questions concerning effects on nontargeted individuals within the same species or other species remain unknown. Horizontal transfer of genes, though lacking supportive experimental or epidemiological investigations, is well established. New hybrid virus progenies resulting from genetic recombination between genetically engineered vaccine viruses and their naturally occurring relatives may possess totally unpredictable characteristics with regard to host preferences and disease-causing potentials. Furthermore, when genetically modified or engineered virus particles break down in the environment, their nuclei acids are released. Appropriate risk management is the key to minimizing any potential risks to humans and environment resulting from the use of these GM vaccines. There is inadequate knowledge to define either the probability of unintended events or the consequences of genetic modifications. The objective of this article is to highlight the limitations in environmental risk assessment and raise awareness of the potential risks involving the use of genetically modified viruses and genetically engineered virus-vector vaccines. PMID:16982535

  20. 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

  1. 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

  2. Inflationary gravitational waves in the effective field theory of modified gravity

    NASA Astrophysics Data System (ADS)

    De Felice, Antonio; Tsujikawa, Shinji

    2015-05-01

    In the approach of the effective field theory of modified gravity, we derive the second-order action and the equation of motion for tensor perturbations on the flat isotropic cosmological background. This analysis accommodates a wide range of gravitational theories including Horndeski theories, its generalization, and the theories with spatial derivatives higher than second order (e.g., Hořava-Lifshitz gravity). We obtain the inflationary power spectrum of tensor modes by taking into account corrections induced by higher-order spatial derivatives and slow-roll corrections to the de Sitter background. We also show that the leading-order spectrum in concrete modified gravitational theories can be mapped on to that in General Relativity under a disformal transformation. Our general formula will be useful to constrain inflationary models from the future precise measurement of the B-mode polarization in the cosmic microwave background.

  3. The accuracy of preoperative axillary nodal staging in primary breast cancer by ultrasound is modified by nodal metastatic load and tumor biology

    PubMed Central

    Dihge, Looket; Grabau, Dorthe A.; Rasmussen, Rogvi W.; Bendahl, Pär-Ola; Rydén, Lisa

    2016-01-01

    Abstract 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

  4. 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

  5. Accounting for Outcome Misclassification in Estimates of the Effect of Occupational Asbestos Exposure on Lung Cancer Death

    PubMed Central

    Edwards, Jessie K.; Cole, Stephen R.; Chu, Haitao; Olshan, Andrew F.; Richardson, David B.

    2014-01-01

    In studies of the health effects of asbestos, lung cancer death is subject to misclassification. We used modified maximum likelihood to explore the effects of outcome misclassification on the rate ratio of lung cancer death per 100 fiber-years per milliliter of cumulative asbestos exposure in a cohort study of textile workers in Charleston, South Carolina, followed from 1940 to 2001. The standard covariate-adjusted estimate of the rate ratio was 1.94 (95% confidence interval: 1.55, 2.44), and modified maximum likelihood produced similar results when we assumed that the specificity of outcome classification was 0.98. With sensitivity assumed to be 0.80 and specificity assumed to be 0.95, estimated rate ratios were further from the null and less precise (rate ratio = 2.17; 95% confidence interval: 1.59, 2.98). In the present context, standard estimates for the effect of asbestos on lung cancer death were similar to estimates accounting for the limited misclassification. However, sensitivity analysis using modified maximum likelihood was needed to verify the robustness of standard estimates, and this approach will provide unbiased estimates in settings with more misclassification. PMID:24352593

  6. Accounting for outcome misclassification in estimates of the effect of occupational asbestos exposure on lung cancer death.

    PubMed

    Edwards, Jessie K; Cole, Stephen R; Chu, Haitao; Olshan, Andrew F; Richardson, David B

    2014-03-01

    In studies of the health effects of asbestos, lung cancer death is subject to misclassification. We used modified maximum likelihood to explore the effects of outcome misclassification on the rate ratio of lung cancer death per 100 fiber-years per milliliter of cumulative asbestos exposure in a cohort study of textile workers in Charleston, South Carolina, followed from 1940 to 2001. The standard covariate-adjusted estimate of the rate ratio was 1.94 (95% confidence interval: 1.55, 2.44), and modified maximum likelihood produced similar results when we assumed that the specificity of outcome classification was 0.98. With sensitivity assumed to be 0.80 and specificity assumed to be 0.95, estimated rate ratios were further from the null and less precise (rate ratio = 2.17; 95% confidence interval: 1.59, 2.98). In the present context, standard estimates for the effect of asbestos on lung cancer death were similar to estimates accounting for the limited misclassification. However, sensitivity analysis using modified maximum likelihood was needed to verify the robustness of standard estimates, and this approach will provide unbiased estimates in settings with more misclassification.

  7. 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.

  8. Graphene-containing carbon aerogel prepared using polyethyleneimine (PEl)-modified graphene oxide (GO) for supercapacitor: effect of polyethyleneimine-modified GO content.

    PubMed

    Lee, Yoon Jae; Lee, Joongwon; Kim, Gil-Pyo; Lee, Eo Jin; Yi, Jongheop; Song, In Kyu

    2014-11-01

    Graphene-containing carbon aerogel was prepared by a sol-gel polymerization of resorcinol-formaldehyde (RF) method using polyethyleneimine (PEL)-modified chemically exfoliated graphene oxide (GO), and its electrochemical performance as an electrode for supercapacitor was examined. The effect of PEI-modified GO content on the physicochemical and electrochemical properties of graphene-containing carbon aerogel was investigated. For comparison, graphene-free carbon aerogel was also prepared. Among the samples, graphene-containing carbon aerogel prepared using 45 wt% PEI-modified GO solution (CA(45PG)) showed the highest BET surface area (784 m2/g) and the largest pore volume (1.71 cm3/g) with well-developed porous structure. Electrochemical properties of graphene-containing carbon aerogel and graphene-free carbon aerogel electrodes were measured by cyclic voltammetry, charge/discharge test, and electrochemical impedance spectroscopy in 6 M KOH electrolyte. Various electrochemical measurements revealed that CA(45PG) showed the highest specific capacitance (261 F/g), the lowest equivalent series resistance (0.16 Ω), and superior capacitive behavior. It is concluded that PEI-modified GO content served as an important factor determining the physicochemical properties and supercapacitive electrochemical performance of graphene-containing carbon aerogel.

  9. 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

  10. Genetic variants in the SWI/SNF complex and smoking collaborate to modify the risk of pancreatic cancer in a Chinese population.

    PubMed

    Zhu, Beibei; Tian, Jing; Zhong, Rong; Tian, Yao; Chen, Wei; Qian, Jiaming; Zou, Li; Xiao, Min; Shen, Na; Yang, Hong; Lou, Jiao; Qiu, Qian; Ke, Juntao; Lu, Xinghua; Song, Wei; Li, Hui; Liu, Li; Wang, Li; Miao, Xiaoping

    2015-09-01

    Pancreatic cancer (PC) is an aggressive malignancy with extremely low 5-year survival rate (<5%). SWItch/Sucrose Non Fermentable (SWI/SNF) complex is a core factor for chromatin-remodeling that utilize energy of ATP hydrolysis to mobilize nucleosomes, and modulate gene transcription. Recent studies have identified recurrent mutations in major components of SWI/SNF in a variety of human cancers, including PC. We conducted a two-stage case-control study to investigate the associations between 14 common variants in 6 genes (SMARCA4, SMCRB1, PBRM1, BRD7, ARID1, and ARID2) encoding major components of the SWI/SNF complex and the risk of PC. Three promising variants, rs11644043, rs11085754, and rs2073389 in the discovery stage comprising 310 cases and 457 controls were further genotyped in the validation stage containing 429 cases and 585 controls. rs11644043 in BRD7 and rs11085754 in SMARCA4 showed consistent significant association with increased risk of PC in both stages, with odds ratios (ORs) and 95% confidence interval (CI) of 2.04 (1.17-3.56) and 1.64 (1.16-2.33) in stage one, and 1.97 (1.24-3.14) and 1.45 (1.04-2.02) in stage two, respectively in a recessive model. Furthermore, the accumulative effects of rs11644043, rs11085754, and rs2073389 in SMARCB1 were observed (P for trend <0.0001). Intriguingly, gene-environmental interactions analysis consistently revealed the potential interactions of rs2073389 (P(add)  - FDR = 6.00 × 10(-4), P(mul)  - FDR = 1.50 × 10(-2)) and rs11085754 (P(add)  - FDR = 0.03) collaborating with smoking to modify the risk of PC. In conclusion, the current study provides evidence that genetic variants of SWI/SNF may contribute to the susceptibility of PC in the Chinese population.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. [Effects of chemically modified sugarcane bagasse on butanol production by immobilized Clostridium acetobutylicum XY16].

    PubMed

    Kong, Xiangping; He, Aiyong; Chen, Jianan; Chen, Wufang; Yin, Chunyan; Chen, Pan; Wu, Hao; Jiang, Min

    2014-02-01

    Sugarcane bagasse modified by polyethylenimine (PEI) and glutaraldehyde (GA) was used as a carrier to immobilize Clostridium acetobutylicum XY16 in the process of butanol production. The effects of chemically modified sugarcane bagasse on batch and repeat-batch fermentations were investigated. Batch fermentation was conducted with an addition of 10 g/L modified sugarcane bagasse and 60 g/L glucose, resulting in a high solvent concentration of 21.67 g/L and productivity of 0.60 g/(L x h) with the treatment of 4 g/L PEI and 1 g/L GA. Compared to the fermentations by free cells and immobilized cells on unmodified sugarcane bagasse, the productivity increased 130.8% and 66.7%, respectively. The fibrous-bed bioreactor also maintained a stable butanol production during repeat-batch fermentations, achieving a maximum productivity of 0.83 g/(L x h) with a high yield of 0.42 g/g.

  17. 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

  18. 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

  19. Relief from cancer chemotherapy side effects with pharmacologic vitamin C.

    PubMed

    Carr, Anitra C; Vissers, Margreet C M; Cook, John

    2014-01-24

    Fatigue is a common, often debilitating, side effect of cancer chemotherapy. Pharmacologic vitamin C has been used as an alternative treatment for the disease itself but its effects on fatigue have not often been documented. Here we report on the case of a woman with recurrent breast cancer, undergoing weekly chemotherapy, with lethargy as a major symptom. Vitamin C (50 g/session) was administered twice weekly and quality of life and multidimensional fatigue symptomology questionnaires were undertaken. Dramatic decreases in fatigue and insomnia were observed, as well as increased cognitive functioning. There were no adverse side effects of i.v. vitamin C.

  20. Effects of modified Shu-Gan-Liang-Xue decoction combined with anastrozole on osteoblastic proliferation and differentiation of MC3T3-E1 cells.

    PubMed

    Zhou, Fei; Han, Shuyan; Zhou, Ning; Zheng, Wenxian; Li, Pingping

    2015-03-01

    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.

  1. 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

  2. Anti-Cancer Effects of Xanthones from Pericarps of Mangosteen

    PubMed Central

    Akao, Yukihiro; Nakagawa, Yoshihito; Iinuma, Munekazu; Nozawa, Yoshinori

    2008-01-01

    Mangosteen, Garcinia mangostana Linn, is a tree found in South East Asia, and its pericarps have been used as traditional medicine. Phytochemical studies have shown that they contain a variety of secondary metabolites, such as oxygenated and prenylated xanthones. Recent studies revealed that these xanthones exhibited a variety of biological activities containing anti-inflammatory, anti-bacterial, and anti-cancer effects. We previously investigated the anti-proliferative effects of four prenylated xanthones from the pericarps; α-mangostin, β-mangostin, γ-mangostin, and methoxy-β-mangostin in various human cancer cells. These xanthones are different in the number of hydroxyl and methoxy groups. Except for methoxy-β-mangostin, the other three xanthones strongly inhibited cell growth at low concentrations from 5 to 20 μM in human colon cancer DLD-1 cells. Our recent study focused on the mechanism of α-mangostin-induced growth inhibition in DLD-1 cells. It was shown that the anti-proliferative effects of the xanthones were associated with cell-cycle arrest by affecting the expression of cyclins, cdc2, and p27; G1 arrest by α-mangostin and β-Mangostin, and S arrest by γ-mangostin. α-Mangostin found to induce apoptosis through the activation of intrinsic pathway following the down-regulation of signaling cascades involving MAP kinases and the serine/threonine kinase Akt. Synergistic effects by the combined treatment of α-mangostin and anti-cancer drug 5-FU was to be noted. α-Mangostin was found to have a cancer preventive effect in rat carcinogenesis bioassay and the extract from pericarps, which contains mainly α-mangostin and γ-mangostin, exhibited an enhancement of NK cell activity in a mouse model. These findings could provide a relevant basis for the development of xanthones as an agent for cancer prevention and the combination therapy with anti-cancer drugs. PMID:19325754

  3. 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.

  4. Cost Effectiveness Analysis of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. A Systematic Review Literature

    PubMed Central

    Benucci, Maurizio; Saviola, Gianantonio; Manfredi, Mariangela; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola

    2011-01-01

    The cost effectiveness of treatments that have changed the “natural history” of a chronic progressive disease needs to be evaluated over the long term. Disease-modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid arthritis (RA) and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage. Our review was focused on revision and critical evaluation of the studies including the literature on cost effectiveness of DMARDs (cyclosporine A, sulphasalazine, leflunomide, and methotrexate). The European League Against Rheumatism (EULAR) recommendations showed that traditional DMARDs are cost effective at the time of disease onset. They are less expensive than biological DMARDs and can be useful in controlling disease activity in early RA. PMID:22162693

  5. Mutant p53-R273H mediates cancer cell survival and anoikis resistance through AKT-dependent suppression of BCL2-modifying factor (BMF).

    PubMed

    Tan, B S; Tiong, K H; Choo, H L; Chung, F Fei-Lei; Hii, L-W; Tan, S H; Yap, I K S; Pani, S; Khor, N T W; Wong, S F; Rosli, R; Cheong, S-K; Leong, C-O

    2015-07-16

    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.

  6. 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

  7. Mutant p53-R273H mediates cancer cell survival and anoikis resistance through AKT-dependent suppression of BCL2-modifying factor (BMF).

    PubMed

    Tan, B S; Tiong, K H; Choo, H L; Chung, F Fei-Lei; Hii, L-W; Tan, S H; Yap, I K S; Pani, S; Khor, N T W; 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Modified Panax ginseng Extract Inhibits uPAR-Mediated α[Formula: see text]β1-Integrin Signaling by Modulating Caveolin-1 to Induce Early Apoptosis in Lung Cancer Cells.

    PubMed

    Hwang, In-Hu; Kwon, Yong-Kyun; Cho, Chong-Kwan; Lee, Yeon-Weol; Sung, Jung-Suk; Joo, Jong-Cheon; Lee, Kyung-Bok; Yoo, Hwa-Seung; Jang, Ik-Soon

    2016-01-01

    Urokinase receptor (uPAR) is enhanced in many human cancer cells and is frequently an indicator of poor prognosis. Activation of [Formula: see text]1-integrin requires caveolin-1 and is regulated by uPAR. However, the underlying molecular mechanism responsible for the interaction between uPAR and [Formula: see text]1-integrin remains obscure. We found that modified regular Panax ginseng extract (MRGX) had a negative modulating effect on the uPAR/[Formula: see text]1-integrin interaction, disrupted the uPAR/integrin interaction by modulating caveoline-1, and caused early apoptosis in cancer cells. Additionally, we found that siRNA-mediated caveoline-1 downregulation inhibited uPAR-mediated [Formula: see text]1-integrin signaling, whereas caveoline-1 up-regulation stimulated the signaling, which suppressed p53 expression, thereby indicating negative crosstalk exists between the integrin [Formula: see text]1 and the p53 pathways. Thus, these findings identify a novel mechanism whereby the inhibition of [Formula: see text]1 integrin and the activation of p53 modulate the expression of the anti-apoptotic proteins that are crucially involved in inducing apoptosis in A549 lung cancer cells. Furthermore, MRGX causes changes in the expressions of members of the Bcl-2 family (Bax and Bcl-2) in a pro-apoptotic manner. In addition, MGRX-mediated inhibition of [Formula: see text]1 integrin attenuates ERK phosphorylation (p-ERK), which up-regulates caspase-8 and Bax. Therefore, ERK may affect mitochondria through a negative regulation of caspase-8 and Bax. Taken together, these findings reveal that MRGX is involved in uPAR-[Formula: see text]1-integrin signaling by modulating caveolin-1 signaling to induce early apoptosis in A549 lung-cancer cells and strongly indicate that MRGX might be useful as a herbal medicine and may lead to the development of new herbal medicine that would suppress the growth of lung-cancer cells.

  14. 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.

  15. A modified and cost-effective method for hair cortisol analysis.

    PubMed

    Xiang, Lianbin; Sunesara, Imran; Rehm, Kristina E; Marshall, Gailen D

    2016-01-01

    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

  16. A modified and cost-effective method for hair cortisol analysis.

    PubMed

    Xiang, Lianbin; Sunesara, Imran; Rehm, Kristina E; Marshall, Gailen D

    2016-01-01

    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.

  17. Inhibitory effect of modified 5'-capped short RNA fragments on influenza virus RNA polymerase gene expression.

    PubMed

    Tado, M; Abe, T; Hatta, T; Ishikawa, M; Nakada, S; Yokota, T; Takaku, H

    2001-11-01

    We have shown previously that the 5'-capped short phosphodiester RNA fragments, Cap decoy, (Gm 12 nt) are potent inhibitors of influenza virus RNA polymerase gene expression. Here we investigate the modified capped RNA derivative containing phosphorothioate oligonucleotides (Cap decoy) as a potential influenza virus RNA polymerase inhibitor. The modified 5'-capped short phosphorothioate RNA fragments (Gms 12-15 nt) with the 5'-capped structure (m7GpppGm) were synthesized by T7 RNA polymerase. The 5'-capped short RNA fragments (Gms 12-15 nt) were encapsulated in liposome particulates and tested for their inhibitory effects on influenza virus RNA polymerase gene expression in the clone 76 cells. The 12-15 nt long Gms RNA fragments showed highly inhibitory effects. By contrast, the inhibitory effects of the 13 nt long short RNA fragments (Gm 13 nt) were considerably less in comparison with the 5'-capped short phosphorothioate RNA fragments (Gms 12-15 nt). In particular, the various Gms RNA chain lengths showed no significant differences in the inhibition of influenza virus RNA polymerase gene expression. Furthermore, the capped RNA with a phosphorothioate backbone was resistant to nuclease activity. These phosphorothioate RNA fragments exhibited higher inhibitory activity than the 5'-capped short RNA fragments (Gm 12 nt). These decoys may prove to be useful in anti-influenza virus therapeutics. PMID:12018680

  18. Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO, and CCFR Consortia

    PubMed Central

    Cheng, Iona; Kocarnik, Jonathan M; Dumitrescu, Logan; Lindor, Noralane M; Chang-Claude, Jenny; Avery, Christy L.; Caberto, Christian P; Love, Shelly-Ann; Slattery, Martha L; Chan, Andrew T; Baron, John A; Hindorff, Lucia A; Park, Sungshim Lani; Schumacher, Fredrick R; Hoffmeister, Michael; Kraft, Peter; Butler, Anne; Duggan, David; Hou, Lifang; Carlson, Chris S; Monroe, Kristine R; Lin, Yi; Carty, Cara L; Mann, Sue; Ma, Jing; Giovannucci, Edward L; Fuchs, Charles S; Newcomb, Polly A; Jenkins, Mark A; Hopper, John L; Haile, Robert W; Conti, David V; Campbell, Peter T; Potter, John D; Caan, Bette J; Schoen, Robert E; Hayes, Richard B; Chanock, Stephen J; Berndt, Sonja I; Kury, Sebastien; Bezieau, Stephane; Ambite, Jose Luis; Kumaraguruparan, Gowri; Richardson, Danielle; Goodloe, Robert J; Dilks, Holli H; Baker, Paxton; Zanke, Brent W; Lemire, Mathieu; Gallinger, Steven; Hsu, Li; Jiao, Shuo; Harrison, Tabitha; Seminara, Daniela; Haiman, Christopher A; Kooperberg, Charles; Wilkens, Lynne R; Hutter, Carolyn M; White, Emily; Crawford, Dana C; Heiss, Gerardo; Hudson, Thomas J; Brenner, Hermann; Bush, William S; Casey, Graham; Marchand, Loic Le; Peters, Ulrike

    2013-01-01

    Objective Genome-wide association studies (GWAS) have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design We examined 13,338 colorectal cancer cases and 40,967 controls from three consortia: Population Architecture using Genetics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p-value of 2.92×10−4 was used to determine statistical significance of the associations. Results Two correlated SNPs— rs10090154 and rs4242382—in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI: 1.07–1.18; P=1.74×10−5), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusion This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer, thus adding colorectal cancer to the list of cancer sites linked to this particular multi-cancer risk region at 8q24. PMID:23935004

  19. 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

  20. 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

  1. Effects of an extract of Celtis aetnensis (Tornab.) Strobl twigs on human colon cancer cell cultures.

    PubMed

    Acquaviva, Rosaria; Sorrenti, Valeria; Santangelo, Rosa; Cardile, Venera; Tomasello, Barbara; Malfa, Giuseppe; Vanella, Luca; Amodeo, Andrea; Genovese, Carlo; Mastrojeni, Silvana; Pugliese, Michela; Ragusa, Monica; Di Giacomo, Claudia

    2016-10-01

    Cancers of the digestive tract, in particular colorectal cancer (CRC), are among those most responsive to dietary modification. Research has shown that approximately 75% of all sporadic cases of CRC are directly influenced by diet. Many natural compounds have been investigated for their potential usefulness as cancer chemopreventive agents as they have been thought to suppress carcinogenesis mainly during the initiation phase due to their radical scavenger activity. Since there is an increasing interest in the in vivo protective effects of natural compounds contained in plants against oxidative damage involved in several human diseases such as cancer, the aim of the present research was to test the effects of a Celtis aetnensis (Tornab.) Strobl twig extract on a human colon carcinoma cell line (Caco2). In order to elucidate the mechanisms of action of this extract, LDH release, GSH content, ROS levels, caspase-3 and γ-GCS expression were also evaluated. The results revealed that the Celtis aetnensis extract reduced the cell viability of the Caco2 cells inducing apoptosis at the lowest concentration and necrosis at higher dosages. In addition, this extract caused an increase in the levels of ROS, a decrease in RSH levels and in the expression of HO-1. The expression of γ-GCS was not modified in the Celtis aetnensis-treated Caco-2 cells. These results suggest an interference of this extract on the oxidant/antioxidant cell balance with consequent cell damage. The present study supports the growing body of data suggesting the bioactivities of Celtis aetnensis (Tornab.) Strobl and its potential impact on cancer therapy and on human health. PMID:27573437

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

    PubMed

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

    2010-08-01

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

  3. 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.

  4. 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

  5. Applicability of modified effective-range theory to positron-atom and positron-molecule scattering

    SciTech Connect

    Idziaszek, Zbigniew; Karwasz, Grzegorz

    2006-06-15

    We analyze low-energy scattering of positrons on Ar atoms and N{sub 2} molecules using the modified effective-range theory (MERT) developed by O'Malley, et al. [J. Math. Phys. 2, 491 (1961)]. We use the formulation of MERT based on exact solutions of the Schroedinger equation with polarization potential rather than low-energy expansions of phase shifts into momentum series. We show that MERT describes the experimental data well, provided that effective-range expansion is performed both for s- and p-wave scattering, which dominate in the considered regime of positron energies (0.4-2 eV). We estimate the values of the s-wave scattering length and the effective range for e{sup +}-Ar and e{sup +}-N{sub 2} collisions.

  6. 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.

  7. Early Life and Environmental Risk Factors Modify the Effect of Acculturation on Hispanic Children's Asthma.

    PubMed

    Chavez-Payan, Paola; Grineski, Sara E; Collins, Timothy W

    2015-01-01

    Acculturation tends to erode Hispanic immigrants' initial health advantage. Using a more nuanced conceptualization of acculturation than previous studies, we explore the associations between acculturation and Hispanic children's asthma. Data came from an observational mail survey of caretakers of Hispanic schoolchildren in El Paso, Texas (N = 1,513). Results from generalized linear models (GzLMs) demonstrate that acculturation was a significant positive predictor of asthma. The addition of interaction terms revealed that prenatal smoking, low birth weight, breastfeeding, and pest exposure significantly modified the effect of acculturation on asthma. Results suggest that although higher levels of acculturation were detrimental overall, the effects were not equally damaging for all Hispanic children. Findings foster an understanding of how the effect of acculturation on Hispanic children's asthma is intensified or attenuated by distinct individual-level risk factors.

  8. Effects of feeding calves genetically modified corn bt11: a clinico-biochemical study.

    PubMed

    Shimada, Nobuaki; Murata, Hideo; Mikami, Osamu; Yoshioka, Miyako; Guruge, Keerthi S; Yamanaka, Noriko; Nakajima, Yasuyuki; Miyazaki, Shigeru

    2006-10-01

    Genetically modified corn Bt11 is insect-resistant and expresses Cry1Ab toxin, an insecticidal protein, in kernels. Although Bt11 corn is considered safe based on animal performance, there are no reports available on the clinico-biochemical effects of feeding it to cattle. In this study, we evaluated the effects of feeding Bt11 to calves, using blood and ruminal clinico-biochemical parameters. Our three-month-long feeding experiment demonstrated that calves (n=6), fed with a ration containing 43.3% of Bt11 corn kernels as dry matter, did not develop any discernible clinical, hematological, biochemical, or ruminal abnormalities as compared with control calves (n=6) fed non-Bt11 corn. The results suggest that the transgenic Bt11 has no negative clinico-biochemical effects on calves.

  9. Anticancer efficacy of a nitric oxide-modified derivative of bifendate against multidrug-resistant cancer cells.

    PubMed

    Ren, Zhiguang; Gu, Xiaoke; Lu, Bin; Chen, Yaqiong; Chen, Guojiang; Feng, Jiannan; Lin, Jizhen; Zhang, Yihua; Peng, Hui

    2016-06-01

    The development of multidrug resistance (MDR) not only actively transports a wide range of cytotoxic drugs across drug transporters but is also a complex interaction between a number of important cellular signalling pathways. Nitric oxide donors appear to be a new class of anticancer therapeutics for satisfying all the above conditions. Previously, we reported furoxan-based nitric oxide-releasing compounds that exhibited selective antitumour activity in vitro and in vivo. Herein, we demonstrate that bifendate (DDB)-nitric oxide, a synthetic furoxan-based nitric oxide-releasing derivative of bifendate, effectively inhibits the both sensitive and MDR tumour cell viability at a comparatively low concentration. Interestingly, the potency of DDB-nitric oxide is the independent of inhibition of the functions and expressions of three major ABC transporters. The mechanism of DDB-nitric oxide appears to be in two modes of actions by inducing mitochondrial tyrosine nitration and apoptosis, as well as by down-regulating HIF-1α expression and protein kinase B (AKT), extracellular signal-regulated kinases (ERK), nuclear factor κB (NF-κB) activation in MDR cells. Moreover, the addition of a typical nitric oxide scavenger significantly attenuated all the effects of DDB-nitric oxide, indicating that the cytotoxicity of DDB-nitric oxide is as a result of higher levels of nitric oxide release in MDR cancer cells. Given that acquired MDR to nitric oxide donors is reportedly difficult to achieve and genetically unstable, compound like DDB-nitric oxide may be a new type of therapeutic agent for the treatment of MDR tumours.

  10. 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

  11. Effect of algal flocculation on dissolved organic matters using cationic starch modified soils.

    PubMed

    Shi, Wenqing; Bi, Lei; Pan, Gang

    2016-07-01

    Modified soils (MSs) are being increasingly used as geo-engineering materials for the sedimentation removal of cyanobacterial blooms. Cationic starch (CS) has been tested as an effective soil modifier, but little is known about its potential impacts on the treated water. This study investigated dissolved organic matters in the bloom water after algal removal using cationic starch modified soils (CS-MSs). Results showed that the dissolved organic carbon (DOC) could be decreased by CS-MS flocculation and the use of higher charge density CS yielded a greater DOC reduction. When CS with the charge density of 0.052, 0.102 and 0.293meq/g were used, DOC was decreased from 3.4 to 3.0, 2.3 and 1.7mg/L, respectively. The excitation-emission matrix fluorescence spectroscopy and UV254 analysis indicated that CS-MS exhibits an ability to remove some soluble organics, which contributed to the DOC reduction. However, the use of low charge density CS posed a potential risk of DOC increase due to the high CS loading for effective algal removal. When CS with the charge density of 0.044meq/g was used, DOC was increased from 3.4 to 3.9mg/L. This study suggested, when CS-MS is used for cyanobacterial bloom removal, the content of dissolved organic matters in the treated water can be controlled by optimizing the charge density of CS. For the settled organic matters, other measures (e.g., capping treatments using oxygen loaded materials) should be jointly applied after algal flocculation. PMID:27372131

  12. Cancer and non-cancer effects in Japanese atomic bomb survivors.

    PubMed

    Little, M P

    2009-06-01

    The survivors of the atomic bombings in Hiroshima and Nagasaki are a general population of all ages and sexes and, because of the wide and well characterised range of doses received, have been used by many scientific committees (International Commission on Radiological Protection (ICRP), United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), Biological Effects of Ionizing Radiations (BEIR)) as the basis of population cancer risk estimates following radiation exposure. Leukaemia was the first cancer to be associated with atomic bomb radiation exposure, with preliminary indications of an excess among the survivors within the first five years after the bombings. An excess of solid cancers became apparent approximately ten years after radiation exposure. With increasing follow-up, excess risks of most cancer types have been observed, the major exceptions being chronic lymphocytic leukaemia, and pancreatic, prostate and uterine cancer. For most solid cancer sites a linear dose response is observed, although in the latest follow-up of the mortality data there is evidence (p = 0.10) for an upward curvature in the dose response for all solid cancers. The only cancer sites which exhibit (upward) curvature in the dose response are leukaemia, and non-melanoma skin and bone cancer. For leukaemia the dose response is very markedly upward curving, indeed largely describable as a pure quadratic dose response, particularly in the low dose (0-2 Sv) range. Even 55 years after the bombings over 40% of the Life Span Study cohort remain alive, so continued follow-up of this group is vital for completing our understanding of long-term radiation effects in people. In general, the relative risks per unit dose among the Japanese atomic bomb survivors are greater than those among comparable subsets in studies of medically exposed individuals. Cell sterilisation largely accounts for the discrepancy in relative risks between these two populations, although other

  13. A genetic variant in MiR-146a modifies digestive system cancer risk: a meta-analysis.

    PubMed

    Li, Ying-Jun; Zhang, Zhen-Yu; Mao, Ying-Ying; Jin, Ming-Juan; Jing, Fang-Yuan; Ye, Zhen-Hua; Chen, Kun

    2014-01-01

    MicroRNAs (miRNAs) negatively regulate gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to digestive system cancers was inconsistent in previous studies. In this study, we conducted a literature search of PubMed to identify all relevant studies published before August 31, 2013. A total of 21 independent case-control studies were included in this updated meta-analysis with 9,558 cases and 10,614 controls. We found that the miR-146a rs2910164 polymorphism was significantly associated with decreased risk of digestive system cancers in an allele model (OR=0.90, 95%CI 0.87-0.94), homozygote model (OR=0.84, 95%CI 0.77-0.91), dominant model (OR=0.90, 95%CI 0.84-0.96), and recessive model (OR=0.85, 95%CI 0.79-0.91), while in a heterozygous model (OR = 0.99, 95% CI 0.89-1.11) the association showed marginal significance. Subgroup analysis by cancer site revealed decreased risk in colorectal cancer above allele model (OR=0.90, 95%CI 0.83- 0.97) and homozygote model (OR=0.85, 95%CI 0.72-1.00). Similarly, decreased cancer risk was observed when compared with allele model (OR=0.87, 95%CI 0.81-0.93) and recessive model (OR=0.81, 95%CI 0.72-0.90) in gastric cancer. When stratified by ethnicity, genotyping methods and quality score, decreased cancer risks were also observed. This current meta-analysis indicated that miR-146a rs2910164 polymorphism may decrease the susceptibility to digestive system cancers, especially in Asian populations.

  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

    Spurdle, Amanda B; Fahey, Paul; Chen, Xiaoqing; McGuffog, Lesley; Easton, Douglas; Peock, Susan; Cook, Margaret; Simard, Jacques; Rebbeck, Tim R; Antoniou, Antonis C; Chenevix-Trench, Georgia

    2010-07-01

    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.

  15. 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

  16. 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.

  17. 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.

  18. Neurobiological effects of melatonin as related to cancer.

    PubMed

    Hoang, Ba X; Shaw, David G; Pham, Phuong T; Levine, Stephen A

    2007-12-01

    Melatonin is a neurohormone naturally found in humans. Melatonin plays a role in maintaining sleep-wake rhythms; supplementation may help to regulate sleep disturbance that occur with jet lag, rotating shift-work and depression. Preliminary study of melatonin has shown potential for use in the treatment of epilepsy, tinnitus, migraine and neurodegenerative diseases. The latest publication in the Journal of Pineal Research by Edward Mills and colleagues has shown a compelling role of melatonin for the treatment of cancer. Melatonin's consistent relationship with cancer has been shown in many studies assessing links between shift work and cancer rates. High levels of melatonin have been linked to slower cancer progression. How melatonin affects cancer remains largely unclear. Although previous studies suggest different possible mechanisms, many of them are far distant from the primary physiological role of melatonin as a neurohormone. Conflicting studies are found on the role of melatonin in neurodegenerative diseases and cancer. In this article, we try to build and substantiate a neurobiological concept for the anticancer effects of melatonin. PMID:18090123

  19. Effect of a six month yoga exercise intervention on fitness outcomes for breast cancer survivors

    PubMed Central

    Hughes, Daniel C.; Darby, Nydia; Gonzalez, Krystle; Boggess, Terri; Morris, Ruth M.; Ramirez, Amelie G.

    2016-01-01

    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 (YE) exercise program. 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

  20. 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

  1. 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.

  2. 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

  3. Amelioration of biodiversity impacts of genetically modified crops: predicting transient versus long-term effects.

    PubMed

    Freckleton, R P; Stephens, P A; Sutherland, W J; Watkinson, A R

    2004-02-01

    It has been suggested that genetically modified herbicide-tolerant crops may benefit biodiversity because spraying of crops may be delayed until later in the growing season, allowing weeds to grow during the early part of the year. This provides an enhanced resource for arthropods, and potentially benefits birds that feed on these. Thus, this technology could enhance biodiversity. Using a review of weed phenologies and a population model, we show that many weeds are unlikely to benefit because spraying is generally delayed insufficiently late in the season to allow most to set seed. The positive effects on biodiversity observed in trials lasting one or two seasons are thus likely to be transient. For one weed of particular significance (Chenopodium album, fat hen) we show that it is unlikely that the positive effects observed could be maintained by inputs of seed during other parts of the rotation. However, we find preliminary evidence that if spraying can be ceased earlier in the season, then a viable population of late-emerging weeds could be maintained. This strategy could benefit weeds in both genetically modified (GM) and non-GM crops, but would probably lead to reduced inputs in GM systems compared with conventional ones.

  4. 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

  5. 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

  6. Polymeric micelles containing reversibly phospholipid-modified anti-survivin siRNA: a promising strategy to overcome drug resistance in cancer.

    PubMed

    Salzano, G; Riehle, R; Navarro, G; Perche, F; De Rosa, G; Torchilin, V P

    2014-02-28

    The discovery that survivin, a small anti-apoptotic protein, is involved in chemoresistance, opens a new scenario to overcome the drug resistance in cancer. It was shown that siRNA can efficiently inhibit the expression of survivin in cancer cells. However, the clinical use of siRNA is still hampered by an unfavorable pharmacokinetic profile. To address this problem, earlier we developed a novel system to deliver siRNA into cancer cells. Namely, we reversibly modified the survivin siRNA with a phosphothioethanol (PE) portion via a reducible disulfide bond and incorporated the resulting siRNA-S-S-PE conjugate into nanosized polyethyelene glycol 2000-phosphatidyl ethanolamine (PEG2000-PE)-based polymeric micelles (PM), obtaining survivin siRNA PM. The activity of these nanopreparations was evaluated by survivin protein down-regulation, tumor cell growth inhibition, and chemosensitization of the treated tumor cells to paclitaxel (PXL). We found a significant decrease of cell viability and down-regulation of survivin protein levels after treatment with survivin siRNA PM in several cancer cell lines. In addition, the down-regulation of survivin by treating cells with survivin siRNA PM, elicited a significant sensitization of the cells to PXL, in both sensitive and resistant cancer cell lines. Finally, we demonstrated successful co-delivery of PXL and survivin siRNA in the same PM leading to superior therapeutic activity compared to their sequential administration. Our results support the use of this new platform for the treatment of the most aggressive tumors. PMID:24099916

  7. Polymeric micelles containing reversibly phospholipid-modified anti-survivin siRNA: a promising strategy to overcome drug resistance in cancer

    PubMed Central

    Salzano, G; Riehle, R; Navarro, Gemma; Perche, Federico; De Rosa, G; Torchilin, VT

    2013-01-01

    The discovery that survivin, a small anti-apoptotic protein, is involved in chemoresistance, opens a new scenario to overcome the drug resistance in cancer. It was shown that siRNA can efficiently inhibit the expression of survivin in cancer cells. However, the clinical use of siRNA is still hampered by an unfavorable pharmacokinetic profile. To address this problem, earlier we developed a novel system to deliver siRNA into cancer cells. Namely, we reversibly modified the survivin siRNA with a phosphothioethanol (PE) portion via a reducible disulfide bond and incorporated the resulting siRNA-S-S-PE conjugate into nanosized polyethyelene glycol2000-phosphatidyl ethanolamine (PEG2000-PE)-based polymeric micelles (PM), obtaining survivin siRNA PM. The activity of these nanopreparations was evaluated by survivin protein down-regulation, tumor cell growth inhibition, and chemosensitization of the treated tumor cells to paclitaxel (PXL). We found a significant decrease of cell viability and down-regulation of survivin protein levels after treatment with survivin siRNA PM in several cancer cell lines. In addition, the down-regulation of survivin by treating cells with survivin siRNA PM, elicited a significant sensitization of the cells to PXL, in both sensitive and resistant cancer cell lines. Finally, we demonstrate successful co-delivery of PXL and survivin siRNA in the same PM leading to superior therapeutic activity compared to their sequential administration. Our results support the use of this new platform for the treatment of the most aggressive tumors. PMID:24099916

  8. Analysis of expression of chorionic gonadotrophin transcripts in prostate cancer by quantitative Taqman and a modified molecular beacon RT-PCR.

    PubMed

    Span, P N; Thomas, C M G; Heuvel, J J; Bosch, R R; Schalken, J A; vd Locht, L; Mensink, E J B M; Sweep, C G J

    2002-03-01

    Expression of human chorionic gonadotrophin (hCG) is associated with trophoblastic, testicular and other malignancies such as bladder, pancreatic, cervical, breast and prostate cancer. In the prostate, however, hCG expression, associated with neuroendocrine cells, is also found in normal tissue. Of the six highly homologous genes that all encode the beta-subunit of hCG, the beta 7 gene is reportedly the only gene expressed in several non-transformed tissues. The beta 3, 5 and 8 genes would be variably expressed in malignant tissue and placenta, but not in normal tissue. To assess to what extent this expression difference can also be found in the prostate, we compared the levels of the different hCG beta transcripts in concurrent normal and cancerous prostate tissues obtained from 17 patients. To this end, we developed a Taqman real-time fluorescent RT-PCR assay for hCG beta, and a quantitative assay specific for the beta 3, 5 and 8 genes, modified from the molecular beacon principle. This latter assay proved highly specific and capable of reliably distinguishing between these hCG beta transcripts that differ in only one nucleotide. Surprisingly, median expression levels of hCG beta were lower in prostate cancer when compared with normal tissue from the same patient. In contrast, hCG beta 3, 5 and 8 transcripts were found in normal tissue and did not differ in prostate cancer, arguing against a specific role of these transcripts in the development of prostate cancer.

  9. Effect of erectile dysfunction following prostate cancer treatment.

    PubMed

    McConkey, Robert

    2015-11-18

    Prostate cancer is the most prevalent non-cutaneous cancer in men worldwide. As a result of increased survival rates, men and their partners are living longer with the sexual sequelae of active treatments for prostate cancer, including surgery, radiotherapy and hormone therapy. The effect of erectile dysfunction on the patient and his partner is complex; many men experience psychosocial effects influenced by their hegemonic masculine beliefs. Some men experience difficulties in addressing their needs and require support while they attempt to reframe their beliefs about masculinity. The PLISSIT model can be used to guide healthcare practitioners in assessing and addressing the needs of this group of patients. The man's partner should be included in assessment and interventions where appropriate. PMID:26576913

  10. Cytotoxic Effects of Loperamide Hydrochloride on Canine Cancer Cells

    PubMed Central

    REGAN, Rebecca Cohen; GOGAL, Robert Michael; BARBER, James Perry; TUCKFIELD, Richard Cary; HOWERTH, Elizabeth Wynne; LAWRENCE, Jessica Ann

    2014-01-01

    Loperamide is a peripheral opiate agonist that can cause apoptosis and G2/M arrest in human cancer cell lines and may sensitize cells to chemotherapy. The objectives of this study were to investigate the effects of loperamide on viability, apoptosis and cell cycle kinetics in canine cancer cells and to establish whether the drug sensitizes cells to doxorubicin. Cell viability was assessed using Alamar Blue. Cell death and cell cycle were studied using flow cytometry with 7-Aminoactinomycin-D (7-AAD) and propidium iodide (PI), respectively. Loperamide decreased cell viability in a dose-dependent fashion and was most effective against canine osteosarcoma cells. In all cell lines, it induced a dose and time dependent apoptosis and resulted in accumulation in G0/G1. When co-incubated with doxorubicin, loperamide induced a synergistic cell kill in canine carcinoma cells. Investigation is warranted into the role of loperamide in the treatment of canine cancer. PMID:25649936

  11. 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

  12. 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.

  13. 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

  14. 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

  15. Differential Effects of Estradiol and Bisphenol A on SET8 and SIRT1 Expression in Ovarian Cancer Cells.

    PubMed

    Hayes, Laura; Weening, Allison; Morey, Lisa M

    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

  16. 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

  17. 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

  18. 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.

  19. Effectiveness of a modified rapid toilet training workshop for parents of children with developmental disabilities.

    PubMed

    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 to the parents of six children with developmental disabilities. In the workshop, parents were taught to implement an instructional protocol that included increased fluid intake, positive reinforcement for correct toileting, scheduled toilet sittings, scheduled chair sittings to teach initiation, neutral redirection for accidents, and procedures to enhance maintenance and generalization. Following the workshop, parents implemented the toilet training protocol at home with their children for 5-8 days, with telephone support from a researcher. Results indicate that the workshop resulted in increased in-toilet urination and defecation and decreased accidents for the five children who completed the study. The results are discussed in relation to previous and future research and implications for practice.

  20. Analgesic and disease modifying effects of interferential current in psoriatic arthritis.

    PubMed

    Walker, U A; Uhl, M; Weiner, S M; Warnatz, K; Lange-Nolde, A; Dertinger, H; Peter, H H; Jurenz, S A

    2006-08-01

    Interferential current (IFC) was suggested to improve the skin manifestations of psoriasis vulgaris, possibly by enhancing the intracellular concentration of cyclic AMP. We assessed the efficacy of IFC on psoriatic arthritis (PsA). Nine consecutive patients were analyzed at baseline and after 16 weeks of IFC therapy. Bipolar IFC was applied twice daily to hands, feet plus all affected joints. IFC improved SF-36 assessed body pain, but not other SF-36 subscales. Morning stiffness, tender joint counts, and physician assessed disease activity improved. In contrast, visual analogue scale assessed pain, CRP and ESR measurements were unchanged. MRI of the most affected hand or foot documented a tendency towards worsened tendinitis, soft tissue swelling, and new joint space narrowing and erosions. Bone scintigraphy showed a trend towards deterioration. New joints became inflamed within treated sites. Thus IFC has analgesic effects in PsA, but does not have a satisfactory disease modifying effect.

  1. 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.

  2. 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.

  3. Lipid-modifying effects of nutraceuticals: An evidence-based approach.

    PubMed

    Sahebkar, Amirhossein; Serban, Maria-Corina; Gluba-Brzózka, Anna; Mikhailidis, Dimitri P; Cicero, Arrigo F; Rysz, Jacek; Banach, Maciej

    2016-01-01

    The present review provides an up-to-date summary of the findings on the lipid-lowering effects of the most important nutraceuticals and functional foods. Based on current knowledge, nutraceuticals might exert significant lipid-lowering, and their use has several advantages: A number of important questions remain to be addressed, including whether longer durations of therapy would result in a better response and the exact safety profile of nutraceuticals, especially at doses higher than those consumed in an average diet. Additionally, data regarding the effects of nutraceutical supplementation on the incidence of cardiovascular outcomes are lacking, and it is not clear whether additional lipid lowering by nutraceuticals can modify the residual cardiovascular risk that remains after statin therapy.

  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. 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

  6. 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.

  7. Cancer-Associated Fibroblasts Modify the Response of Prostate Cancer Cells to Androgen and Anti-Androgens in Three-Dimensional Spheroid Culture

    PubMed Central

    Eder, Theresa; Weber, Anja; Neuwirt, Hannes; Grünbacher, Georg; Ploner, Christian; Klocker, Helmut; Sampson, Natalie; Eder, Iris E.

    2016-01-01

    Androgen receptor (AR) targeting remains the gold standard treatment for advanced prostate cancer (PCa); however, treatment resistance remains a major clinical problem. To study the therapeutic effects of clinically used anti-androgens we characterized herein a tissue-mimetic three-dimensional (3D) in vitro model whereby PCa cells were cultured alone or with PCa-associated fibroblasts (CAFs). Notably, the ratio of PCa cells to CAFs significantly increased in time in favor of the tumor cells within the spheroids strongly mimicking PCa in vivo. Despite this loss of CAFs, the stromal cells, which were not sensitive to androgen and even stimulated by the anti-androgens, significantly influenced the sensitivity of PCa cells to androgen and to the anti-androgens bicalutamide and enzalutamide. In particular, DuCaP cells lost sensitivity to enzalutamide when co-cultured with CAFs. In LAPC4/CAF and LNCaP/CAF co-culture spheroids the impact of the CAFs was less pronounced. In addition, 3D spheroids exhibited a significant increase in E-cadherin and substantial expression of vimentin in co-culture spheroids, whereas AR levels remained unchanged or even decreased. In LNCaP/CAF spheroids we further found increased Akt signaling that could be inhibited by the phosphatidyl-inositol 3 kinase (PI3K) inhibitor LY294002, thereby overcoming the anti-androgen resistance of the spheroids. Our data show that CAFs influence drug response of PCa cells with varying impact and further suggest this spheroid model is a valuable in vitro drug testing tool. PMID:27598125

  8. Cancer-Associated Fibroblasts Modify the Response of Prostate Cancer Cells to Androgen and Anti-Androgens in Three-Dimensional Spheroid Culture.

    PubMed

    Eder, Theresa; Weber, Anja; Neuwirt, Hannes; Grünbacher, Georg; Ploner, Christian; Klocker, Helmut; Sampson, Natalie; Eder, Iris E

    2016-01-01

    Androgen receptor (AR) targeting remains the gold standard treatment for advanced prostate cancer (PCa); however, treatment resistance remains a major clinical problem. To study the therapeutic effects of clinically used anti-androgens we characterized herein a tissue-mimetic three-dimensional (3D) in vitro model whereby PCa cells were cultured alone or with PCa-associated fibroblasts (CAFs). Notably, the ratio of PCa cells to CAFs significantly increased in time in favor of the tumor cells within the spheroids strongly mimicking PCa in vivo. Despite this loss of CAFs, the stromal cells, which were not sensitive to androgen and even stimulated by the anti-androgens, significantly influenced the sensitivity of PCa cells to androgen and to the anti-androgens bicalutamide and enzalutamide. In particular, DuCaP cells lost sensitivity to enzalutamide when co-cultured with CAFs. In LAPC4/CAF and LNCaP/CAF co-culture spheroids the impact of the CAFs was less pronounced. In addition, 3D spheroids exhibited a significant increase in E-cadherin and substantial expression of vimentin in co-culture spheroids, whereas AR levels remained unchanged or even decreased. In LNCaP/CAF spheroids we further found increased Akt signaling that could be inhibited by the phosphatidyl-inositol 3 kinase (PI3K) inhibitor LY294002, thereby overcoming the anti-androgen resistance of the spheroids. Our data show that CAFs influence drug response of PCa cells with varying impact and further suggest this spheroid model is a valuable in vitro drug testing tool. PMID:27598125

  9. Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells

    PubMed Central

    2010-01-01

    Background Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells. Methods HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed. Results 5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21Cip1 and p27Kip1 and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer

  10. Vitamin D: direct effects of vitamin D metabolites on bone: lessons from genetically modified mice.

    PubMed

    Eisman, John A; Bouillon, Roger

    2014-01-01

    The vitamin D endocrine system has clear beneficial effects on bone as demonstrated by prevention of rickets in children and by reducing the risk of osteomalacia or osteoporosis in adults or elderly subjects. Depending on the design of the study of genetically modified animals, however, 1,25(OH)2D and the vitamin D receptor (VDR) may have no effect, beneficial or even deleterious direct effects on bone. We present here a comprehensive model of the direct effects of vitamin D on bone. In case of sufficient calcium supply, vitamin D and its metabolites can improve the calcium balance and facilitate mineral deposition in bone matrix largely without direct effects on bone cells, although some beneficial effects may occur via mature osteoblasts, as demonstrated in mice with osteoblast-specific overexpression of VDR or 1α-hydroxylase. In case of calcium deficiency, however, 1,25(OH)2D enhances bone resorption, whereas simultaneously inhibiting bone mineralization, so as to defend serum calcium homeostasis at the expense of bone mass. This dual role probably provides a survival benefit for land vertebrates living in a calcium-poor environment.

  11. 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

  12. 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.

  13. The Effects of 17β-estradiol in Cancer are Mediated by Estrogen Receptor Signaling at the Plasma Membrane

    PubMed Central

    Acconcia, Filippo; Marino, Maria

    2011-01-01

    Two different isoforms of the estrogen receptors (i.e., ERα and ERβ) mediate pleiotropic 17β-estradiol (E2)-induced cellular effects. The ERs are principally localized in the nucleus where they act by globally modifying the expression of the E2-target genes. The premise that E2 effects are exclusively mediated through the nuclear localized ERs has been rendered obsolete by research over the last 15 years demonstrating that ERα and ERβ proteins are also localized at the plasma membranes and in other extra-nuclear organelles. The E2 modulation of cancer cell proliferation represents a good example of the impact of membrane-initiated signals on E2 effects. In fact, E2 via ERα elicits rapid signals driving cancer cells to proliferation (e.g., in breast cancer cells), while E2-induced ERβ rapid signaling inhibits proliferation (e.g., in colon cancer cells). In this review we provide with an overview of the complex system of E2-induced signal transduction pathways, their impact on E2-induced cancer cell proliferation, and the participation of E2-induced membrane-initiated signals in tumor environment. PMID:21747767

  14. IKK inhibition increases bortezomib effectiveness in ovarian cancer

    PubMed Central

    Singha, Bipradeb; Gatla, Himavanth Reddy; Phyo, Sai; Patel, Atish; Chen, Zhe-Sheng; Vancurova, Ivana

    2015-01-01

    Ovarian cancer is associated with increased expression of the pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8), which induces tumor cell proliferation, angiogenesis, and metastasis. Even though bortezomib (BZ) has shown remarkable anti-tumor activity in hematological malignancies, it has been less effective in ovarian cancer; however, the mechanisms are not understood. We have recently shown that BZ unexpectedly induces the expression of IL-8 in ovarian cancer cells in vitro, by IκB kinase (IKK)-dependent mechanism. Here, we tested the hypothesis that IKK inhibition reduces the IL-8 production and increases BZ effectiveness in reducing ovarian tumor growth in vivo. Our results demonstrate that the combination of BZ and the IKK inhibitor Bay 117085 significantly reduces the growth of ovarian tumor xenografts in nude mice when compared to either drug alone. Mice treated with the BZ/Bay 117085 combination exhibit smallest tumors, and lowest levels of IL-8. Furthermore, the reduced tumor growth in the combination group is associated with decreased tumor levels of S536P-p65 NFκB and its decreased recruitment to IL-8 promoter in tumor tissues. These data provide the first in vivo evidence that combining BZ with IKK inhibitor is effective, and suggest that using IKK inhibitors may increase BZ effectiveness in ovarian cancer treatment. PMID:26267322

  15. 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…

  16. 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…

  17. Effects of exercise interventions during different treatments in breast cancer.

    PubMed

    Fairman, Ciaran M; Focht, Brian C; Lucas, Alexander R; Lustberg, Maryam B

    2016-05-01

    Previous findings suggest that exercise is a safe and efficacious means of improving physiological and psychosocial outcomes in female breast cancer survivors. To date, most research has focused on post-treatment interventions. However, given that the type and severity of treatment-related adverse effects may be dependent on the type of treatment, and that the effects are substantially more pronounced during treatment, an assessment of the safety and efficacy of exercise during treatment is warranted. In this review, we present and evaluate the results of randomized controlled trials (RCTs) conducted during breast cancer treatment. We conducted literature searches to identify studies examining exercise interventions in breast cancer patients who were undergoing chemotherapy or radiation. Data were extracted on physiological and psychosocial outcomes. Cohen's d effect sizes were calculated for each outcome. A total of 17 studies involving 1,175 participants undergoing active cancer therapy met the inclusion criteria. Findings revealed that, on average, exercise interventions resulted in moderate to large improvements in muscular strength: resistance exercise (RE, = 0.86), aerobic exercise (AE, = 0.55), small to moderate improvements in cardiovascular functioning (RE, = 0.45; AE, = 0.17, combination exercise (COMB, = 0.31) and quality of life (QoL; RE, = 0.30; AE, = 0.50; COMB, = 0.63). The results of this review suggest that exercise is a safe, feasible, and efficacious intervention in breast cancer patients who are undergoing different types of treatment. Additional research addressing the different modes of exercise during each type of treatment is warranted to assess the comparable efficacy of the various exercise modes during established breast cancer treatments.

  18. Effects of exercise interventions during different treatments in breast cancer.

    PubMed

    Fairman, Ciaran M; Focht, Brian C; Lucas, Alexander R; Lustberg, Maryam B

    2016-05-01

    Previous findings suggest that exercise is a safe and efficacious means of improving physiological and psychosocial outcomes in female breast cancer survivors. To date, most research has focused on post-treatment interventions. However, given that the type and severity of treatment-related adverse effects may be dependent on the type of treatment, and that the effects are substantially more pronounced during treatment, an assessment of the safety and efficacy of exercise during treatment is warranted. In this review, we present and evaluate the results of randomized controlled trials (RCTs) conducted during breast cancer treatment. We conducted literature searches to identify studies examining exercise interventions in breast cancer patients who were undergoing chemotherapy or radiation. Data were extracted on physiological and psychosocial outcomes. Cohen's d effect sizes were calculated for each outcome. A total of 17 studies involving 1,175 participants undergoing active cancer therapy met the inclusion criteria. Findings revealed that, on average, exercise interventions resulted in moderate to large improvements in muscular strength: resistance exercise (RE, = 0.86), aerobic exercise (AE, = 0.55), small to moderate improvements in cardiovascular functioning (RE, = 0.45; AE, = 0.17, combination exercise (COMB, = 0.31) and quality of life (QoL; RE, = 0.30; AE, = 0.50; COMB, = 0.63). The results of this review suggest that exercise is a safe, feasible, and efficacious intervention in breast cancer patients who are undergoing different types of treatment. Additional research addressing the different modes of exercise during each type of treatment is warranted to assess the comparable efficacy of the various exercise modes during established breast cancer treatments. PMID:27258052

  19. 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.

  20. Effects of radiation and temperature on iodide sorption by surfactant-modified bentonite.

    PubMed

    Choung, Sungwook; Kim, Minkyung; Yang, Jung-Seok; Kim, Min-Gyu; Um, Wooyong

    2014-08-19

    Bentonite, which is used as an engineered barrier in geological repositories, is ineffective for sorbing anionic radionuclides because of its negatively charged surface. This study modified raw bentonite using a cationic surfactant (i.e., hexadecyltrimethylammonium [HDTMA]-Br) to improve its sorption capability for radioactive iodide. The effects of temperature and radiation on the iodide sorption of surfactant-modified bentonite (SMB) were also evaluated under alkaline pH condition similar to that found in repository environments. Different amounts of surfactant, equivalent to the 50, 100, and 200% cation-exchange capacity of the bentonite, were used to produce the HDTMA-SMB for iodide sorption. The sorption reaction of the SMB with iodide reached equilibrium rapidly within 10 min regardless of temperature and radiation conditions. The rate of iodide sorption increased as the amount of the added surfactant was increased and nonlinear sorption behavior was exhibited. However, high temperature and γ-irradiation ((60)Co) resulted in significantly (∼2-10 times) lower iodide Kd values for the SMB. The results of FTIR, NMR, and XANES spectroscopy analysis suggested that the decrease in iodide sorption may be caused by weakened physical electrostatic force between the HDTMA and iodide, and by the surfactant becoming detached from the SMB during the heating and irradiation processes.

  1. Effects of Radiation and Temperature on Iodide Sorption by Surfactant-Modified Bentonite

    SciTech Connect

    Choung, Sungwook; Kim, Min Kyung; Yang, Jungseok; Kim, Min-Gyu; Um, Wooyong

    2014-08-04

    Bentonite, which is used as an engineered barrier in geological repositories, is ineffective for sorbing anionic radionuclides because of its negatively charged surface. This study modified raw bentonite using a cationic surfactant (i.e., hexadecyltrimethylammonium [HDTMA]-Br) to improve its sorption capability for radioactive iodide. The effects of temperature and radiation on the iodide sorption of surfactant-modified bentonite (SMB) were evaluated under alkaline pH condition similar to that found in repository environments. Different amounts of surfactant, equivalent to the 50, 100, and 200% cation-exchange capacity of the bentonite, were used to produce the HDTMA-SMB for iodide sorption. The sorption reaction of the SMB with iodide reached equilibrium rapidly within 10 min regardless of temperature and radiation conditions. The rate of iodide sorption increased as the amount of the added surfactant was increased and nonlinear sorption behavior was exhibited. However, high temperature and γ-irradiation (60Co) resulted in significantly (~2–10 times) lower iodide Kd values for the SMB. The results of Fourier transform infrared spectroscopy analysis suggested that the decrease in iodide sorption may be caused by weakened physical electrostatic force between the HDTMA and iodide, and by the surfactant becoming detached from the SMB during the heating and irradiation processes.

  2. Effect of test method on SSC performance of modified 13Cr steel

    SciTech Connect

    Kimura, Mitsuo; Miyata, Yukio; Toyooka, Takaaki; Nakano, Yoshifumi; Murase, Fumio; Takojima, Kozo

    1998-12-31

    Effect of test method on SSC performance of modified 13Cr martensitic stainless steel (0.025C-13Cr-Ni-Mo) are investigated. The SSC for martensitic stainless steel initiates at the pitting and propagates by hydrogen embrittlement. The pH stability of the test solution affects the test results. SSC threshold stress for modified 13Cr steel in the stable solution is higher than that in the unstable solution. This difference seems to depend on the pH value in the pitting, since a great volume of hydrogen enters into steel at low pH condition and causes SSC. The SSC susceptibility for subsize specimens is higher than that for full size specimens. The oxygen in the test solution causes pitting. The deaeration procedure affects the SSC test result. The deaerated test solution should be transferred to test vessel. The SSC performance for martensitic stainless steel should be evaluated by full size test specimens under stable pH condition.

  3. 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).

  4. The effectiveness of existing and modified cleaning regimens in a Welsh hospital.

    PubMed

    Griffith, C J; Obee, P; Cooper, R A; Burton, N F; Lewis, M

    2007-08-01

    Hospital cleaning currently has a high media profile. The effectiveness of an existing ward-cleaning regimen was assessed at selected sites over a 14 day period and shown to be highly variable. The cleaning regimen was subsequently modified in two stages, both changes involving a rinse stage and substituting cloths with disposable paper towels. One modification continued using the existing detergent; the other replaced detergent with a quaternary ammonium sanitiser. Both modifications yielded significantly lower and more consistent bacterial counts. Assessment of residual organic soil using adenosine triphosphate (ATP) detection demonstrated that failure rates (measurements exceeding benchmark clean value of 500 relative light units (RLU)) fell from 86-100% after existing cleaning methods, to 0-14% after modified cleaning. Maximum ATP readings fell from 163,870 to 2289 RLU. Incorporating a quaternary ammonium sanitiser into the cleaning regimen produced a further slight, but not significant, improvement in cleaning efficacy. These findings suggest that simple improvements can be made to existing cleaning regimens to increase their efficacy. PMID:17655976

  5. Enzyme-modified field effect transistors based on surface-conductive single-crystalline diamond.

    PubMed

    Härtl, Andreas; Baur, Barbara; Stutzmann, Martin; Garrido, Jose A

    2008-09-01

    Enzyme-modified field effect transistors (ENFETs) were realized using surface-conductive single-crystalline diamond films. The enzymes penicillinase and acetylcholinesterase were immobilized onto the active area of diamond-based electrolytic solution gated FETs, using different organic linker molecules and cross-linking chemistries. The active area of the devices was patterned to generate enzyme-modified regions next to surface-conductive regions. Penicillinase was chosen as a robust model system, but the main focus of the present paper is on acetylcholinesterase, an enzyme essential for many neuronal signal transduction processes. All the different ENFETs show a clear and specific response to the corresponding substrate, penicillin and acetylcholine. The device response is based on the pH sensitivity of the surface-conductive active area and is enabled by the local pH change induced during the enzymatic reaction. The devices demonstrate promising stability and characteristic variations of the enzymatic activity with measurement conditions. Furthermore, the results from the ENFET measurements were compared with the results of spectrophotometric experiments, carried out with enzymes immobilized on diamond substrates and also with free enzymes in solution. This allows an analysis of the enzyme kinetics, as well as qualitative comparison of the different functionalization methods employed in this study.

  6. 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

  7. 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.

  8. 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.

  9. Effects of sintering atmosphere on the physical and mechanical properties of modified BOF slag glass

    NASA Astrophysics Data System (ADS)

    Dai, Wen-bin; Li, Yu; Cang, Da-qiang; Zhou, Yuan-yuan; Fan, Yong

    2014-05-01

    This study proposes an efficient way to utilize all the chemical components of the basic oxygen furnace (BOF) slag to prepare high value-added glass-ceramics. A molten modified BOF slag was converted from the melting BOF slag by reducing it and separating out iron component in it, and the modified BOF slag was then quenched in water to form glasses with different basicities. The glasses were subsequently sintered in the temperature range of 600-1000°C in air or nitrogen atmosphere for 1 h. The effects of different atmospheres on the physical and mechanical properties of sintered samples were studied by using differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) and by conducting experiment on evaluating the sintering shrinkage, water absorption and bulk density. It is found that the kinetics of the sintering process is significantly affected by sintering atmosphere. In particular, compared with sintering in air atmosphere, sintering in N2 atmosphere promotes the synergistic growth of pyroxene and melilite crystalline phases, which can contribute to better mechanical properties and denser microstructure.

  10. Effect of acid concentration and treatment time on acid-alcohol modified jackfruit seed starch properties.

    PubMed

    Dutta, Himjyoti; Paul, Sanjib Kumar; Kalita, Dipankar; Mahanta, Charu Lata

    2011-09-15

    The properties of starch extracted from jackfruit (Artocarpus heterophyllus Lam.) seeds, collected from west Assam after acid-alcohol modification by short term treatment (ST) for 15-30min with concentrated hydrochloric acid and long term treatment (LT) for 1-15days with 1M hydrochloric acid, were investigated. Granule density, freeze thaw stability, solubility and light transmittance of the treated starches increased. A maximum decrease in the degree of polymerisation occurred in ST of 30min (2607.6). Jackfruit starch had 27.1±0.04% amylose content (db), which in ST initially decreased and then increased with the severity of treatment; in LT the effect was irregular. The pasting profile and granule morphology of the treated samples were severely modified. Native starch had the A-type crystalline pattern and crystalline structure increased on treatment. FTIR spectra revealed slight changes in bond stretching and bending. Colour measurement indicated that whiteness increased on treatment. Acid modified jackfruit seed starch can have applications in the food industry.

  11. Effect of acid concentration and treatment time on acid-alcohol modified jackfruit seed starch properties.

    PubMed

    Dutta, Himjyoti; Paul, Sanjib Kumar; Kalita, Dipankar; Mahanta, Charu Lata

    2011-09-15

    The properties of starch extracted from jackfruit (Artocarpus heterophyllus Lam.) seeds, collected from west Assam after acid-alcohol modification by short term treatment (ST) for 15-30min with concentrated hydrochloric acid and long term treatment (LT) for 1-15days with 1M hydrochloric acid, were investigated. Granule density, freeze thaw stability, solubility and light transmittance of the treated starches increased. A maximum decrease in the degree of polymerisation occurred in ST of 30min (2607.6). Jackfruit starch had 27.1±0.04% amylose content (db), which in ST initially decreased and then increased with the severity of treatment; in LT the effect was irregular. The pasting profile and granule morphology of the treated samples were severely modified. Native starch had the A-type crystalline pattern and crystalline structure increased on treatment. FTIR spectra revealed slight changes in bond stretching and bending. Colour measurement indicated that whiteness increased on treatment. Acid modified jackfruit seed starch can have applications in the food industry. PMID:25212133

  12. 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.

  13. RGD-modifided oncolytic adenovirus exhibited potent cytotoxic effect on CAR-negative bladder cancer-initiating cells

    PubMed Central

    Yang, Y; Xu, H; Shen, J; Yang, Y; Wu, S; Xiao, J; Xu, Y; Liu, X-Y; Chu, L

    2015-01-01

    Cancer-initiating cell (CIC) is critical in cancer development, maintenance and recurrence. The reverse expression pattern of coxsackie and adenovirus receptor (CAR) and αν integrin in bladder cancer decreases the infection efficiency of adenovirus. We constructed Arg-Gly-Asp (RGD)-modified oncolytic adenovirus, carrying EGFP or TNF-related apoptosis-inducing ligand (TRAIL) gene (OncoAd.RGD-hTERT-EGFP/TRAIL), and applied them to CAR-negative bladder cancer T24 cells and cancer-initiating T24 sphere cells. OncoAd.RGD-hTERT-EGFP had enhanced infection ability and cytotoxic effect on T24 cells and T24 sphere cells, but little cytoxicity on normal urothelial SV-HUC-1 cells compared with the unmodified virus OncoAd.hTERT-EGFP. Notably, OncoAd.RGD-hTERT-TRAIL induced apoptosis in T24 cells and T24 sphere cells. Furthermore, it completely inhibited xenograft initiation established by the oncolytic adenovirus-pretreated T24 sphere cells, and significantly suppressed tumor growth by intratumoral injection. These results provided a promising therapeutic strategy for CAR-negative bladder cancer through targeting CICs. PMID:25973680

  14. [Current Status and Effectiveness of Perioperative Oral Health Care Management for Lung Cancer and Esophageal Cancer Patients].

    PubMed

    Nishino, Takeshi; Takizawa, Hiromitsu; Yoshida, Takahiro; Inui, Tomohiro; Takasugi, Haruka; Matsumoto, Daisuke; Kawakita, Naoya; Inoue, Seiya; Sakiyama, Shoji; Tangoku, Akira; Azuma, Masayuki; Yamamura, Yoshiko

    2016-01-01

    The effectiveness of perioperative oral health care management to decrease the risk of postoperative pneumonia have been reported lately. Since 2014, we introduced perioperative oral health care management for lung cancer and esophageal cancer patients. We report current status and effectiveness of perioperative oral health care management for lung cancer and esophageal cancer patients. Every 100 cases of lung cancer and esophageal cancer patients treated by surgery were classified 2 group with or without perioperative oral health care management and compared about postoperative complications retrospectively. In the lung cancer patients, the group with oral health care management could prevent postoperative pneumonia significantly and had shorter length of hospital stay than the group without oral health care management. In the esophageal cancer patients, there was little occurrence of postoperative pneumonia without significant difference between both group with or without oral health care management. A large number of esophageal cancer patients received neo-adjuvant chemotherapy and some patients developed oral mucositis and received oral care treatment before surgery. Treatment for oral mucositis probably improved oral environment and affected prevention of postoperative pneumonia. Perioperative oral health care management can prevent postoperative pneumonia of lung cancer and esophageal cancer patients by improvement of oral hygiene.

  15. Statins and cancers.

    PubMed

    Stryjkowska-Góra, Aleksandra; Karczmarek-Borowska, Bożenna; Góra, Tomasz; Krawczak, Katarzyna

    2015-01-01

    Statins (inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) are a group of drugs used to treat lipid disorders. They inhibit cholesterol synthesis at an early stage of the biosynthesis pathway, thus eliminating numerous metabolites involved in the cycle. Numerous studies point to different possible effects of statins on cancer cells. Statins inhibit growth of a tumor, invasion and metastasis formation. They block the production of isoprenoids, which are necessary for post-translational modifications of many proteins, including those involved in normal cell signaling. They also contribute to the reduction in the expression of vascular endothelial growth factor, sensitize tumor cells to NK cell activity, and modify the body inflammatory response. Due to different pharmacokinetic properties of individual statins, they may have opposite effects on the risk of cancer. Currently, most information on the effects of statins on the risk of developing cancer is obtained from observational studies. The studies have different results depending on the location of cancer. The protective effect of statins was observed in the meta-analysis of numerous studies including prostate cancer, stomach cancer, esophagus cancer, and hepatocellular carcinoma; however, it has not yet been confirmed that statins influence the risk of developing colorectal cancer, breast cancer, or lung cancer. The protective effect of statins on the development of many kinds of cancer can be a valuable and easy way to reduce morbidity. However, further research is necessary to thoroughly determine the value of this group of drugs. PMID:26557755

  16. Sleep duration modifies effects of free ad libitum school meals on adiposity and blood pressure.

    PubMed

    Hjorth, Mads F; Sjödin, Anders; Dalskov, Stine-Mathilde; Damsgaard, Camilla Trab; Michaelsen, Kim F; Biltoft-Jensen, Anja; Andersen, Rikke; Ritz, Christian; Chaput, Jean-Philippe; Astrup, Arne

    2016-01-01

    Insufficient sleep can potentially affect both energy intake and energy expenditure, resulting in obesity and reduced cardiometabolic health. The objective of the study was to investigate if habitual sleep duration of 8- to 11-year-olds modifies the effect of free ad libitum school meals on cardiometabolic markers, body composition, dietary intake, and physical activity. For 2 consecutive 3-month periods, this cluster-randomized, controlled, cross-over trial provided 530 children with school meals or usual lunch brought from home. Dietary intake, activity, and sleep were measured simultaneously for 7 consecutive days using dietary records and accelerometers. Short- and long-sleeping children were defined as lower and upper tertile of sleep duration. Body composition, blood pressure, blood lipids, and homeostatic model assessment of insulin resistance (HOMAIR) were measured/calculated. Overall, school meals compared with lunch from home had positive effects on physical activity and blood pressure in long-sleeping children and negative effects on body fat in short-sleeping children. Short-sleeping children increased fat mass compared with long-sleeping children by 0.21 (95% confidence interval 0.03-0.38) kg, android fat mass by 0.02 (0.001-0.04) kg, waist circumference by 0.73 (0.23-1.24) cm, blood pressure by 1.5 (0.4-2.6) mm Hg, fat intake by 1.1 (0.2-2.0) percentage of energy, and decreased total physical activity by 7.2 (1.6-12.7) % (all P ≤ 0.04), while HOMAIR and blood lipids were not modified by sleep duration (all P ≥ 0.32). In conclusion, the susceptibility to increase abdominal adiposity and blood pressure when exposed to dietary changes can potentially be explained by too little sleep, which results in increased caloric intake and reduced physical activity. PMID:26647154

  17. Sleep duration modifies effects of free ad libitum school meals on adiposity and blood pressure.

    PubMed

    Hjorth, Mads F; Sjödin, Anders; Dalskov, Stine-Mathilde; Damsgaard, Camilla Trab; Michaelsen, Kim F; Biltoft-Jensen, Anja; Andersen, Rikke; Ritz, Christian; Chaput, Jean-Philippe; Astrup, Arne

    2016-01-01

    Insufficient sleep can potentially affect both energy intake and energy expenditure, resulting in obesity and reduced cardiometabolic health. The objective of the study was to investigate if habitual sleep duration of 8- to 11-year-olds modifies the effect of free ad libitum school meals on cardiometabolic markers, body composition, dietary intake, and physical activity. For 2 consecutive 3-month periods, this cluster-randomized, controlled, cross-over trial provided 530 children with school meals or usual lunch brought from home. Dietary intake, activity, and sleep were measured simultaneously for 7 consecutive days using dietary records and accelerometers. Short- and long-sleeping children were defined as lower and upper tertile of sleep duration. Body composition, blood pressure, blood lipids, and homeostatic model assessment of insulin resistance (HOMAIR) were measured/calculated. Overall, school meals compared with lunch from home had positive effects on physical activity and blood pressure in long-sleeping children and negative effects on body fat in short-sleeping children. Short-sleeping children increased fat mass compared with long-sleeping children by 0.21 (95% confidence interval 0.03-0.38) kg, android fat mass by 0.02 (0.001-0.04) kg, waist circumference by 0.73 (0.23-1.24) cm, blood pressure by 1.5 (0.4-2.6) mm Hg, fat intake by 1.1 (0.2-2.0) percentage of energy, and decreased total physical activity by 7.2 (1.6-12.7) % (all P ≤ 0.04), while HOMAIR and blood lipids were not modified by sleep duration (all P ≥ 0.32). In conclusion, the susceptibility to increase abdominal adiposity and blood pressure when exposed to dietary changes can potentially be explained by too little sleep, which results in increased caloric intake and reduced physical activity.

  18. Inhibition of rhotekin exhibits antitumor effects in lung cancer cells

    PubMed Central

    ZHANG, WEIZHEN; LIANG, ZHENYU; LI, JING

    2016-01-01

    Lung cancer is the leading cause for cancer-related death, however, the pathogenesis mechanism is poorly understood. Although the rhotekin (RTKN) gene has been reported to encode an effector for the Rho protein that has critical roles in regulating cell growth, the role of RTKN in lung cancer has not been investigated. In clinical lung cancer patient tumor samples, we identified that the RTKN gene expression level was significantly higher in tumor tissues compared to that of the adjacent normal tissues. To investigate the molecular mechanisms of RTKN in lung cancer, we established RTKN stable knock-down A549 and SPC-A-1 lung adenocarcinoma cell lines using lentiviral transfection of RTKN shRNA and evaluated the antitumor effects. The results showed that RTKN knock-down inhibited lung adenocarcinoma cell viability, induced S phase arrest and increased cell apoptosis. In addition, RTKN knock-down inhibited lung cancer cell invasion and adhesion. Further analysis showed that the S phase promoting factors cyclindependent kinase (CDK)1 and CDK2 levels were decreased in RTKN knock-down cells, and that the DNA replication initiation complex proteins Minichromosome maintenance protein complex (MCM)2 and MCM6 were decreased as well in RTKN knock-down cells. These results indicated that the RTKN protein was associated with lung cancer in clinic samples and exerted anticancer activity in lung adenocarcinoma cells through inhibiting cell cycle progression and the DNA replication machinery. These findings suggest that RTKN inhibition may be a novel therapeutic strategy for lung adenocarcinoma. PMID:26935528

  19. Gompertzian stochastic model with delay effect to cervical cancer growth

    SciTech Connect

    Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti; Bahar, Arifah

    2015-02-03

    In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

  20. Gompertzian stochastic model with delay effect to cervical cancer growth

    NASA Astrophysics Data System (ADS)

    Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti; Bahar, Arifah

    2015-02-01

    In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

  1. Effect of BRCA germline mutations on breast cancer prognosis

    PubMed Central

    Baretta, Zora; Mocellin, Simone; Goldin, Elena; Olopade, Olufunmilayo I.; Huo, Dezheng

    2016-01-01

    Abstract Background: The contribution of BRCA germline mutational status to breast cancer patients’ prognosis is unclear. We aimed to systematically review and perform meta-analysis of the available evidence of effects of BRCA germline mutations on multiple survival outcomes of breast cancer patients as a whole and in specific subgroups of interest, including those with triple negative breast cancer, those with Ashkenazi Jewish ancestry, and patients with stage I–III disease. Methods: Sixty studies met all inclusion criteria and were considered for this meta-analysis. These studies involved 105,220 breast cancer patients, whose 3588 (3.4%) were BRCA mutations carriers. The associations between BRCA genes mutational status and overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) were evaluated using random-effect models. Results: BRCA1 mutation carriers have worse OS than BRCA-negative/sporadic cases (hazard ratio, HR 1.30, 95% CI: 1.11–1.52) and worse BCSS than sporadic/BRCA-negative cases among patients with stage I–III breast cancer (HR 1.45, 95% CI: 1.01–2.07). BRCA2 mutation carriers have worse BCSS than sporadic/BRCA-negative cases (HR 1.29, 95% CI: 1.03–1.62), although they have similar OS. Among triple negative breast cancer, BRCA1/2 mutations carriers had better OS than BRCA-negative counterpart (HR 0.49, 95% CI: 0.26–0.92). Among Ashkenazi Jewish women, BRCA1/2 mutations carriers presented higher risk of death from breast cancer (HR 1.44, 95% CI: 1.05–1.97) and of distant metastases (HR 1.82, 95% CI: 1.05–3.16) than sporadic/BRCA-negative patients. Conclusion: Our results support the evaluation of BRCA mutational status in patients with high risk of harboring BRCA germline mutations to better define the prognosis of breast cancer in these patients. PMID:27749552

  2. 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.

  3. 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

  4. 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

  5. Specific combinations of the chromatin-modifying enzyme modulators significantly attenuate glioblastoma cell proliferation and viability while exerting minimal effect on normal adult stem cells growth.

    PubMed

    Alexanian, Arshak R; Huang, Yi-Wen

    2015-11-01

    The discoveries of recent decade showed that all critical changes in cancer cells, such as silencing of tumor-suppressor genes and activation of oncogenes, are caused not only by genetic but also by epigenetic mechanisms. Although epigenetic changes are somatically heritable, in contrast to genetic changes, they are potentially reversible, making them good targets for therapeutic intervention. Covalent modifications of chromatin such as methylation and acetylation of histones and methylation of DNA are the important components of epigenetic machinery. In this study, we investigated the effect of different modulators of DNA and histone covalent-modifying enzymes on the proliferation and viability of normal adult stem cells, such as human bone marrow mesenchymal stem cells (hMSCs), and on malignant tumor cells, such as glioblastoma (GB) D54 cells. Results demonstrated that specific combinations of histone methyltransferases and deacetylases inhibitors significantly attenuated D54 cells viability but having only a small effect on hMSCs growth. Taken together, these studies suggest that specific combinations of histone covalent modifiers could be an effective treatment option for the most aggressive type of primary brain tumors such as glioblastoma multiforme.

  6. Preparation and in vitro antitumor effects of cytosine arabinoside-loaded genipin-poly-l-glutamic acid-modified bacterial magnetosomes.

    PubMed

    Liu, Yuan-Gang; Dai, Qing-Lei; Wang, Shi-Bin; Deng, Qiong-Jia; Wu, Wen-Guo; Chen, Ai-Zheng

    2015-01-01

    To solve the problem of synthesized magnetic nanoparticles in cancer therapy, a new drug delivery system synthesized from bacteria was used to load cytosine arabinoside (Ara-C). Genipin (GP) and poly-l-glutamic acid (PLGA) were selected as dual cross-linkers. The preparation and characterization of Ara-C-loaded GP-PLGA-modified bacterial magnetosomes (BMs) (ABMs-P), as well as their in vitro antitumor effects, were all investigated. Transmission electron micrographs (TEM) and Fourier transform infrared (FTIR) spectroscopy suggested that Ara-C could be bound to the membrane of BMs modified by GP-PLGA. The diameters of the BMs and ABMs-P were 42.0±8.6 nm and 74.9±8.2 nm, respectively. The zeta potential revealed that the nanoparticles were stable. Moreover, this system exhibited optimal drug-loading properties and long-term release behavior. The optimal encapsulation efficiency and drug-loading were 64.1%±6.6% and 38.9%±2.4%, respectively, and ABMs-P could effectively release 90% Ara-C within 40 days, without the release of an initial burst. In addition, in vitro antitumor experiments elucidated that ABMs-P is cytotoxic to HL-60 cell lines, with an inhibition rate of 95%. The method of coupling drugs on BMs using dual cross-linkers is effective, and our results reveal that this new system has potential applications for drug delivery in the future.

  7. The effect of cancer treatment on cognitive function.

    PubMed

    Asher, Arash; Myers, Jamie S

    2015-07-01

    Cognitive dysfunction is an increasingly recognized complication of cancer and its treatment. Most research in this arena has found that a subset of patients appear to be vulnerable to this complication even after treatment has ended, and often have difficulties with multitasking, short-term memory, word-finding, attention, or concentration. The mechanisms underlying these cognitive changes are not fully elucidated but may include direct neurotoxic effects of therapy, oxidative damage, and genetic predisposition. Compelling evidence has accumulated for the role of immune dysregulation and neurotoxicity from inflammatory cytokines. A gold standard for subjective or objective assessment of cancer treatment-related cognitive changes has yet to be established. Current options to assess cognitive function include neuropsychological testing, functional neuroimaging, and subjective assessments. Pharmacologic treatment options for this clinical problem are modest and limited. Nonpharmacologic treatments, including cognitive rehabilitation programs, are an emerging area of research for the management of cancer treatment-related cognitive changes.

  8. The effect of cancer on suicide among elderly Holocaust survivors.

    PubMed

    Nakash, Ora; Liphshitz, Irena; Keinan-Boker, Lital; Levav, Itzhak

    2013-06-01

    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 persons with cancer, 60 years and over, diagnosed in Israel between 1999 and 2007. The standardized incidence ratios were not significantly different between the exposed and nonexposed groups (men: 0.90, 95% CI 0.60-1.19; women: 0.95, 95% CI 0.55-1.37). Past exposure to maximum adversity did not increase the suicide risk among persons with cancer.

  9. [Renal late effects in patients treated for cancer in childhood].

    PubMed

    Sudour-Bonnange, Hélène; Vanrenterghem, Audrey; Nobili, François; Guigonis, Vincent; Boudailliez, Bernard

    2015-01-01

    Impaired renal function may occur following multimodal treatment of cancer in childhood. Renal late effects caused by chemotherapy, renal surgery and/or radiotherapy are now well described; but little is known about their prevalence and time of development. Herein, we provide a synthesis of the different renal complications that may occur with their physiopathology in relation with specific treatment exposures. This review summarized the literature that supported the recommendations issued by the long-term follow-up group of the "Société française des cancers de l'enfant (SFCE)" for childhood cancer survivors at risk for nephrotoxicity (www.sfce.org ; www.soc-nephrologie.org/SNP/index.htm). We developed these monitoring elements and the lifestyle recommendations for all asymptomatic survivors.

  10. Reversing of multidrug resistance breast cancer by co-delivery of P-gp siRNA and doxorubicin via folic acid-modified core-shell nanomicelles.

    PubMed

    Wu, Yang; Zhang, Yu; Zhang, Wei; Sun, Chunlong; Wu, Jianzhong; Tang, Jinhai

    2016-02-01

    Multidrug resistance (MDR) remains one of major limitation for the successful treatment of many cancers including breast cancer. Co-delivery of chemotherapeutic drugs and small interfering RNA (siRNA) has been developed because of its ability to generate synergistic anticancer effects via different mechanisms of action, to reverse MDR and increase the efficacy of chemotherapeutic drugs in cancer therapy. Herein, we employed a kind of efficient multifunctional tumor targeted nanomicelles (PECL3) for the co-delivery of hydrophobic anti-cancer drugs and siRNA. This kind of nanomicelles were constructed by folic acid (FA)-decorated PEG-b-(PCL-g-PEI)-b-PCL triblock copolymers, which were synthesized through "click chemistry" and "ring opening" polymerization. Driven by the "core-shell" structure and the electrostatic interaction, this triblock copolymer could efficiently encapsulate P-glycoprotein (P-gp) siRNA and doxorubicin (DOX). The obtained nanomicelles can prevent renal clearance, RNase degradation and aggregation in circulation. Compared to the non-specific delivery, these FA functionalized nanomicelles could efficiently deliver P-gp siRNA to reducing both P-gp expression levels and IC50 value of the DOX in DOX-resistant breast cancer cells (MCF-7/ADR). Additionally, in vivo results showed that DOX loaded PECL3 (D-PECL3) micelles could reduce toxicity of DOX on nontarget tissues and significantly inhibited MCF-7/ADR tumor growth through encapsulating DOX in the micelles and deliver them to target tumor region. Taken together, these results proof that PECL3 micelles could co-deliver siRNA and drug to inhibit MDR tumor growth. These results suggested that the co-delivery of DOX and siRNA in tumor-targeting nanomicelles could excite synergistic effect of gene therapy and chemotherapy, thus can efficiently reverse MDR cancer and kill the cancer cells. PMID:26655793

  11. Information seeking regarding tobacco and lung cancer: effects of seasonality.

    PubMed

    Zhang, Zhu; Zheng, Xiaolong; Zeng, Daniel Dajun; Leischow, Scott J

    2015-01-01

    This paper conducted one of the first comprehensive international Internet analyses of seasonal patterns in information seeking concerning tobacco and lung cancer. Search query data for the terms "tobacco" and "lung cancer" from January 2004 to January 2014 was collected from Google Trends. The relevant countries included the USA, Canada, the UK, Australia, and China. Two statistical approaches including periodogram and cross-correlation were applied to analyze seasonal patterns in the collected search trends and their associations. For these countries except China, four out of six cross-correlations of seasonal components of the search trends regarding tobacco were above 0.600. For these English-speaking countries, similar patterns existed in the data concerning lung cancer, and all cross-correlations between seasonal components of the search trends regarding tobacco and that regarding lung cancer were also above 0.700. Seasonal patterns widely exist in information seeking concerning tobacco and lung cancer on an international scale. The findings provide a piece of novel Internet-based evidence for the seasonality and health effects of tobacco use.

  12. Potential Effects of Pomegranate Polyphenols in Cancer Prevention and Therapy

    PubMed Central

    Turrini, Eleonora; Ferruzzi, Lorenzo; Fimognari, Carmela

    2015-01-01

    Cancer is the second leading cause of death and is becoming the leading one in old age. Vegetable and fruit consumption is inversely associated with cancer incidence and mortality. Currently, interest in a number of fruits high in polyphenols has been raised due to their reported chemopreventive and/or chemotherapeutic potential. Pomegranate has been shown to exert anticancer activity, which is generally attributed to its high content of polyphenols. This review provides a comprehensive analysis of known targets and mechanisms along with a critical evaluation of pomegranate polyphenols as future anticancer agents. Pomegranate evokes antiproliferative, anti-invasive, and antimetastatic effects, induces apoptosis through the modulation of Bcl-2 proteins, upregulates p21 and p27, and downregulates cyclin-cdk network. Furthermore, pomegranate blocks the activation of inflammatory pathways including, but not limited to, the NF-κB pathway. The strongest evidence for its anticancer activity comes from studies on prostate cancer. Accordingly, some exploratory clinical studies investigating pomegranate found a trend of efficacy in increasing prostate-specific antigen doubling time in patients with prostate cancer. However, the genotoxicity reported for pomegranate raised certain concerns over its safety and an accurate assessment of the risk/benefit should be performed before suggesting the use of pomegranate or its polyphenols for cancer-related therapeutic purposes. PMID:26180600

  13. The effect of cancer warning statements on alcohol consumption intentions.

    PubMed

    Pettigrew, Simone; Jongenelis, Michelle I; Glance, David; Chikritzhs, Tanya; Pratt, Iain S; Slevin, Terry; Liang, Wenbin; Wakefield, Melanie

    2016-02-01

    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 attitudinal, intentions and demographic items, the survey included an online simulation that exposed respondents to one of six cancer warning statements delivered across a range of situational contexts. Half of the statements made general reference to cancer and half mentioned specific forms of cancer. Respondents reported on the believability, convincingness and personal relevance of the warning statements. Pre- and post-exposure data were captured relating to respondents' alcohol consumption intentions. Of the six statements tested, Alcohol increases your risk of bowel cancer produced the highest scores across all outcome measures. All statements produced favorable changes in alcohol consumption intentions, including among high-risk drinkers. There is thus the potential for these and similar statements to be used as a suite of rotating warning messages located on alcoholic beverage labels and applied in various public education contexts. PMID:26787351

  14. Effect of a dietary fiber (beet fiber) on dimethylhydrazine-induced colon cancer in Wistar rats.

    PubMed

    Thorup, I; Meyer, O; Kristiansen, E

    1992-01-01

    The modifying effect of a dietary fiber, Fibeta (beet fiber), on experimentally induced colorectal cancer was studied in Wistar rats. The rats were fed a powdered semisynthetic casein-based diet in which the carbohydrate pool was substituted with Fibeta as the sole source of fiber. Dimethylhydrazine dihydrochloride (DMH-2HCl) was used as initiator in a dose of 20 mg/kg body wt and given by gavage once a week for 10 weeks. Throughout the experiment the rats were offered the diets with different levels of fiber in a preinitiation period of 8 weeks, during the initiation, or in a 30-week postinitiation period. The study was terminated after one year. A protective effect of the fiber was not found at any stage of the colorectal carcinogenic process. Even though differences (not statistically significant) in tumor incidences were seen, these did not reflect any effect of the high or low fiber intake during the study. Analysis for volatile fatty acids in cecal content showed that continuous feeding with a fiber-rich diet resulted in significant increase in most of the volatile fatty acids. The relative change was highest for butyric acid. These findings do not support the hypothesis that butyric acid has a protective effect on colorectal cancer. The tumor yield in the present study was low compared with that reported in the literature, and possible causes for this are discussed.

  15. Evaluating Shielding Effectiveness for Reducing Space Radiation Cancer Risks

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Kim, Myung-Hee Y.; Ren, Lei

    2007-01-01

    We discuss calculations of probability distribution functions (PDF) representing uncertainties in projecting fatal cancer risk from galactic cosmic rays (GCR) and solar particle events (SPE). The PDF s are used in significance tests of the effectiveness of potential radiation shielding approaches. Uncertainties in risk coefficients determined from epidemiology data, dose and dose-rate reduction factors, quality factors, and physics models of radiation environments are considered in models of cancer risk PDF s. Competing mortality risks and functional correlations in radiation quality factor uncertainties are treated in the calculations. We show that the cancer risk uncertainty, defined as the ratio of the 95% confidence level (CL) to the point estimate is about 4-fold for lunar and Mars mission risk projections. For short-stay lunar missions (<180 d), SPE s present the most significant risk, however one that is mitigated effectively by shielding, especially for carbon composites structures with high hydrogen content. In contrast, for long duration lunar (>180 d) or Mars missions, GCR risks may exceed radiation risk limits, with 95% CL s exceeding 10% fatal risk for males and females on a Mars mission. For reducing GCR cancer risks, shielding materials are marginally effective because of the penetrating nature of GCR and secondary radiation produced in tissue by relativistic particles. At the present time, polyethylene or carbon composite shielding can not be shown to significantly reduce risk compared to aluminum shielding based on a significance test that accounts for radiobiology uncertainties in GCR risk projection.

  16. ErbB Inhibitory Protein [EBIP]: A Modified Ectodomain of EGFR Synergizes with Dasatinib to Inhibit Growth of Breast Cancer Cells

    PubMed Central

    Nautiyal, Jyoti; Yu, Yingjie; Aboukameel, Amro; Kanwar, Shailender; Das, Jayanta K; Du, Jianhua; Patel, Bhaumik; Sarkar, Fazlul H.; Rishi, Arun K.; Mohammad, Ramzi; Majumdar, Adhip P. N.

    2010-01-01

    Many solid tumors including breast cancer show increased activation of several growth factor receptors, specifically EGFR and its family members (EGFRs) as well as c-Src, a non-receptor tyrosine kinase that promote proliferation, inhibit apoptosis and induce metastasis. We hypothesize that inhibition of c-Src and EGFRs will be an effective therapeutic strategy for triple negative breast cancer. To test our hypothesis we used a c-Src specific inhibitor dasatinib (BMS-354825; Bristol-Myers Squibb) and our newly developed ErbB Inhibitory Protein (EBIP), a potential pan-erbB inhibitor in breast cancer cells. EBIP is composed of 1-448 amino acids of the ectodomain of human EGFR to which the 30 amino acids epitope (known as “U” region) of rat EGFR-Related Protein (ERRP) is fused at the C-terminal end. The combination of dasatinib and EBIP was found to be highly effective in inhibiting the growth of 4 different breast cancer cells (MDA-MB-468, SKBr-3, MDA-MB-453 and MDA-MB-231) that express different levels of EGFRs. In EGFR overexpressing MDA-MB-468 cells, the combination, but not monotherapy markedly stimulated apoptosis mediated by caspases -9 and 8 and attenuated activation of EGFR and Src as well as tyrosine kinase activity. EBIP also inhibited heregulin-induced activation of HER-2 and HER-3 in MDA-MB-453 breast cancer cells. The combination therapy was highly effective in suppressing tumor growth (∼90% inhibition) in MDA-MB-468 derived xenografts in SCID mice. The latter could be attributed to induction of apoptosis. We conclude that combining dasatinib and EBIP could be an effective therapeutic strategy for breast cancer by targeting EGFRs and Src signaling. PMID:20515951

  17. Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.

    PubMed

    Wei, Wei-Jun; Shen, Chen-Tian; Song, Hong-Jun; Qiu, Zhong-Ling; Luo, Quan-Yong

    2016-09-01

    Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad β-blocker propranolol and β2-specific antagonist ICI118551, but not β1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate‑buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial. PMID:27432558

  18. Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier.

    PubMed

    Weitzel, Douglas H; Tovmasyan, Artak; Ashcraft, Kathleen A; Boico, Alina; Birer, Samuel R; Roy Choudhury, Kingshuk; Herndon, James; Rodriguiz, Ramona M; Wetsel, William C; Peters, Katherine B; Spasojevic, Ivan; Batinic-Haberle, Ines; Dewhirst, Mark W

    2016-06-01

    Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy-induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have recently shown that MnTnBuOE-2-PyP(5+) (Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium -2-yl)porphyrin) rescued RT-induced white matter damage in cranially-irradiated mice. Radiotherapy is not used in isolation for treatment of brain tumors; temozolomide is the standard-of-care for adult glioblastoma, whereas cisplatin is often used for treatment of pediatric brain tumors. Therefore, we evaluated the brain radiation mitigation ability of MnTnBuOE-2-PyP(5+) after either temozolomide or cisplatin was used singly or in combination with 10 Gy RT. MnTnBuOE-2-PyP(5+) accumulated in brains at low nanomolar levels. Histological and neurobehavioral testing showed a drastic decrease (1) of axon density in the corpus callosum and (2) rotorod and running wheel performance in the RT only treatment group, respectively. MnTnBuOE-2-PyP(5+) completely rescued this phenotype in irradiated animals. In the temozolomide groups, temozolomide/ RT treatment resulted in further decreased rotorod responses over RT alone. Again, MnTnBuOE-2-PyP(5+) treatment rescued the negative effects of both temozolomide ± RT on rotorod performance. While the cisplatin-treated groups did not give similar results as the temozolomide groups, inclusion of MnTnBuOE-2-PyP(5+) did not negatively affect rotorod performance. Additionally, MnTnBuOE-2-PyP(5+) sensitized glioblastomas to either RT ± temozolomide in flank tumor models. Mice treated with both MnTnBuOE-2-PyP(5+) and radio-/chemo-therapy herein demonstrated brain radiation mitigation. MnTnBuOE-2-PyP(5+) may well serve as a normal tissue radio-/chemo-mitigator adjuvant therapy to standard brain cancer treatment regimens. Environ. Mol. Mutagen. 57:372-381, 2016. © 2016 Wiley Periodicals, Inc.

  19. Digoxin is a selective modifier increasing platinum drug anticancer activity.

    PubMed

    Bogush, T A; Chernov, V Yu; Dudko, E A; Shprakh, Z S; Bogush, E A; Polotsky, B E; Tjulandin, S A; Davydov, M I

    2016-05-01

    Using the model of breast cancer Ehrlich ascites tumor in mice, we showed that a sigle intraperitoneal injection of cardiac glycoside digoxin 1 h before the intraperitoneal injection of cisplatin increased the anticancer effect of the cytostatic drug more than twice when recalculated for the dose. It is assumed that the modifying effect of digoxin is determined by the direct inhibition of glycolysis in tumor cells. Taking into account the design of the study, we consider promising the clinical evaluation of the effectiveness of digoxin as a modifier of cisplatin efficiency in intracavitary therapy of ascites cancers with pleural and abdominal dissenmination. PMID:27417726

  20. Comparative antitumor effect among GM-CSF, IL-12 and GM-CSF+IL-12 genetically modified tumor cell vaccines.

    PubMed

    Miguel, A; Herrero, M J; Sendra, L; Botella, R; Algás, R; Sánchez, M; Aliño, S F

    2013-10-01

    Genetically modified cells have been shown to be one of the most effective cancer vaccine strategies. An evaluation is made of the efficacy of both preventive and therapeutic antitumor vaccines against murine melanoma, using C57BL/6 mice and irradiated B16 tumor cells expressing granulocyte and macrophage colony-stimulating factor (GM-CSF), interleukin-12 (IL-12) or both. Tumor was transplanted by the injection of wild-type B16 cells. Tumor growth and survival were measured to evaluate the efficacy of vaccination. Specific humoral response and immunoglobulin G (IgG) switch were evaluated measuring total IgG and IgG1 and IgG2a subtypes against tumor membrane proteins of B16 cells. In preventive vaccination, all treated groups showed delayed tumor growth. In addition, the group vaccinated to express only GM-CSF achieved 100% animal survival (P<0.005). Vaccination with GM-CSF+IL-12-producing B16 cells yielded lesser results (60% survival, P<0.005). Furthermore, all surviving animals remained disease-free after second tumor implantation 1 year later. The therapeutic vaccination strategies resulted in significantly delayed tumor growth, mainly using B16 cells producing GM-CSF+IL-12 cytokines, with 70% tumor growth inhibition (P<0.001)-although none of the animals reached overall survival. The results obtained suggest that the GM-CSF+IL-12 combination only increases the efficacy of therapeutic vaccines. No differences in classical regulatory T cells were found among the different groups.

  1. Combined effects of gamma-irradiation and modified atmosphere packaging on quality of some spices.

    PubMed

    Kirkin, Celale; Mitrevski, Blagoj; Gunes, Gurbuz; Marriott, Philip J

    2014-07-01

    Thyme (Thymus vidgaris L.), rosemary (Rosmarinus officinalis L.), black pepper (Piper nigrum L.) and cumin (Cuminum cyminum L.) in ground form were packaged in either air or 100% N2 and γ-irradiated at 3 different irradiation levels (7kGy, 12kGy, 17kGy). Total viable bacterial count, yeast and mould count, colour, essential oil yield and essential oil composition were determined. Microbial load was not detectable after 12kGy irradiation of all samples. Irradiation resulted in significant changes in colour values of rosemary and black pepper. The discolouration of the irradiated black pepper was lower in modified atmosphere packaging (MAP) compared to air packaging. Essential oil yield of irradiated black pepper and cumin was lower in air packaging compared to MAP. Gamma-irradiation generally decreased monoterpenes and increased oxygenated compounds, but the effect was lower in MAP. Overall, spices should be irradiated under an O2-free atmosphere to minimise quality deterioration.

  2. Spatial interactions in a modified Daisyworld model: Heat diffusivity and greenhouse effects.

    PubMed

    Alberti, T; Primavera, L; Vecchio, A; Lepreti, F; Carbone, V

    2015-11-01

    In this work we investigate a modified version of the Daisyworld model, originally introduced by Lovelock and Watson to describe in a simple way the interactions between an Earth-like planet, its biosphere, and the incoming solar radiation. Here a spatial dependency on latitude is included, and both a variable heat diffusivity along latitudes and a simple greenhouse effect description are introduced in the model. We show that the spatial interactions between the variables of the system can locally stabilize the coexistence of the two vegetation types. The feedback on albedo is able to generate equilibrium solutions which can efficiently self-regulate the planet climate, even for values of the solar luminosity relatively far from the current Earth conditions.

  3. Modified atmosphere packaging of precooked vegetables: effect on physicochemical properties and sensory quality.

    PubMed

    Barbosa, Carla; Alves, M Rui; Rocha, Susana; Oliveira, M Beatriz P P

    2016-03-01

    This study aims at verifying the effect of three modified atmosphere packaging (MAP) conditions, all with high CO2 and residual or low O2 contents (%O2/%CO2: 0/40; 2.5/40 and 2.5/60), on the quality preservation of several species of precooked vegetables (cabbage, carrots, green beans and bell peppers). The study was carried out for different storage periods (up to 28 days and 6 sampling periods). Physicochemical parameters (pH, acidity, moisture and ash contents, antioxidant activity, colour, and texture), microbial growth, organoleptic properties and consumer acceptability were assessed. Concerning physicochemical parameters and microbial growth only slight changes without any consistent tendency were observed. This was also confirmed by the trained panel that could not discriminate samples with different storage times. Best preservation conditions were obtained with 0%O2/40%CO2, promoting a shelf life extension of almost 12 days more comparing to commercial conditions presently used.

  4. Mesomeric Effects of Graphene Modified with Diazonium Salts: Substituent Type and Position Influence its Properties.