Cholesterol as Carcinogen: I. Sarcoma Induction by Cholesterol in a Sensitive Strain of Mice II. Croton Oil a Complete Carcinogen

EARLIER papers in this series (see e.g. Hieger, 1959) have presented experimental results showing that: (a) the carcinogenic factor in the unsaponifiable fraction of human tissue (liver, lung, kidney, muscle) is cholesterol; (b) commercial cholesterol injected subcutaneously induces sarcoma in mice and stringent purification of such cholesterol does not impair its potency; (c) different strains of mice and even different batches of the same pure strain show gross differences of susceptibility to carcinogenesis by cholesterol; (d) the solvents used for administering the cholesterol (e.g. olive oil) have a very low sarcoma-inducing potency (5 tumours in 1122 mice). The first part of this paper deals with an explanation of (c), i.e. the differences in susceptibility to cholesterol. The table shown below (Table I) summarises the results of experiments carried out on cholesterol as carcinogen subsequent to those described in the 1959 paper. Where the "Code " (laboratory labelling) of an experiment carries an asterisk ( *), the mice were housed in a room where hydrocarbon-carcinogens (e.g. benzopyrene) are used (in order to test the effects of contamination). All other experiments were carried out in a room free from hydrocarbon-carcinogens. It is obvious from the results that atmospheric contamination by powerful carcinogens does not carry any risk to experiments where cholesterol is being tested. The experiments are entered in the table in the order in which they were carried out, that is to say, Experiment 1 was started then 2, then 3, etc. This arrangement is useful in demonstrating that no appreciable part of the carcinogenic potency of the active preparations can be attributed to possible variations in the composition of successive batches of the vehicle (olive oil) which is a commercial product, and therefore different samples (hospital dispensary quality) might well have differences in composition owing to seasonal variations or to geographical changes in the source of the olive crop. For example, Experiment 27 gave a high yield of tumours but Experiment 28 a very low yield; since theseCHOLESTEROL AS CARCINOGE

Veteran Transition Center\u27s Coming Home Program

This paper states the process in which a transitional housing program was revised to better suit the needs of the clients served by Veterans Transition Center. It includes a literature review of the issues faced by homeless veterans and some of the information gathered from community agencies that were willing to share their experiences in drug/alcohol recovery and transitional housing programs

A study of how political candidates use persuasive messages on Twitter, specifically toward women voters

This purpose of this qualitative research is to analyze how political candidates use persuasive messages on Twitter, specifically toward women voters. The use of Twitter by political candidates has become extremely more prevalent since its inception in 2006. Using a rhetorical analysis of 600 tweets between six candidates for the U.S. Senate race in 2018, this study was able to determine how political candidates are using Twitter to convey messages to voters. Once the messages were coded and analyzed, the researcher discovered three main themes: ethos, acclaim, and leadership qualities. The majority of the tweets posted by the six candidates were designed to persuade the voter that the candidate was more favorable than others, more appealing, and typically more credible or created a sense of confidence in voting for this candidate. One of most surprising results of the study was the lack of women-specific messaging. While women make up the largest demographic of undecided voters, the percentage of tweets geared toward women-only was only three percent. Future studies could use this research to determine if the messaging strategies used for Twitter during the election also resulted in winning the Senate seat.by Lauren F. HiegerIncludes bibliographical reference

Type 2 Diabetes related to chronic health disease, health status, and effect on quality of life

Background In the United States, 29.1 million people, or 9.3% of the population have diabetes mellitus (CDC, 2014). The total cost of diabetes in the United States has been estimated at $245 billion, which included the direct medical costs as well as the reduced productivity (CDC, 2014). Diabetes greatly increases the risk of other chronic illnesses such as coronary heart disease, myocardial infarction (MI), retinopathy, nephropathy and stroke. These chronic conditions may cause serious harm or even death. Objectives The objectives of this study are to determine the prevalence of chronic health diseases among diabetic adults in the United States, and describe the demographic characteristics as well as the health, lifestyle, satisfaction with life and care received as well as the utilization of care by diabetic adults with chronic diseases. Methods This study is based on a secondary data analysis based on data from the Behavioral Risk Factor Surveillance System (BRFSS, 2013). We performed descriptive statistics to describe the diabetic population. We conducted multinomial logistic regression analysis to examine the effects of the main predictors of stroke, heart attack, coronary heart disease, nephropathy, and retinopathy on health status. We further conducted negative binomial regression analysis to investigate the independent effects of stroke, heart attack, coronary heart disease, nephropathy, and retinopathy on the number of days during which diabetics reported their physical and mental health as being not good in the past month, as well as the number of visits to the doctor in the past 12 months. Results In the U.S., 25,234,904 adults stated they had been diagnosed with diabetes by a healthcare professional Four out of ten adults with diabetes were 65 years and older, and close to three out of ten of them were between the ages of 55-64 years. Close to six out of ten adults with diabetes was Non-Hispanic white. Over half of people with diabetes were also obese as compared to a quarter of those without diabetes. Close to two out of ten diabetic adults reported having a visual impairment secondary to diabetes; 14% reported having suffered a heart attack or a coronary heart disease, and 9% reported having been diagnosed with stroke or nephropathy. Over the past month, diabetic adults with either of the chronic diseases reported poor good physical health for an average of 18 days, and poor mental health for an average of 15 days. Although 14% of people with diabetes reported their health as being very good, only 9% for diabetics with retinopathy, 8% of diabetics who had sustained a stroke or a heart attack, 6% and 5% of those who have been diagnosed with a coronary heart disease or a nephropathy, respectively reported the same. A higher proportion of adults without diabetes than with diabetes reported being very satisfied with life (47% vs. 37%), and 65% were very satisfied with the care they received. Multinomial logistic and regressions further revealed that stroke, heart attack, coronary heart disease, nephropathy, and retinopathy have a deleterious effect on the health status of diabetics, and increase the number of days spent in poor physical and mental health. Conclusions The results of this study indicate that diabetes has a great impact on the quality of life of these individuals, and has the potential to cause multiple chronic illnesses if it goes untreated. It also greatly impacts the mental and physical health status of each person in a negative way. With U.S. healthcare in disarray, lack of access to care for diabetic patients is extremely relevant to the results in this study. Healthcare professionals, especially nurses, play a key role in the prevention and management of diabetes through education. This in addition to the use of interdisciplinary teams will allow diabetic patients a more wholesome healthcare experience that provides all necessary information and treatment needed

Investigation of the key chemical structures involved in the anticancer activity of disulfiram in A549 non-small cell lung cancer cell line

© 2018 The Author(s). Background: Disulfiram (DS), an antialcoholism medicine, demonstrated strong anticancer activity in the laboratory but did not show promising results in clinical trials. The anticancer activity of DS is copper dependent. The reaction of DS and copper generates reactive oxygen species (ROS). After oral administration in the clinic, DS is enriched and quickly metabolised in the liver. The associated change of chemical structure may make the metabolites of DS lose its copper-chelating ability and disable their anticancer activity. The anticancer chemical structure of DS is still largely unknown. Elucidation of the relationship between the key chemical structure of DS and its anticancer activity will enable us to modify DS and speed its translation into cancer therapeutics. Methods: The cytotoxicity, extracellular ROS activity, apoptotic effect of DS, DDC and their analogues on cancer cells and cancer stem cells were examined in vitro by MTT assay, western blot, extracellular ROS assay and sphere-reforming assay. Results: Intact thiol groups are essential for the in vitro cytotoxicity of DS. S-methylated diethyldithiocarbamate (S-Me-DDC), one of the major metabolites of DS in liver, completely lost its in vitro anticancer activity. In vitro cytotoxicity of DS was also abolished when its thiuram structure was destroyed. In contrast, modification of the ethyl groups in DS had no significant influence on its anticancer activity. Conclusions: The thiol groups and thiuram structure are indispensable for the anticancer activity of DS. The liver enrichment and metabolism may be the major obstruction for application of DS in cancer treatment. A delivery system to protect the thiol groups and development of novel soluble copper-DDC compound may pave the path for translation of DS into cancer therapeutics.This work was supported by grant from British Lung Foundation (RG14–8) and Innovate UK (104022).Published versio

Disulfiram modulated ROS–MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties

BACKGROUND: Previous studies indicate that disulfiram (DS), an anti-alcoholism drug, is cytotoxic to cancer cell lines and reverses anticancer drug resistance. Cancer stem cells (CSCs) are the major cause of chemoresistance leading to the failure of cancer chemotherapy. This study intended to examine the effect of DS on breast cancer stem cells (BCSCs). METHODS: The effect of DS on BC cell lines and BCSCs was determined by MTT, western blot, CSCs culture and CSCs marker analysis. RESULTS: Disulfiram was highly toxic to BC cell lines in vitro in a copper (Cu)-dependent manner. In Cu-containing medium (1 mu M), the IC50 concentrations of DS in BC cell lines were 200-500 nM. Disulfiram/copper significantly enhanced (3.7-15.5-fold) cytotoxicity of paclitaxel (PAC). Combination index isobologram analysis demonstrated a synergistic effect between DS/Cu and PAC. The increased Bax and Bcl2 protein expression ratio indicated that intrinsic apoptotic pathway may be involved in DS/Cu-induced apoptosis. Clonogenic assay showed DS/Cu-inhibited clonogenicity of BC cells. Mammosphere formation and the ALDH1(+VE) and CD24(Low)/CD44(High) CSCs population in mammospheres were significantly inhibited by exposure to DS/Cu for 24 h. Disulfiram/copper induced reactive oxygen species (ROS) generation and activated its downstream apoptosis-related cJun N-terminal kinase and p38 MAPK pathways. Meanwhile, the constitutive NF kappa B activity in BC cell lines was inhibited by DS/Cu. CONCLUSION: Disulfiram/copper inhibited BCSCs and enhanced cytotoxicity of PAC in BC cell lines. This may be caused by simultaneous induction of ROS and inhibition of NF kappa B. British Journal of Cancer (2011) 104, 1564-1574. doi: 10.1038/bjc.2011.126 www.bjcancer.com Published online 12 April 2011 (C) 2011 Cancer Research U