Breast Cancer Survivors

Chemo Secrets From a Breast Cancer Survivor

Undergoing chemotherapy can be one of the most terrifying things that you go through in your life. One of the most frightening things about chemotherapy is the lack of real information that most people have about it, and the unknown makes it so much more frightening as a result. This eBook, written by a young cancer survivor gives you the real story about what chemo is all about. The most valuable information you can get about chemotherapy is from someone that has already experienced it. This PDF eBook allows you to download and read it as soon as your order it. You can begin your journey of reassurance as soon as you want! Because that's what this is about: chemo does not have to be a terrifying unknown! Other people have gone through it before, and want to help you through it as well! This eBook is the guide through chemo that many people wish they could have had, and now you can have it yourself! More here...

Chemo Secrets From a Breast Cancer Survivor Overview

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Can an Energy Source Be Isolated from Matter

Chapter 5 characterizes lights from various sources and based on their sources. It shows that with such scientific characterization it becomes evident why sunlight is the essence of life and artificial light (dubbed as white light) is the essence of death. The problems associated with artificial lights, ranging from depression and breast cancer to myopia (Chhetri and Islam 2008), are explained in terms of the characterization done in this chapter. It is shown that a natural light source is a necessary condition of sustainability. However, it is not sufficient as the process of converting the energy source into light must not be unsustainable.

Variation in DNA repair capacity

The reduced repair capacity phenotypes for damage induced by gamma radiation, bleomycin (a radiomimetic agent), and benzo a pyrene-diol epoxide (BPDE) behave as independent traits.77 This is consistent with the expectation that damage induced by bleomycin and ionizing radiation is primarily strand breaks and oxidized bases, repaired by genes in the NHEJ, HR, and BER pathways, while BPDE induces bulky adducts (like UV-induced pyrimidine dimers) that are repaired by the NER pathway. Scott and colleagues have found decreased repair capacity for ionizing radiation induced damage in G0 cells from breast cancer cases using a micronucleus based lymphocyte assay6978 79 as well as reduced repair capacity in G2 cells from other individuals.69,79 The independence of the G0 and G2 repair capacities was interpreted as indicative of the two assays measuring independent mechanisms or pathways, e.g., G0 cells primarily using genes in BER and NHEJ pathways, G2 cells using HR and DRC pathways.69 80 81...

Detection of tamoxifenDNA adducts in human endometrium

32P-postlabeling combined with chromatography has been used to detect tamoxifen-DNA adducts in endometrial tissue.2325,55 However, conflicting evidence has been published regarding the detection of tamoxifen-DNA adducts in human tissues. Using a 32P-postlabelling-TLC technique, Car-michael and his colleagues failed to detect tamoxifen adducts in the endometrium of tamoxifen-treated patients.23 Applying a 32P-postlabeling HPLC analysis, Hemminki et al. detected a putative tamoxifen-induced adduct in endometrial tissues obtained from breast cancer patients 25 the level of tamoxifen adducts reported was 0.29-0.82 adducts 108 bases standard markers were not used. Also using a 32P-postlabeling-HPLC analysis, Carmichael et al.24 reported they were unable to reproduce the results of the study by Hemminki et al.25

Other antiestrogen drugs

Tamoxifen is a hepatocarcinogen in rats while toremifene, a chlorinated tamoxifen analog (Figure 9.2), is not.19,59 Although toremifene, like tamoxifen, has estrogenic effects on the human endometrium,60 the formation of toremifene-DNA adducts in the liver of rats was two-orders of magnitudes less than that of tamoxifen.19 Therefore, genotoxic effects of tamoxifen are thought to be involved in development of rat hepatocarcinoma. Toremifene has been used for breast cancer chemotherapy in the United States since 1998. Raloxifene (Figure 9.2), a selective estrogen response modifier, reduced the incidence of breast cancer in women at high risk of developing this disease.61 Unlike tamoxifen, raloxifene is unlikely to react with DNA due to In view of their reduced genotoxicity, there is reason for physicians to consider raloxifene and toremifene in recommending drugs for the chemo-prevention of breast cancer in women at high risk of developing this disease. Tamoxifen-DNA adducts fulfill an...

Chemical Hazard Assessment

Validated through the Organisation for Economic Cooperation and Development (OECD),5 that are designed to address different toxic endpoints by various exposure routes. Testing for general toxicity may extend from acute (short-term, i.e. one or a few days) to chronic (greater than 13 weeks) while, in some cases, reproductive effects may be investigated over two generations or more. Where exposure via the air is expected to be important, the inhalation route may be used in the toxicity testing if skin contact is likely, assessment of irritation and sensitization potential is likely to be included. An aspect of much current uncertainty as to its toxicological significance is endocrine disruption, by which a substance has the potential to interact with, or otherwise adversely affect, hormonal systems.6 To some scientists, endocrine disruption is an important toxic endpoint in its own right, while others see it simply as a perturbation in normal physiological processes that may or may not...

Tamoxifen is a carcinogen

The antiestrogen tamoxifen is widely used as first-line endocrine therapy for breast cancer patients more than 500,000 women in the United States are currently being treated with this drug.5 A randomized clinical trial designed for healthy women at high risk of developing this disease showed that therapeutic doses of tamoxifen reduced the risk of invasive breast cancer by approximately 50 .6 Subsequently, tamoxifen was approved in 1998 for use as a chemopreventive agent. Unfortunately, the use of tamoxifen in breast cancer patients is associated with an increased risk of endometrial cancer.712 A similar observation was made during the breast cancer chemo-prevention trial.6

Exposure to POPs and other congeners

Incidence of breast utero or early postnatal exposure to total PCBs with neurodevelopmental deficits in offspring. However, there are many inconsistencies in these correlational studies, and these include the sample timing for PCB analysis (e.g., in utero cord blood, breast milk), analyte quantitation (e.g., individual congeners, total PCBs, TEQs), and differences in neurodevelopmental testing. Increased levels of POPs have been observed in case-control studies using other patient groups (e.g., breast cancer), and there has been considerable variability between studies in these correlations. Delineating the potential role of POPs in various diseases must take into account several factors including biological plausibility, time of exposure, and other factors that will be discussed.

Convergence of Nonprofit Groups Environmental and Public Health Agendas

Now at the beginning of the 21st century, environmental and public health groups are joining together to address shared concerns. For example, the website of the Breast Cancer Fund in California offers a review of scientific evidence linking chemical exposures to disease incidence.72 So too does the website of Physicians for Social Responsibility.73 In New York State, breast cancer activists focusing on avoidable chemical exposures have adopted the slogan Prevention is the Cure.74 The Collaborative on Health and the Environment is bringing together health-affected groups with health professionals and researchers and environmental organizations.75 In 2002, the Center for Children's Health and the Environment at Mount Sinai Medical Center in New York City paid the New York Times to publish several display advertisements on chemical exposure and disease linkages.76 For

Biomarkers of genetic integrity or damage

Aneuploidy, i.e., abnormal chromosome number, can be detected using fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes.103 Multiple probes can be employed to evaluate numerous chromosomes in a single cell.104 The chromosomes usually evaluated when assessing sperm with FISH are the sex chromosomes as these appear to be most at risk for nondisjunction, suggesting that there is a chromosome-specific variation in nondisjunction frequencies.105 FISH has been used to assess factors that may induce sperm aneuploidy in humans such as advanced maternal and paternal age, cancer chemotherapy, and radiation.106-108 The techniques show promise for assessing lifestyle factors like tobacco, caffeine, and alcohol109,110 as well as environmental exposures including seasonal air pollution, pesticides, and heavy metals.111-114

Major Organic Pollutants 821 Organochlorine Insecticides 8211 Background

Of Swedish waters is linked to uterine occlusions and stenoses in female ringed seal, resulting in reproductive failure and, consequently, a rapid decrease of the seal population (Helle et al. 1976a, b). The insecticide dichlorodiphenyltrichloroethane (Fig. 8.1) has been banned in the developed world for many years, though is in widespread use in the developing world. Various dichlorodiphenyltrichloroethane metabolites have endocrine effects, including blocking the action of male hormones. Dichlorodiphenyltrichloroethane is metabolized in the body to dichlorodiphenyldi-chloroethylene, and both these compounds persist in the body fat. It is interesting to note that body fat concentrations in the USA have reduced from 15 mg kg in 1955 to less than 5 mg kg in 1980, though this is pretty high, due to the ban in dichlorodi-phenyltrichloroethane use (IEH 1995) . Many hormone-related effects on wildlife have been ascribed to dichlorodiphenyltrichloroethane, including thinning of eggshells,...

WHAT ABouT The Real World

Ibarluzea et al. (2004) measured 16 persistent organochlorine pollutants in blood serum of breast cancer patients and in women not suffering from breast cancer. While none of the 16 individual chemicals were elevated in the serum of breast cancer cases, the total estrogenic load found in patients was higher than that in controls. Damgaard et al. (2006) observed an association between congenital cryptorchid-ism1 and a summative parameter of the levels of certain organochlorine pesticides in mothers' milk. Swan et al. (2005) found that decreases in anogenital distance2 among male infants are associated with prenatal phthalate exposure. Earlier, Pierik et al. (2004) identified paternal exposures to pesticides and smoking as factors associated with these congenital malformations. Very recently, Main et al. (2007) found associations between the sum of polybrominated diphenyl ethers in breast milk and cryptorchidisms in newborn boys. Fernandez et al. (2007b) reported associations between...

MixTuRE EFFEcTs AT LoW LEvELs

Hermens et al. (1985b) combined 33 chemicals that can be grouped into 2 classes with presumably differing modes of action. The mixture produced 50 mortality in fish when all components were present at 4 of their individual EC50. It was assumed that these concentrations were below NOECs, although NOECs were not estimated in this study. It is therefore conceivable that some chemicals may have been present at levels above their NOECs, and this point may be particularly relevant with compounds that exhibit shallow dose-response curves. Utilizing a cell proliferation assay with human breast cancer MCF-7 cells, Payne et al. (2001) tested a mixture of mitogenic agents with differing modes of action (estrogen receptor agonists, an antiandrogenic agent, and others). A significant proliferative effect was observed when these chemicals were present at concentrations equivalent to 25 to 100 of their individual NOECs.

Combinations of Endocrine Disruptors

Comparatively few examples exist where the validity of IA has been assessed. Hermens et al. (1985b) combined 33 chemicals, which can be grouped into 3 classes with presumably differing modes of action. The observed combination effects were slightly lower than predicted using CA, but IA was not specifically evaluated. In a study utilizing a cell proliferation assay with human breast cancer MCF-7 cells, Payne et al. (2001) tested a mixture of 2 estrogen receptor agonists (o,p'-DDT, p,p'-DDT), 1 antiandrogenic agent (p,p'-DDE), and a chemical that induces cell division by as yet poorly defined mechanisms ( -HCH). IA and CA predicted the observed effects equally well.

Disease

Bjorn Lomborg addressed some of these issues in his controversial book The Skeptical Environmentalist.5 He used data from reputable sources such as the World Health Organisation to show that US cancer death rates, when adjusted for changes in life expectancy and the prevalence of smoking, have steadily declined over the last 50 years, by about 30 over the period. Changes in breast cancer rates can be explained by increases in the age when women have children, decreases in the number of children they bear, and by increase in body weight. Other cancer rates show complex changes over the period, but in some cases there have been dramatic declines - e.g. women have experienced a decline in cancers of the uterus by 81 , and stomach cancer rates have declined even more, for men and women. This last change is most likely to be mainly a result of improvements in diet (more fresh fruit and vegetables).

Applications

Malignant melanoma is an increasingly serious clinical problem, with a high mortality rate among humans due to the failure of melanoma cells to respond to cytotoxic treatment in the form of radiation and chemotherapy. A selective strategy toward the treatment of malignant melanoma is called melanocyte-directed enzyme prodrug therapy (Jordan et al. 2001). Instead of tyrosine itself, a derivate coupled with an inactive prodrug serves as substrate in the biosynthetic pathway that converts tyrosine into melanin (Prota et al. 1994). This would allow selective conversion of inactive prodrugs into cytotoxic drugs in melanoma cells.

Carcinogenicity

First classified as probably carcinogen for humans (class B2) by the US EPA in 1987 71 , aldrin and dieldrin were then described as ''not likely human carcinogen'' 72,73 , since reported epidemiologic studies showed no correlation between pesticide exposure and cancer 74,75 . POPs and PCBs contamination of the environment is suspected to be the cause of the increasing incidence of breast cancer in European countries 76 . DDT is classified by International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (group 2B) 30 .

Ongoing Studies

Safe and his colleagues at the Texas A & M University are studying the antiestrogenic responses in rodents and human breast cancer cells in culture of a series of 1,3,6,8-substituted CDFs (FEDRIP 1992, 1993). The project involves characterization of the antiestrogenic response in human cells, determination of the mechanism of action of these chemicals, and determination of anti- tumorigenic effects of these compounds in nude athymic mice.

Alkyl Phenols

Gene transcription in transfected cells and the growth of breast cancer cell lines. This study employed a wide range of cell lines and receptors such as human breast cancer cell lines MCF7 and ZR- 75-1, chicken embryo fibroblasts, rainbow trout hepatocytes and a mouse oestrogen receptor. All these cell lines and receptors showed oestrogenic responses to alkylphenols, proving the response of oestrogen receptors to alkylphenols. These plastics find application in food and drink packaging, while the resins are generally used as lacquers to coat metal products such as food cans, bottle tops and water supply pipes (ENDS 1995). Le et al. (2008) found that bioactive BPA was liberated from both new and used polycarbonate drinking bottles and were migrated at a similar rate into water at room temperature. Bisphenol A is extensively used for all kind of products like computer housings, carpets, upholstery, for car paintings and flame retardants such as tetrabromobisphenol A. The liquid in some...

Biochemical Assays

Because of the fact that there is no requirement of a light source, the instrumentation for BRET assays is simpler and cheaper 52 which makes these assays very valuable in high-throughput screening. BRET has been mainly used in protein-protein interaction research, for example in studying the b2-adrenergic b-arrestin interaction 53 and the determination of insulin receptor activity 54,55 , where the latter is governed by a conformational change in the b-subunits of the receptor, bringing them into close proximity. The FP technology has been applied to, i.e. the soluble estrogen receptor 56 , the G-protein coupled delta-opioid receptor 57 and the ligand-gated ion channel serotonin 5HT3 receptor 57,58 . This receptor is involved in rapid signal transduction in the central nervous system and the peripheral nervous system. Strong interest for this receptor has been provoked by the ability of 5HT3 receptor antagonists to treat emesis caused by anticancer chemotherapy. Moreover,...

BDNA repair capacity

Several variants are associated with altered DNA repair capacity. Spitzet al.,111 reported that variant alleles at amino acid residues 312 and 751 of ERCC2 (XPD) were associated with reduced repair capacity in lymphocytes from individuals in a lung cancer cohort. Being homozygous for a variant allele in either XPC or XPD was associated with reduced capacity to repair UV-induced DNA damage as assayed by the host reactivation assay in a cohort of healthy subjects (Q. Wei, pers. comm.). Not surprisingly, variation in the BER gene XRCC1 was not associated with UV repair capacity. The ERCC2 751Gln variant was associated with a reduced capacity for repairing ionizing radiation using a cytogenetic-based assay112 and for removing UV-induced DNA damage.113 Hu et al.,114 report that the APE1 148Glu allele was associated with prolonged mitotic delay in lymphocytes exposed to ionizing radiation in breast cancer patients. In addition, lymphocytes from women with at least three variant alleles of...

Richard A Liroff15

Hormone disruption refers to a chemical's ability to mimic or block the action of the body's own hormones, or its ability to interfere with normal hormone production or breakdown in some way. Chemicals that are able to disrupt sex and thyroid hormones have been particularly under the spotlight, but other hormones, such as those of the adrenal gland, may also be subject to disruption. The overall result appears to be damage to reproductive, immune, and nervous systems, and increases in birth defects, selected cancers, and learning disabilities. For the last three decades, there has been a disconcerting increase in the incidence of such human health disorders as breast cancer, testicular cancer, hypospadias (a birth defect where the urethra does not open at the end of the penis) and learning disabilities.

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