The loss of muscle mass leading to cachexia is rarely identified in early lung cancer. Fasting blood and muscle biopsy were collected in 59 non-small cell lung cancer (NSCLC) and 16 non-cancer patients, at the beginning of thoracic surgery. Serum C-reactive protein (CRP), and IL-6 were higher in NSCLC. In weight-losing NSCLC, food intake and serum albumin were lower, CRP, and TNF-alpha were higher. Although the expression of genes of the ubiquitin-proteasome system was not different, ubiquitinated-protein levels were lower and negatively correlated with ph-FOX01 in weight-losing patients. This would suggest lower muscle proteolytic rates in the early stages of NSCLC. Ph-FOXO1 also related to the degree of weight loss and stage of NSCLC. These data suggest that in early stages of the disease, weight and muscle loss could be mainly due to reduced food intake, rather than accelerated proteolysis, which reinforces the potential for successful dietary interventions to prevent or delay the onset of cachexia.

Research on the putative health benefits has indicated that kefir, a traditional fermented milk, might have antimutagenic and antitumor properties. The major objective of the present thesis was to isolate and identify antitumor compounds in cow's milk kefir and investigate the possible mechanisms involved. High speed centrifugation (HSC), molecular weight cut-off filtration (MWCO), size exclusion high performance liquid chromatography (SEC-HPLC) and reverse phase-HPLC (RP-HPLC) were utilized for fractionation of kefir and a cell culture model was developed to screen for the antiproliferative effects of the kefir fractions. The antiproliferative effects of bacteria-free extracts from different fermentation stages of kefir production, as well as bacteria-free extracts from milk and yogurt were compared. The results showed that extracts from an early stage of fermentation (i.e., kefir mother culture) and the final commercial kefir product both exerted dose-dependent inhibition effects on human mammary tumor MCF-7 cells, yogurt extracts showed less potent antiproliferative effects, while pasteurized milk extracts showed no antiproliferative effects. No antiproliferative effects of the kefir extracts were observed on human mammary epithelial cells (HMEC) whereas the yogurt extracts showed antiproliferative action in HMEC cells at a high dose. A fraction of the kefir mother culture isolated by HSC, MWCO and RP-HPLC contained components that inhibited MCF-7 cell growth and had no effect on HMEC cells. Characterization of the bioactive fraction using mass spectrometry (MS) indicated that the main components in the fraction are likely fragments of kefiran and/or ceramide containing compounds such as gangliosides. The growth inhibitory effect may be mainly caused by the induction of TNF-alpha in MCF-7 cells. Whole extracts of kefir depleted glutathione (GSH) in MCF-7 cells, while the SEC-HPLC Fraction 7 and the RP-HPLC Fraction 30 induced GSH produc

Typescript / Bibliography: leaves 127-139 / x, 139 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 1988

Thesis (MNutr)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: Background: The role of antioxidants and adequate nutrition in the prevention and course of cancer treatment is globally recognised in nullifying the effects of free radicals and increasing the nutritional status of children during treatment. Objective: To investigate whether children with cancer meet their Dietary Reference Values and Safe Intakes for antioxidants, energy and protein. Design: Single centre prospective study. Setting: Children were recruited from the East of England Primary Treatment Centre using convenience sampling over 8 months. Forty-two children and adolescents diagnosed with a Solid tumour, Lymphoma or Leukaemia were eligible for data analysis (n=20 male; n=22 female). Method: Data was collected with an Estimated Food Record (EFR) in the 1st (EFR1) and 3rd month (EFR2) post-diagnosis. In the week following EFR completion, parents and/or children were contacted to complete four non-consecutive days of 24-hr food recalls. Data was categorised into diet alone, diet + food supplement (FS), tube feeding (tube) or diet + multi-vitamin-mineral supplementation (VMS). Malnutrition was determined by weight-for-age z-scores. Nutrient intake was compared to the Recommended Nutrient Intake (RNI), the Estimated Average Requirements (EAR) and the Lower Recommended Nutrient Intake (LRNI). Result: The sample consisted of 33% (n=14) diagnosed with Leukaemia, 24% (n=10) with Lymphoma and 43% (n=18) with Solid tumours. Sixty seven percent (n=28) underwent chemotherapy and 33% (n=14) a combination of therapies. Significant correlations were seen between the assessment tools in the diet alone category for both months for; vitamins A, C, E, selenium and protein and for EFR1 for zinc and energy. In both months greater numbers of children achieved ≥100% of requirements for diet + VMS (EFR 1; p<0.05; EFR2 p<0.05) than for other feeding modes. Vitamin C achieved the highest intakes compared to the RNI at 773% (EFR1) and 829% (EFR2). Intakes above 200% of the RNI were seen for vitamins A, C, E, selenium and zinc. No significant differences were seen between modes of feeding in either month for selenium or zinc. Vitamin A (EFR1≤ 100% diet alone p<0.05) and zinc (EFR1≤ 100% diet alone p=0.02) met the least of the LRNI in the 1st month compared to other antioxidants. No statistical significant difference was observed between the number of children attaining their EAR’s between the 3 modes of feeding in the 1st month and 3rd month. In the 1st month 27% (n=8) of participants consumed vitamin and/or mineral supplements, 18% in the 3rd month (n=4). In the 1st month 5% (n=2) of children were moderately malnourished and 10% (n=4) in 3rd month. Conversely in the 1st month 3% (n=1) were overweight and 3% (n=1) obese; the leukaemia group predominant. Conclusion: The research tools showed good correlation. Children using vitamin and/or mineral supplements mostly achieved their RNI’s compared to other feeding modes. Across feeding modes some children achieved antioxidant intakes above 200% RNI. LRNI’s on diet alone were not achieved for vitamin A and zinc. The study showed Leukaemics as having a higher prevalence of obesity. More research is required to determine the clinical implications of these findings. / AFRIKAANSE OPSOMMING: Agtergrond: Die rol van anti-oksidante en voldoende voeding in die voorkoming en verloop van kanker behandeling word wêreldwyd erken vir vernietiging van die effek van vry radikale en die verbetering van voedingstatus van kinders tydens behandeling. Doelwit: Om ondersoek in te stel of kinders met kanker hul Dieet Verwysingswaardes en Veilige Innames vir anti-oksidante, energie en proteïen bereik. Ontwerp: Enkel sentrum prospektiewe studie. Omgewing: Kinders was gewerf deur middel van gerieflikheidsteekproefneming oor 8 maande vanaf die “East of England Primary Treatment Centre”. Twee-en-veertig kinders en adolessente gediagnoseer met 'n Soliede tumor, Limfoom of Leukemie het in aanmerking gekom vir dataanalise (n=20 manlik, n=22 vroulik). Metode: Data was ingesamel met ‘n Geskatte Voedsel Rekord (GVR) in die eerste (GVR1) en derde maand (GVR2) na diagnose. In die week na voltooiing van die GVR is ouers en/of kinders gekontak om vier onopeenvolgende dae van 24-uur herroepe te voltooi. Data was verdeel in dieet alleen, dieet + voedsel supplement (VS), buisvoeding (buis) of dieet + multi-vitamien-mineraal supplementasie (VMS). Wanvoeding was bepaal deur middel van gewig-vir-ouderdom z-tellings. Nutriënt inname was vergelyk met die Aanbevole Nutriënt Inname (ANI), die Geskatte Gemiddelde Behoeftes (GGB) en die Laer Aanbevole Nutriënt Inname (LANI). Resultate: Die steekproef het bestaan uit 33% (n=14) gediagnoseer met Leukemie, 24% (n=10) Limfoom en 43% (n=18) Soliede tumore. Sewe-en-sestig persent (n=28) het chemoterapie ontvang en 33% (n=14) ‘n kombinasie van terapieë. Betekenisvolle korrelasies was waargeneem tussen die assesseringsinstrumente in die dieet alleen kategorie vir beide maande vir vitamiene A, C, E, selenium en proteïen en vir GVR1 ook vir sink en energie. In beide maande het ‘n groter aantal kinders ≥100% van hul behoeftes bereik vr dieet+VMS (GVR1; p<0.05; GVR2 p<0.05) as vir ander modi van voeding. Vitamien C het die hoogste innames bereik vergeleke met die ANI teen 773% (GVR1) en 829% (GVR2). Innames bo 200% van die ANI was waargeneem vir vitamiene A, C, E, selenium en sink. Geen betekenisvolle verskille was waargeneem tussen modi van voeding in enige maand vir selenium en sink nie. Vitamien A (GVR1≤100% dieet alleen p<0.05) en sink (GVR1≤100% dieet alleen p=0.02) het die minste van die LANI bereik in die eerste maand vergeleke met ander anti-oksidante. Geen statisties beduidende verskil was waargeneem tussen die aantal kinders wat hul GGB’s bereik het tussen die 3 voedingswyses in die eerste en derde maande nie. In die eerste maand het 27% (n=8) van deelnemers vitamien en/of mineraal supplemente ingeneem, en 18% (n=4) in die derde maand. In die eerste maand was 5% (n=2) van kinders matig wangevoed en 10% (n=4) in die derde maand. In die eerste maand was 3% (n=1) van kinders oorgewig en 3% (n=1) vetsugtig, die leukemie groep spesifiek. Gevolgtrekking: Die navorsingsinstrumente het goeie korrelasie getoon. Kinders wat vitamien en/of mineraal supplemente gebruik het het meestal hul ANI’s bereik vergeleke met ander modi van voeding. Oor voeding modi het sommige kinders anti-oksidant innames bo 200% ANI bereik. LANI’s op dieet alleen was nie bereik vir Vitamien A en sink nie. Hierdie studie het aangetoon dat dié met Leukemia ‘n hoër prevalensie van oorgewig/vetsug getoon het. Meer navorsing is nodig om die kliniese implikasies van die bevindinge te bepaal.

Colon cancer is a leading cause of cancer related deaths worldwide. Lifestyle factors such as diet and exercise have been implicated as important agents in colon cancer development and progression. Epidemiological, in vivo and in vitro studies have found that n-3 polyunsaturated fatty acids (PUFAs) reduce colon carcinoma. The role of n-6 PUFAs remains a controversial topic, with studies indicating both promoting and preventing capabilities published. In order to better understand the effects of PUFAs on colon carcinoma, it is important to have an understanding of how they will be broken down in the body. During this study, in silico metabolism of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) predicted the formation of hydroxy-, di-hydroxy- and epoxy-FAs. A gas chromatography-mass spectrometry method was developed and validated for the detection of these PUFAs and their cytochrome P450 (CYP) metabolites. A human liver microsomal system for the in vitro metabolism of EPA, DHA and AA was optimised in terms of microsomal and PUFA concentration. The system resulted in the metabolism of the positive control, lauric acid, to 12-hydroxy-lauric acid but was unable to metabolise the PUFAs of interest. EPA, DHA and AA reduced cell viability in the colon carcinoma cell lines SW480 and SW620 in the micromolar concentration range (25 – 200 μM). The CYP epoxidation metabolite of EPA, 17, 18-epoxyeicosatetraenoic acid (17, 18-EpETE) resulted in a significant reduction in SW480 cell viability relative to the parent compound at lower concentrations (25 and 50 μM). Annexin V apoptosis analysis revealed that EPA and 17, 18- EpETE did not result in apoptosis in SW480 cells at a concentration of 25 μM and over an incubation period of 24 hours. A significant reduction in reactive oxygen species production was seen in SW480 cells after incubation with 25 μM 17, 18-EpETE for 24 hours. EPA and 17, 18-EpETE were implicated in the reduction of colon cancer metastasis since they were able to reduce SW480 migration and anchorage independent cell growth. These results indicate that the dietary intake of EPA, DHA and AA may be beneficial to one’s health due to the negative effects that these PUFAs had on colon carcinoma. Future studies are needed to confirm these benefits and compare the effects of the PUFAs to their CYP-metabolites.

No description available.

No description available.

It is believed that the presence of certain trace elements in the skin may play an important role in the formation of melanomas. In this work, neutron activation analysis and x-ray fluorescence analysis were used to determine trace element concentrations in cancerous, noncancerous and normal swine skin samples and in non-cancerous and normal swine tissue samples. In-vivo x-ray fluorescence analysis was also used to determine trace element concentrations in cancerous, non-cancerous, and normal swine skin. Data on forty-eight trace elements in each sample were obtained and correlated. The limited number of cancerous samples made definitive conclusions about trace element imbalances uncertain. Nevertheless, the in-vivo XRFA method was shown to be a very useful method for trace element determination. Additionally, good base line data were obtained for trace element concentrations in a variety of organs of Sinclair miniature swine. / Master of Science

This thesis consists of a brief description on cancer, carcinogenesis, the changes in the type and level of dietary fat available in our diets over time and association with the development of certain diseases. The main focus of this research was on omega 6 and omega 3 essential fatty acids (EFA) and their interaction with regards to carcinogenesis.

非傳染性疾病是目前全球最常見的疾病之一。不健康的食相信是導致非傳染性疾病增加的主要因素之一。因此，我們就食對乳腺癌的形成和膽固醇代謝調控的影響進行了研究。 / 在去除卵巢的祼鼠模型中，我們研究了長期和短期熱量限制對乳腺癌腫瘤增殖的影響。14週齡的小鼠被隨機分為5組：自由攝食組 (AL)；熱量攝入控制在AL80% 的20%CCR組；熱量攝入控制在AL的70% 的30%CCR組；熱量攝入控制在AL的65% 的35%CCR組和短期熱量限制 （SCR）組 (前3.5週熱量攝入控制在AL的65%，之後的13.5週自由攝食)。10週後，熱量限制組的腫瘤體積明顯較AL組小 (P < 0.05)。排除攝食對體重的影響，SCR組的腫瘤重量明顯較AL組小 (P < 0.05)。本實驗結果表明，在此動物模型中，短期熱量限制能有效抑制乳腺癌細胞的增殖。 / 此外，我們還研究了芹菜素在肝細胞中對膽固醇代謝的影響。芹菜素是一種常見的黃酮類化合物。研究發現，在WRL-68細胞中，芹菜素能夠劑量依賴性的抑制3 - 羥基-3 - 甲基 - 戊二酸單酰輔酶還原酶 (HMGCR)和固醇調節元件結合蛋白-2 (SREBP-2) 信使RNA和蛋白的表達及其啟動子的轉錄活性。綜上所述，在肝細胞中，芹菜素能有效抑制HMGCR和SREBP-2的表達，從而達到降低膽固醇的效果。 / 總括而言，本研究表明在去除卵巢的祼鼠模型中，短期熱量限制能有效抑制乳腺癌細胞的生長和芹菜素能有效抑制HMGCR和SREBP-2的表達。 / Non-communicable diseases (NCD) are one of the leading causes of mortality in the developed and under-developing countries. Diet is a major risk factor of NCD. In the present study, effects of diet modification on breast cancer development and cholesterol metabolism were investigated. / In the first part of this study, the effect of chronic and short-term calorie restriction (CR) on breast tumor growth in ovariectomized nude mice was investigated. The calorie-restricted dietary regimen limited the total fat intake only. 14 week-old ovariectomized female nude mice were randomly assigned to ad libitum fed (AL), 20%CCR (17-week 80% of AL), 30%CCR (17-week 70% of AL), 35%CCR (17-week 65% of AL) and short-term CR (3.5-week 65% of AL followed by 13.5-week 100% AL consumption) groups. Starting from 10 weeks after transplant of cells, the tumor volumes in all calorie-restricted groups were significantly smaller (P < 0.05) than that in ad libitum control. At sacrifice, the tumor weight in short-term CR was significantly smaller (P < 0.05) than that in ad-libitum control after normalized with body weight. This indicated that short-term CR could suppress tumor in this model. / In the second part of this study, the effect of apigenin on cholesterol metabolism was investigated. Apigenin is one of the most abundant flavonoids. In the present study, we investigated the effect of apigenin on several cholesterol-related gene expression in hepatic cells. In WRL-68 cells treated with apigenin, promoter transcription activity, mRNA and protein expression of HMGCR and SREBP-2 were significantly decreased in a dose-dependent manner. Taken together, we concluded that apigenin inhibited HMGCR and SREBP-2 gene expressions in hepatic cells, which might elicit the hypocholesterolemic effects. / In conclusion, our study has demonstrated that short-term CR could significantly block the breast tumor growth in a mice model and apigenin could inhibit the expression of HMGCR and SREBP-2 in liver cell lines. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Wong, Tsz Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 83-99). / Abstracts also in Chinese. / ACKNOWLEGEMENTS --- p.i / ABSTRACT --- p.ii / 摘要 --- p.iv / list of abbreviations --- p.v / list of figures --- p.vii / list of tables --- p.IX / TABLE of CONTENTS --- p.X / Chapter 1 --- CHAPTER 1 --- p.1 / General Introduction --- p.1 / Chapter 1.1 --- Calorie Restriction and the Prevention of Postmenopausal Breast Cancer --- p.2 / Chapter 1.1.1 --- Breast Cancer --- p.2 / Chapter 1.1.2 --- Epidemiology of Excess Body Weight and Cancer Risk --- p.3 / Chapter 1.1.3 --- Calorie Restriction and Cancer Prevention --- p.7 / Chapter 1.1.4 --- Mechanistic Targets of Calorie Restriction --- p.8 / Chapter 1.1.4.1 --- Effect of Calorie Restriction on Estrogen --- p.8 / Chapter 1.1.4.1 --- Effect of Calorie Restriction on Cell Cycle Regulation --- p.12 / Chapter 1.1.4.1 --- Effect of Calorie Restriction on Apoptosis --- p.14 / Chapter 1.2 --- Effect of Apigenin on Cholesterol Homeostasis --- p.17 / Chapter 1.2.1 --- Cardiovascular Disease and Blood Cholesterol --- p.17 / Chapter 1.2.2 --- Molecular Regulation of Cholesterol Metabolism --- p.21 / Chapter 1.2.2.1 --- HMG-CoA Reductase --- p.21 / Chapter 1.2.2.2 --- CYP7A1 --- p.24 / Chapter 1.2.2.3 --- Apolipoprotein A-1 --- p.26 / Chapter 1.2.2.4 --- Low Density Lipoprotein Receptor --- p.29 / Chapter 1.2.2.5 --- Sterol Regulatory Element Binding Proteins --- p.31 / Chapter 1.2.3 --- Flavonoid and its Association with Cholesterol Metabolism --- p.36 / Chapter 1.2.4 --- Apigenin: A Potential Alternative --- p.39 / Chapter 2 --- CHAPTER 2 --- p.41 / MATERIALS AND METHODS --- p.41 / Chapter 2.1 --- Chemicals and Materials --- p.41 / Chapter 2.1.1 --- Chemicals --- p.41 / Chapter 2.1.2 --- Plasmids --- p.41 / Chapter 2.2 --- Cell Culture --- p.41 / Chapter 2.2.1 --- Maintainance of Cells --- p.41 / Chapter 2.2.2 --- Preparation of Cell Stock --- p.42 / Chapter 2.2.3 --- Cell Recovery from Liquid Nitrogen Stock --- p.42 / Chapter 2.3 --- Measurement of Cell viability --- p.43 / Chapter 2.4 --- Semi-Quantitative and Quantitative RT-PCR Assay --- p.43 / Chapter 2.4.1 --- RNA Isolation and cDNA Synthesis --- p.43 / Chapter 2.4.2 --- Quantitative Real Time PCR Assay --- p.43 / Chapter 2.4.2.1 --- Real Time PCR Using TaqMan Probe --- p.43 / Chapter 2.4.2.2 --- Real Time PCR Using SYBR Green Dye --- p.44 / Chapter 2.4.2.3 --- Statistical Analysis of 2⁻ΔΔ{U+A7F0}{U+1D40} Comparative Gene Expression --- p.44 / Chapter 2.5 --- Western Blot Analysis --- p.46 / Chapter 2.6 --- Measurement of Promoter Activity --- p.46 / Chapter 2.6.1 --- Plasmid Preparation --- p.46 / Chapter 2.6.2 --- Transient Transfection and Dual-Luciferase Assay --- p.47 / Chapter 2.7 --- Animal Experiment Design --- p.47 / Chapter 2.7.1 --- Animal Model and Dietary Regimens --- p.47 / Chapter 2.7.2 --- Tissue Sample Collection --- p.50 / Chapter 2.7.3 --- Plasma Estradiol Determination --- p.50 / Chapter 2.7.4 --- Protein and RNA extraction --- p.50 / Chapter 2.8 --- Statistical Analysis --- p.50 / Chapter 3 --- Chapter 3 --- p.51 / EFFECT OF CHRONIC AND short-term calorie restriction on breast tumor growth in ovariectomized nude mice --- p.51 / Chapter 3.1 --- Introduction --- p.51 / Chapter 3.2 --- Objectives --- p.52 / Chapter 3.3 --- Results --- p.53 / Chapter 3.3.1 --- Food Intakes, Body, Liver and Uterus Wet Weights of the Mice --- p.53 / Chapter 3.3.2 --- Tumor Development --- p.57 / Chapter 3.3.3 --- Plasma Estradiol Level --- p.62 / Chapter 3.3.4 --- Estradiol Responsive Gene expression in Tumors --- p.63 / Chapter 3.3.5 --- Cell Apoptotic and Cell Cycle-Regulated Protein expression in Tumors --- p.65 / Chapter 3.4 --- Discussion --- p.67 / Chapter 4 --- CHAPTER 4 --- p.69 / Apigenin inhibits the expression of hmg-coa reductase and srebp-2 in hepatic cells --- p.69 / Chapter 4.1 --- Introduction --- p.69 / Chapter 4.2 --- Objectives --- p.70 / Chapter 4.3 --- Results --- p.70 / Chapter 4.3.1 --- Effect of Apigenin on Cell Viability --- p.70 / Chapter 4.3.2 --- Effect of Apigenin on HMGCR, CYP7A1, LDLR, ApoA-1, SREBP-1 and SREBP-2 mRNA expressions --- p.72 / Chapter 4.3.3 --- Effect of Apigenin on HMGCR, LDLR, ApoA-1 and SREBP-2 Promoter Transcription Activity --- p.75 / Chapter 4.3.4 --- Effect of Apigenin on HMGCR, SREBP-1 and SREBP-2 Protein Expression --- p.77 / Chapter 4.3.5 --- Role of Estrogen Receptor in Apigenin induced SREBP-2 Inhibition --- p.79 / Chapter 4.4 --- Discussion --- p.80 / Chapter 5 --- CHAPTER 5 --- p.82 / SUMMARY --- p.82 / References --- p.83