21/02/2005

NO:41
AU:Leonard TK; Mohs ME; Watson RR
TI:Nutrient Intakes: Cancer Causation And Prevention.
SO:Prog Food Nutr Sci. 1986. 10(3-4). P 237-77.
AB:High intakes of the macronutrients--proteins, lipids, and carbohydrates in the form of excess energy-have some cancer stimulating properties. On the contrary, epidemiologic and animal laboratory data indicate that high-level supplementation of some micronutrients--certain vitamins, minerals, and lipotropes, as well as some non-nutrients, most notably various types of dietary fiber, may be useful in the prevention of cancer. A wealth of data exists for macronutrients whereas most micronutrients are almost unstudied concerning their role in cancer prevention. Vitamins A, E, and C and selenium are the most well-studied micronutrients, and are recognized as effective with significant anticancer effects, at least in animal models. There are minimal data to suggest that some other micronutrients may also exert varying degrees of incidence reduction on one or more types of cancer. This is most true for folic acid, manganese, molybdenum, copper, the amino acids phenylalanine and methionine, and the lipotrope choline. Zinc and vitamins B1, B2, B6, B12 and pantothenic acid have even less data, and some data are contradictory. Therefore, it is premature to make recommendations concerning their usefulness in cancer prevention at present.

NO:42
AU:Sky-Peck HH
TI:Trace Metals And Neoplasia.
SO:Clin Physiol Biochem. 1986. 4(1). P 99-111.
AB:Numerous trace metals induce cancerous growths in various animal species in vivo and cause mutagenic or chromosomal transformations in cells-cultured cells in vitro. The most potent is probably nickel. The present review indicates that arsenic, cadmium, chromium, nickel and probably beryllium are associated with malignant neoplasms in humans. Inhalation of these metals during processing at refineries has lead to a greater incidence of pulmonary carcinoma as well as other forms of cancer. There is an inverse relationship between the amount of selenium in the environment and the death rate from cancer in humans. Evidence is presented in this review indicating that mutagenic metal ions alter the fidelity of DNA synthesis. This has been demonstrated with purified DNA polymerases using both synthetic and natural DNA templates in vitro, and by mutagenic or carcinogenic effects in vivo. The need for further studies of the molecular effects of metal ions on DNA replication, RNA transcription and translation is indicated by these results.

NO:43
AU:Watson RR
TI:Immunological Enhancement By Fat-soluble Vitamins, Minerals, and trace metals: a factor in cancer prevention.
SO:Cancer Detect Prev. 1986. 9(1-2). P 67-77.
AB:High intakes of some fat-soluble vitamin or trace metals have been associated with a decreased risk of cancer. A mechanism to help explain their anticancer action might be immunosuppression during deficiency or immuno-enhancement with high intakes. In vitro, retinol suppressed T-lymphocyte functions, whereas high dietary vitamin A enhanced macrophage functions. High intakes of vitamin E can enhance some anticancer, immune defenses. Selenium excess was not very suppressive of immune functions in vitro, but did retard tumor cell growth. Selenium and zinc deficiencies are associated with immunosuppression. Enhanced immune functions by high intakes of trace elements and vitamins provide a mechanism to explain in part the concomitant decreased cancer incidence.

NO:44
AU:Reilly JJ Jr; Gerhardt AL
TI:Modern Surgical Nutrition.
SO:Curr Probl Surg. 1985 Oct. 22(10). P 1-81.

NO:45
AU:Taylor A
TI:Therapeutic Uses Of Trace Elements.
SO:Clin Endocrinol Metab. 1985 Aug. 14(3). P 703-24.
AB:The properties of trace elements which feature in their therapeutic activity are: binding to macromolecules (enzymes, nucleic acids, etc.) with disturbance of biological function, and interaction with other elements. These properties, particularly the binding to large molecules, are far from specific, an observation which is reflected in the very wide range of diseases in which trace elements are employed. While metal compounds have been administered for several centuries, the scientific basis for treatment with trace elements began with the use of gold compounds, initially in patients with tuberculosis and later those with rheumatoid arthritis. Although many other drugs have been developed, some of which also include metal complexes, gold has retained an important position in the treatment of this condition. The gold-induced effects upon the immunological aspects of RA are also observed in other conditions with autoimmune involvement. The antineoplastic potential of metal complexes will be further exploited by the development of less toxic compounds--of platinum and possibly also of other metals. At the same time there are improvements in the protocols for administration which increase the range of cancers responding to treatment. Perturbation of gastrointestinal activity represents another area where trace elements have an important therapeutic role, both in the control of intraluminal acidity and in the adjustment of nutrient availability. A fourth significant area of trace element therapeutics involves the central nervous system where the use of lithium has provided spectacular results in the treatment of affective and other disorders. With a very wide range of other conditions in which they are employed, therapeutic uses provide somewhat unusual illustrations of the importance of trace elements in human disease.

NO:46
AU: Hopkins GJ; Carroll KK
TI:Role Of Diet In Cancer Prevention.
SO:J Environ Pathol Toxicol Oncol. 1985 Jul. 5(6). P 279-98.

NO:47
AU:Tobey RA; Tesmer JG
TI:Differential Response Of Cultured Human Normal and tumor cells to trace element-induced resistance to the alkylating agent melphalan.
SO:Cancer Res. 1985 Jun. 45(6). P 2567-71.
AB:Previous studies using cultured Chinese hamster cells indicated that pretreatment of the cells with the trace elements copper, selenium, and/or zinc resulted in increased survival of the metal-induced cultures following subsequent exposure to mono- and bifunctional alkylating agents. To ascertain whether a comparable protective response could be activated in human-derived material, a series of human normal and tumor cells was treated with these trace elements and later challenged with the alkylating agent melphalan, prior to determination of the surviving fraction via colony formation. Normal human cells derived from either newborn infants or adults exhibited an increase in survival of 7- to 9-fold when pretreated with zinc alone that increased to approximately 16-fold when these normal cells were induced with all three trace elements. In contrast, comparable pretreatment of tumor cell populations resulted in an increase in survival of 1.7-fold or less, with most types of tumors exhibiting no induced protection. These observations describing a differential inducibility of normal and tumor cells raise the possibility of a novel approach for selectively sparing normal tissue in patients undergoing treatment with alkylating agents. Possible ramifications to cancer chemotherapy are discussed.

NO:48
AU:Petrakis NL
TI:Biologic banking in cohort studies, with special reference to blood.
SO:Natl Cancer Inst Monogr. 1985 May. 67P 193-8.
AB:Those who conduct cohort studies in cancer epidemiology increasingly use biochemical analyses as an important component. Some of the potentially important considerations when banked blood is used include the conditions and temperature of storage, effects of thawing, and the stability of specific substances under prolonged subfreezing temperatures. I have reviewed a selected number of biochemical substances.

NO:49
AU:Roekens E; Deelstra H; Robberecht H
TI:Trace Elements In Human Milk, Selenium a case study.
SO:Sci Total Environ. 1985 Mar 15. 42(1-2). P 91-108.
AB:Longitudinal changes of the trace element (Fe, Cu, Zn, Mn, Mo, Cr, Co, As, Se) composition of human milk are discussed. The mean daily intake of breast fed infants is compared with the intake of infants fed cow's milk and with recommended dietary allowances. Parameters which can be used to check the selenium status are discussed. Clinical consequences of selenium deficiency are discussed.

NO:50
AU:Vretlind A
TI:[General aspects of parenteral feeding of patients with malignant neoplasms]
SO:Vestn Akad Med Nauk SSSR. 1985. (7). P 7-14.

NO:51
AU:Segal B; Segal R; Cotrau M
TI:[Anticancer Food Factors]
SO:Rev Med Chir Soc Med Nat Iasi. 1985 Jan-Mar. 89(1). P 105-8.

NO:52
AU:Nordman E
TI:[An Oncologist's Point Of View On cancer and miracle medicines]
SO:Nord Med. 1985. 100(4). P 120-1.

NO:53
AU:Hoffman FA
TI:Micronutrient Requirements Of Cancer Patients.
SO:Cancer. 1985 Jan 1. 55(1 SUPPL). P 295-300.
AB:Several major factors may influence the micronutrient requirements of the patient with cancer. These factors include the metabolic state of the malignancy and its effects on host metabolism, the catabolic effects of antineoplastic therapy, and other physiologic stresses commonly associated with the treatment of cancer, i.e., surgery, fever and infection. Although the nutritional importance of vitamins, minerals and trace elements is recognized, the optimal daily dose that will preserve lean body mass without enhancing tumor growth, is not known. Recommended Dietary Allowances (RDAs), where established, are based on populations with nonmalignant diseases. However, supplementation with vitamins, minerals, and certain trace elements is recommended for the cancer patient who requires prolonged parenteral support, since clinically relevant deficiency states have been described. The effect of malignancy on the metabolism of several of these micronutrients (iron, ascorbic acid, alpha tocopherol, selenium, zinc, copper) is discussed.

NO:54
AU:Fernandes G
TI:Nutritional Factors: Modulating Effects On Immune function and aging.
SO:Pharmacol Rev. 1984 Jun. 36(2 SUPPL). P 123S-129S.

NO:55
AU:Bowman BB; Kushner RF; Dawson SC ; Levin B
TI:Macrobiotic Diets For Cancer Treatment And prevention.
SO:J Clin Oncol. 1984 Jun. 2(6). P 702-11.

NO:56
TI:Coal gasification.
SO:IARC Monogr Eval Carcinog Risk Chem Hum. 1984 Jun. 34P 65-99.

NO:57
TI:Coke production.
SO:IARC Monogr Eval Carcinog Risk Chem Hum. 1984 Jun. 34P 101-31. UI

NO:58
AU:Sauberlich HE
TI:Implications Of Nutritional Status On Human biochemistry, physiology, and health.
SO:Clin Biochem. 1984 Apr. 17(2). P 132-42.
AB:Optimum nutrition is the level of intake that should promote the highest level of health. Although excess caloric intake will lead to obesity, a deficit in nutrition may result in a tissue depletion of essential nutrients that can lead to biochemical changes and eventually to clinical signs and symptoms. Nutrition requirements may differ according to sex, age, activity, or physiological state and can be influenced by drugs, smoking, alcohol, and other factors. With ever-increasing sedentary life styles and less physically demanding jobs, the resulting reduced caloric requirements have made it more difficult to make nutritionally sound food choices. Nutrition is the single most important component of preventive health care. Diet has been associated with cancer, heart disease, diabetes, stroke and hypertension, arteriosclerosis, and cirrhosis of the liver. The ability of the human to respond to stresses, such as altitude, heat, trauma, surgery, and infection can be influenced by nutritional status. Nutritional status is reflected in a variety of metabolic processes that provide the basis for a number of methods for its assessment.

NO:59
AU:Chan M; Elgar M; Trotter JM
TI:Role Of Trace Elements In Cancer.
SO:Aust Nurses J. 1984 Feb. 13(7). P 5-6.

NO:60
AU:McKenna G; Wright M
TI:Clinical. 2. Eating Your Defences.
SO:Nurs Mirror. 1983 Dec 14. 157(24). P 33-5.

NO:61
AU:Arai K; Conley BA; Nemir P Jr
TI:Reduction Of Dithizone-reactive Granules Of Blood granulocytes in humans and rats bearing tumor.
SO:J Lab Clin Med. 1983 Aug. 102(2). P 286-97.
AB:To confirm scattered reports suggesting a significant reduction of dithizone-reactive granules of granulocytes in neoplastic diseases, the peripheral blood of 20 normal adults, 22 patients with non-malignant diseases, and 39 cancer patients were studied by using a modified dithizone staining method and scoring of the stained granules. The dithizone score in the cancer patients was significantly (p less than 0.001) lower than those in the normal controls or the noncancer patients, with mean scores of 226.0 +/- 6.3 (S.E.), 277.5 +/- 4.7, and 265.9 +/- 5.8, respectively. When compared with the lower limit (score 233) of the 95% confidence interval of a normal score distribution, 24 (61.5%) of the 39 cancer patients showed abnormally low scores, and one (2.4%) of the 42 individuals without cancer exhibited a low score (p less than 0.001). No relationship was found between the score and the patient's age, total serum protein, serum globulin, serum albumin, albumin/globulin ratio, absolute numbers of neutrophils or lymphocytes, or serum zinc level. In the rats transplanted with syngeneic tumor, the dithizone score progressively declined as the tumor increased in size, with a close negative correlation (r = -0.81) in a manner best fitting a power curve. This change was not found in the control rats injected with killed tumor cells. These results indicate that the dithizone-reactive granules of the granulocytes significantly decreased in a tumor-bearing host. The mechanisms are not known and this staining method can not be considered as a diagnostic tool, but this phenomenon appears to have potential usefulness in the systemic effect of solid tumor.

NO:62
AU:Drucker H
TI:Assessment: an overview.
SO:Sci Total Environ. 1983 Jun. 28P 467-78.

NO:63
AU:Robson JR
TI:Vitamins And Trace Elements In Cancer patients.
SO:J Parenter Sci Technol. 1983 May-Jun. 37(3). P 87-8.

NO:64
AU: Ronnlund RD ; Suskind RM
TI:Iron, Zinc, And Other Trace Elements' effect on the immune response.
SO:J Pediatr Gastroenterol Nutr. 1983. 2 SUPPL 1(SUPPL 1). P S172-80.

NO:65
AU:Dionigi R
TI:Immunological Factors In Nutritional Assessment.
SO:Proc Nutr Soc. 1982 Sep. 41(3). P 355-71.

NO:66
AU:Zumkley H; Bertram HP; Preusser P; Kellinghaus H; Straub C; Vetter H
TI:Renal Excretion Of Magnesium And Trace elements during cisplatin treatment.
SO:Clin Nephrol. 1982 May. 17(5). P 254-7.
AB: Plasma and urine concentrations of platinum, magnesium, zinc and copper were measured in 15 patients treated with cisplatin. The renal excretion rates of platinum, magnesium, zinc and copper were markedly increased. In plasma markedly elevated levels of platinum could be found and were accompanied by decreased concentrations of magnesium, potassium and calcium. The plasma concentrations of zinc and copper showed only slight changes. Our results indicate, that cisplatin may influence renal excretion of some electrolytes and trace elements by a specific factor and/or by alteration in renal function.

NO:67
AU:Capel ID; Pinnock MH; Williams DC; Hanham IW
TI:The Serum Levels Of Some Trace and bulk elements in cancer patients.
SO:Oncology. 1982. 39(1). P 38-41.
AB:The levels of copper, zinc, calcium, manganese and magnesium have been monitored in the sera of patients suffering from various types of cancer. Only serum copper appeared to be of any diagnostic significance, its levels being above the normal reported range in the breast cancer, leukaemia and Hodgkin's lymphoma patients. In the case of breast cancer, serum copper is progressively elevated according to the stage of the disease. Serum calcium levels were also significantly lower in patients with tumours of the breast, gastrointestinal tract and cervix. The results suggest that serum copper levels could be of prognostic significance in breast cancer patients receiving radiotherapy.

NO:68
AU:Shah SS; Ranade SS; Phadke RS; Kasturi SR
TI:Significance Of Water Proton Spin-lattice Relaxation times in normal and malignant tissues and their subcellular fractions--II.
SO:Magn Reson Imaging. 1982. 1(3). P 155-64.

NO:69
AU:Demetrakopoulos GE; Brennan MF
TI:Tumoricidal Potential Of Nutritional Manipulations.
SO:Cancer Res. 1982. 42(2 SUPPL). P 756s-765s.
AB:Perturbations of specific nutrient availability is the basis of a large number of chemotherapeutic modalities used in cancer treatment. The creation of transient nutrient deprivation states by deficient diets (deficiency), nutrient destruction or displacement (depletion), the presence of antimetabolites or analogs (deficiency state), or combinations of the above has shown significant antitumor effect in several animal and human cancers. Pair-fed isocalonic diets deficient in micronutrients such as carbohydrates (with or without gluconeogenesis inhibition) or micronutrients such as zinc or pyridoxine have demonstrated antitumor potential. Amino acid depletion by enzymes such as L-asparaginase or L-glutaminase has become a popular modality for treatment of human leukemias. Purine and pyrimidine analogs or folate antimetabolites have been used successfully for several decades in the treatment of human tumors. Excess pyridoxine in tissue culture has demonstrated antineoplastic potential. Dietetic supplementation with naturally occurring sugars, sugar derivatives, or analogs has also demonstrated tumorotropic effects.

NO:70
AU:Shklar G AD:Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, Boston, MA 02115, USA.
TI:Mechanisms Of Cancer Inhibition By Anti-oxidant nutrients.
SO:Oral Oncol. 1998 Jan. 34(1). P 24-9.
AB:The cancer inhibitory properties of anti-oxidant micronutrients have been well established in experimental animal models and cell culture studies. Human studies have also tended to indicate an inhibition of various forms of cancer and the regression of some precancerous lesions. The biological mechanisms for cancer inhibition and regression are now gradually becoming understood, and the anti-oxidant nutrients appear to act through a number of pathways common to most of the agents studied. These various micronutrients appear to act through a complex group of "common pathways" of anticancer activity based upon three major mechanisms: (1) tumour inhibition by immune cytokines; (2) stimulation of cancer suppressor genes, such as "wild type" p53, and diminished expression or dysregulation of oncogenes such as mutant p53 and H-ras; (3) inhibition of tumour angiogenesis through the inhibition of angiogenesis-stimulating factors such as TGF alpha. Retinoid action differs, in some respects, from other micronutrient anticancer mechanisms and appears to relate to its stimulation of cellular differentiation and resultant apoptosis of neoplastic cells. Combinations of anti-oxidant nutrients have been shown to be synergistic in their anticancer activity, probably due to their optimal anticancer activity at different oxygen potentials. Selectivity in the action on cancer cells, as opposed to normal cells, is a major feature of the anti-oxidant micronutrients.

NO:71
AU:Gey KF AD:Department of Biochemistry and Molecular Biology, University of Berne , Switzerland .
TI:Vitamins E Plus C And Interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer.
SO:Biofactors. 1998. 7(1-2). P 113-74.
AB:Antioxidants are crucial components of fruit/vegetable rich diets preventing cardiovascular disease (CVD) and cancer: plasma vitamins C, E, carotenoids from diet correlate prevalence of CVD and cancer inversely, low levels predict an increased risk of individuals which is potentiated by combined inadequacy (e.g., vitamins C + E, C + carotene, A + carotene); self-prescribed rectification of vitamins C and E at adequacy of other micronutrients reduce forthcoming CVD, of vitamins A, C, E, carotene and conutrients also cancer; randomized exclusive supplementation of beta-carotene +/- vitamin A or E lack benefits except prostate cancer reduction by vitamin E, and overall cancer reduction by selenium; randomized intervention with synchronous rectification of vitamins A + C + E + B + minerals reduces CVD and counteracts precancerous lesions; high vitamin E supplements reveal potentials in secondary CVD prevention. Plasma values desirable for primary prevention: > or = 30 mumol/l lipid-standardized vitamin E (alpha-tocopherol/cholesterol > or = 5.0 mumol/mmol); > or = 50 mumol/l vitamin C aiming at vitamin C/vitamin E ratio > 1.3-1.5; > or = 0.4 mumol/l beta- (> or = 0.5 mumol/l alpha+ beta-) carotene. CONCLUSIONS: In CVD vitamin E acts as first risk discriminator, vitamin C as second one; optimal health requires synchronously optimized vitamins C + E, A, carotenoids and vegetable conutrients.

NO:72
TI:Micronutrients And Human Cancer Risks--prospects For prevention. Joint International Symposium of the Danish Cancer Society, European Cancer Prevention Organization and National Food Agency of Denmark. Aarhus, Denmark, 21-24 May 1997. Abstracts.
SO:Eur J Cancer Prev. 1997 Oct. 6(5). P 479-500.

NO:73
AU:Malvy DJ; Arnaud J; Burtschy B; Sommelet D; Leverger G; Dostalova L; Amedee-Manesme O AD:INSERM U056, Hospital Center of Bicetre, France.
TI:Antioxidant Micronutrients And Childhood Malignancy During oncological treatment.
SO:Med Pediatr Oncol. 1997 Sep. 29(3). P 213-7.
AB:Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc, and selenium, and cholesterol and related proteins for 170 children with newly diagnosed malignancy were measured at diagnosis and 6 months after initiation of treatment, and compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited between 1986 and 1989. At diagnosis, age- and sex-adjusted serum concentrations of retinol, beta-carotene, zinc, and alpha-tocopherol were significantly inversely associated with cancer. No significant decreases in mean values were observed at 6 month, except for the alpha-tocopherol-to-cholesterol ratio in patients with bone tumors and serum zinc in bone tumors and central nervous system malignancies. An increase during the period of treatment was found for retinol and selenium in leukemia patients. beta-carotene was maintained at the initial concentrations determined prior to therapy. These findings provide further information about micronutrient requirements in children with cancer.

NO:74
AU:Buiatti E AD:Centro di Documentazione per la Salute (CDS), Bologna, Italy.
TI:The Role Of Chemoprevention In Cancer control.
SO:Salud Publica Mex. 1997 Jul-Aug. 39(4). P 310-7.
AB:Chemoprevention can be defined as the use of chemical compounds or medicines to prevent the occurrence of precancerous lesions (markers) or to slow down or revert the progression of clinically established disease. The use of randomized trial design is considered the gold standard for evaluating the preventive value of chemicals against cancer, since they control for confounding and avoid information bias. The principal school in relation to cancer control through chemoprevention is based on studies of cancer and diet. Initially, ecological studies set the cornerstone, but later case-control studies supported the hypothesis of an inverse association between foods and cancer risk (principally epithelial), suggesting that determined micronutrients participate as protection in this process. Other studies include specific chemical analyses, which have potential problems that could lead to erroneous conclusions, such as sample and measurement errors. During this decade randomized intervention trials have been carried out to test this hypothesis, but conclusions have been so diverse and the designs used have been so different in terms of levels of exposure, that consistent conclusions are not possible. We can conclude that using studies with randomized, double-blind, controlled designs is interesting, but problems remain to be solved, including: agent selection, the design to be chosen, and especially the balance between benefits sought and secondary effects, including cost-effectiveness, since some chemicals cannot compete with other preventive or therapeutic measures.

NO:75
AU:Favero A; Salvini S; Russo A; Parpinel M; Negri E; Decarli A; La Vecchia C; Giacosa A; Franceschi S AD:Servizio di Epidemiologia, Centro di Riferimento Oncologico, Aviano, Italy.
TI:Sources Of Macro- And Micronutrients In Italian women: results from a food frequency questionnaire for cancer studies.
SO:Eur J Cancer Prev. 1997 Jun. 6(3). P 277-87.
AB:The knowledge of major sources of macro- and micronutrients is essential in order to interpret differences in the diet-cancer link in various geographical areas and to provide better nutritional guidelines. For this purpose we took advantage of the control group of a case-control study on breast cancer carried out in six Italian areas. The dietary habits of 2,588 cancer-free women aged 20-74 years (median age 56) were elicited between 1991 and 1994 by means of an interviewer-administered food frequency questionnaire (FFQ) that included 78 foods or food groups, in addition to several questions on general dietary pattern (e.g., fat in seasoning). Bread was the first contributor for total energy (12%), protein (8%) and starch (32%) intake, whereas, for saturated fatty acid, the first sources were different types of cheese (28%); for monounsaturated fatty acids the dressing oils of salad and tomatoes (12%); and, for sugars, apples and pears (19%). Raw vegetables and fresh fruit represented the most important source of most vitamins. The first contributors of vitamin C and beta-carotene were citrus fruits (29%) and raw carrots (17%), respectively. Thus, between 40 and 80% of specific macronutrient intake and up to 90% intake of several micronutrients were derived from the first ten foods or food groups. Often, the major contributors to the intake of a specific component were foods with a relatively low content, but eaten in large quantities. This work further highlights the specificity of nutrient sources in southern European populations.

NO:76
AU:Neeman M; Abramovitch R; Schiffenbauer YS; Tempel C AD:Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
TI:Regulation Of Angiogenesis By Hypoxic Stress: from solid tumours to the ovarian follicle.
SO:Int J Exp Pathol. 1997 Apr. 78(2). P 57-70.
AB:The preovulatory follicle provides a unique physiological example of rapid growth accompanied by neovascularization, two processes that are generally characteristic of pathologies such as wound repair or malignancy. During the hours preceding ovulation, follicular growth is accompanied by elevated levels of messenger RNA for vascular endothelial growth factor (VEGF). Angiogenic activity, mediated by VEGF, is manifested in the peripheral blood vessels surrounding the follicle, that show capillary sprouting and increased vascular permeability. Following ovulation, rapid infiltration of capillaries through the follicular wall is essential for the formation of the corpus luteum. In this review we compare the preovulatory follicle with a popular model of avascular solid tumour growth, namely the multicellular tumour spheroid, in particular the role of hypoxic stress in the regulation of angiogenesis in both systems.

NO:77
AU:Ferguson LR AD:Cancer Research Laboratory, Faculty of Medicine and Health Sciences, University of Auckland, New Zealand.
TI:Micronutrients, Dietary Questionnaires And Cancer.
SO:Biomed Pharmacother. 1997. 51(8). P 337-44.
AB:There is increasing evidence that many chemicals, although present in the diet at only low levels, play an important role in protection against cancer. Micronutrients are defined as nutrients present in the body in amounts less than 0.005% of body weight. Some micronutrients suggested to play a protective role in cancer are beta-carotene, vitamin E and vitamin C. In addition to those chemicals with an established role in nutrition, there is also a less well-defined group of chemicals, often referred to as phytochemicals, which may prove even more important. Examples here are a group of sulphur-containing chemicals present in brassicaceous vegetables, such as broccoli and cabbage, that appear to be very effective anticarcinogens. Epidemiology will be essential in accurately defining the role of phytochemicals and micronutrients in cancer. However, the large prospective studies that would be most desirable increasingly utilize food frequency questionnaires containing a limited number of questions. Such an approach has been well validated for macronutrients. However, there is often less accurate information available on micronutrients and phytochemicals, and the food combinations necessary (and acceptable) for macronutrients may be inappropriate for these other factors. It would be most desirable that fruits and vegetables are individually itemized or grouped according to plant families rather than macronutrient status. This may be the most appropriate way of identifying potentially novel protective factors in the diets of countries such as Morocco or New Zealand.

NO:78
AU:Reddy BS AD:Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, New York, USA.
TI:Micronutrients as chemopreventive agents.
SO:IARC Sci Publ. 1996. (139). P 221-35.
AB:The concept of chemoprevention of cancer by micronutrients is based upon evidence from human epidemiology and from studies of animal carcinogenesis models for cancer-inhibiting potential of certain minerals and vitamins. These micronutrients are diverse with respect to chemical structures and physiological effects, and include calcium, selenium, carotenoids, and vitamins A, C, D and E. The dietary intake of various micronutrients has been observed to alter significantly the incidence and mortality of a variety of human cancers including those of the oesophagus, stomach, colon, breast and cervix. Studies of laboratory animal models have also provided relevant mechanistic and efficacy data on the role of specific micronutrients as well as minor non-nutrients of dietary origin in the carcinogenic process. Micronutrients and such minor non-nutrients have been found to modulate the formation and bioactivation of carcinogens, modify the promotion and progression of carcinogenesis, alter cellular and host defences, and affect cellular differentiation-ultimately leading to variations in tumour incidences. Our understanding of biochemical and biological mechanisms of carcinogenesis and of inhibition of initiation, promotion and progression by particular micronutrients-both naturally occurring forms and their synthetic analogues-has made it possible to develop strategies for clinical intervention by these agents. It is possible that intervention with individual micronutrients and minor non-nutrients, and/or with a combination of such compounds with different modes of action, will prevent, delay or reverse the process of carcinogenesis and thus reduce the incidence of and mortality due to human cancers. A number of Phase II clinical trials have been initiated with the objective of identifying and evaluating intermediate biomarkers that will be used as surrogate end points for cancer. Several surrogate end points have been standardized and validated for their specificity. The results are very encouraging.

NO:79
AU:Riboli E; Slimani N; Kaaks R AD:Unit of Nutrition and Cancer, International Agency for Research on Cancer, Lyon, France.
TI:Identifiability of food components for cancer chemoprevention.
SO:IARC Sci Publ. 1996. (139). P 23-31.
AB:Epidemiological studies have consistently reported a reduction in risk for several cancer sites in relation to high consumption of vegetables and fruit. These findings stimulated further research aimed at identifying which compounds in fruit and vegetables are responsible for the reduction in cancer risk. Epidemiological and laboratory studies suggested that some micronutrients, particularly vitamin C, vitamin E, beta-carotene, selenium, magnesium and zinc, could reduce the risk of cancers of the oral cavity, lung, oesophagus and stomach, while dietary fibre was more specifically related to a reduced risk of colorectal cancer. However, the results of large randomized trials on various combinations of vitamins and minerals at supranutritional doses have so far failed to confirm this hypothesis or have found very weak effects. These results should stimulate profound re-thinking of the methods that led to the selection of specific molecules with potential chemopreventive action. From a methodological point of view, little attention has so far been given to four main limitations of nutritional epidemiology, which have direct bearing on the extrapolation of results from foods to food components. Measurements of micronutrient intakes through simple dietary questionnaires and current food composition tables lack precision and specificity. Micronutrient intakes are often highly correlated in nature because micronutrients tend to share the same food sources. Attribution of cancer risk to a single food constituent can be misleading if multicollinearity of dietary variables is not recognized. The etiological meaning of nutritional biomarkers is not straightforward because circulating levels of nutrients reflect not only dietary intake but also complex metabolic regulations. Studies have not considered the physical characteristics of foods, which are important determinants of physiological responses. Understanding the multidimensional nature of diet and of its relationship with different cancers is a major scientific challenge. Epidemiological studies combining detailed dietary questionnaires, appropriate food composition tables, multiple biomarkers, and appropriate statistical methods may provide better measurements of the relationships between cancer risk and specific dietary patterns and therefore contribute to the identification of food components with hitherto unforeseen potential interest for cancer prevention.

Parte 1