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Cancer

Issue 56

CASCINU and colleagues, Section of Experimental Oncology, Azienda Osedaliera S. Salvatoire, Pesaro, Italy set out to investigate calcium and vitamin supplementation on colorectal cell proliferation.
Background: Calcium and anti-oxidant vitamins such as A, C and E have been shown to reduce colorectal epithelial proliferation and therefore may be chemoprotective in colorectal cancer.
Methods: Ninety patients with resected colorectal cancer were enrolled in a randomized clinical trial (RCT) in which they received (daily for 6 months) either a combination of vitamin A (30,000 IU), vitamin C (1g), vitamin E (70mg) and calcium (2g) or an indistinguishable placebo. Cell proliferation of the normal colonic mucosa was assessed at time of surgery, 6 and 12 months using the antibody to proliferating cell nuclear antigen (PCNA) and a mean total PCNA labelling index was calculated (PCNALI).
Results: Of the 90 patients enrolled, 34 of the treatment group and 43 of the placebo group were assessable. After both 6 and 12 months the PCNALI was reduced in both groups compared to baseline with a slight advantage to treatment group at 6 months (treatment 34%, placebo 28%). However there was no statistically significant differences, either compared with baseline or between groups.
Conclusions: This RCT shows that dietary calcium and vitamins A, C and E does not reduce cell kinetics of colon epithelium in patients with colorectal cancer and highlights the importance of control groups in such trials.
Cascinu S et al. Effects of calcium and vitamin supplementation on colon cell proliferation in colorectal cancer. Cancer Investigation 18(5): 411-6. 2000.

LIU, Shen and ONG, Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore investigated the effect of a Chinese herbal medicine (Salvia miltiorrhiza) on human hepatic cells.
Background: Salvia miltiorrhiza (SM) is a traditional Chinese herbal medicine, commonly used to treat liver diseases in China for centuries. Earlier studies have indicated that SM exhibits anti-tumour properties, but its mechanism remains to be elucidated. In this study, the authors evaluated the molecular mechanism of SM in a human hepatoma cell line HepG(2).
Results: SM exerted clear cytotoxic effects, and strongly inhibited the proliferation of HepG(2) cells. It was also observed that SM treatment caused apoptotic cell death as evaluated by: a) morphological changes by using acridine orange/ethidium bromide staining; b) DNA fragmentation by TdT-mediated dUTP nick end labelling (TUNEL); and c) sub-G(1) cell analysis. Furthermore, depletion of intracellular glutathione (GSH) and reduction of mitochondrial membrane potential were found to be involved in the initiation of apoptosis by SM.
Liu J et al. Salvia miltiorrhiza inhibits cell growth and induces apoptosis in human hepatoma HepG(2) cells. Cancer Letters 153(1-2): 85-93. May 2000.

VAN FLEET, Psychiatry Section, University of Texas M.D. Anderson Cancer Center, Houston, USA. vanfleet@audumla.mdacc.tmc.edu reviews the use of relaxation and imagery for symptom management in cancer treatment.
Background: Relaxation and imagery are commonly used to treat various side effects of cancer and its treatment. This is discussed and described by the author, including suggestions for enhancing assessment, and brief instructions for implementing basic interventions.
Discussion: The nursing literature has often encouraged nurses to use relaxation and imagery to assist patients in managing pain, nausea, vomiting, and anxiety. Frequently, the literature has presented these techniques as being simple, harmless interventions requiring little assessment, planning, or individualization.
Conclusions: Simplistic, generalized approaches may result in suboptimal treatment or deleterious responses. The author suggests that the implications for nursing practice is that clinicians must assess and collaborate with patients in developing an appropriate strategy that fits the individual's preferences and beliefs.
Van Fleet S. Relaxation and imagery for symptom management: improving patient assessment and individualizing treatment. Oncology Nursing Forum 27(3): 501-10. Apr 2000.

VINCETI and colleagues, Department of Hygiene, Microbiology & Biostatistics, University of Modena and Reggio Emila, Modena, Italy reviewed (133 references) the link between the trace element selenium and the aetiology of cancer.
Discussion: The relationship between the trace element selenium and cancer remains elusive and intriguing, despite a large body of epidemiological studies on the matter. The authors discuss the problem of the inconsistent methodology used in this field of work, including misclassification of exposure, effect modification, confounding and other sources of bias, as well as the conflicting outcomes of cohort studies of selenium exposure and subsequent cancer risk. They highlight a Finnish study initiated in 1984 which has yet to show any relationship between increased selenium intake and reduced cancer incidence. In conclusion, they suggest studies on populations with an unusually high or low environmental selenium exposure may allow us to investigate this possible link between selenium and the etiology of cancer.
Vinceti M et al. The epidemiology of selenium and human cancer. Tumori 86(2): 105-18. Mar-Apr 2000.

Issue 55

BABU and colleagues, Department of Medical Biochemistry, Dr. ALM Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India. studied the effects of co-administration of vitamins C and E with tamoxifen treatment in women with breast cancer.
Background: Tamoxifen, a non-steroidal antioestrogen, has been used in the hormonal treatment for breast cancer. The hepatic oestrogen effect of tamoxifen causes severe triglyceridaemia. The combined effects of tamoxifen, vitamin C and vitamin E upon plasma lipid and lipoprotein is important, because vitamin C and vitamin E encumber the lipid abnormalities instigated by tamoxifen.
Methods: The authors carried out supplementation with vitamin C (500 mg) and vitamin E (400 mg) for a period of 90 days together with tamoxifen (10 mg twice daily) to postmenopausal breast cancer patients.
Results: In the tamoxifen-treated patients, total cholesterol (TC), free cholesterol (FC), phospholipids (PL), free fatty acids (FFA), low density lipoprotein cholesterol (LDL) levels were decreased and the triglycerides (TG), ester cholesterol (EC), high density lipoprotein cholesterol (HDL) and very low density lipoprotein cholesterol (VLDL) levels were increased. Combination therapy reduced all the cholesterol levels and VLDL, LDL. TG levels were significantly decreased and HDL, EC levels were significantly increased.
Conclusions: These results suggest that tamoxifen treatment is the most effective when co-administered with vitamin C and vitamin E, which reduce the tamoxifen-induced hypertriglyceridaemia.
Babu JR et al. Salubrious effect of vitamin E and vitamin E on tamoxifen-treated women in breast cancer with reference to plasma lipid and lipoprotein levels. Cancer Letters 151(1): 1-5. 3 Apr 2000.

Comments: I look forward to seeing these vitamins (C and E) being added to breast cancer tamoxifen regimes.

SHIRATAKI and colleagues, Faculty of Pharmaceutical Sciences, Josai
University, Saitama, Japan compared the cytotoxicity of grape seed extracts
with grape peel extracts upon human oral tumour cells lines.
Methods: The authors used methanol and 70% methanol extracts of grape
seed and grape peel extracts and studied their ability to kill two human
oral tumour cell lines using ESR spectroscopy.
Results: Methanol and 70% methanol extracts of grape seed selectively
killed two human oral tumour cell lines more efficiently than human
gingival fibroblasts. ESR spectroscopy revealed that these extracts
produced radicals under alkaline conditions and enhanced the radical
intensity of sodium ascorbate at higher concentrations. However, lower
concentration of these extracts slightly reduced the radical intensity
of sodium ascorbate and scavenged superoxide anion, generated by hypoxanthine
and xanthine oxidase reaction.
Conclusions: These data and properties of grape seed extracts suggest
their possible application for cancer prevention.
Shirataki Y et al. Selective cytotoxic activity of grape peel and seed
extracts against oral tumor cell lines. Anticancer Research 20(1A):
423-6. Jan-Feb 2000.

BATTISTI and colleagues, OU of Neurometabolic Disease, Institute of
Neurological Sciences, University of Sienna, Italy studied vitamin E
serum levels in patients with gastric cancer.
Background: The authors write that alpha-tocopherol has been reported
to play an important role against oxidative damage and in the inhibition
of cell transforming and mutagenesis.
Methods: The authors analyzed vitamin E serum levels in 51 gastric cancer
patients in different stages of the disease, and in 49 age-matched controls.<br>
Results: All patients had normal values of alpha-tocopherol; however,
when patients were grouped according to histotype of gastric lesions,
there was a significant vitamin E increase in diffuse gastric cancer
histotype compared to the intestinal histotype.
Conclusions: These results suggest that there may be a correlation between
vitamin E serum levels and gastric cancer histotype.
Battisti C et al. Vitamin E serum levels and gastric cancer: results
from a cohort of patients in Tuscany, Italy. Cancer Letters 151(1):
15-8. 3 Apr 2000.

MEHTA and colleagues, University of Florida College of Medicine, Department
of Pediatrics, University of Florida, Gainesville Florida 32610 USA
evaluated patients with breast cancer undergoing bone marrow transplantation
(BMT) to determine if acquiescence to further adjunctive experimental
therapy related to psychological distress.
Background: The authors write that use of alternative therapy for breast
cancer outside of the hospital setting has been identified as a marker
of psychological distress. They ponder whether acquiescence to experimental
therapies within the medical setting might also be a sign of psychological
distress.
Methods: The authors studied psychological test results of 42 breast
cancer patients undergoing BMT at the University of Florida between
January and December 1997. These tests included the Medical Outcomes
Short Form Health Survey, the Beck Depression Inventory, the State-Trait
Anxiety Inventory and the Medical Coping Modes Questionnaire.
Results: Women who accepted adjunctive experimental therapy had significantly
higher trait anxiety and poorer role functioning compared to women who
did not.
Conclusions: These findings suggest that psychological distress may
be a factor in medical decision-making, even within the medical setting.
Prospective research in this area is warranted.
Mehta P et al. Acquiescence to adjunctive experimental therapies may
relate to psychological distress: pilot data from a bone marrow transplant center. Bone Marrow Transplantation 25(6): 673-6. Mar 2000.

Comments: I find these results extremely interesting. Worded another
way, these data may suggest that women are being psychologically pressured
into accepting aggressive cancer treatment regimes.

Issue 54

SHKLAR and OH, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, Boston, Massachusetts USA. gerald_shklar@hms.harvard.edu review (103 references) the literature regarding the significant cancer preventive potential of vitamin E.
Results: Vitamin E has been shown to possess cancer preventive properties in many different cancer sites, ranging from oral and pharyngeal to prostate cancer. There is an extensive experimental basis for this clinical cancer inhibition, with the experimental background including animal studies (experimental pathology, immunology and molecular biology, synergism, selectivity and safety), in vitro biochemical studies, and human studies (epidemiology and biomarkers, prevention of many pathologic entities other than cancer.
Shklar G and Oh SK. Experimental basis for cancer prevention by vitamin E. Cancer Investigation 18(3): 214-22. 2000.

STEINMAUS and colleagues, Division of Occupational and Environmental Medicine, University of California at San Francisco USA write that in 1996 there were more than 300,000 new cases of bladder cancer diagnosed worldwide.
Methods: Apart from tobacco smoking, occupation and other factors, diet may play a role in the cause of this illness. The authors conducted a meta-analysis to review the epidemiological studies linking six dietary factors to bladder cancer. These factors included retinol, beta-carotene, fruits, vegetables, meat and fat.
Results: There were increased risks of bladder cancer associated with diets low in fruit intake (relative risk (RR) = 1.40), and slightly increased risks associated with diets low in vegetable intake (RR - 1.16). There were increased risks identified in diets high in fat intake (RR = 1.37), but not for diets high in meat intake (RR = 1.08). No increased risks were identified for diets low in retinol (RR = 1.01), or beta-carotene (RR = 1.10) intake.
Conclusions: These data suggest that a diet high in fruits and vegetables and low in fat may help prevent bladder cancer; however, the individual dietary components responsible for reducing risk remain undetermined.
Steinmaus CM et al. Diet and bladder cancer: a meta-analysis of six dietary variables. American Journal of Epidemiology 151(7): 693-702. 1 Apr 2000.

NEGRI and colleagues, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. Evanegri@irfmn.mnegri.it  studied the relation between selected micronutrients and oral and pharyngeal cancer risk.
Methods: The authors conducted a case-control study between January 1992 and November 1997 in Italy and Switzerland. Included in this study were 754 patients with histologically confirmed oral cancers (344 of the oral cavity and 410 of the pharynx) admitted to the major teaching and general hospitals in the study areas. Controls were 1,775 people with no history of cancer admitted to hospitals in the same areas for acute, non-neoplastic diseases. The authors investigated dietary habits using a validated food-frequency questionnaire, and odds ratios (Ors) were calculated following allowance for age, sex, centre, education, occupation, body mass index, smoking and drinking habits and non-alcohol energy intake.
Results: ORs for the continuous analysis were 0.95 for retinol, 0.61 for carotene, 0.91 for lycopene, 0.83 for vitamin E, 0.74 for vitamin E, 0.63 for vitamin C, 0.82 for thiamine, 0.87 for riboflavin, 0.59 for vitamin B6, 0.61 for folic acid, 0.62 for niacin, 0.91 for calcium, 0.88 for phosphorus, 0.65 for potassium, 0.82 for iron, 0.67 for non-alcohol iron and 0.89 for zinc. ORs were similar for the two sexes and age strata. With regard to the combined intake of vitamins C and E and carotene, the protective effect of each nutrient was more pronounced, or restricted to individuals with low intake of the other two. Association with vitamin C and carotene was independent of smoking and drinking habits, while that with vitamin E was less evident in those heavily exposed to alcohol or tobacco.
Conclusions: In general, the more a micronutrient was correlated to total vegetable and fruit intake, the stronger was its protective effect against oral cancer.
Negri E et al. Selected micronutrients and oral and pharyngeal cancer. International Journal of Cancer 86(1): 122-7. 1 Apr 2000.

Issue 53

BALZARINI and colleagues, Rehabilitation and Palliative Care Department, National Cancer Institute, Milan, Italy assessed the effects of homoeopathic Belladonna 7cH and X-ray 15cH associated in the treatment of acute radiodermatitis.
Methods: The authors conducted a randomized double-blind placebo-controlled clinical trial with 66 patients operated on for breast cancer and who were undergoing radiotherapy. Over ten weeks the following parameters were assessed: breast skin colour, warmth, swelling and pigmentation. Assessment and follow-up were during radiotherapy, during recovery, 15 and 30 day after the end of radiotherapy.
Results: Differences in the scores of the Index of Total Severity during Radiotherapy were not statistically significant; however there was a trend towards a better activity of the homoeopathic medicine compared to placebo. The data on Total Severity during recovery showed a statistically significant benefit of the active medicines over placebo. The homoeopathic medicines had particular effectiveness on the heat of the skin. The limited number of patients and the dosage used may have interfered with the significance of the results, which were not affected by chemotherapy and hormonotherapy.
Balzarini A et al. Efficacy of homeopathic treatment of skin reactions during radiotherapy for breast cancer: a randomised, double-blind clinical trial. The British Homoeopathic Journal 89(1): 8-12. Jan 2000.

TAMAYO and colleagues, Foresight Link Corporation, Ontario Canada review (198 references) the literature regarding the herbal mixtures Essiac and Flor-Essences, which are sold as nutritional supplements used by patients to treat chronic conditions, particularly cancer.
Background: Evidence of anticancer activity for the herbal teas is limited to anecdotal reports recorded for about 40 years in Canada. Individual case reports suggest that the tea improves quality of life, alleviates pain, and in some cases, impacts cancer progression. Experimental studies using individual herbs have demonstrated evidence of biological activity including antioxidant, antioestrogenic, immunostimulant, antitumour and anticholeretic actions. However, research demonstrating these positive experimental effects has not been translated to the clinical setting.
Planned Research: No clinical studies of Essiac or Flor-essence are published; however a clinical study is being planned for the British Columbia Cancer Agency by the University of Texas-Center for Alternative Medicine (UT-CAM) and Tzu-Chi Institute for Complementary and Alternative Medicine.
Tamayo C et al. The chemistry and biological activity of herbs used in Flor-Essence herbal tonic and Essiac. Phytotherapy Research 14(1): 1-14. Feb 2000.

BYLUND and colleagues, Department of Oncology, University of Umea, Umea, Sweden. Annika.Byland@germed.umu.se studied whether dietary intervention could inhibit tumour growth of an androgen-sensitive human prostate cancer.
Methods: LNCaP cells were transplanted into nude-mice. Animals were provided different diets: the control diet (corn starch, sucrose, etc,) the rye bran (RB) and the soy protein (SCC) diets. Tumour take, tumour growth and prostate specific antigen (PSA) secretion were studied during 9 weeks.
Results: Palpable tumours developed in 75% of the tumour-cell injected sites of animals fed the control diet; whereas palpable tumours were seen in only 30% of the animals on the RB diet and 50% on the SCC diet. The tumours which grew to palpable size in the rye (RB) and soy(SCC) groups were smaller and secreted less PSA than those in the control group. Tumour cell apoptosis was increased in the rye and soy groups; however, cell proliferation was unaffected. The addition of fat to the rye diet reduced its effect upon prostate cancer growth.
Conclusions: Factors in rye bran and soy protein may inhibit prostate cancer growth. This effect is more apparent for rye than in soy. Further studies are required in order to identify the effective agents and to explain the mechanisms of action.
Bylund A et al. Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice. The Prostate 42(4): 304-14. 1 Mar 2000.

Comments: This may be an exceedingly important result and one that should be followed up in great detail.

KIM and colleagues, Department of Public Health Sciences, University of Toronto, Ontario Canada studied the associations between prediagnostic energy, fat, vitamin A intake and survival from prostate cancer.
Methods: 207 men with prostate cancer from Toronto and 201 men from Vancouver provided diet histories at diagnosis between 1989-92 and were followed for survival from prostate cancer. 263 men (135 from Toronto, 128 from Vancouver) were included in the final analysis.
Results: After adjustments for clinical stage, histologic grade, and other factors, there were significantly lower risks of dying from prostate cancer in the highest compared with the lowest tertiles of monounsaturated fat intakes in both cities and in the combined city analyses (hazard ratio (HR) = 0.3). Survival from prostate cancer was significantly higher for men in the highest tertile of energy intake in Toronto (HR = 0.1), compared with Vancouver where these men were relatively worse (HR = 2.6). Other nutrients were either not consistently or not significantly associated with prostate cancer survival in the two cities.
Conclusions: There was a consistent and significant inverse association between premorbid intake of monounsaturated fat and risk of death from prostate cancer. The inconsistent results for energy intake between cities may potentially be attributed to non-respondent bias in Toronto.
Kim DJ et al. Premorbid diet in relation to survival from prostate cancer (Canada). Cancer Causes and Control 11(1): 65-77. Jan 2000.
Comments: Again, the fat connection. The less fat, the higher the survival rate.

BRENNAN and colleagues, Unit of Environmental Cancer Epidemiology, International Agency for Research on Cancer, Lyon, France. Brennan@iarc.fr studied the role of dietary patterns and specific dietary nutrients in the aetiology of lung cancer in non-smokers.
Methods: The authors conducted a multicentre case-control study, in which 506 non-smoking incident lung cancer cases were identified in the 8 centres, along with 1045 non-smoking controls. A quantitative food-frequency questionnaire assessed dietary habits, from which measures of total carotenoids, beta-carotene and retinol nutrient intake were estimated.
Results: Protective effects against lung cancer were found for high consumption of tomatoes (odds ratio (OR) = 0.5), lettuce (OR = 0.6), carrots (OR = 0.8), margarine (OR = 0.7) and cheese (OR = 0.7). Weak protective effects were seen for high consumption of all carotenoids (OR = 0.8), beta-carotene (OR = 0.8) and retinol (OR = 0.9). Protective effects for high levels of fruit consumption were restricted to squamous cell carcinoma (OR = 0.7) and small cell carcinoma (OR = 0.7); these were not apparent for adenocarcinoma (OR = 0.9). Excess risk associated with meat, butter and eggs was restricted to squamous and small cell carcinomas, but not for adenocarcinomas.
Conclusions: This evidence suggests that the public health significance of increasing vegetable consumption among the bottom third of the population would include a reduction in the incidence of lung cancer among lifetime non-smokers by at least 25% and possibly more. A similar protective effect for increased fruit consumption may be present for squamous cell and small cell lung carcinomas.
Brennan P et al. A multicenter case-control study of diet and lung cancer among non-smokers. Cancer Causes and Control 11(1): 49-58. Jan 2000.

Issue 52

WYATT and colleagues, College of Nursing, Michigan State University, East Lansing USA conducted a study to assess the use of complementary therapies among older cancer patients.
Methods: The authors conducted a survey of 699 older cancer patients from Michigan, aged 64 years or older and who had received a diagnosis of breast, colorectal, prostate or lung cancer, at 4 and 6 weeks into their cancer treatment. Outcome measures included self-reported physical symptoms, depressive symptomatology, optimism, spirituality and use of conventional and complementary health services.
Results: About 33% of older cancer patients reported using complementary therapies. These people were more likely to be women breast cancer patients with a higher level of education. The three most frequently used therapies were exercise, herbal therapy and spiritual healing. Users of complementary therapies were significantly more optimistic than nonusers. There were significant differences between users and nonusers regarding types of physical symptoms experience; however there were no reported differences about depressive symptomatology or spirituality.
Conclusions: Oncology providers should be aware that one third of their older patients are supplementing conventional care with complementary therapies and become knowledgeable regarding the safety and efficacy of exercise programmes, herbal and vitamin therapies and spiritual healing. It would be useful to develop a system within cancer centres whereby cancer patients could easily report their use of complementary therapies, enabling providers to work in partnership with their patients.
Wyatt GK et al. Complementary therapy use among older cancer patients. Cancer Practice 7(3): 136-44. May-Jun 1999.

Comments: Pity that the authors' goal in compiling information about complementary cancer therapies appears to be more of concern that therapies such as exercise, spiritual healing and herbal and vitamin supplements could be harmful! A bit rich compared to the fairly brutal and toxic cancer treatments of surgery, chemotherapy and radiotherapy!

McKEOWN, Vitamin K Laboratory, Jean Mayer USDA Human Nutrition Research Center, Tufts University, Boston MA 02111, USA reviews (32 references) the field regarding antioxidants and breast cancer risk.
Results: The author writes that a recent prospective study found that the consumption of fruits and vegetables which were high in specific carotenoids and vitamins reduced breast cancer risk in premenopausal women. The observed protection might not be due to the anticarcinogenic mechanism of a single nutrient; further prospective studies which relate blood and dietary micronutrients to risk of breast cancer should be carried out.
McKeown N. Antioxidants and breast cancer. Nutrition Reviews 57(10): 321-4. Oct 1999.

SLATTERY and colleagues, University of Utah Medical School, Salt Lake City USA mslatter@dfm.utah.edu write that carotenoids have numerous biological properties which may underpin a role of them as chemopreventive agents; however, apart from beta-carotene, little is known regarding how dietary carotenoids are associated with cancers, including colon cancer. The authors evaluated the associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin and beta-cryptoxanthin and risk of colon cancer.
Methods: Data were collected from 1993 case subjects with first primary incident adenocarcinoma of the colon and from 2410 control subjects. Dietary data were collected from a detailed diet-history questionnaire; nutrient values for dietary carotenoids were obtained from the USDA Coordinating Center carotenoid database 1998.
Results: Lutein was inversely associated with colon cancer in both men and women (odds ratio (OR) for upper quintile relative to lowest quintile of intake: 0.83. The greatest inverse association was observed among patients in whom colon cancer was diagnosed when they were young (OR: 0.66), and in those with tumours located in the proximal segment of the colon (OR: 0.65). Associations with other carotenoids were unremarkable.
Conclusions: The major dietary sources of lutein in patients with colon cancer and in control subjects were spinach, broccoli, lettuce, tomatoes, oranges and orange juice, carrots, celery and greens. These data suggest that incorporating these foods into the diet may help reduce risk of colon cancer.
Slattery ML et al. Carotenoids and colon cancer. The American Journal of Clinical Nutrition 71(2): 575-82. Feb 2000.

EICHHOLZER and colleagues, Institute of Social and Preventive Medicine, University of Zurich, Switzerland eichholz@swissonline.ch write that low serum cholesterol has been associated with an increased risk of cancer mortality in various studies, which has led to uncertainty regarding the benefits of lower blood cholesterol. The authors evaluated the association between low blood cholesterol (<5.16 mmol/L) and cancer, placing special emphasis upon the potential confounding effect of antioxidant vitamins.
Methods: Plasma concentrations of cholesterol and antioxidant vitamins were measured in 1971-73 in 2974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed.
Results: 290 of the participants had died from cancer: 87 from lung, 30 from prostate, 28 from stomach and 22 from colon cancer. Group means for plasma cholesterol concentrations did not differ significantly between survivors and those who died from cancer at any of the studied sites. With plasma cholesterol, vitamins C and E, retinol, carotene, smoking and age accounted for in a Cox model, increased total cancer mortality in lung, prostate and colon but not in stomach cancer mortality was observed in men >60 years of age with low plasma cholesterol. When the data from the first 2 years of follow-up were excluded from the analysis, the relative risk estimates remained practically unchanged with regard to lung cancer, but decreased for colon, prostate and overall cancer.
Conclusions: Increased cancer mortality risks associated with low plasma cholesterol were not explained by the confounding effect of antioxidant vitamins, but were attributed in part to the effect of pre-existing cancer.
Eichholzer M et al. Association of low plasma cholesterol with mortality for cancer at various sites in men: 17-y follow-up of the prospective Basel study. The American Journal of Clinical Nutrition 71(2): 569-74. Feb 2000.

FREEMAN and colleagues, Midwest Center for Health Services and Policy Research, Department of Veterans Affairs, Edward Hines, Jr. Hospital, Hines IL, USA conducted a study to evaluate how prostatic levels of antioxidants relate to plasma levels and self-reported usual dietary intake, which may aid in interpreting studies of antioxidant exposure and prostate cancer risk.
Methods: Plasma and prostatic tissue levels of tocopherols, carotenoids and retinol were measured in 47 men undergoing radical prostatectomy or transurethral prostatectomy between July 1996 and April 1997. Dietary intake was measured using a questionnaire.
Results: Prostatic levels of tocopherols and carotenoids (but not retinol) were significantly correlated with plasma levels; the strongest correlations were associated with lycopene, beta-carotene and gamma-tocopherol (0.56, 0.54 and 0.52, respectively). Relative concentrations of tocopherols and carotenoids in prostate tissue were proportionate to those in plasma; however, no correlation between prostatic levels and reported dietary intake was observed. Adjustment for energy intake, body mass index and serum lipids did not impact these relations.
Conclusions: These data suggest that plasma levels of tocopherols and carotenoids better reflect prostatic exposure then self-reported usual dietary intake.
Freeman VL et al. Prostatic levels of tocopherols, carotenoids, and retinol in relation to plasma levels and self-reported usual dietary intake. American Journal of Epidemiology 151(2): 109-18. 15 Jan 2000.

Comments: Another nail in the coffin for the reliability of food questionnaires frequently used in epidemiological research.

Issue 51

DIXON-SHANIES and SHAIKH, The New York College of Osteopathic Medicine of the New York Institute of Technology, Old Westbury, NY 11568-8000 USA write that epidemiological research has suggested that phytoestrogen-rich foods may afford protection against breast cancer and that phytoestrogens including genistein have been reported to both inhibit and stimulate human breast cancer cell growth.
Methods: The authors tested the phytoestrogens genistein, daidzein, biochanin A and coumestrol.
Results: Genistein, daidzein, biochanin A and coumestrol inhibited serum-stimulated growth in T-47D and MCF-7 breast cancer cells at concentrations of 10-100 microM. Furthermore, extracts of the oestrogenic herbs, including hops, black cohosh and vitex inhibited the growth of T-47D cells.
Conclusions: The results of these in vitro tests suggest that various herbs and phytoestrogens may potentially have a role in the prevention of breast cancer in humans.
Dixon-Shanies D and Shaikh N. Growth inhibition of human breast cancer cells by herbs and phytoestrogens. Oncology Reports 6(6): 1383-7. Nov-Dec 1999.

WANG and RUSSELL, Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, MA, USA write that a large body of observational epidemiological studies has consistently demonstrated that individuals who eat more fruits and vegetables, which are rich in carotenoids, and people with a higher serum beta-carotene levels have a lower risk of cancer, particularly lung cancer. However, two human intervention studies which used high-dose beta-carotene supplements reported an increased risk for lung cancer among smokers. The authors review (82 references) the evidence in this contentious field.
Results and Discussion: Recent in vitro and in vivo studies have shown that beta-carotene itself may act as an anticarcinogen, but its oxidised products may actually facilitate carcinogenesis. This research supports the hypothesis that the carcinogenic response to high-dose beta-carotene supplementation reported in the human intervention trials is related to the instability of the beta-carotene molecule in the free radical-rich environment in the lungs of cigarette smokers. This is especially possible because smoke also causes decreased tissue levels of other antioxidants, such as ascorbate and alpha-tocopherol, which usually have a stabilizing effect upon the unoxidized form of beta-carotene.
Conclusions: Nutritional intervention using a combination of antioxidants (beta-carotene, alpha-tocopherol and vitamin C) as anticarcinogenic agents, may be an appropriate way to rationally and realistically reduce cancer risk.
Wang XD and Russell RM. Procarcinogenic and anticarcinogenic effects of beta-carotene. Nutrition Reviews 57(9 Pt 1): 263-72. Sep 1999.

Comments: This is a highly important review, due to the sensational publicity which attended the original publication of the Finnish Beta-Carotene Study several years ago. Beta-carotene, in the "free radical-rich environment" of a smoker’s lungs, may be unstable and its oxidised products may contribute to carcinogenesis. Particularly as smoking also decreases levels of other potent antioxidants including vitamins C and E. For another study demonstrating yet other horrific effects of cigarette smoking, please also see Zhang et al under Nutritional Status.

KIM, Department of Medicine, St Michael’s Hospital, Toronto, Ontario, Canada writes that folate is an important cofactor in the transfer of one-carbon moieties and plays a key role in DNA synthesis, repair and methylation. Furthermore, the role of folate has greatly evolved from the prevention of macrocytic anaemia to the prevention of cardiovascular disease and neural tube defects. The author reviews (42 references) the role of folate in cancer prevention.
Results: Published epidemiological, animal and clinical evidence suggest that folate may play a role in cancer prevention. The author cites two recently published large, prospective epidemiological studies which suggest that maintaining adequate levels of serum folate or moderately increasing folate intakes from dietary sources and vitamin supplements may significantly reduce the risk of pancreatic and breast cancer, respectively. The protective effect of folate appears to be operative in people at risk for developing these cancers, in particular male smokers for pancreatic cancer and women regularly consuming a moderate amount of alcohol, for breast cancer.
Conclusions: Because the expanding role of folate nutrition in cancer prevention has major public health implications, research is needed in order to clearly elucidate the effect of folate upon carcinogenesis.
Kim YI. Folate and cancer prevention: a new medical application of folate beyond hyperhomocysteinemia and neural tube defects. Nutrition Reviews 57(10): 314-21. Oct 1999.

ROSE and CONNOLLY, Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, NY 10595 USA. david@westnet.com write that epidemiological and experimental evidence demonstrates that long-chain omega-3 fatty acids (FAs), which occur at high levels in some fish oils, exert protective effects against common cancers, particularly those of the breast, colon and perhaps, prostate. The authors review (260 references) the field.
Results and Discussion: Multiple mechanisms are thought to be involved in this chemopreventive activity, including the suppression of neoplastic transformation, inhibition of cell growth, enhanced apoptosis and antiangiogenicity. A common feature of the majority of these biological effects is the inhibition of eicosanoid production from omega-6 FA precursors. Several of the known risk factors for breast and colon cancer may be favourably modified using omega-3 FA supplementation. The implementation of clinical chemoprevention trials is now feasible.
Rose DP and Connolly JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacology and Therapeutics 83(3): 217-44. Sep 1999.

NORRISH and colleagues, Department of Community Health, University of Auckland, New Zealand write that, according to experimental studies, the risk of prostate cancer may be reduced with intake of long-chain n-3 polyunsaturated fatty acids derived from marine foods, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Few human studies, however have been conducted because of the difficulties involved in assessing the dietary intake of these fatty acids. The authors conducted a population-based case-control study in New Zealand to investigate the relationship between prostate cancer risk and EPA and DHA in erythrocyte biomarkers.
Methods: 317 prostate cancer cases and 480 age-matched community controls participated in this study during 1996-97.
Results: Reduced prostate cancer risk was associated with high erythrocyte phosphatidylcholine levels of EPA (relative risk rr = 0.59) and DHA (rr = 0.62).
Conclusions: The results of this study support evidence from in vitro experiments for a reduced risk of prostate cancer associated with dietary fish oils, possibly acting via the inhibition of arachidonic acid-derived eicosanoid biosynthesis.
Norrish AE et al. Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case-control study. British Journal of Cancer 81(7): 1238-42. Dec 1999.

Issue 50

VAN DAM, Nederlands Kanker Instituut/Antoni van Leeuwenhoek ziekenhuis, afd. Psychosociaal Onderzoek en Epidemiologie, Amsterdam investigated the prevalence of use by cancer patients of alternative diets and other therapies.
Methods: A written survey was distributed among 429 patients visiting the outpatient cancer clinic of the Antoni van Leeuwenhoek in Amsterdam, in patients were questioned about their use of alternative therapies, reasons for using these therapies and expenses incurred. 405 (patients participated in the study.
Results: 121 patients (30%) used an alternative therapy. 51 patients (13%) used an alternative diet, of which 63% used the Houtsmuller diet (diet developed by former internist Dr AJ Houtsmuller, who was cured of aggressive melanoma, which had already metastasised to the kidneys. His regime incorporates practices from Gerson, Moerman, Issels, Kelly and psycho-neuro-immunology as per Prof Dr Ballieux, as well as vitamin and mineral supplements). 12 years previously, only 8% of patients used an alternative diet, mainly the Moerman diet, a precursor of the Houtsmuller diet. 70 patients (17%) used other alternative therapies, including homoeopathy, vitamins, herbs and psycho-spiritual therapies. The costs of particularly the Houtsmuller diet were about Dfl 480 per month, which were not covered by insurance. Greater than half the patients using a diet felt that it would either cure them, delay tumour progression, or both.
Conclusions: Compared with 12 years previous, the number of cancer patients using alternative diets and other alternative therapies had increased by about 80%. The Houtsmuller diet had supplanted the Moerman diet and was used by 63% of patients using diet.
Van Dam FS. Increased use of alternative diets and other alternative treatments for cancer patients: Houtsmuller (diet) is in, Moerman (diet) is out. Nederlands tijdschrift voor geneedskunde 143(27): 1421-4. 3 Jul 1999.

Comments: The fact that only13% of cancer patients in this survey used a diet as a therapy is disappointing to me, given the huge amount of published research and clinical evidence regarding the importance of diet in cancer aetiology and progression.

ZAZA and colleagues, Department of Oncology, University of Western Ontario, Canada. zaza@julian.uwo.ca write that cancer patients suffer unnecessarily due to the inadequate use of pain medication and other interventions, contributed in part by the under-utilisation of nonpharmacological strategies (NPS). The authors studied health care professionals’ familiarity with and perceptions regarding (NPS) for managing cancer pain and assessed their interest in learning more about NPS as adjuncts to pharmacological analgesics.
Methods: The authors surveyed 214 health care professionals at 2 cancer treatment centres in Ontario, Canada. The questionnaire included questions regarding 11 psychological strategies (i.e. imagery) and 8 other NPS (i.e. acupuncture). The response rate was 67% (141/214).
Results: Respondents were found to be the least familiar with autogenic training, operant conditioning and cognitive therapy. Apart from radiation and surgery, health professionals most commonly reported recommending support groups (67%),imagery (54%), music or art therapy (49%) and meditation (43%) for managing cancer pain. These respondents were most interested to learn more about acupuncture, massage therapy, therapeutic touch, hypnosis, and biofeedback. They were somewhat familiar with most of the 19 NPS presented; however, they used or recommended few NPS for managing cancer pain.
Conclusions: Health professionals’ interest in NPS has important implications for the supportive care of cancer patients.
Zaza C et al. Health care professionals’ familiarity with non-pharmacological strategies for managing cancer pain. Psycho-oncology 8(20: 99-111. Mar-Apr 1999.

Comments: It is pathetic that health professionals are so ignorant of many effective practices for pain relief, especially hypnosis and acupuncture.

ZHAO and colleagues, Center for Cancer Causation and Prevention, AMC Cancer Research Center, Denver, CO 80214 USA write that procyanidins in grape seeds are known to exert anti-inflammatory, anti-arthritic and anti-allergic activities, prevent skin ageing, scavenge oxygen free radicals and inhibit UV radiation induced peroxidation activity. Because many of these events are associated with tumour promotion stages of carcinogenesis, the authors suggest that grape seed polyphenols and procyanidins could be anticarcinogenic and/or anti-tumour promoting agents. The authors assessed the anti-tumour promoting effect of a polyphenolic fraction isolated from grape seeds (GSP).
Methods: The authors used the 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol 13-acetate (TPA)-promoted SENCAR mouse skin two stage carcinogenesis protocol as a model system.
Results: Following tumour initiation with DMBA, topical application of GSP at doses of 0.5 and 1.5 mg/mouse/application resulted in a highly significant inhibition of TPA tumour promotion. The anti-tumour promoting effects of GSP were dose dependent and reduced tumour incidence (35 and 60% inhibition), tumour multiplicity (60 and 83% inhibition) and tumour volume (67 and 87% inhibition) at both 0.5 and 1.5 mg GSP, respectively. Based upon these results, the authors attempted to isolate and identify the individual polyphenols present in GSP and to assess their antioxidant activity. Nine individual polyphenols were identified as catechin, epicatechin, procyanidins B1-B5 and C1 and procyanidin B5-3’-gallate. Five of these individual polyphenols, assessed for antioxidant activity significantly inhibited epidermal lipid peroxidation. Procyanidin B5-3’-gallate showed the most potent antioxidant activity.
Conclusions: These results for the first time show that grape seed polyphenols possess high anti-tumour promoting activity due to the strong antioxidant effect of procyanidins. Grape seed polyphenols in general and procyanidin B5-3’-gallate in particular should be studied in more detail to be developed as cancer chemopreventive and/or anticarcinogenic agents.
Zhao J et al. Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation-promotion protocol and identification of procyanidin B5-3’-gallate as the most effective antioxidant constituent. Carcinogenesis 20(9): 1737-45. Sep 1999.

Comments: Great research study! Not only have the authors demonstrated that grape seeds possess potent anti-tumour and anti-carcinogenic activity, but they have also separated, analysed and identified the procyanidin fractions with the anti-cancer activity. For what more can one ask? The more cynical among us might ask, that assuming that naturally-occurring procyanidins from grape seeds are probably not patentable, will any profit-seeking pharmaceutical company develop this as a drug? Please email me with your comments – sandra@positivehealth.com.

LEE and FAIR, Department of Surgery and Prostate Diagnostic Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 USA write that surgeons continue to be faced with difficulties in treating prostate cancer, which remains the leading cause of cancer and the second leading cause of cancer-related deaths in men. Additionally, in the era of the prostate-specific antigen (PSA), physicians must also determine which if any therapies are appropriate for the treatment of a biochemical or PSA relapse. The authors review (79 references) the evidence regarding certain nutrients in carcinogenesis and cancer progression.
Results and Discussion: The authors consider the role of diet in prostate carcinogenesis, and the rationale for dietary manipulation as a treatment strategy for the prevention of primary and secondary (recurrent) prostate cancer.
Lee CT and Fair WR. The role of dietary manipulation in biochemical recurrence of prostate cancer after radical prostatectomy. Seminars in Urologic Oncology. 17(3): 154-63. Aug 1999.

GRANT, NASA Langley Research Center, Hampton, Vermont USA. wbgrant@norfolk.infi.net writes that the aetiology of prostate cancer has not yet been fully resolved in the scientific and medical literature. However, the non-fat portion of milk and calcium are emerging as leading dietary risk factors, with lycopene in tomatoes and vitamin D apparently being risk reduction factors.
Methods: The author conducted an ecologic (multi-country statistical) study to investigate dietary links to prostate cancer. Mortality data from 1986 for various age groups in 41 countries are compared with national consumer macronutrient supply values for 1983 and tomato supply values for 1985.
Results: In 28 countries with more than 5 kcal/day of tomatoes in the consumer supply, a linear combination of non-fat milk (risk factor) and tomatoes (risk reduction factor) had the highest statistical association with prostate cancer mortality rates for men over the age of 35. For 13 countries with fewer than 6 kcal/day of tomatoes, non-fat milk had the highest association for men aged 65-74 years. For 41 countries combined, the non-fat portion of milk had the highest association with prostate cancer mortality rates for men aged 65-74 years.
Conclusions: These results support the results of other cohort studies which have found the non-fat portion of milk to have the highest association with prostate cancer, likely due to the calcium, and tomatoes to reduce the risk of prostate cancer, most likely due to lycopene.
Grant WB. An ecologic study of dietary links to prostate cancer. Alternative Medicine Review 4(3): 162-9. Jun 1999.

Issue 49

WELLISCH and colleagues, Department of Psychiatry, UCLA School of Medicine 90024 USA conducted a pilot study to determine the effects upon depression and anxiety of group intervention in high-risk relatives of breast cancer patients.
Methods: 36 relatives of breast cancer patients participated in a 6-session, 12-hour group intervention study consisting of educational and psychosocial components.
Results: There was a significant reduction of depression symptoms, as defined on the Center for Epidemiologic Studies Depression Scale. Additionally, there was a significant reduction in anxiety symptoms as defined on the State-Trait Anxiety Inventory state scale.
Conclusions: The results of this pilot study demonstrated the efficacy of the group intervention model in reducing symptoms of depression and reactive (not chronic) anxiety.
Wellisch DK et al. Depression and anxiety symptoms in women at high risk for breast cancer: pilot study of a group intervention. The American Journal of Psychiatry 156(10): 1644-5. Oct 1999.

SHAH and colleagues, Washington University School of Medicine, St Louis, Missouri USA shahs@msnotes.wustl.edu studied the effect of energy healing upon in vitro tumour cell growth.
Methods: The authors used the cell culture model similar to that used by oncologists to assess the effects of chemotherapeutic agents. An energy healer was selected, based on his ability to influence this model. The authors assessed the effects of energy treatment, compared to cells left at ambient temperature and to a control treatment – a medical student mimicking the healer.
Results: A chi-square test comparing a medical student’s and the practitioner’s ability to inhibit tumour cell growth by 15% associated the practitioner with inhibition of tumour cell proliferation. The magnitude of change was too close to the assay’s intrinsic margin of error, making the quantitative data difficult to interpret.
Conclusions: Although energy healing appears to influence several indices of growth in the in vitro tumour cell proliferation, these assays are limited in their ability to define and prove the existence of this phenomenon Therefore, more sensitive biological assays are required for further study in this field.
Shah S et al. A study of the effect of energy healing on in vitro tumor cell proliferation. The Journal of Alternative and Complementary Medicine 5(4): 359-65. Aug 1999.

ISHIHARA and colleagues, Department of Hygiene and Public Health (I), School of Medicine, Tokyo Women’s Medical University, Japan investigated the effect of the timing of stressor application upon transplanted tumour cells and its possible regulation by an immunomodulator.
Methods: Male C57 BL/6N mice were administered a rotational stressor for 7 days relative to tumour cell inoculation, i.e. stressor following inoculation of Lewis lung cancer cells, stressor during inoculation and stressor prior to inoculation.
Results: Stressor application and tumour cell inoculation caused transient decreases in body weight, particularly in mice stressed following inoculation. Compared to control mice, those mice exposed to the stressor during, or prior to inoculation showed significant increases in the number of metastatic foci. Early administration of an immunomodulator, PSK, significantly attenuated the increase in metastatic foci in stressed mice. Weights of thymus gland and spleen 14 days following inoculation were similar across the three stressor and control groups. Application of the stressor reduced NK cell activity of the normal mice, as well as tumour bearing mice. The lowest pre-inoculation NK cell activity was in mice stressed for 7 days starting on the day of inoculation. NK cell activity decreased in tumour bearing mice stressed at the time of tumour inoculation. Decreased NK cell activity was reversed at day 14 following tumour inoculation. Compared to mice exposed to the stressor prior to or during inoculation, mice exposed after inoculation showed the lowest level of NK cell activity. Treatment with PSK reduced these changes significantly.
Conclusions: The above results suggest that the rotational stress reduces splenic NK cell activity, which may influence the magnitude of tumour metastasis, depending upon time of tumour cell injection. Additionally, administration of an immunomodulator may counteract reduction of NK cell activity.
Ishihara Y et al. Time-dependent effects of stressor application on metastasis of tumor cells in the lung and its regulation by an immunomodulator in mice. Psychoneuroendocrinology 24(7): 713-26. Oct 1999.

SENGUPTA and DAS, Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Calcutta, India write that among the many carotenoids, lycopene has recently received attention due to its putative association in reducing cancer risk, including breast, prostate and pancreas. The authors review the literature (47 references).
Results and Discussion: A number of studies have attempted to determine the bioactive levels of lycopene in human tissues, and the influence of plant food and cancer upon carotenoids. Experimental studies have also suggested the protective role of lycopene during carcinogenesis.
Conclusions: These observations justify further exploration and evaluation of the biological function of lycopene alone or in combination with other chemical compounds in tomato for use in cancer prevention.
Sengupta A and Das S. The anti-carcinogenic role of lycopene, abundantly present in tomato. European Journal of Cancer Prevention 8(4): 325-30. Aug 1999.

YAMAMOTO and colleagues, Department of Pathology II, Kansai Medical University, Moriguchi, Osaka, Japan studied the effects of eicosapentaenoic acid (EPA) and an angiogenesis inhibitor (TNP-470) upon breast cancer cell growth in 4 human breast cancer cell lines.
Methods: The human breast cancer cell lines were MDA-MB-231, T-47D, MDF-7, KPL-1 and MKL-F.
Results: EPA and TNP-470 alone both demonstrated tumour growth inhibition in all five cell lines, in a time- and dose-dependent manner. In combination, a synergistic effect was seen at high concentrations. EPA plus TNP-470 treatment provoked apoptosis, which was verified by the appearance of sub G1 populations, DNA fragmentation and cell morphology. In combination, expression of Bax and Bcl-xS, the apoptosis-enhancing proteins, was more up-regulated that of Bcl-2 and Bcl-xL, the apoptosis-suppressing proteins, was more down-regulated compared to the use of EPA orTNP-470 alone, suggesting that their synergistic effect was due to an acceleration of apoptosis.
Yamamoto D et al. Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP-470 on human breast cancer cells. Breast Cancer Research and Treatment 55(2): 149-60. May 1999.

Comments: To a molecular biologist (as I am) it is extremely reassuring when researchers discover how nutrients such as EPA actually suppress cancer growth, at the molecular level. This will filter down into patient care, probably within a 5-year period, when it will probably be possible to induce apoptosis and cause the cancer cells to commit suicide.

Issue 48

GRAY and colleagues, Psychosocial and Behavioural Research Unit, Toronto-Sunnybrook Regional Cancer Centre, Ontario, Canada. Ross_gray@cancercare.on.ca conducted a questionnaire to determine the attitudes, practices and knowledge of 3 groups of complementary practitioners regarding women’s cancers.
Methods: National samples were obtained for naturopathic doctors and chiropractors; the sample of massage therapists was drawn from Ontario. The survey questionnaire was posted, followed by a reminder card and a second mailing of the questionnaire. The surveyed elicited practitioners’ reported responses to patients’ suspicious symptoms, their perceptions of patients’ motivations for seeking treatment, their (practitioners’) satisfaction with interactions with conventional practitioners, their perceptions of their role in the care of women with or at risk of cancer, and their perceptions of their knowledge about women’s cancers, and specifically ovarian cancer.
Results: 894 questionnaires were returned (56% response rate). The overwhelming majority of practitioners who saw women with symptoms possibly related to cancer referred them to a family physician or cancer specialist. The women’s motivations for seeking complementary treatments were to maximise their quality of life, to seek natural approaches to healing and to try to stay well when their cancer is in remission. Most respondents were dissatisfied with patient-related communication with family doctors and cancer specialists. A majority of the complementary practitioners indicated they had an important role to play in the care of women with cancer, and expressed interest in further education regarding ovarian cancer.
Conclusions: All the professions in this survey, although differing among each other, shared an interest in being involved in caring for women with cancer, and in continuing their education in order to help them better serve their clients.
Gray RE et a. Complementary health practitioners’ attitudes, practices and knowledge related to women’s cancers. Cancer Prevention and Control. 3(1): 77-82. Feb 1999.

Green and colleagues, Epidemiology and Population Health Unit, Queensland Institute of Medical Research, Brisbane, University of Queensland, Australia. AdeleG@qimr.edu.au write that the use of sunscreens on the skin may prevent sunburn; however it is not known whether long-term use can prevent skin cancer. There is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals; however, evidence of its effects in human beings is limited.
Methods: The authors conducted a randomised controlled clinical trial. Participants, 1621 residents of Nambour in southeast Queenland Australia, were assigned to one of four treatment group: 1) daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms and hands and betacarotene supplementation of 30 mg daily; 2) sunscreen plus placebo tablets; 3) betacarotene only; or 4) placebo only. Endpoints after 4.5 years of follow-up were incidence of basal-cell and squamous-cell cancers, for people treated for newly diagnosed disease and number of tumours which occurred. The analysis of the sunscreen’s effect was based only on skin cancers which developed on the sites of daily application. All analyses were by intention to treat.
Results: 1838 participants underwent full skin examination by a dermatologist in the follow-up period. 250 of these individuals developed 758 new skin cancer during follow-up. There were no significant differences in incidence of first new skin cancers between groups randomly assigned daily sunscreen and no sunscreen. Also, there was no significant difference between the betacarotene and placebo groups in the incidence of either cancer. There was no effect upon the incidence of basal-cell carcinoma by sunscreen use or by betacarotene regarding number of tumours; however the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no-daily sunscreen group.
Discussion: There were no harmful effects of daily use of sunscreen. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma appears to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There were no beneficial or harmful effects upon the rates of either type of skin cancer as a result of betacarotene supplementation.
Green A et al. Daily sunscreen application and betaacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet 354(9180) 723-9 28 Aug 1999.

Comments: With the incidence of skin cancer rising due, supposedly to greater unprotected sun exposure, these results reporting significant reductions in squamous-cell cancer following the use of sunscreen are encouraging.

HAYON and colleagues, Department of Clinical Biochemistry, Faculty of Health Sciences, Soroka Medical Center, Beer Sheva, Israel studied the antitumour activity of non-steroidal antioestrogens, including Tamoxifen and its derivatives, in leukaemia and lymphoblastic cell lines.
Methods: The authors studied the effects of tamoxifen and its derivatives, clomiphene and nafoxidine in promyelocytic leukaemia HL60 and T lymphblastic MOLT3 cell lines.
Results: Tamoxifen and derivatives clomiphene and nafoxidine caused reduction of cell viability in a dose-dependent manner. The drugs demonstrated differences in the potency after four days incubation, with nafoxidine being the most efficient inhibitor and tamoxifen the least active. Apoptosis was induced, as measured by the DNA ladder pattern and formation of pre G0/G1 population detected by flow cytometry analysis of DNA. The drugs’ effect was counteracted by antioxidants, alpha-tocopherol (vitamin E) the most effective. N-acetyl L-cysteine reversed mainly decrease in cell viability, but was less effective upon apoptosis. The protein kinase inhibitor GF109203X attenuated apoptosis induced by clomiphene in MOLT3 cells.
Conclusions: These results suggest that the antileukaemic activity of these antioestrogens is mediated by oxidative stress and protein kinase C (PKC) activation. Tripheylethylene antioestrogens and their derivaties may be used as antileukaemic drugs which kill cells by apoptosis mediated by oxidative stress and activation of PKC.
Hayon T et al. Non-steroidal antiestrogens induce apoptosis in HL60 and MOLT3 leukemic cells; involvement of reactive oxygen radicals and protein kinase C. Anticancer Research 19(3A): 2089-93. May-Jun 1999.

MAEHLE and colleagues, Department of Toxicology, National Institute of Occupational Health, Oslo, Norway Lovise.mahle@klinmed.uio.no write that various mechanisms for the inhibition by n-3 fatty acids (FA) upon tumour progression have been proposed. The authors studied the relationship between inhibition of growth of lung cancer cells and lipid peroxidation products.
Methods: To test whether the inhibition of the growth of subscutaneously transplanted A427 lung cancer cells may be due to an increased level of lipid peroxidation products, mice were fed diets supplemented with corn oil (CO), olive oil (OO) or K85, a mixture of ethyl esters of n-3 FAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
Results: Tumours in the n-3 FA group showed reduced growth. Peroxidation products, measured by the thiobarbituric acid reactive test (TBARS) showed higher levels in tumours from the n-3 FA fed mice than from the other diet groups. The growth inhibitory effects and the elevated TBARS level in the n-3 FA group were counteracted by vitamin E supplement in the diet. Cu/ZN-superoxide dismutase (SOD) activity in liver did not differ greatly among the groups. The cell proliferation rate was significantly lower in the K85 diet group compared to the other diet groups.
Conclusions: These results demonstrate the growth inhibitory effects of n-3 fatty acids upon lung cancer cells in mice.
Maehle L et al. Growth of human lung adenocarcinoma in nude mice is influenced by various types of dietary fat and vitamin E. Anticancer Research 19(3A): 1649-55. May-Jun 1999.

ZHOU and colleagues, Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 USA characterised the ability of dietary soybean components to inhibit the growth of prostate cancer in mice and alter tumour biomarkers associated with angiogenesis.
Background: Soy isoflavones (genistein or daidzein) or soy phytochemical concentrate inhibit the growth of prostate cancer cells LNCaP, DU 145 and PC-3 in vitro but only at supraphysiologic concentrations i.e., 50% inhibitory concentrations (IC50). G2-M arrest and DNA fragmentation consistent with apoptosis of prostate cancer cells are also observed at concentrations causing growth inhibition. In contrast, the in vitro proliferation of vascular endothelial cells was inhibited by soy phytochemicals at much lower concentrations.
Methods: The authors evaluated the ability of dietary soy phytochemical concentrate soy protein isolate to inhibit the growth of the LNCaP human prostate cancer in severe combined immune-deficient mice. Mice inoculated with LNCaP cells were randomly assigned to one of six dietary groups based on the AIN-76A formulation for 3 weeks. A 2 x 3 factorial design was used with two protein sources (20% casein vs soy protein) and 3 levels of soy phytochemical concentrate (0, 0.2 and 1.0% of the diet).
Results: Soy components did not alter body weight gain or food intake. Compared with Casein-fed controls, the tumour volumes after 3 weeks were reduced by 11% by soy protein, 19% by 0.2% soy phytochemical concentrate, 28% by soy protein with 0-.2% soy phytochemical concentrate, 30% by 1.0% soy phytochemical concentrate and 40% by soy protein with 1.0% soy protein with 1.0% soy phytochemical concentrate. Histological examination of the tumour tissue showed that consumption of soy products significantly reduced tumour cell proliferation, increased apoptosis and reduced microvessel density. Angiogenic protein insulin-like growth factor-I was reduced in the circulation of mice fed soy protein and phytochemical concentrate.
Conclusions: These data suggest that dietary soy products may inhibit experimental prostate tumour growth by a combination of direct effects upon tumour cells and by indirect effects upon tumour neovasculature.
Zhou JR et al. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. The Journal of Nutrition 129(9): 1628-35. Sep 1999.

Comments: As researchers’ attentions become more and more focussed upon the clinical properties of phytonutrients, we will learn much more about their underlying mode of action and how they appear to be able to inhibit cancer growth.

CHEW and colleagues, Department Animal Sciences, Washington State University, Pullman 99164-6320 USA. boonchew@wsu.edu studied, in mice, the anticancer activities of beta-carotene, astaxanthin and canthaxanthin against the growth of breast tumours.
Methods: Mice, inoculated with WAZ-2T tumour cells, were fed a synthetic diet containing 0, 0.2 or 0.4% beta-carotene, astaxanthin or canthaxanthin.
Results: there were no detectable carotenoids in the plasma or tumour tissues of unsupplemented mice. The concentrations of plasma astoxanthin were greater than beta-carotene and canthaxanthin. However, in tumour tissues, the concentration of canthaxanthin was higher than that of beta-carotene and astaxanthin. Generally, all three carotenoids decreased breast tumour volume. Breast tumour growth inhibition by astaxanthin was dose-dependent and was higher than from canthaxanthin and beta-carotene. Those mice fed 0.4% beta-carotene or canthaxanthin did not demonstrate further increased tumour growth inhibition compared to those given 0.1% of each carotenoid. The lipid peroxidation activity in tumours was lower in mice fed 0.4% astaxanthin, but not in mice fed beta-carotene and canthaxanthin.
Conclusions: Beta-carotene, canthaxanthin and especially astaxanthin inhibit the growth of breast tumours in mice and also influence the anti-tumour activity.
Chew BP et al. A comparison of the anticancer activities of dietary beta-carotene, canthaxanthin and astaxanthin in mice in vivo. Anticancer Research 19(3A): 1849-53. May-Jun 1999.

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