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Cancer

Issue  93

WEIGER and co-workers, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA, wendy_weiger@hms.harvard.edu, analyze the problem of advising patients who seek complementary and alternative medical therapies for cancer.
Background: Many patients with cancer use complementary and alternative medical (CAM) therapies. Physicians need authoritative information on CAM therapies in order to be able to advise patients who seek these interventions.
Methods: Meta-analysis of current evidence on the efficacy and safety of selected CAM therapies, covering dietary modification and supplementation, herbal medicine, acupuncture, massage, exercise and psychological mind-body therapies. Possible effects on disease progression and survival are considered, and also possible palliative effects. Risks for direct adverse effects as well as risks of interactions with conventional treatments are evaluated.
Results and conclusions: For each therapy, the current balance of evidence on efficacy and safety points to whether the therapy is to be recommended, accepted or discouraged. An example of the latter is high-dose vitamin A supplementation. The strategy allows the development of provision of responsible, evidence-based, patient-centred advice to persons with cancer who seek CAM therapies.
Weiger WA, Smith M, Boon H, Richardson MA, Kaptchuk TJ, Eisenberg DM. Advising patients who seek complementary and alternative medical therapies for cancer. Annals of Internal Medicine 137 (11): 889-903, Dec 2002.

CAI and colleagues, Oncology Center, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China, have conducted a clinical trial of traditional Chinese medicine in patients with lung cancer undergoing radiotherapy.
Background: The aim of the study was to study the effects of radiotherapy in combination with traditional Chinese medicine (TCM) in patients with non-small cell lung cancer.
Methods: In this randomized controlled trial, 92 patients with non-small cell lung cancer were randomized into two groups. 50 received a combination of radiotherapy and TCM, and 42 received only radiotherapy. Adverse effects and quality of life were observed in all patients after treatment.
Results: The incidence of adverse effects was much lower in the combination group, and significantly greater improvement in quality of life was found in the group receiving the combination treatment (p = 0.01).
Conclusions: TCM in combination with radiotherapy can reduce the adverse effects of radiotherapy and improve the quality of life for patients with non-small cell lung cancer.
Cai HB, Dai FG, Min QF, Shi M, Miao JX, Luo RC. Clinical study of the effects of radiotherapy in combination with traditional Chinese medicine on non-small cell lung cancer. Ti I chuen I ta hsueeh hsueeh pao 22 (12): 1112-1113, Dec 2002.
Comment: Now, how often have you heard of a cancer patient being prescribed traditional Chinese medicine, along with their radiotherapy. When this starts to become mainstream, then we know that the research message has finally reached even the most intractable oncologists.

GOODSTINE and colleagues, Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA, have found a possible relationship between the ratio of n-3 and n-6 fatty acids in the diet and the risk of breast cancer in premenopausal women.
Background: Recent research has suggested that an increased n-3 polyunsaturated fatty acid intake and/or and increased (n-3)/(n-6) ratio is associated with a lower breast cancer risk. This case-control study investigates the association between intake of n-3 and other fatty acids, and the (n-3)/(n-6) ratio and breast cancer risk.
Methods: Information from two related case-control studies in Connecticut was combined. Information was available on a total of 565 women with breast cancer and 554 controls. The controls were a combination of hospital-based and population-based. Information on dietary intake was elicited with a standard food frequency questionnaire.
Results: In the full study population there were no significant trends for any macronutrient or fatty acid when the highest and lowest quartile of intake were compared. However when analysis was restricted to premenopausal women, the highest compared to the lowest quartile of the (n-3)/(n-6) ratio was associated with a nonsignificant lower risk for breast cancer. This lower risk became significant when the study was restricted to the population-based controls.
Conclusions: The results are consistent with the hypothesis that a higher (n-3)/(n-6) polyunsaturated fatty acid ratio in diet may reduce the risk of breast cancer in premenopausal but not necessarily in postmenopausal women.
Goodstine SL, Zheng T, Holford TR, Ward BA, Carter D, Owens PH, Mayne ST. Dietary (n-3)/(n-6) fatty acid ratio: possible relationship to premenopausal but not postmenopausal breast cancer risk in US women. The Journal of Nutrition 133 (5): 1409-1414, May 2003.

LEACH and colleagues, Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA, review (71 references) the chemoprevention of prostate cancer with a focus on key opportunities and clinical trials.
Abstract: The list of potential agents for prostate cancer prevention continues to grow. It includes COX-2 inhibitors, vitamin D, soy, isoflavonoids, low-fat diet, and many others. As prospective trials are completed and the correlations with molecular genetics are developed, it seems certain that specific recommendations, tailored to individual patients, will emerge. Ultimately it can be foreseen that the main focus of prostate cancer control with shift from early detection and treatment to prevention.
Leach R, Pollock B, Basler J, Troyer D, Naylor S, Thompson IM. Chemoprevention of prostate cancer. Focus on key opportunities and clinical trials. The Urologic Clinics of North America 30 (2): 227-237, May 2003.

PRADEEP and KUTTAN, Amala Cancer Research Centre, Thrissur-Kerala, India, report on the effect of beta-carotene on lung cancer metastasis in mice.
Background: The aim of the study was to investigate the effect of beta-carotene (pro-vitamin A) on the inhibition of lung cancer metastasis in mice.
Methods: The compound was administered to the mice after tumour induction.
Results: Beta-carotene produced a significant reduction (71.4%) in tumour nodule formation. Abnormal levels of connective tissue components that are normally found in animals with lung cancer were greatly reduced towards normal. Animals treated with beta-carotene survived for up to 69 days. Histopathology of lung tissue of the beta-carotene treated animals was consistent with these findings.
Conclusions: The results show the anti-metastatic activity of beta-carotene in mouse lung cancer.
Predeep CR, Kuttan G. Effect of beta-carotene on the inhibition of lung metastasis in mice. Phytomedicine 10 (2-3): 159-164, Mar 2003.
Comment: This result ought to be broadcast on the main news; instead one never hears of these kinds of results – a reduction by 71.4% of tumour nodule formation for lung cancer!! If these results were replicated in humans, then perhaps the dismal prognosis and life expectancy with lung cancer might start to be improved.

Issue 92

SHAPIRO and co-workers, Department of Psychology, University of Arizona, Tucson, AZ 85721, USA, shaunashapiro@aol.com, have studied the efficacy of mindfulness-based stress reduction in the treatment of sleep disturbance in women with breast cancer.
Background: The diagnosis of breast cancer elicits greater distress than any other diagnosis. Therefore it seems important to investigate stress reduction interventions for women with breast cancer.
Methods: This study is part of a larger randomized controlled study on mindfulness-based stress management, The current analysis looks at the effects of the intervention on sleep disturbances.
Results: Both mindfulness-based stress reduction and a free choice
control condition produced significant improvement on daily diary sleep quality measures, though neither showed significant improvement on sleep efficiency. Participants in the mindfulness-based stress reduction who reported greater mindfulness practice improved significantly more on the sleep quality measures most strongly associated with distress.
Conclusions: Mindfulness-based stress reduction shows some promise as a means to improve the quality of sleep in women with breast cancer who experience sleep disturbances as a result of their distress.
Shapiro SL, Bootzin RR, Figueredo AJ, Lopez AM, Schwartz GE. The efficacy of mindfulness-based stress reduction in the treatment of sleep disturbance in women with breast cancer: an exploratory study. Journal of Psychosomatic Research 54 (1): 85-91, Jan 2003.

MALIN et al., Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA, have studied the relationship between fruit and vegetable intake and the risk of breast cancer.
Background: High fruit and vegetable intake has been linked to a lower risk of breast cancer but evidence is inconsistent. In this population-based case control study among Chinese women in Shanghai, the associations between vegetables, fruits and breast cancer were investigated.
Methods: 1,459 incident breast cancer cases and 1,556 frequency-matched controls were included in the study. Dietary habits were assessed by in-person interviews. Logistic regression was used to compute adjusted adds ratios and 95% confidence intervals.
Results: There was no association between breast cancer risk and total vegetable intake. The risk of breast cancer decreased however with increasing intake of dark yellow-orange vegetables, Chinese white turnips, and certain dark green vegetables. Intake of fruits, except apples and watermelons, was inversely associated with breast cancer risk.
Conclusions: This study suggests that high intake of certain vegetables and fruits may be associated with a lower risk for breast cancer.
Malin AS, Qi D, Shu XO, Gao YT, Friedmann JM, Jin F, Zheng W. Intake of fruits, vegetables and selected micronutrients in relation to the risk of breast cancer. Internarional Journal of Cancer 105 (3): 413-418, Jun 2003.

PATHAK and colleagues, Cancer Biomarkers and Prevention Group, Department of Oncology, University of Leicester, Leicester LE2 7LX, UK, have reviewed (95 references) the chemoprevention of prostate cancer by antioxidant agents in the diet and hormonal manipulation.
Abstract: Prostate cancer is the most commonly diagnosed solid cancer and the second leading cause of cancer-related death in men in the Western world. There is an increased need to prevent the onset of this cancer, and to delay or reverse carcinogenesis. An example is the reversal of neoplasia by hormonal manipulation using anti-oestrogens in breast cancer or anti-androgens in prostate cancer. Epidemiological data suggest that dietary intake of antioxidants may be protective. These agents include vitamins D and E, soy, lycopene, and selenium. 5-alpha reductase inhibitors may also constitute a potential chemoprevention. The efficacy of chemopreventive agents needs to be ascertained in randomized, placebo-controlled clinical trials of suitable groups of high-risk individuals. In addition, reliable assays of potential biomarkers of the efficacy of an intervention need to be developed.
Pathak SK, Sharma RA, Mellon JK. Chemoprevention of prostate cancer by diet-derived antioxidant agents and hormonal manipulation (Review). International Journal of Oncology 22 (1): 5-13, Jan 2003.

WILKINSON and CHODAK, Midwest Prostate and Urology Health Center, Weiss Memorial Hospital, Chicago, IL 60640, USA, simonwilkinson@hotmail.com, have compiled a critical review (153 references) of complementary therapies for prostate cancer.
Abstract: Relatively little is known about the aetiology of prostate cancer, and research into treatment lags behind research in to treatment of other common cancers. However the popularity of complementary treatments is growing. This article provides a critical review of recent evidence for dietary modifications, food supplements, and herbal treatments in prostate cancer prevention and treatment. Despite encouraging data for some of these interventions, it is generally agreed that only randomized controlled trials can produce the basis for universal guidelines. Such trials are complex and require lengthy follow-up periods. Until the data are available, health care professionals need to improve their knowledge and understanding of the current evidence for or against complementary therapies in prostate cancer.
Wilkinson S, Chodak GW. Critical review of complementary therapies for prostate cancer. Journal of Clinical Oncology 21 (11): 2199-2210, Jun 2003.
Comment: What a catch-22 we are in regarding cancer research. Whenever positive clinical evidence emerges regarding nutritional or dietary approaches, it is never enough, because it isn’t in the form of a long-term randomized control trial, which the authors acknowledge are complex and must be followed up for lengthy periods. Humans are not rats; they cannot be fed rigidly controlled diets and kept in cages to standardize their environmental exposure to carcinogens and other toxic substances. What we don’t lack, however, is a large population of cancer patients, which could be randomized into trials testing various dietary regimes and supplements, herbal medicines, stress control programmes, etc. The cancer equivalent of the Dean Ornish Heart disease programs. How many more tens of thousands of cancer deaths will we have to suffer before we start using the nutritional and other substances we already have.

Issue 91

BEN-ELiYAHU, Biopsychologu Research Unit, Department of Psychology, Tel Aviv University, Israel, shamgar@post.tau.ac.il, has reviewed (100 references) the promotion of tumour metastases by surgery and stress, with a focus on the immunological basis and implications for psychoneuroimmunology.
Abstract: This review emphasizes a psychoneuroimmunology perspective of the hypothesis that surgical excision of a primary tumour can promote tumour metastasis. The empirical and theoretical basis for control of metastasis by cell-mediated immunity is established, and the interactive role of non-immunological risk factors is assessed. Various aspects of surgery that suppress cell-mediated immunity are described, together with the neuroendocrine mechanisms mediating suppression by stress and surgery. It is concluded that immunosuppression can be
deleterious, especially when surgery is conducted early. The most sensitive period for metastasis is immediately post surgery. Interventions aiming at reducing stress and immunosuppression should be used peri-operatively and in a multimodal therapeutic fashion. The reduction of immunosuppression induced by surgery and perioperative stress should be seen as an important adjunct in the treatment of cancer.
Ben Eliyahu S. The promotion of tumor metastasis by surgery and stress: immunological basis and implications for psychoneuroimmunology. Brain, Behavior, and Immunity 17 Suppl 1: S27-36, Feb 2003.

HARTMAN and colleagues, Nutrition Department, Pennsylvania State University, University Park, PA 16802, USA, tjh@psu.edu, have connected toenail selenium content and lung cancer in male smokers.
Background: The object of this study was to evaluate the selenium concentrations in toenails as a marker for the risk of lung cancer in smokers in Finland.
Methods: This case-control study was nested within the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. The substudy included 250 randomly selected incident lung cancer cases and 250 controls. Odds ratios and 95% confidence intervals were determined using conditional logistic regression methods. The analysis was complicated by the fact that Finland began to supplement agricultural fertilizers with selenium in 1984, which led to drastically increased toenail selenium levels in the general population. Subjects who entered the study before that time generally showed much lower levels of selenium, and this had to be corrected for.
Results: The odds ratios for men in the highest quartile of toenail selenium levels, compared to those in the lowest quartile, was 0.20 for men enrolled pre 1984 and 0.61 for others.
Conclusions: The results of this study show that low selenium status may be a associated with a higher risk for lung cancer.
Hartman TJ, Taylor PR, Alfthan G, Fagerstrom R, Virtamo J, Mark SD, Virtanen M, Barrett MJ, Albanes D. Toenail selenium concentration and lung cancer in male smokers (Finland). Cancer Causes and Control 13 (10): 923-928, Dec 2002.
Comment: These result show that men enrolled pre-1984 with the highest selenium levels had 20% risk of lung cancer compared with men in the lowest quartile. In those men enrolled later than 1984, the risk was still less – 61%. A powerful result!

ITO and colleagues, Department of Public Health, Fujita Health University School of Health Sciences, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, yoshiito@fujita-hu.ac.jp, have investigated serum carotenoids and mortality from lung cancer.
Background: The aim of the study was to investigate whether high serum levels of carotenoids, tocopherols, and folic acid decrease the risk of lung cancer.
Methods: This was a case-control study nested in the Japan Collaborative Cohort Study. A total of 39,140 individuals provided serum samples at baseline between 1988 and 1990. During an 8-year follow up, 147 cases of death from lung cancer were identified. 311 controls were selected from the surviving population, matched for gender, age and participating institution. Serum levels of antioxidants were measured in serum samples. Odds ratios for lung cancer death were estimated using conditional logistic models.
Results: The risk of death from lung cancer for the highest quartile of serum alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, and canthaxanthin, was significantly lower than for the lowest quartile. Odds ratios, adjusted for smoking, were between 0.21 and 0.46. The odds ratios for zeaxanthin/lutein and folic acid tended to be lower but were not statistically significant. Serum total cholesterol was also inversely related to the risk of death from lung cancer: the odds ratio for the highest versus the lowest quartile was 0.39.
Conclusions: Higher levels of serum carotenoids such as alpha- and beta-carotene may play a role in preventing death from lung cancer in Japan.
Ito Y Wakai K, Suzuki K, Tamakoshi A, Seki N, Ando M, Nishino Y, Kondo T, Watanabe Y, Ozasa K, Ohno Y. Serum carotenoids and mortality from lung cancer: a case-control study nested in the Japan Collaborative Cohort (JACC) study. Cancer Science 92 (1): 57-63, Jan 2003.
Comment: Again, as in the above study, the risk of death from lung cancer was significantly lower in those with the highest levels of serum carotenoids.

LOPEZ-SAEZ and co-workers, Department of Medicien, University of Cadiz School of Medicine, c/Dr. Maranon 6, E-11002 Cadiz, Spain, juanbosco.lopez@uca.es, have studied selenium and breast cancer.
Background: Controversy surrounds the relationship between low serum levels of selenium and reduced activity of selenium-dependent enzymes (such as glutathione peroxidase) and an increased risk of breast cancer.
Methods: In this case-control study, the serum concentrations of selenium were compared in 200 women with breast cancer, 100 healthy women, and 100 women with chronic diseases.
Results: Mean serum concentrations of selenium in women with breast cancer were 81.1 micrograms/litre, and in women with other diseases they were 98.5 micrograms/litre (p = 0.0001).
Conclusions: Alterations in selenium concentrations in women with breast cancer appear to be a consequence of the disease rather than a cause. Very low selenium status could be due to the nature of cancer.
Lopez-Saez JB, Senra-Varela A, Pousa-Estavez L. Selenium in breast cancer. Oncology 64 (3): 227-231, 2003.

Issue 90

YANG and colleagues, Taichung Veterans General Hospital, Chung-Shan Medical College, Taiwan, Republic of China, have described a holistic outcome measurement for terminally ill cancer patients.
Background: This cross-sectional study examined holistic outcomes in terms of quality of life, patient satisfaction with the care offered, and cost of care, and also looked for different outcomes with different care patterns.

Methods: 123 terminally ill cancer patients and 101 nurses were recruited from 4 hospitals in Taiwan. Care patterns were categorized into four groups: hospice inpatients, hospice team consultation, home hospice care services, conventional acute care.
Results: Hospice inpatients had a higher quality of life, a higher level of satisfaction and a lower cost of care than patients in other groups. Home hospice care service users had better psychological wellbeing than others. Nurses experienced higher work satisfaction with hospice inpatients.
Conclusions: The study makes a contribution to identifying patterns of care for the terminally ill that provide the best patient outcomes in a holistic fashion.
Yang KP, Yin TJ, Lee LC, Hsu N, Huang JM. Holistic outcome measurement for terminally ill cancer patients in medical centers in Taiwan. Journal of Nursing Research 9 (3): 43-56, Jun 2001.

DEVINE, School of Nursing, University of Wisconsin-Milwaukee, Milwaukee, WI, USA, ecd@uwm.edu, has meta-analyzed the effect of psycho- educational interventions on cancer pain.
Methods: 25 intervention studies were analyzed for effects of psycho-educational measures on pain in adult cancer patients.
Results: Across all the studies analyzed, a significant beneficial effect of psycho-educational interventions was found. Some studies were methodologically flawed. When the best studies were meta-analyzed, there was still a significant effect. Reasonably strong evidence exists for the benefits of relaxation-based cognitive-behavioural interventions, education about analgesic medication, and supportive counselling.
Conclusions: Psycho-educational interventions are not a substitute for analgesia but are an adjuvant therapy. Assessment and clinical judgement are critical. The interventions must be acceptable to patients and not too burdensome for people in pain.
Devine EC. Meta-analysis of the effect of psychoeducational interventions on pain in adults with cancer. Oncology Nursing Forum 30 (1): 75-89, Jan-Feb 2003.

VOGT and co-workers, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7246, USA, review (53 references) serum selenium and the risk of prostate cancer in black and white Americans.
Background: Prostate cancer is the most common cancer in men in the USA, with incidence rates in black men being the highest in the world. The aetiology of the disease and the reasons for this disparity in black and white men remain unknown. Here, the hypothesis is tested that there might be a connection with selenium which is known to act as preventive against prostate cancer.
Methods: Selenium concentrations were measured in the blood serum of 212 patients with prostate cancer and 233 healthy controls that included comparable numbers of black and white American men aged between 40 and 79.
Results: Serum selenium was inversely associated with the risk of prostate cancer, with similar patterns in black and white men. It was also found that this inverse association with selenium was strongest in men with low serum vitamin E concentrations.
Conclusions: A moderately decreased risk of prostate cancer at higher selenium concentrations is shown. This finding can now be extended to black men across the USA.
Vogt TM, Ziegler RG, Graubard BI, Swanson CA, Greenberg RS, Schoenberg JB, Swanson GM, Hayes RB, Mayne ST. Serum selenium and risk of prostate cancer in US blacks and whites. International Journal of Cancer103 (5): 664-670, Feb 2003.

ZHU and co-workers, Department of Gastroenterology, The Ninth People’s Hospital, Shanghai Second Medical university, Shanghai 200011, China, report on the effect of folic acid on the development of stomach and other gastrointestinal cancers.
Background: The aim of the study was to evaluate the roles of folic acid and beta-carotene in the chemoprevention of gastrointestinal tumours.
Methods: In a randomized, double-blinded, placebo-controlled trial, 216 patients with atrophic gastritis were randomly assigned to one of four groups: (1) folic acid 20 mg per day for 2 years, supplemented with vitamin B12; (2) beta-carotene 30 mg per day for one year followed by 30 mg twice weekly for one year; (3) synthetic beta-carotene in the same dosage; (4) placebo. Follow-up continued from 1994 to 2001.
Results: A total of 7 new cancers were diagnosed in the follow-up period. Of these, 3 stomach cancers, 1 colon cancer and 1 oesophageal cancer were in the placebo group, and 1 stomach cancer each in the two beta-carotene groups. No new cancer was diagnosed in the folic acid group. This amounts to a significant reduction in the folic acid group compared to the placebo group with p = 0.04. Taken together, the three intervention groups display a highly significant decrease in occurrence of GI cancer. The folic acid group showed obvious improvements in gastric mucosal lesions, with more patients showing lesions reversed or stable atrophy and reversed intestinal metaplasia.
Conclusions: This trial shows a preventive effect of folic acid on
gastrointestinal cancers. A similar effect of beta-carotene was also observed. In addition folic acid may be valuable in the treatment of atrophic gastritis.
Zhu S, Mason J, Shi Y, Hu Y, Li R, Wang M, Zhou Y, Jin G, Xie Y, Wu G, Xia D, Qian Z, Song H, Zhang L, Russell R, Xiao S. Th e effect of folic acid on the development of stomach and other gastrointestinal cancers. Chinese Medical Journal 116 (1): 15-19, Jan 2003.

FUJIKI and colleagues, Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-Cho, Tokushima 770-8514, Japan, hfujiki@ph.bunri-u.ac.jp, reported on new cancer preventive agents from traditional herbal medicine.
Background: Herbal medicines are increasingly attracting attention as cancer preventive agents. This study identifies and describes two new agents, geraniin and corilagin.
Methods: The cancer preventive effects of various extracts of plants used in traditional herbal medicine were tested in several experiments using cells in culture.
Results: A leaf extract from Acer nikoense was found to inhibit tumour necrosis factor-alpha secretion. The active principles were geraniin and corilagin. The effective concentrations were in the same range as that of the active principle from green tea (EGCG) which has been known to act as a cancer preventive for some time. Geraniin was found to prevent the formation of skin tumours.
The authors further review recent results from studies with EGCG which has been found to be particularly effective in combination with the cancer preventive drugs tamoxifen and sulindac.
Conclusions: The authors urge strongly that the potential of traditional herbal medicines be investigated more closely for their cancer preventive effects.
Fujiki H, Suganuma M, Kurusu M, Okabe S, Imayoshi Y, Taniguchi S, Yoshida T. New TNF-alpha releasing inhibitors as cancer preventive agents from traditional herbal medicine and combination cancer prevention study with EGCG and sulindac or tamoxifen. Mutation Research 523-524: 119-125, Feb-Mar 2003.

MOTOHASHI and co-workers, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588, Japan, motohashi@my-pharm.ac.jp, have studied kiwi fruit extracts in the prevention and treatment of cancer.
Background: According to Chinese tradition, kiwi fruit is both a preventative and therapeutic agent against cancer.
Methods: Kiwi gold fruit were extracted successively with hexane, acetone, methanol, and 70% methanol, and further fractionated chromatographically on silica gel. These fractions were then used for bioassays.
Results: Five fractions (2 fractions of the hexane extract, 2 fractions of the acetone extract, and a fraction of the methanol extract) showed selective cytotoxic activity against human oral tumour cell lines. Several fractions of the 70% methanol extract showed anti-HIV activity, inhibited free radical generation and acted as radical scavengers. All fractions showed some antimicrobial activity, with more lipophilic fractions generally more active, although none of the fractions were active against Helicobacter pylori.
Conclusions: Gold kiwi fruit contains various valuable bioactive materials which can be separated from each other.
Motohashi N, Shirataki Y, Kawase M, Tani S, Sakagami H, Satoh K, Kurihara T, Nakashima H, Mucsi I, Varga A, Molnar J. Cancer orevention and therapy with kiwifruit in Chinese folklore medicine: a study of kiwifruit extracts. Journal of Ethnopharmacology 81 (3): 357-364, Aug 2002.

WARTENBERG and colleagues, Department of Neurophysiology, University of Cologne, Cologne, Germany, have shown that in cultured cells tumour-induced angiogenesis is inhibited by plant ingredients used in Traditional Chinese Medicine.
Background: The formation of new blood vessels (angiogenesis) is a prerequisite for excessive tumour growth. New blood vessels can only invade the tumour tissue after the extracellular protein scaffolding, the extracellular matrix, has been degraded by proteolytic enzymes called metalloproteinases (MMPs). It has therefore been suggested that if these MMPs were inactivated, the growth of solid tumours would be inhibited. In this study, antioxidant plant ingredients used in traditional Chinese medicines have been investigated for their capacity to inhibit MMPs.
Methods: The cells used were co-cultures of embryoid bodies and multicellular prostate tumour cell aggregates. The embryoid bodies transiently secreted MMPs. The secretion of MMPs was measured in the presence and absence of antioxidant ingredients, and also the formation of new blood vessels in the tumour cells.
Results: When the two cell types were cultured together, the secretion of MMPs was increased. This was due to reactive oxygen species produced by the tumour cells, and it was totally abolished by the reactive oxygen scavenger, Vitamin E. Incubation of the embyoid
bodies with baicalein, epicatechin, berberine, and acetoside, all herbal ingredients used in Traditional Chinese Medicine, significantly inhibited angiogenesis in tumour cells and decreased intracellular reactive oxygen levels. Tumour-induced angiogenesis in the tumour cells was totally inhibited by vitamin E.
Conclusions: The Chinese herbal ingredients tested show indeed a capacity to inhibit the growth of solid tumours. It is concluded that the production of MMPs necessary for new blood vessels to invade the tumour tissue is triggered by reactive oxygen species generated by the tumour.
Wartenberg M, Budde P, De Marees M, Gruenheck F, Tsang SY, Huang Y, Chen ZY, Hescheler J, Sauer H. Inhibition of tumour-induced angiogenesis and matrix-metalloproteinase expression in confrontation cultures of embryoid bodies and tumour spheroids by plant ingredients used in traditional Chinese medicine. Laboratory Investigation 83 (1): 87-98, Jan 2003.

Issue 89

SAMPSON, Stanford University School of Medicine, Stanford, CA, USA, reviews (46 references) controversies in cancer and the mind, particularly the effects of psychosocial support.
Background: Interest in effects of consciousness on health and illness has generated several lines of enquiry into the mind and cancer. In animal studies, some cancers were sensitive to hormonal and stress influences but these findings did not translate into humans. Major surveys found no relationship between stress and cancer generation or growth, such as were hypothesized to occur through neuro-immunologic mechanisms. The proposal of a typical ‘cancer personality’ was also not confirmed, and neither were initial observations that depression and stress affected cancer.
Results and conclusions: The last of these hypotheses to survive was that psychosocial support affected longevity and the course of cancer. Initial positive results were not confirmed, and it is concluded that psychosocial support may result in better adjustment and quality of life but does not directly affect the evolution of human cancer.
Sampson W . Controversies in cancer and the mind: effects of psychosocial support. Seminars in Oncology 29 (6): 595-600, Dec 2002.
Comments: These are complicated issues not easily studied nor results readily generalized into the huge numbers of people developing cancer over their lifetime. One cannot ignore the large body of evidence already established regarding Psychoneuroimmunology nor dismiss the potential links between stress, personality and cancer; however, there is a fine line between positing these relationships and cancer patients ending up blaming themselves for causing their cancer or not curing it successfully.

BAGGA and colleagues, Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095, USA, have described polyunsaturated essential fatty acids in breast adipose tissue from women with and without breast cancer.
Background: Animal studies suggest that polyunsaturated fatty acids of the omega-6 class (n-6 class), found in corn and safflower oil, may give rise to metabolites that promote the development of mammary tumours, whereas omega-3 (n-3) polyunsaturated fatty acids, found in fish oils, can inhibit these effects. This study was designed to examine the relationship between the polyunsaturated fatty acids found in breast fatty tissue and the risk of breast cancer; specifically to test the hypothesis that breast cancer is positively associated with the content of linoleic acid and arachidonic acid, and negatively correlated with the content of eicosapentaenoic and docosahexaenoic acids in breast adipose tissue.
Methods: Breast adipose tissue was collected from 73 breast cancer patients and 74 controls with macromastia. The fatty acid levels were determined using gas-liquid chromatography. A logistic regression model was used to obtain odds ratio estimates.
Results: The age-adjusted n-6 polyunsaturate content was significantly higher in cancer patients than in controls (p = 0.02). There was a trend in the data suggesting that, at a given level of n-6 polyunsaturates, n-3 polyunsaturates may have a protective effect (p = 0.06).
Conclusions: Total n-6 polyunsaturated fatty acids may be contributing to breast cancer in the USA, and n-3 polyunsaturated fatty acids, found in oily fish, may have a protective effect
Bagga D, Anders KH, Wang HJ, Glaspy JA. Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer. Nutrition and Cancer 42 (2): 180-185, 2002.

NI and colleagues, Department of Urology, University of Rochester, Rochester, NY 14642, USA, have found that vitamin E succinate inhibits human prostate cancer cell growth by modulating cell cycle regulating machinery.
Background: Several studies have shown that vitamin E is a chemopreventive agent for prostate cancer. alpha-Tocopheryl succinate, a close derivative of vitamin E, modulates cancer cell growth, but little is known about how this happens.
Results: It is shown that vitamin E succinate causes human prostate cancer cell LNCaP to arrest during its G1 phase. This is accomplished through significantly decreased production of the cell cycle regulatory proteins cyclin D1, D3, and E, as well as cdk2 and 4 but not 6. Furthermore, vitamin E succinate reduces cdk4 kinase activity, Rb phosphorylation, and cyclin E messenger RNA production. It is also shown that selenium acts by a different mechanism to prevent prostate cancer.
Conclusions: These results suggest that the vitamin E-mediated preventive effect against prostate cancer is a consequence of multiple alterations in the cell cycle regulatory machinery.
Ni J, Chen M, Zhang Y, Li R, Huang J, Yeh, S. Vitamin E succinate inhibits human prostate cancer cell growth via modulating cell cycle regulatory machinery. Biochemical and Biophysical Research Communications 300 (2): 357-363, Jan 10, 2003.

SHANNON and colleagues, Portland VA Research Foundation, Oregon 97201, USA, shannoja@ohsu.edu, have investigated the dietary risk factors for cervical carcinoma in Bangkok, Thailand.
Background: Although infection with the human papilloma virus appears to be a necessary condition for the development of cervical cancer, most women infected with this virus do not in fact develop the disease. It seems reasonable to assume that there must be co-factors involved in the growth of cervical carcinoma. This study was conducted in order to assess the possible effects of dietary factors.
Methods: A total of 184 inpatients with cervical cancer and 509 controls were recruited from clinics associated with the Siriraj hospital in Bangkok. They were administered a food frequency questionnaire and tested for human papilloma virus DNA in cervical cells. Odds ratios in relation to intake of foods high in vitamin C, folate, vitamin E, vitamin A, beta-carotene, retinol, and cruciferous vegetables were estimated. Logistic regression in case-control comparisons and in case-case comparisons adjusted for papilloma virus status was used.
Results: High intake of foods rich in vitamin A, and particularly high retinol foods, were associated with a reduced risk of in-situ cervical cancer and also, albeit less strongly, with a reduced risk of invasive as compared to in-situ cervical carcinoma. No association was found between the risk of cervical cancer and any of the other foods tested.
Conclusions: Increasing intake of foods high in vitamin A, particularly retinol (a form of vitamin A), may reduce the risk of in-situ cervical cancer, and at highest intake levels, reduce the risk of progression to invasiveness. If these results are confirmed by other researchers, they suggest a possible public health strategy to reduce the incidence of cervical cancer.
Shannon J, Thomas DB, Ray RM, Kestin M, Koetsawang A, Koetsawang S, Chitnarong K, Kiviat N, Kuypers J. Dietary risk factors for invasive and in-situ cervical carcinomas in Bangkok, Thailand. Cancer Causes and Control 13 (8): 691-699, Oct 2002.

TOKUDOME and co-workers, Department of Health Promotion and Preventive Medicine, Nagoya City University Graduate School of Medical Sciences, Japan, tokudome@med.nagoya-cu.ac.jp, present the rationale and study design of dietary intervention in patients operated for tumours of the colorectum.
Abstract: The authors have implemented a randomized controlled dietary intervention in patients who have undergone polypectomy for tumours of the colorectum, in order to elucidate potential benefits of n-3 polyunsaturated fatty acids on the development of colorectal tumours. Individuals in the experimental group were advised not only to decrease their total intake of fatty and oily foods, specifically those containing n-6 polyunsaturated fatty acids, but also to increase specifically foods containing n-3 polyunsaturated fatty acids. Those in the control group were cautioned to reduce their total fat intake. Patient compliance and adherence to advice was assessed with a semi-quantitative food frequency questionnaire, and also by measuring fatty acid concentrations in plasma, red blood cell membranes, and sigmoid colon samples. For endpoints to assess tumour suppressive effects of n-3 polyunsaturated fatty acids, the number/multiplicity, sizes and incidence of colorectal tumours were compared between experimental and control group after 12 and 24 months. On the specified assumption, the number of pairs needed for statistical significance was calculated to be approximately 60-80. A randomized controlled trial is under way to secure sufficient patient numbers, sustain compliance and minimize dropouts.
Tokudome S, Yokoyama K, Kamiya T, Seno K, Okuyama H, Kuriki K, Cheng J, Nakamura T, Fujii T, Ichikawa H, Itoh M. Rationale and study design of dietary intervention in patients polypectomized for tumours of the colorectum. Japanese Journal of Clinical Oncology 32 (12): 550-553, Dec 2002.
Comments: The above research studies demonstrate the considerable evidence accumulating regarding the therapeutic benefits of vitamins A, C and E and various essential fatty acids in the prevention and treatment of a number of cancers.

Issue 88

SLOMAN, The Hebrew University, School of Nursing, Jerusalem, Israel, sloman@netvision.net.il, reports a trial of relaxation and imagery for anxiety and depression control in cancer patients.
Background: The aim of the trial was to compare the effects of progressive muscle relaxation and guided imagery on anxiety, depression, and the quality of life in people with advanced cancer.
Methods: In this community-based study, 56 people with advanced cancer were recruited in Sidney, Australia. All were experiencing anxiety and depression. They were randomly assigned to four groups:1) progressive muscle relaxation training; 2) guided imagery training; 3) both of these treatments; and 4) no treatment. Anxiety, depression, and quality of life were assessed before and after treatment using the Hospital Anxiety and Depression scale and the Functional Living Index-Cancer scale.
Results and conclusions: There was no significant improvement for anxiety found, but significant positive changes occurred for depression and quality of life.
Sloman R. Relaxation and imagery for anxiety and depression control in community patients with advanced cancer. Cancer Nursing 25 (6): 432-435, Dec 2002.

LIVINY and co-workers, Institute of Biochemistry, Food science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel, have found that lycopene inhibits proliferation and enhances gap junctional communication in KB-1 human oral tumour cells.
Background: Cell to cell communications via gap junctions is considered to be a key factor in tissue homeostasis, and its alteration is associated with cancer. Experimental and epidemiological data suggest that carotenoids, particularly lycopene and beta-carotene, can reduce the risk of certain cancers. The purpose of this study was to assess whether these compounds interact at some stage with the carcinogenesis process.
Methods: KB-1 cells from a human oral cavity tumour were incubated in culture with different concentrations of lycopene or beta-carotene.
Results: Lycopene strongly and in a dose-dependent manner inhibited proliferation of KB-1 cells. beta-Carotene was a far less efficient inhibitor of the proliferation of these cells. Lycopene significantly upregulated both the transcription and the expresion of connexin-43, a gap junction protein. beta-Carotene tended to upregulate connexin-43 expression. Gap-junctional communication was measured by dye transfer and electron microscopy showed that lycopene enhanced gap-junctional communication between the cancer cells, whereas beta-carotene was less effective. beta-Carotene was avidly and rapidly incorporated into KB-1 cells, whereas lycopene uptake into cells took place only after longer incubation periods and at high concentrations.
Conclusions: The present study supports the hypothesis that carotenoids in general, and lycopene in particular, may be effective anticarcinogenic agents in oral cancers.
Liviny O, Kaplan I, Reifen R, Polak-Charcon S, Madar Z, Schwartz B. Lycopene inhibits
proliferation and enhances gap-junction communication of KB-1 human oral tumor cells. The Journal of Nutrition 132 (12): 3754-3759, Dec 2002.
Comments: Oral cancers have a fairly dismal prognosis and surgical treatments often interfere with appearance and functions such as speech, eating and digestion. Hence the importance of following up this research if lycopene may be an effective anticancer agent.

COHEN and colleagues, American Acupuncture Center, Berkeley, CA, USA, review (69 references) traditional Chinese medicine in the treatment of breast cancer.
Abstract: Current recommendations for the treatment of breast cancer are based on the tenets of biology and pharmacology together with a growing body of evidence from the literature. Despite advances in conventional medical screening and treatments, there are limitations to their benefits, especially in advanced disease. Oriental medicine has enjoyed a rising popularity because it is less invasive and offers a more ‘natural’ approach to health and quality of life. Unfortunately definitive literature on these therapies is scant and has not been incorporated into mainstream medicine. Traditional Chinese Medicine (TCM) is a standardized system of diagnosis and therapy and can thus serve as a model for scientific inquiry. The holistic and individualized nature of TCM still presents formidable challenges to rigorous clinical testing, and as a result most published work in the field is in the form of anecdotal reports and uncontrolled studies. Among the components of TCM, herbal preparations possess complex biological activities that could affect many aspects of carcinogenesis. Many of these have been studied extensively. But few clinical trials have been conducted to test specific hypotheses regarding the mode of action of TCM. The studies highlighted in this review provide some evidence of safety but generally do not possess the design and results to verify clinical effectiveness. Nevertheless, the authors propose that the theory of TCM coupled with laboratory studies can serve as a basis for the design of more definitive trials or TCM for breast cancer. Some existing treatment
initiatives in the area of breast cancer prevention and treatment are outlined.
Cohen I, Tagliaferri M, Tripathy D. Traditional Chinese medicine in the treatment of breast cancer. Seminars in Oncology 29 (6): 563-574, Dec 2002.
Comments: Further clinical trials to discover how TCM may be useful both for prevention and treatment of breast cancer would be an extremely useful contribution to our knowledge base for breast cancer treatment.

OH and SMALL, Lank Center for Genitourinary Oncology, Department of Adult Oncology, Dana Faber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA, review (34 references) complementary and alternative (CAM) therapies for prostate cancer.
Background: Little is known about the efficacy of CAM therapies for prostate cancer.
Results and discussion: Epidemiological studies suggest a link between intake of certain micronutrients and prostate cancer, but there exist limited prospective data supporting a chemopreventative or anticancer value of these agents. One of the most studied treatments is PC-SPES, a combination of eight herbal therapies. Studies in cell lines of human prostate cancer demonstrate significant dose-dependent reductions in cell viability. Clinical studies yielded a reduction of prostate-specific antigen levels in patients with prostate cancer. Toxicity was mild although there was a low risk of thrombosis associated with the treatment.
Recently manufacture of PC-SPES has been halted after it became known that the herbal combination was contaminated with warfarin. Other contaminants were subsequently found.
The review also considers available data on other alternative therapies for prostate cancer.
Oh WK, Small EJ. Complementary and alternative therapies in prostate cancer. Seminars in Oncology 29 (6): 575-584, Dec 2002.

Issue 87

DUNWOODY and co-workers, University of Ulster, Jordanstown, County Antrim, Northern Ireland, reported on cancer patients’ experiences and evaluations of aromatherapy massage in palliative care.
Background: Aromatherapy is a popular choice for cancer patients wishing to make use of complementary therapies. Quantitative studies have shown that aromatherapy may reduce psychological distress and enhance symptom control in cancer patients. However little is known about personal meanings patients attach to the therapy.
Methods: A focus group interview was used to explore patients’ experiences of aromatherapy.
Results: Eight themes emerged from the analysis, six of which have been acknowledged to an extent by previous authors: De-stressing effects of aromatherapy, the counselling role of the therapist, aromatherapy as a reward, patient empowerment, communication through touch, and negative aspects of the service. Two apparently new themes emerged concerned with the safety of the context, and preconceived perceptions of the value of aromatherapy as a treatment of cancer patients.
Conclusions: The implications of these findings are discussed in relation to the perceived role of counselling, collaborative practice and training in complementary therapies.
Dunwoody L, Smyth A, Davidson R, et al. Cancer patients’ experiences and evaluations of aromatherapy massage in palliative care. International Journal of Palliative Nursing 8 (10): 497-504, Oct 2002.

LOUIS and KOWALSKI, Department of Nursing, University of Nevada, Las Vegas, USA, describe the use of aromatherapy with hospice patients to decrease pain, anxiety, and depression, and to promote an increased sense of wellbeing.
Background: This controlled study attempts to measure the effects of humidified lavender oil therapy in cancer patients.
Methods: 17 cancer patients were assessed for vital signs, and also for pain, anxiety, depression, and sense of wellbeing using 11-point verbal analog scales, on three different days before and after a 60-minute session consisting of either no treatment, water humidification , or humidification with a 3% solution of essential oil of lavender.
Results: A small positive change in blood pressure and pulse, pain, anxiety, depression and sense of wellbeing was found after either of the treatments. After the control session, a slight improvement in vital signs, depression, and sense of wellbeing but not in pain or anxiety was found.
Louis M, Kowalski SD. Use of aromatherapy with hospice patients to decrease pain, anxiety, and depression and to promote a sense of well-being. The American Journal of Hospice and Palliative Care 19 (6): 381-386, Nov-Dec 2002.

Comment: CAM therapies are often chosen by patients on the basis of personal preference and the meaning attached to a particular experience. This ensures that they enhance their own empowerment and benefit from the healing effects of physical pleasure and positive beliefs about the treatment. Often this is forgotten in evidence-based medicine, and studies like the above which explore personal experience of CAM users are to be highly welcomed.

Issue 86

ANGEN and colleagues, Department of Psychosocial Resources, Tom Baker Cancer Centre, Calgary, Alberta, Canada, introduce Tapestry, a retreat programme of support for persons living with cancer. This article describes the provision and preliminary evaluation of a residential retreat program called Tapestry which was developed in an effort to mitigate the negative psychological sequelae of a cancer diagnosis and treatment. Retreats offer psychosocial support for people living with cancer. They provide a respite and the opportunity to address the isolation and other existential issues arising from a cancer diagnosis. Tapestry has been provided six times a year since 1998. While the face value and demand for more holistic care programmess continues to grow, few residential psychosocial programs are offered under the auspices of conventional cancer care centres, and little has been done to evaluate their value as a forum for psychosocial care delivery.

Angen MJ, MacRae JH, Simpson JSA, Hundleby M et al. Tapestry: a retreat program of support for persons living with cancer. Cancer Practice 10 (6): 297-304, Nov-Dec 2002.

Comment: I have recently attended the Penny Brohn Memorial lecture, which was inspiringly delivered by Grace Adamson, who described the need to address and the therapeutic and clinical benefits of attending to cancer patients’ psychological/emotional/spiritual needs in an integrated approach. This event was attended by an awesome group of high-powered professionals from across the cancer-care spectrum, and so it is hoped that these ventures will spread their effects.

WANG and co-workers, Affiliated Hospital of Nantong Medical College, Nantong 226001, China, found an alteration of vitamin E levels in patients with pancreatic adenocarcinoma.

Background: The objective of this study was to investigate the alterations in vitamin E levels in patients with pancreatic adenocarcinoma and explore its mechanism of action.

Methods: A comparative analysis of serum vitamin E levels was conducted in patients with various pancreatic diseases.

Results: Patients with chronic pancreatitis, acute pancreatitis, and pancreatic adenocarcinoma all had significantly lower serum vitamin E levels than healthy controls. Amongst the three groups of pancreatic diseases, patients with carcinoma had significantly lower vitamin E levels than either of the other two disorders.

Conclusions: Significant reduction in vitamin E levels occurs in patients with pancreatic cancer. This suggests that oxidation and anti-oxidation imbalances might be involved in the pathogenesis of pancreatic adenocarcinoma.

Wang DF, Qu XC, Dai ZQ, et al. Alteration of vitamin E levels in patients with pancreatic adenocarcinoma. Ti I Chuen I Ta Hsueeh Hsueeh Pao 22 (3): 210-211, Mar 2002.

Issue 85

STANDISH and co-workers, University Research Institute, Kenmore, Washington, USA, describe naturopathic treatment for breast cancer in North America.

Background: The use of Complementary and Alternative Medicine (CAM) is rising in the US, especially for breast cancer patients. Typically it is delivered by licensed naturopathic physicians using individualized treatment plans.

Methods: A cross-sectional survey in two parts was mailed out to all licensed naturopathic physicians in the USA and Canada (1,356 practitioners). 642 completed the screening form (part 1 of the survey). Of these, 333 were eligible for part 2, a 13-page survey. Of these, 161 (48%) completed the survey. The main outcome measures were demographics of the participating naturopaths, development of treatment plans, CAM therapies used, and the perceived efficacy of treatment interventions.

Results: Of the survey respondents, 104 practised in the USA and 57 in Canada. 107 were women and 54 were men. In the development of naturopathic treatment plans, naturopaths most often considered the stage of cancer, the patient’s emotional constitution, and the conventional therapies used. To monitor patients, 64% of respondents used diagnostic imaging, 57% considered the patient’s quality of life, and 51% used physical examination. The most common CAM therapies used were dietary counselling (94%), herbal medicines (88%), antioxidants (84%), and nutritional supplements (84%). The most common specific agents prescribed were vitamin C (39%), coenzyme Q-10 (34%) and Hoxsey formula (29%).

Comments: The above survey points out the stark difference between cancer treatment regimes carried out by naturopathic as compared with allopathic physicians. A most vital piece of research that to my knowledge has been lacking for many decades is the comparison of outcomes of cancer patients using natural, non-cytotoxic treatments with those of patients subjected to the usual chemotherapy and radiotherapy cancer treatments. This type of research is almost impossible to conduct since it is illegal for cancer to be treated (by physicians) with any other treatments other than surgery, chemotherapy, radiation therapy or experimental drugs treatments. Many splendid and brilliant physicians who have pioneered alternative approaches have been subjected over the past century to the most brutal sanctions, including imprisonment, being struck off the medical register and exile.

VENKATESWARAN and colleagues, Division of Urology, Sunnybrook and Women’s College Health Science Centre, Toronto, Ontario, Canada, describe the modulation of cell proliferation and cell cycle regulators by vitamin E in human prostate carcinoma cells.

Background: Vitamin E has been put forward as a candidate for the prevention of prostate cancer. This effect may be in part due to inhibition of the cell cycle rather than only due to vitamin E’s action as an antioxidant. The study aimed to test whether vitamin E induces an arrest of the cell cycle mediated by alterations in cell cycle regulatory proteins including cyclin E, cdk2 and p27.

Methods: Cells in culture were incubated with and without alpha- tocopherol (vitamin E) succinate at 20 micrograms per millilitre, then fixed and stained with propidium iodide for flow cytometry analysis. In parallel experiments, total protein was extracted and analyzed immunologically with cyclin E antibodies for expression of cell cycle regulators.

Results: Flow cytometry revealed a dramatic reduction of percentage of cells in the S phase in response to vitamin E in two different cell lines (69% and 95%, respectively). This was accompanied by a 3-fold increase of the cell cycle regulator protein p27.

Conclusions: The study demonstrates that at physiological concentrations vitamin E induces profound cell cycle arrest mediated by up-regulation of p27. This observation provides a theoretical basis for the cancer prevention effect of vitamin E.

Venkateswaran V, Fleshner NE, Klotz LH. Modulation of cell proliferation and cell cycle regulators by vitamin E in human prostate carcinoma cell lines. The Journal of Urology 168 (4 Pt 1): 1576-1582, Oct 2002.

NAKAJI and colleagues, Department of Hygiene, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan, nakaji@cc.hirosaki-u.ac.jp, investigate the relationship between mineral and trace element concentrations in drinking water and stomach cancer mortality in Japan.

Background: The incidence and mortality from gastric cancer in Japan are the highest in the world. This is thought to be connected to dietary habits, particularly a high salt intake. The relationship between mineral and trace element intake and gastric carcinogenesis is however poorly researched.

Methods: Epidemiological study relating the concentrations of 14 elements in drinking water from 36 water treatment plants to the geographical distribution of gastric cancer mortality rates. Multiple regression analysis was performed.

Results: The relationship was found to be significant in men for zinc, lead, strontium, and selenium; in women it was significant for lead, strontium, and gold.

Conclusions: It is suggested that selenium and zinc may act to prevent gastric cancer. However there was no significant relationship observed between sodium and gastric carcinogenesis, although other studies have suggested such a link.

Nakaji S, Fukuda S, Sakamoto J, Sugawara K, Shimoyama T, Umeda T, Baxter D. Relationship between mineral and trace element concentrations in drinking water and gastric cancer mortality in Japan. Nutrition and Cancer 40 (2): 99-102, 2001.

JEDRYCHOWSKI and co-workers, Epidemiology and Proventive Medicine, Coll. Med. Jagellonian University, Cracow, Poland, describe the relationship between alcohol intake and the risk of colorectal cancer at low levels of micronutrient intake.

Background: The purpose of the study was to assess the relationship between alcohol consumption and simultaneous intake of micronutrients that may have a protective function against colorectal cancer.

Methods: Hospital-based case control study in Cracow, Poland. 180 cases of colorectal cancer were compared to an equal number of age-matched controls. A food frequency questionnaire covering 148 food items was used to assess typical dietary patterns.

Results: A consistent inverse association was found between the risk of colorectal cancer and the intake of retinol, thiamine or antioxidant micronutrients such as vitamins C and E or carotene. Furthermore, alcohol intake was found to be an important risk factor for colorectal cancer in a dose-dependent manner. The combination of high consumption of alcohol with deficient intake of retinol, carotene, and vitamins C and E shows a noticeably higher risk of colorectal cancer.

Conclusions: The data support the assumption that high alcohol consumption in combination with low intake of micronutrients increases considerably the risk of colorectal cancer.

Jedrychowski W, Steindorf K, Popiela T, Wahrendsorf J, Tobiasz AB, Kulig J, Penar A. Alcohol consumption and the risk of colorectal cancer at low levels of micronutriant intake. Medical Science Monitor 8(5): CR357-363, May 2002.

MALILA and colleagues, National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland, nea.malila@cancer.fi, investigate dietary and serum alpha-tocopherol, beta-carotene, retinol, and the risk of colorectal cancer in male smokers.

Background: The objective was to study the association between dietary and serum antioxidant vitamins and the risk of colorectal cancer in smoking men.

Methods: A prospective cohort study within a randomized placebo-controlled trial testing supplementation with alpha-tocopherol (50 mg/day), beta-carotene (20 mg/day) or both for their cancer prevention effects. 26,951 middle-aged male smokers took part in a cancer prevention trial with complete dietary and serum data available. Out of these, 184 were diagnosed with colorectal cancer during the 8 year follow-up. Relative risks were calculated with Cox proportional hazards models adjusting for trial supplementation, age, body mass index, serum cholesterol, cigarettes smoked per day, and physical activity.

Results: There was no significant association between dietary vitamin C or E, alpha- or gamma-tocopherol, retinol, alpha- or beta-carotene, lycopene or lutein + zeaxanthin and the risk of colorectal cancer. Serum alpha-tocopherol, beta-carotene, or retinol was also not associated with colorectal cancer risk.

Conclusions: These data support the results from previous studies in which no association between dietary antioxidant vitamins and carotenoids and the risk of colorectal cancer was found.

Malia N, Virtamo J, Virtanen M, Pietinen P, Albanes D, Teppo L. Dietary and serum alpha- tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers. European Journal of Clinical Nutrition 56 (7): 615-621, Jul 2002.

LIU et al., Food Engineering Research Center of State Education Ministry, Zhongshan University, Guangzhou 510275, People’s Republic of China, found antitumour activity of germinating spores of Ganoderma luicidum.

Background: To investigate a potential anticancer agent.

Methods: The inhibitory effects of dormant spores, germinating spores, sporoderm-broken germinating spores, and lipids extracted from the germinating spores of the fungus Ganoderma lucidum on the growth of mouse hepatoma, sarcoma S-180, and reticulocyte sarcoma L-II cells were measured.

Results: The sporoderm-broken spores showed much higher antitumour activity than whole spores. Lipid extracts had remarkable antitumour effects and inhibited three tumours with an inhibition of 89–90%.

Liu X, Yuan JP, Chung CK, Chen XJ. Antitumor activity of the sporoderm-broken germinating spores of Ganoderma lucidum. Cancer Letters 182 (2): 155-161, Aug 2002.

SALAZAR-MARTINEZ and colleagues, Center for Research in Population Health, National Institute of Public Health, Cuernavaca, Mexica, esalazar@correo.insp.mx, investigate nutritional determinants of ovarian cancer risk.

Background: In recent years, diet has been recognised as an important factor in the development of ovarian cancer even though results have not been consistent. This study evaluates dietary factors related to the risk of ovarian cancer in Mexican women.

Methods: Case-control study in a Social Security hospital in Mexico City, evaluating 84 new cases of ovarian cancer and 629 controls. A validated questionnaire with 116 items about food intake was used. Analysis of nutrients was performed with the residual method adjusted for total energy intake and other predictor variables through logistic regression methods.

Results: The nutrients negatively associated with risk of ovarian cancer were retinol and vitamin D. Carbohydrates were positively associated with risk of ovarian cancer, whereas tortilla intake did not show any association with ovarian cancer.

Conclusions: The diet of the Mexican population is typically rich in carbohydrates as corn is the main energy source. Vitamins such as retinol and vitamin D were shown to be associated with ovarian cancer in a way that suggests they can act as protectants.

Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez LLG, Escudero de los Rios P, Hernandez AM. Nutritional determinants of epithelial ovarian cancer risk: a case-control study in Mexico. Oncology 63 (2): 151-157, 2002.

SMITH and colleagues, University of Colorado Health Sciences Center, School of Nursing, Box C-288, 4200 East Ninth Avenue, Denver, CO 80262, USA. marlaine.smith@uchsc.edu, assessed the outcomes of therapeutic massage for cancer in-patients.

Background: The purpose of the study was to examine the effects of therapeutic massage on pain, sleep quality, symptom distress, and anxiety in patients hospitalized for cancer treatment.

Methods: Quasi-experimental controlled study with 41 patients admitted for cancer treatment receiving therapeutic massage, and 21 patients receiving a control therapy, nurse interaction. Variables measured before and after treatment were a numerical pain scale, a Likert-type scale measuring distress from pain, the Verran Snyder-Halpern Sleep Scale, McCorkle and Young’s Symptom Distress Scale, and the Spielberger State Anxiety Inventory. ANOVA and t-tests were used to analyse differences in mean scores within and between groups.

Results: Mean scores for pain, sleep quality, symptom distress, and anxiety improved from baseline in the treatment group; in the control group, only anxiety improved. Statistically significant interactions were found for pain, symptom distress, and sleep. Sleep improved only slightly in the treatment group but deteriorated significantly in the control group.

Conclusions: The study supports therapeutic massage as a valuable nursing tool for cancer patients receiving chemotherapy or radiation therapy.

Smith MC, Kemp J, Hemphill L, Vojir CP. Outcomes of Therapeutic Massage for Hospitalized Cancer Patients. Journal of Nursing Scholarship 34 (3): 257-262, 2002.

BARNETT and co-workers, Department of Surgery, Southern Illinois University School of Medicine, Springfield 62794, USA, find that vitamin E succinate inhibits liver metastases of colon cancer.

Background: Vitamin E Succinate (VES) shows promise as an anti-cancer nutrient. It is thought to promote the dormancy of colon tumours and inhibit liver metastases.

Methods: The effect of VES on colon cancer cells was measured both in vitro (in cultured colon cancer cells) and in vivo in an animal model. Cellular proliferation and apoptosis were measured. Correlation coefficients and independent t-tests were used for statistical analysis.

Results: VES significantly and specifically inhibited cell proliferation and promoted apoptosis of cancer cells in vitro. A reduction of liver metastases by 40% was found in vivo. Tumour cell apoptosis was significant, as was the inhibition of cell proliferation in vivo.

Conclusions: This is the first report of VES inhibition of colon cancer tumour metastases. VES inhibits the growth of colon cancer cells in vitro and in vivo. The mechanism of VES anti-tumour action appears to involve promotion of tumour cell apoptosis and inhibition of tumour cell proliferation. Further studies of Vitamin E Succinate as an agent to promote dormancy of colon cancer and prevent liver metastases are supported.

Background: Several studies on dietary antioxidant micronutrients (vitamins A, C, E, and beta-carotene) suggest protection against ovarian cancer that may be achieved by higher levels. No studies have, however, examined vitamin supplements.

Methods: A food frequency questionnaire with additional questions about supplements was used on 168 epithelial ovarian cancer patients, on 159 community controls, and on 92 hospital-based control patients. Antioxidant consumption from both diet and supplements was calculated.

Results: In multivariate analysis, the highest levels of total intake of vitamins C and E from supplements were protective; consumption of antioxidants from diet alone was unrelated to risk. The levels associated with protection against ovarian cancer were well above the current US Recommended Dietary Allowances: above 363 mg/day for vitamin C, and above 75 mg/day for vitamin E.

Conclusions: These findings support the hypothesis that the antioxidant vitamins C and E from supplements are related to a reduced risk of epithelial ovarian cancer.

Comment: That vitamin E succinate inhibits cell proliferation and promotes apoptosis of colon cancer cells, and that antioxidant vitamins C and E from supplements are protective against epithelial ovarian cancer are highly significant results. I sincerely hope that the EU and CODEX scientific committees read the results of such research while they contemplate eliminating such potentially life-saving supplements from consumer use.

FERNANDES-BANARES et al., Department of Gastroenterology, Hospital Universitari Germans Trias I Pujol, Badalona, Spain, assessed serum selenium levels and the risk of colorectal adenomas in a geographical region with low selenium status.

Background: Selenium is an essential nutrient that may have anticarcinogenic effects. Previous studies on possible relationships between serum selenium concentrations and colorectal adenomas have yielded controversial results. Here, the association of serum selenium status and large colorectal adenomas in subjects living in a poor selenium region was investigated.

Methods: Serum selenium levels were measured in 28 patients with large adenomatous polyps, 24 patients with colorectal adenocarcinomas, and 35 age-matched healthy individuals. Logistic regression analysis was performed after correcting for confounding variables.

Results: Among subjects under 60 years of age, significantly lower selenium levels were found in both patient groups (p = 0.0001). There were no differences in over-60s. Subjects with higher selenium status had a lower probability to be in the adenoma group than subjects with lower selenium status. This probability was more pronounced in subjects under 60 and not significant in older subjects.

Conclusions: The results suggest that high selenium status may decrease the risk of large adenomas in regions of low selenium in persons under 60. However the results will need to be confirmed in additional epidemiological studies before recommendations about selenium supplementation in patients with colon adenomas can be made.

Fernandez-Banares F, Cabre E, Esteve M, Mingorance MD, Abad-LacruzA, Lachica M, Gil A, Gassull MA. Serum Selenium and risk of large size colorectal adenomas in a geographical region with a low selenium status. The American Journal of Gastroenterology 97 (8): 2103-2108, Aug 2002.

KIM and MILNER, Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20892, USA, reviewed (66 references) the molecular targets for Selenium in cancer prevention.

Background: Selenium has anticarcinogenic and antitumourogenic properties, as revealed by mounting evidence. Unfortunately, the amounts needed to bring about these effects in humans remain elusive.

Results and conclusions: If there is a positive response to exaggerated selenium intakes, it will likely depend on a variety of factors such as consumption of other dietary constituents and variation in a host of genetic pathways involved with cancer. Several biological mechanisms are probably involved including depressed carcinogen bioactivation, reduced cell proliferation, and increased apoptosis.

Kim YS, Milner J. Molecular targets for selenium in cancer prevention. Nutrition and Cancer 40 (1): 50-54, 2001.

LODI et al., Dipartimento di Medicina Chirurgia e Odontaria, Universita degli Studi di Milano, Italia, E: giovanni.lodi@unimi.it, reviewed (38 references) randomized trials for the treatment of oral leukoplakia.

Background: Oral leukoplakia is a relatively common oral lesion that undergoes malignant transformation in varying proportions of cases. The aim of this review was to assess the effectiveness of treatments for leukoplakia.

Methods: Randomized controlled trials (RCTs) were identified by searching medical databases, hand-searching relevant specialist journals, and contacting oral medicine specialists throughout Europe. RCTs were assessed for quality on the basis of method of allocation concealment, blindness of the study, and loss of participants. Data were analyzed by calculating relative risk of malignant transformation which was the main outcome in the studies.

Results: Six studies were included in the review. Four tested vitamin A and retinoids; the other agents tested were bleomycin, mixed tea, and beta carotene. None of the treatments tested showed a benefit when compared to placebo. Treatment with beta carotene and vitamin A or retinoids was associated with better rates of clinical remission. It is noteworthy that the possible effectiveness of surgical interventions including laser therapy and cryotherapy has never been studied in an RCT.

Conclusions: To date there is no evidence of effective treatment preventing malignant transformation of oral leukoplakia.

Lodi G, Sardella A, Bez C, Demarosi F, Carrassi A. Systematic review of randomized trials for the treatment of oral leukoplakia. Journal of Dental Education 66 (8): 896-902, Aug 2002.

CURRIER and MILLER, Department of Anatomy and Cell biology, McGill University, Montreal, Quebec, Canada, studied the effect of immunization with killed tumour cells, with and without feeding of Echinacea purpurea, on erythroleukaemic mice.

Background: Tumour amelioration through immunization/vaccination is a practice for which experimental and clinical support is growing. Combination therapies prove to be more efficient than treatment with single agents.

Methods: Extract of E. Purpurea, a natural killer cell stimulant, was fed for periods of 9 days or 3 months after the onset of leukaemia to mice which had been immunized 5 weeks earlier with killed leukaemia cells.

Results: Immunized mice had a significantly prolonged life-span compared to non-immunized mice. An even greater proportion of mice in the E. purpurea group survived. Natural killer cells were very significantly elevated in mice receiving E. purpurea extract.

Conclusions: The results demonstrate that combination therapy involving specific tumour cell immunization followed by daily phytotherapy sensitized the immune cells and led to greatly enhanced life span as compared to immunization alone.

Currier NL, Miller SC. The effect of immunization with killed tumor cells, with/without feeding of Echinacea purpurea in an erythroleukemic mouse model. The Journal of Alternative and Complementary Medicine 8 (1): 49-58, Feb 2002.

Issue 82

COHEN, of the American Heart Foundation, Valhalla, New York 10595, USA, Lcohen@AHF.org, reviewed (75 references) the literature regarding the influence of nutrition on prostate cancer. A combination of epidemiological studies, animal model and in vitro experiments was reviewed.

Background: Little is known about the aetiology of prostate cancer, and treatment of advanced forms of the disease has had limited success.

Discussion: Natural components of the diet including n-3 PUFA, lycopene (a carotenoid), and the trace element selenium, may serve as chemoprotective agents that suppress the growth and dissemination of cancerous prostate cells. Soy isoflavones should however be regarded with caution as adjuvants to chemotherapy until further study. It is suggested that future studies should focus on different forms and doses of selenium and tomato carotenoids.

Comments: As the majority of surgical treatments available for prostate cancer have the possibility of dire side effects, progress using treatment with nutritional elements need to be speedily implemented into current oncology treatment programmes.

MURRAY and coworkers, Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555-1048, USA, further evaluated the role of the enzyme protein kinase C beta-II in colon carcinogenesis.

Background: These researchers have previously shown that colonic protein kinase C beta-II is induced during colon carcinogenesis in humans and rodents, and that elevated levels of the enzyme in transgenic mice enhanced colon carcinogenesis.

Methods: Investigation of transgenic mice as animal model.

Results: It was shown that dietary omega-3 fatty acids inhibit colonic protein kinase C beta-II and block the associated enhanced carcinogenesis.

Conclusion: These data indicate that dietary omega-3 fatty acids prevent colon cancer, at least in part, through inhibition of protein kinase C beta-II signalling pathways.

JAMISON and colleagues, Department of Urology, Summa Health System/Northeastern Ohio Universities College of Medicine, 2209 State Route 44, P. O. Box 95, Rootstown, Ohio 44272-0095, USA, jmj@neoucom.edu, reviewed (68 references) the antitumour activity of Vitamins C and K3 by preferential killing of tumour cells by autoschizis, a novel type of necrosis.

Background: Vitamin C and Vitamin K3, administered at a ratio of 100:1, show synergistic antitumour activity and preferentially kill tumour cells by autochizis. This type of cell death is characterized by exaggerated membrane damage and progressive loss of cytoplasm. The cell nucleus becomes smaller, cell size decreases, and most organelles surround the nucleus in a narrow band of cytoplasm. There appears to be a G1/S block in the cell cycle, diminished DNA synthesis, and increased hydrogen peroxide levels.

Discussion: The crucial factor in autoschizis is believed to be high levels of oxidative stress, inducing elevated calcium levels and activating DNAse I and DNAse II, thus leading to DNA degradation in the tumour cells. Recent experiments indicate that Vitamins C and K3 increase the lifespan of tumour-bearing mice and reduce the growth rate of solid tumours without any significant toxicity.

BRIVIBA and colleagues, Institute of Nutritional Physiology, Federal Research Centre for Nutrition, Karlsruhe, Germany, analysed the mechanism by which beta-carotene (Vitamin A) inhibits growth of cancer cells.

Background: Epidemiological studies indicate that beta-carotene is able to modulate the risk of cancer. It has been reported to inhibit the growth of cancer cells, but little is known about the molecular mechanisms of this effect.

Methods: beta-Carotene was added to human colon carcinoma cells in culture, and the cells were assayed for apoptosis using the Annexin-V assay.

Results: In confluent cells, beta-carotene showed only low cytotoxic effects in concentrations up to 30 micromolar. However in growing cells, similar concentrations of beta-carotene were strongly cytotoxic and induced apoptosis. Exposure of cells to retinol, a derivative of beta-carotene, showed no such effects.

Conclusion: beta-Carotene at dietary relevant concentrations can inhibit growth of human colon carcinoma cells in vitro by inducing apoptosis in proliferating cells.

HOSTANSKA and colleagues, Department of Internal Medicine, University Hospital Zürich, Switzerland, analysed the anticarcinogenic activities of total extracts of fresh versus dried Hypericum perforatum (St. John’s wort) on human tumour cells in vitro, and compared these activities in the dark and after exposure to white light illumination.

Background: Hypericum p. extracts are effective in the treatment of mild-to-moderate depression. Further, the component hypericin demonstrates light-dependent cell toxicity (phototoxicity) and can be used in the form of phototherapy as an anticancer agent.

Methods: The tumour cells examined were K562, U937 (leukaemia cells lines) and LN229 glioblastoma cell lines. Effects of the Hypericum p. extracts and of hypericin in the dark and after exposure to 7.5 J/cm2 white light illumination were compared with those on normal human astrocytes (NHAs). Toxicity was assessed by calculation of LC50 values, and growth retardation by calculation of GI50 values. The mechanism of cytotoxicity/growth inhibition was determined by examining treated tumour cells under the light microscope and also by investigating phosphatidylserine exposure on the outer plasma membrane using Annexin-V binding with flow cytometry after 24 hours. Finally, the hyperforin contents of fresh versus dried Hypericum p. extracts were compared and evaluated with respect to their growth inhibition activities both in the dark and after white light exposure.

Results: Non-illuminated Hypericum p. extracts showed low cytotoxicity: the LC50 was between 1.9 and 4.1 mg/ml (corresponding to 10.3-17.3 M hypericin and 114.4-190.7 M hyperforin) after 48 hours of treatment. However, non-illuminated Hypericum p. extracts did show dose-dependent growth inhibition of tumour cells: the GI50 values for the fresh and dried plant extracts respectively were 0.43-1.77 mg/ml (2.3-9.7 M hypericin, 26.1-106.7 M hyperforin) and 0.59-3.03 mg/ml (2.5-12.8 M hypericin, 24.2-124.7 M hyperforin). Fresh Hypericum p. extracts showed more potent growth inhibition of the leukaemia cell lines K562 and U937 than of LN229 cells or NHAs: the GI50 values were about 7-fold lower than the corresponding LC50 values for K562 and U937 cells, but were almost the same as the LC50 values for LN229 cells and NHAs. After 48 hours’ treatment, GI50 values for K562 and U937 cells were 432 and 799 g/ml respectively, compared with 1767 and 2900 g/ml respectively for LN229 cells and NHAs (p<0.05). Light-exposed Hypericum p. extracts showed greater cytotoxicity and growth inhibition than non-illuminated extracts: LC50 and GI50 values were reduced to values that corresponded with LC50 and GI50 values for phototoxic hypericin of 3.7-7.4 and 1.3-3.5 M respectively. Light exposure also increased the growth inhibition activity of Hypericum p. extracts on glioblastoma LN229 cells: after light exposure, the GI50 for LN229 cells was 582 g/ml compared with 1050 g/ml for NHAs (p=0.006). Light microscopic examination of treated tumour cells and Annexin-V binding studies confirmed that Hypericum p. extracts caused apoptosis (‘programmed cell death’) of cells in the absence of illumination. Fresh Hypericum p. extracts were found to contain 47% more hypericin than dried extracts, and the GI50 values for non-illuminated fresh plant extract in K562, U937 and LN229 cell lines respectively were 73%, 77% and 58% of those of the dried extract (p<0.05). Under 7.5 J/ cm2 white light illumination, fresh and dried Hypericum p. extracts displayed similar growth inhibitory and cytotoxic effects; this was a result of the phototoxic activity of hypericin (corresponding concentrations being in the range 1.3-3.5 M).

Conclusion: Hypericum p. extracts show growth inhibition and cytotoxic (apoptotic) activities that are not dependent on light exposure; however, light exposure potentiates these activities. The constituent hyperforin appears to be at least partly responsible for these effects in the dark.

MA and coworkers, Department of Biochemistry, Center for Biopharmaceutical Research and State Key Laboratory for Biocontrol, College of Life Science, Zhongshan University, Guangzhou, Peoples Republic of China, tested the possible cytotoxic effects of a constituent (isoliquiritigenin) of the traditional Chinese herb licorice on human stomach cancer cells in vitro.

Background: There is evidence that the traditional Chinese herb licorice has anti-tumour effects and the main constituent responsible for this action may be isoliquiritigenin.

Methods: The effects of isoliquiritigenin were examined in vitro in cultured human gastric cancer MGC-803 cells. Analytical methods included flow cytometry and fluorescent probes (Fluo-3 and Rh123). Evidence of cell death (apoptosis) including effects on membrane potentials, mitochondria, intracellular free calcium concentration and molecular structure were investigated.

Results: