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Cancer

Issue 47

REINHARDT, Ambulanz fur Hamatologie und Onkologie, Klinikum Bayreuth, Germany studied the influence of musical rhythm upon synchronisation and coordination of heart rate in cancer patients with chronic pain.
Methods: The author conducted a randomised pilot study with 28 patients suffering chronic cancer pain in a stable phase of cancer. The intervention was a 14-day training of a relaxation therapy for improving falling asleep, which included a 30-minute lullaby-like, rhythmically dominated music with gradually decreasing tempi. The control group received no training. The outcome measures included continuous registration of heart rate and its comparison with musical beat on day 1 and 15; analysis of the degree of synchronisation – coordination of systole and musical central time point; time of falling asleep and the patient’s subjective evaluation of the relaxation therapy and pain intensity.
Results: Patients in the relaxation group showed an increasing synchronisation and coordination of heart rate and musical beat. At a tempo of between 48 and 42 beats per minute there occurred a very stable 2:3 synchronisation. Those patients reporting the best relaxation and analgesic effects showed the most synchronisation. Relaxation therapy led to an improvement of falling asleep and a decrease in consumption of analgesics.
Conclusions: Lullaby-like music within a specific range of tempi may induce a trainable synchronisation of heart rate, associated with the formation and intensity of a relaxation reaction. Although further investigations are promising, substantial improvement in the methodology and documentation of these effects are required.
Reinhardt U. Investigations into synchronisation of heart rate and musical rhythm in a relaxation therapy in patients with cancer pain. Forschende Komplementaermedizin 6(3): 135-41. Jun 1999.

NIWA and colleagues, Department of Obstetrics, Gifu University School of Medicine, Japan. Kniwa@cc.gifu-u.ac.jp studied, in mice, the effects of Glycyrrhizae radix (G1 radix) upon endometrial cancer.
Methods: Levels of mRNA and oncoproteins induced by oestrodiol-17 beta (E2) were assayed by reverse transcription-polymerase chain reaction and Southern blot analysis and immunohistochemical methods. For long-term assays, 98 female mice were given N-methyl-N-nitrosourea (MNU) (1 mg100 g body wt) and normal saline (as controls) into left and right uterine corpora. They were divided into 4 groups: 1) 0.625% G1 radix- and 5 ppm E2-containing diet; 2) 5 ppm E2-containing diet; 3) 0.625) G1 radix-containing diet; and 4) basal diet alone.
Results: 2 weeks of G1 radix treatments decreased levels of c-fos/jun mRNA and corresponding oncoproteins induced by E2. G1 radix treatment significantly decreased uterine weights and incidences of uterine endometrial atypical hyperplastic and malignant lesions.
Conclusions: G1 radix possesses inhibitory effects upon E2-related endometrial cancer in mice, mediated the suppression of oestrogen-induced expression of c-fos/jun genes.
Niwa K et al. Preventive effects of Glycyrrhizae radix extract on estrogen-related endometrial carcinogenesis in mice. Japanese Journal of Cancer Research 90(7): 726-32. Jul 1999.

Issue 46

GONZALEZ and ISAACS conducted a 2-year, unblinded, 1-treatment arm, 10-patient, pilot prospective case study to study the effects of proteolytic enzymes, diet, nutritional supplements and detoxification procedures to treat patients with inoperable stage II-IV pancreatic cancer.
Methods: From January 1993 to April 1996 10 patients with inoperable, biopsy-proven pancreatic adenocarcinoma were entered into the trial which took place from the authors’ private practice. The patients were treated with large doses of orally ingested pancreatic enzymes, nutritional supplements, detoxification procedures and an organic diet. An 11th patient was added to the study after a patient dropped out. All 11 patients are considered in the data tabulation. Patients followed the treatment at home, under the supervision of the authors.
Results: As at 12 January 1999, of the 11 patients entered into the study, 9 (81%) survived one year, 5 (45%) survived two years, and at this time 4 have survived three years. Two patients are alive and doing well: one at three years, the other at 4 years. These results are far above the 25% survival at one year and 10% survival at two years for all stages of pancreatic adenocarcinoma reported in the National Cancer Data Base from 1995.
Conclusions: The results of this pilot study suggests that an aggressive nutritional therapy with large doses of pancreatic enzymes may lead to significantly increased survival over what would normally be expected for patients with inoperable pancreatic adenocarcinoma.
Gonzalez NJ and Isaacs LL Evaluation of pancreatic proteolytic enzyme treatment of adenocarcinoma of the pancreas, with nutrition and detoxification support. Nutrition and Cancer 33(2): 117-24. 1999.

Comments: The above results are truly astonishing and should be read as headlines throughout the world. 81% of Gonzalez and Isaacs’ patients survived one year as compared to only 25% of patients who normally survive for one year, and that 45% survived 2 years, compared to merely 10% in the usual statistics! Although this is a small study, for those patients whose lives were and are being prolonged, this is highly significant. Let us now see the funds required to properly research this protocol!

BOHLKE and colleagues, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115 USA write that although several dietary compounds are hypothesised to have anticarcinogenic properties, the role of specific micronutrients in the development of breast cancer remains unclear. The authors conducted an assessment from a case-control study in Greece regarding intake of vitamins A, C and E and beta-carotene in relation to breast cancer risk.
Methods: 820 women with histologically confirmed breast cancer were compared with 1548 control women. Dietary data were collected via a 115-item semiquantitative food frequency questionnaire and modelled by logistic regression, adjusting for total energy intake and established breast cancer risk factors, as well as mutual adjustment among the micronutrients.
Results: Among premenopausal women, beta-carotene, vitamins C and E were inversely associated with breast cancer risk. However, after mutual adjustment among the three nutrients, only beta-carotene remained significant; odds ratio (OR) for a one-quintile increase in beta-carotene intake was 0.84.
Discussion: The inverse association between beta-carotene intake and breast cancer risk was, however, slightly weaker than the previously observed association with vegetable intake within the data, raising the possibility that the observed beta-carotene effect is accounted for by another component of vegetables.
Bohlke K et al. Vitamins A, C and E and the risk of breast cancer: results from a case-control study in Greece. British Journal of Cancer 79(1): 23-9. Jan 1999.

BAKER and colleagues, Department of Pharmacology and Toxicology, College of Pharmacy, and Department of Chemistry, University of Arizona, Tucson, Arizona 85721-0207 USA write that recent intervention trials reported that smokers given dietary beta-carotene supplementation demonstrated an increased risk of lung cancer and overall mortality. Beta-carotene has been proposed to promote lung cancer by acting as a prooxidant in the smoke-exposed lung.
Methods: The authors examined the interactions of cigarette smoke with beta-carotene in model systems.
Results: Both whole smoke and gas-phase smoke oxidised beta-carotene in toluene to several products, which included carbonyl-containing polyene chain cleavage products and beta-carotene epoxides. A major reaction product was 4-nitro-beta-carotene, both cis and all-trans isomers, formed by nitrogen oxides in smoke. The hypothesis that smoke-driven beta-carotene auto-oxidation exerts prooxidant effects was tested in a liposome system. Lipid peroxidation in liposomes exposed to gas-phase smoke was modestly inhibited by the incorporation of 0.1 mol % beta-carotene. Both the lipid soluble antioxidant alpha-tocopherol and the water soluble antioxidant ascorbate were oxidised more slowly by gas-phase smoke exposure in liposomes containing beta-carotene.,
Conclusions: These data demonstrate that beta-carotene exerts weak antioxidant effects against smoke-induced oxidative damage in vitro. It is unlikely that a prooxidant effect of beta-carotene occurs under biologically relevant conditions or is responsible for the increased lung cancer incidence in the smokers who consumed beta-carotene supplements.
Baker DL et al. Reactions of beta-carotene with cigarette smoke oxidants. Identification of carotenoid oxidation products and evaluation of the prooxidant/antioxidant effect. Chemical Research in Toxicology 12(6): 535-43. Jun 1999.

Comments: One more piece of the puzzle in the ongoing saga of beta-carotene and cigarette smoke.

RAO and colleagues, Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada. V.rao@utoronto.ca write that tomatoes and tomato products containing lycopene the antioxidant carotenoid, have been shown in recent studies to reduce the risk of cancer. The authors conducted a study to investigate the serum and prostate tissue lycopene and other major carotenoid concentrations in cancer patients and controls.
Methods: 12 prostate cancer patients and 12 age-matched controls participated in the study. Serum lipid and protein oxidation was measured, along with lycopene and carotenoid levels.
Results: Compared to the controls, significantly lower serum and tissue lycopene levels (44%, and 78%) were observed in cancer patients. Serum and tissue beta-carotene and other major carotenoids did not differ between the two groups. Serum protein thiol levels were significantly lower in cancer patients, although there was no difference in serum lipid peroxidation between the groups.
Conclusions: The results of this study demonstrates that the status of lycopene but not other carotenoids in prostate cancer patients is different from controls. The role of dietary lycopene in preventing oxidative damage of biomolecules and thereby reducing prostate cancer risk should be assessed in future studies.
Rao AV et al. Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study. Nutrition and Cancer 33(2): 159-64 1999.

SCHWARTZBAUM and colleagues, The Ohio State University, College of Medicine and Public Health, and Comprehensive Cancer Center, Columbus, Ohio 43210 USA Schwartzbaum.1@osu.edu conducted a pilot study to investigate the relationship between dietary energy, cured meat and vitamin E in glioma (malignant growth) development.
Methods: The authors sought to determine whether: 1) high levels of energy intake increased glioma risk; 2) the relationship between cured meat consumption and glioma risk can be attributed to confounding by energy intake; and 3) alpha-tocopherol modifies caloric intake and gamma-tocopherol modifies cured meat consumption. The authors identified 40 age-sex-race matched glioma sets and obtained serum vitamin C and alpha- and gamma-tocopherol levels for 23 of these sets.
Results: Glioma risk increased with quartile of total dietary energy, following adjustments for fat, protein and nitrite-containing meat consumption.
Discussion: Although positive associations between individual cured meats and glioma risk decreased when adjusted for caloric intake, the small sample size makes it difficult to confidently interpret the results. Serum alpha-tocopherol appears to modify the effect of calories and gamma-tocopherol may modify the effect of cured meat upon glioma risk. Although the observed interaction is predicted by experimental research, these findings are based upon small numbers, and larger studies are required to further evaluate these preliminary findings.
Schwartzbaum JA et al. Hypotheses concerning roles of dietary energy, cured meat, and serum tocopherols in adult glioma development. Neuroepidemiology 18(3): 156-66. 1999.

Issue 45

HUANG and colleagues, Graduate Institute of Medicine and School of Technology for Medical Sciences, Kaohsiung Medical College, Taiwan, Republic of China studied the association between oxidative stress and trace elements in women with breast cancer.
Methods: Malondialdehyde (MDA) was determined in serum of breast cancer patients (n = 35) and controls (n = 35) using high performance liquid chromatography (HPLC); trace elements by atomic absorption spectrophotometry.
Results: There was significantly increased lipid peroxidation in the serum of the breast cancer patients; concentrations of zinc and iron remained unchanged. Compared with the control group, however, the mean level of serum copper in breast cancer was significantly higher. Also, the mean serum selenium level in stage III breast cancer patients was significantly lower than in the control group and a positive correlation was observed between copper and MDA levels in the breast cancer patient group but not in the controls.
Conclusions: The present results demonstrate an association between oxidative stress and trace elements in breast cancer patients. The increased oxidative stress may be the result of changes in the levels of certain trace elements.
Huang YL et al. Association between oxidative stress and changes of trace elements in patients with breast cancer. Clinical Biochemistry 32(2): 131-6. Mar 1999.

Comments: The above research demonstrates the current research intensity devoted to understanding the causes of major cancers such as prostate and breast cancers. Included in these research studies are considerable efforts regarding diet and nutritional factors.

Issue 44

BURSTEIN and colleagues, Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115 USA analysed the use of alternative medicine by women who had received standard therapy for early-stage breast cancer and who had been diagnosed between September 1993 and September 1995.
Methods: 480 women with newly diagnosed early-stage breast cancer were recruited from a state-wide cohort of women participating in a study of how women choose cancer treatment. Alternative medical treatments, conventional therapies and health-related quality of life were evaluated.
Results: New use of alternative medicine following breast cancer surgery was reported by 28.1% of women. This use was not associated with choices regarding standard medical therapies. 10.6% of the women had used alternative medicine prior to breast cancer diagnosis. The women who initiated the use of alternative medicine following surgery reported a worse quality of life then women who had never used alternative medicine. The mental health scores were similar at baseline between the two groups of women; however, 3 months following surgery, the use of alternative medicine was independently associated with depression, fear of recurrence of cancer, lower scores for mental health and sexual satisfaction, more physical symptoms as well as symptoms of greater intensity. All groups of women reported improving quality of life one year following surgery.
Conclusions: In women with newly diagnosed early-stage breast cancer who had been treated with standard therapies, the new use of alternative medicine was a marker of greater psychosocial distress and worse quality of life.
Burstein HJ et al. Use of alternative medicine by women with early-stage breast cancer . New England Journal of Medicine 340(22): 1733-9. Jun 3 1999.

Comments: Perhaps it is too early to classify women using alternative medicine as having a worse quality of life when, one year after, all the women reported an improving quality of life.

WARRICK and colleagues, Wharton Head and Neck Centre, The Toronto Hospital/Princess Margaret Hospital, Ontario, Canada studied the prevalence of alternative medicine use in head and neck cancer patients and its correlation with demographics and tumour characteristics.
Methods: This was a cross-sectional survey study conducted a 2 tertiary cancer centres, with 200 consecutive outpatients, consisting of a 10- to 25-minute patient interview administered by a primary investigator. The main outcome measures were demographic markers, tumour characteristics, conventional treatment mode, attitudes regarding alternative medicine, source of exposure to alternative medicine, therapeutic rationale, treatment efficacy, sources of information, and discussions with physicians regarding alternative medicine.
Results: 38.5% (n = 77) of 200 patients had used alternative medicine for some purpose; 22.5% (n = 45) of 200 did so for head and neck cancer. There was increased use of alternative medicine in younger patients, having a post-secondary education, higher personal income and Indo-Asian extraction. In patients using alternative anticancer therapy, increased use was noted with patients with tumours of the nasopharynx, nonsquamous cell carcinoma pathology and recurrent disease. There was no association between conventional mode of treatment and alternative medicine use. Physicians were believed to be the most knowledgeable regarding alternative medicine, whereas the usual proponents of alternative medicine were identified least frequently.
Conclusions: Alternative cancer therapy use among patients with head and neck cancer was 22.5%. There was increased use in younger, affluent, better educated patients and those of Indo-Asian extraction. Patients view physicians as being knowledgeable regarding alternative medicine. Otolaryngologists ought to be more informed regarding alternative medicine in order to counsel patients more effectively.
Warrick PD et al. Use of alternative medicine among patients with head and neck cancer. Archives of Otolaryngology 125(5): 573-9 May 1999.

RICHARDSON and colleagues, University of Texas-Houston School of Public Health USA review the literature (59 references) and write that, despite the widespread practice of complementary/alternative medicine (CAM), researchers face problems recruiting patients to randomised clinical trials, because of strict exclusion criteria and barriers to participation. Inadequate numbers of patients diminish the ability to researchers to detect an effect and generalise the findings. The authors describe the recruitment experience of a CAM trial, detail the reasons for non-participation and contrast participants and non-participants regarding demographic, clinical and treatment-related variables.
Methods: Eligible women were from Houston, spoke English had primary breast cancer (excluding Stage IV) and were 1 to 30 months post-treatment with no steroids, tamoxifen, substance abuse, psychiatric, heart disease or immune deficiency. The enrolment process involved an introductory letter and brochure, telephone calls and reminder post cards. Potential participants were advised that the study would require blood samples (30 cc) to assess immune function; psychosocial measures to assess emotional well-being, quality-of-life, social support and coping strategies; and possible assignment to 6 weekly support or imagery sessions. Factors influencing recruitment were assessed by stratified analysis and multivariate logistic regression.
Results: Of 158 eligible participants, 30% (n = 47) consented to participate. The primary reasons for non-participation included work/childcare (33.3%), transportation/travel (30.6%), and lack of interest (24.3%). Participants were more likely to be 40-54 years of age rather than younger or older, divorced/separated, and able to pay some/all medical expenses. Divorced or separated women appeared to be more likely to participate, regardless of financial status.
Conclusions: Researchers need to assess the impact of exclusion criteria and must recognise the special needs of their target population. Although age, marital status, and pay status were the strongest predictors of participation, these factors are not amenable to intervention. Researchers could boost recruitment to studies by providing interventions available during the day and evening to accommodate working women, child care services, transportation, or reimbursement for travel costs.
Richardson MA et al. Recruitment for complementary/alternative medicine trials: who participates after breast cancer. Annals of Behavioral Medicine. 20(3): 190-8. Summer 1998.

ALBANES, Cancer Prevention Studies branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD, 20892-7058 USA. daa@nih.gov writes that the conflicting evidence of the relation between beta-carotene and lung cancer in humans serves as a poignant case study regarding what types of evidence are sufficient to support or change a nutrition recommendation. The author reviews (37 references) the available evidence of the relation between beta-carotene and lung cancer, including data regarding beta-carotene intake from diet and supplements, beta-carotene biochemical status and vegetable and fruit consumption, and discusses the role of this evidence to make nutrition recommendations.
Results: More than 30 case-control and cohort studies have been conducted over many years in various countries which have indicated that people who eat more vegetables and fruit, foods rich in carotenoids and carotenoids (beta-carotene in particular) as well as those with higher blood beta-carotene concentrations, have a reduced risk of lung cancer than those people eating fewer such foods or with lower beta-carotene concentrations. In contrast, the results from large, controlled trials of beta-carotene supplementation do not support the observed beneficial associations or a role for supplemental beta-carotene in lung cancer prevention; rather they provide evidence for adverse, i.e. excess lung cancer incidence and overall mortality in smokers.
Conclusions: These findings require that caution be exercised in recommending supplemental beta-carotene, particularly for smokers, and argue against changing the vegetable-fruit recommendations in the direction of greater nutrient specificity.
Albanes D. Beta-carotene and lung cancer: a case study. American Journal of Clinical Nutrition 69(6): 1345S-1350S. Jun 1999.

Comments: Perish the thought that anyone should suggest to people that they eat more fruit and vegetables, or that they take supplements. It is typical of reductionist clinical trials to test a particular isolated substance i.e. beta-carotene, rather than the real nutrient, which acts within a broad mix of nutrients, be they carotenoids, tocopherols or other nutrient complexes. Of course, we should all eat liberally, with many vegetables and fruits daily. Unless you do your own cooking throughout your work day, have you seen such foods available in your sandwiches or in most restaurants?

Issue 43

VERHOEF and colleagues, Department of Community Health Sciences, The University of Calgary, Alberta, Canada. mverhoef@ucalgary.ca write that alternative therapy use in brain tumour patients is unknown, but that it may be frequent and appears to be important to those who utilise it. The authors characterised alternative therapy use in brain tumour patients.
Methods: 167 brain tumour patients attending a cancer centre in southern Alberta completed a prospective questionnaire-based survey, while physicians completed forms describing clinical information regarding disease status.
Results: There was a response rate of 91% (167/184). 24% of patients used alternative therapies, often more than one therapy at the same time. The motivation to use these therapies was influenced by the desire for patient-focused treatment, and a perceived need to take charge. Users of alternative therapy were younger, more likely to be on sick or disability leave, to come in for repeat visits and to have received conventional treatments. These users also tended to have lower quality of life with respect to physical well-being, functional well-being, and a specific brain tumour subscale. Clinical variables, including disease status, tumour type and Karnofsky Performance Score were not related to use of alternative therapy use. Major changes in number and types of alternative therapy use occurred during the study period. There were no major side effects or tumour responses seen with alternative therapies.
Conclusions: Alternative therapy use in brain tumour patients is common and may reflect unmet patient needs with respect to cancer care within the current system of health care delivery.
Verhoef MJ et al. Alternative therapy use in neurologic diseases: use in brain tumor patients. Neurology 52(3): 617-22. Feb 1999.,

NAGATA and colleagues, Department of Public Health, Gifu University, School of Medicine, Japan studied the relationship of dietary and serum vitamin A to subsequent cervical cancer.
Methods: The authors followed up on 134 women diagnosed with cervical dysplasia, who were attending for Pap screening in Miyagi, Japan between October 1987 and September 1988. The authors conducted personal interviews and took blood samples on the date of diagnosis of cervical dysplasia. The women were followed up with cervical smear and colposcopy at about 3-monthly intervals until end of February 1995. During the follow-up, 8 women (5.9%) developed cancer in situ or invasive cervical cancer, and 106 (79.1%) reverted to normal.
Results: The rate of progression of the cancer in situ or invasive cervical cancer was 4.5 times higher in women with lower serum retinol levels than those with higher serum retinol levels.
Conclusions: These results suggest an association of low serum retinol level with development of cervical cancer.
Nagata C et al. Serum retinol level and risk of subsequent cervical cancer in cases with cervical dysplasia. Cancer Investigation 17(4): 253-8. 1999.

ELATTAR and VIRJI, Hormone Research Laboratory, University of Missouri-Kansas City, School of Dentistry 64108 USA researched the effect of treating human tongue cancer cells with vitamin E.
Methods: The authors treated human tongue squamous carcinoma cell SCC-25 with physiological concentrations of vitamin E succinate (VES), varying from 0.001 to 50 micromoles/L.
Results: Treatment with vitamin E in concentrations of 0.001 to 50 micromoles/L resulted in significant dose-dependent stimulation of cell growth, whereas pharmacological doses of vitamin E (100-154 micromoles/L) induced significant inhibition of cell growth.
Discussion: The authors discuss the possible anticarcinogenic mechanisms of action of vitamin E.
Elattar TM and Virji AS Biphasic action of vitamin E on the growth of human oral squamous carcinoma cells. Anticancer Research 19(1A): 365-8. Jan-Feb 1999.

ASANO and colleagues, Department of Physiology, School of Medicine, Showa University, Tokyo, Japan investigated the antitumour action of the derivative of ascorbic acid (vitamin C), sodium 5,6-benzylidene-L-ascorbate (SBA), to determine whether it is mediated via oxidation-involved mechanisms.
Methods: The authors used 3 different systems – in vivo 3’-methyl-4-dimethylaminoazobenzene (DAB)-induced rat hepatocellular (liver) carcinoma, its homogenate (semi in vivo) and cultured cells (in vitro).
Results: Oral intake of DAB irreversibly caused liver cancer in rats; maximum cancer incid ence after 4 months. Intravenous administration of SBS induced vacuolar, eisinophilic degeneration and nuclear debris, producing greater amounts of ESR signal of ascorbate radical and hydrogen peroxide (H2O2)-derived chemiluminescence (CL) (H2O2)-CL) in the cancerous tissue than in the normal tissue. When SBA was added directly to the homogenates, higher amounts of ascorbate radical and H2O2-CL were generated in cancerous tissues. When SBA was added to the RPM medium supplemented with 10% foetal bovine serum, methionine was oxidised to methionine sulfoxide and H2O2 was produced in amounts to sufficiently induce apoptosis (cell death) in human promyelocytic leukaemic HL-60 cells. The cytotoxic activity of SBA was significantly reduced by catalase.
Conclusions: The results of this study suggest that antitumour activity of SBA in vivo may be due, at least in part, to H2O2, produced from SBA.
Asano K et al. Production of hydrogen peroxide in cancerous tissue by intravenous administration of sodium 5,6-benzylidene-L-ascorbate. Anticancer Research 19(1A): 229-36. Jan-Feb 1999.

WITENBERG and colleagues, Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel studied the effect of ascorbic acid (vitamin C) loading upon apopto sis in the human myeloid leukaemia cell line HL-60.
Methods: The human myeloid leukaemia cell line HL-60 transports the oxidised form of ascorbic acid, dehydroascorbic acid (DHA) and accumulates reduced ascorbic acid. The authors studied the effect of ascorbic acid loading on apoptosis induced by serum- and glucose-free culture and by oxidative stress induced by hydrogen peroxide (H2O2).
Results: Studies of uptake accumulation indicated that incubation of HL-60 cells with DHA resulted in the accumulation of intracellular ascorbic acid, which decreased when cells were incubated in DHA-free medium. Exposure of HL-60 cells to increasing concentrations of H2O2 resulted in dose-dependent intracellular accumulation of peroxides, accompanied by a decrease in intracellular ascorbic acid and an increase in apoptosis. There was a dramatic decrease in intracellular ascorbic acid when preloaded HL-60 cells were exposed to 150 microM H2O2; a dose-dependent protective effect of DHA was observed. Ascorbic acid loading also provided strong protection from apoptosis associated with serum- and glucose-free culture. Exposure of HL-60 cells to 150 microM H2O2 resulted in decreased Bcl-2 expression associated with enhance apoptosis. There was no significant variation of Bcl-2 expression following exposure of Hl-60 cells, loaded with ascorbic acid, to 150 microM H2O2, and only a slight increase in apoptosis.
Conclusions: These results demonstrate that ascorbic acid can inhibit apoptosis induced by oxidative stress in HL-60 cells.
Witenberg B et al. Inhibition by ascorbic acid of apoptosis induced by oxidative stress in HL-60 myeloid leukemia cells. Biochem Pharmacol 57(7): 823-32. Apr 1 1999.

Issue 42

KOLCABA and FOX, College of Nursing, University of Akron, Ohio USA researched the effectiveness of customised guided imagery for increasing comfort in women with early stage breast cancer undergoing radiation therapy.
Methods: The authors conducted a clinical trial with 53 women, aged 37-81, with 26 in the experimental group and 27 in the control group with stage I or II breast cancer, about to commence radiation therapy. The experimental group listened to a guided imagery audiotape once daily for the duration of the study. The Radiation Therapy Comfort Questionnaire was self-administered at 3 time points: prior to the intervention, the beginning of radiation therapy (Time 1), 3 weeks later (Time 2), and 3 weeks following completion of radiation therapy (Time 3). The State Anxiety Inventory was administered at Time 1 only. The main research variable was the effect of the use of guided imagery upon comfort with anxiety as a control variable.
Results: There was a significant overall increase in differences in comfort between the treatment and control groups; the treatment group had higher comfort over time. The data also showed a significant linear trend in the differences between groups.
Conclusions: Guided imagery is an effective intervention for enhancing the comfort of women undergoing radiation therapy for early stage breast cancer, especially during the first 3 weeks of radiation therapy. Guided imagery audiotapes specifically designed for this group are resource effective with regard to cost, personnel and time.
Kolcaba K and Fox C. the effects of guided imagery on comfort of women with early stage breast cancer undergoing radiation therapy. Oncol Nurs Forum 26(1): 67-72. Jan-Feb 1999.

ROOMI and colleagues, Linus Pauling Institute, Oregon State University, Corvallis 97331 USA write that in recent years L-ascorbic acid (AA) and its isomers have raised considerable interest as anticancer agents, although the mechanism has remained unknown.
Methods: The authors write that AA isomers are almost identical in their physical and chemical properties, but they differ widely in their biological properties. AA, a lactone sugar has a number of reactive positions, especially at 2- and 6-. There are a number of studies regarding the cytotoxic effect of AA and its isomers on malignant and nonmalignant cell lines; however, no work has been reported on the comparative effects of substitutions at these active sites. In this study, the authors investigated the comparative cytotoxicity of substitutions on the malignant leukaemia P388 cell line in culture. Results: All 2-substituted and the 2,6-substituted AA derivatives tested were found to be nontoxic and ineffective in preventing cell growth. In contrast, all 6-substituted AA derivatives were highly toxic at all levels, even at the lowest concentrations (1 microg/ml).
Conclusions: These results suggest that substitution at 2-, 6- and 2,6-positions in AA have a varying effect upon toxicity. The 2-, and 2,6-substituted AA derivatives are stable compounds, resistant to hydrolysis which render them inactive. The cytotoxicity of the 6-substituted derivatives may be explained by one of the following mechanisms, which need to be explored: 1) the hydrolysis rate may differ; or 2) the chemical structure itself may affect toxicity. Further studies are in progress to understand the mechanism.
Roomi MW et al. Cytotoxic effect of substitution at 2-, 6-, and 2,6-positions in ascorbic acid on malignant cell line. Cancer Biochem Biophy 16(4): 295-300. Nov 1998.

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