|
Anyone with any type of cancer, especially breast cancer or prostate cancer, may benefit by considering alternative therapies and recent scientifically-documented approaches to treatment.
Phone: (616) 453-1477 Fax: (616) 453-1846 Dihydrotestosterone (DHT), a breakdown product of the male hormone testosterone, is the primary agent responsible for prostate cancer growth. (DHT is also an important factor in male pattern baldness, benign prostate enlargement, and other unpleasant aspects of aging.) Since the prescription drug Proscar (finasteride) blocks the conversion of testosterone to DHT, it is currently being tested to see if it helps to prevent prostate cancer. The extract of the saw palmetto berry blocks the activity of DHT by a different mechanism than Proscar. Since saw palmetto extract has virtually no adverse effects, saw palmetto supplements may be a much safer method of preventing prostate cancer. No studies have conclusively tested this hypothesis, but saw palmetto has been used safely for centuries. The scientific studies on saw palmetto have been done on the sterol extract of the berries, which is a widely-used prescription medicine in Europe. It is available in the U.S. without a prescription. Look for the words European Standard on the saw palmetto extract sold by manufacturers such as Solaray. The following are a few of the references to the medical literature on the potential benefits of coenzyme Q-10 and melatonin in the prevention and treatment of breast cancer. The coenzyme Q-10 studies are potentially very important and badly in need of follow-up and confirmation by other medical teams. The work being done on birth control pills and hormone replacement therapy using melatonin (in combination with other hormones) also promises to have a major impact in the prevention and treatment of breast cancer. (See the chapter on Melatonin.) Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases Lockwood K.; Moesgaard S.; Yamamoto T.; Folkers K. Institute for Biomedical Research, University of Texas at Austin, Austin, TX 78712 USA Biochemical and Biophysical Research Communications (USA) , 1995, 212/1 (172-177). Over 35 years, data and knowledge have internationally evolved from biochemical, biomedical and clinical research on vitamin Q10 (coenzyme Q10; CoQ10) and cancer, which led in 1993 to overt complete regression of the tumors in two cases of breast cancer. Continuing this research, three additional breast cancer patients also underwent a conventional protocol of therapy which included a daily oral dosage of 390 mg of vitamin Q10 (Bio-Quinone of Pharma Nord) during the complete trials over 3-5 years. The numerous metastases in the liver of a 44-year-old patient 'disappeared,' and no signs of metastases were found elsewhere. A 49-year-old patient, on a dosage of 390 mg of vitamin Q10, revealed no signs of tumor in the pleural cavity after six months, and her condition was excellent. A 75-year-old patient with carcinoma in one breast, after lumpectomy and 390 mg of CoQ10, showed no cancer in the tumor bed or metastases. Control blood levels of CoQ10 of 0.83-0.97 and of 0.62 microg/ml increased to 3.34-3.64 and to 3.77 microg/ml, respectively, on therapy with CoQ10 for patients A-MRH and EEL. Apparent partial remission of breast cancer in 'high risk' patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10 Lockwood K.; Moesgaard S.; Hanioka T.; Folkers K. Private Outpatient Clinic, 5.3 Malmogade, Copenhagen Denmark MOL. ASP. MED. (United Kingdom) , 1994, 15/SUPPL. (S231-S240) Thirty-two typical patients with breast cancer, aged 32-81 years and classified 'high risk' because of tumor spread to the lymph nodes in the axilla, were studied for 18 months following an Adjuvant Nutritional Intervention in Cancer protocol (ANICA protocol). The nutritional protocol was added to the surgical and therapeutic treatment of breast cancer, as required by regulations in Denmark. The added treatment was a combination of nutritional antioxidants (Vitamin C: 2850 mg, Vitamin E: 2500 iu, beta-carotene 32.5 iu, selenium 387 microg plus secondary vitamins and minerals), essential fatty acids (1.2 g gamma linolenic acid and 3.5 g n-3 fatty acids) and Coenzyme Q10 (90 mg per day). The ANICA protocol is based on the concept of testing the synergistic effect of those categories of nutritional supplements, including vitamin Q10, previously having shown deficiency and/or therapeutic value as single elements in diverse forms of cancer, as cancer may be synergistically related to diverse biochemical dysfunctions and vitamin deficiencies. Biochemical markers, clinical condition, tumor spread, quality of life parameters and survival were followed during the trial. Compliance was excellent. The main observations were: (1) none of the patients died during the study period. (the expected number was four.) (2) none of the patients showed signs of further distant metastases. (3) quality of life was improved (no weight loss, reduced use of pain killers). (4) six patients showed apparent partial remission. Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10 Lockwood K.; Moesgaard S.; Folkers K. Malmogade 5, Copenhagen Denmark BIOCHEM. BIOPHYS. RES. COMMUN. (USA) , 1994, 199/3 (1504-1508). Relationships of nutrition and vitamins to the genesis and prevention of cancer are increasingly evident. In a clinical protocol, 32 patients having -'high-risk'- breast cancer were treated with antioxidants, fatty acids, and 90 mg. of CoQ10. Six of the 32 patients showed partial tumor regression. In one of these 6 cases, the dosage of CoQ10 was increased to 390 mg. In one month, the tumor was no longer palpable and in another month, mammography confirmed the absence of tumor. Encouraged, another case having a verified breast tumor, after non-radical surgery and with verified residual tumor in the tumor bed was then treated with 300 mg. CoQ10. After 3 months, the patient was in excellent clinical condition and there was no residual tumor tissue. The bioenergetic activity of CoQ10, expressed as hematological on immunological activity, may be the dominant but not the sole molecular mechanism causing the regression of breast cancer. Melatonin modulation of estrogen-regulated proteins, growth factors, and proto-oncogenes in human breast cancer Molis TM; Spriggs LL; Jupiter Y; Hill SM Department of Anatomy, Tulane University School of Medicine, New Orleans, LA 70112, USA. J Pineal Res (DENMARK) Mar 1995, 18 (2) p93-103. The growth-inhibitory actions of the pineal hormone, melatonin, on human breast tumor cells and the possible association between this inhibition and melatonin's down-regulation of the estrogen receptor (ER) expression were examined in the ER-positive, estrogen-responsive MCF-7 human breast tumor cell line. As previously reported, melatonin dramatically inhibits the growth of these breast tumor cells and down-regulates ER levels in these cells, suggesting that the modulation of ER may be an important mechanism by which melatonin inhibits breast cancer cell growth. In the present studies, Northern blot analysis was used to examine the expression of estrogen-regulated transcripts known to be involved in estrogen's mitogenic actions. Melatonin, at a physiologic concentration (10(-9) M), rapidly, significantly, and, in some cases, transiently elevated the steady-state mRNA levels of growth stimulatory products such as TGF alpha, c-myc, and pS2, which are normally up-regulated in response to estrogen. Conversely, melatonin decreased the expression of other factors normally up-regulated by estrogen, such as progesterone receptor and c-fos. Significant stimulation of the expression of the growth-inhibitory factor TGF beta was seen with melatonin treatment, potentially supporting the concept that melatonin's growth-inhibitory activity is mediated through the breast tumor cells' estrogen-response pathway. The early regulation of many of these products by melatonin suggests that mechanisms more rapid than the down-regulation of ER are important in melatonin's modulation of their expression. However, the long-term modulation of these transcripts (12-48 hr) may be heavily influenced by melatonin's down-regulation of ER expression. These results clearly define the need for additional in depth studies to dissect the cellular events leading to melatonin-induced growth inhibition in breast tumor cells. Hypotheses: melatonin/steroid combination contraceptives will prevent breast cancer Cohen M; Small RA; Brzezinski A Center for Reproductive Medicine and Breast Cancer Prevention, Letta Center, AMR Pharm Holland B.V. Breast Cancer Res Treat (NETHERLANDS) Mar 1995, 33 (3) p257-64. The use of the conventional combination oral contraceptives (containing ethinyl-estradiol and a progestin) is associated with reduced risk of ovarian and endometrial cancer. However, prolonged use of these pills before first term pregnancy apparently increases the risk of pre menopausal breast cancer. We propose that the pineal gland hormone melatonin, combined with a progestin, as a new and novel oral contraceptive combination might prevent breast cancer in long term users. This hypothesis is based on the assumption that women have a propensity to develop breast cancer which correlates with number of ovulatory cycles over their lifetime. In evolution, the phylogenetic point at which women became sensitive to breast cancer evolved at a transfer point of the mechanism of ovulation from seasonal ovulation, which is still common in many mammalian species, to the current human pattern of continuous ovulatory cycles. We suggest that melatonin/ovarian-steroid contraceptive will restore the lost mechanism of endogenous anovulation, and thus, by preventing continuous epithelial breast cell proliferation, will reduce the risk of breast cancer in long-term users. Hormonal profiles in women with breast cancer Zumoff B Department of Medicine, Beth Israel Medical Center, New York, USA. Obstet Gynecol Clin North Am (UNITED STATES) Dec 1994, 21 (4) p751-72. The literature findings on endogenous hormonal profiles in women with breast cancer are reviewed in detail. It is concluded that four sets of findings are valid: (1) diminished adrenal androgen production, probably genetic, in women with premenopausal breast cancer; (2) ovarian dysfunction (luteal inadequacy plus increased testosterone production) in breast cancer at all ages; (3) increased 16 alpha-hydroxylation of estradiol in breast cancer at all ages; and (4) evidence that prolactin is a permissive risk factor for breast cancer, and that the pregnancy-induced decrease in prolactin levels may account for the protective effect of early pregnancy against breast cancer. (176 Refs.) Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone Lissoni P; Barni S; Meregalli S; Fossati V; Cazzaniga M; Esposti D; Tancini G Divisione di Radioterapia Oncologica, San Gerardo Hospital, Monza, Milan, Italy. Br J Cancer (ENGLAND) Apr 1995, 71 (4) p854-6. Recent observations have shown that the pineal hormone melatonin (MLT) may modulate oestrogen receptor (ER) expression and inhibit breast cancer cell growth. On this basis, we have evaluated the biological and clinical effects of a concomitant melatonin therapy in women with metastatic breast cancer who had progressed in response to tamoxifen (TMX) alone. The study included 14 patients with metastasis who did not respond (n = 3) to therapy with TMX alone or progressed after initial stable disease (SD) (n = 11). Melatonin was given orally at 20 mg day-1 in the evening, every day starting 7 days before TMX, which was given orally at 20 mg day-1 at noon. A partial response was achieved in 4/14 (28.5%) patients (median duration 8 months). The treatment was well tolerated in all cases, and no melatonin-induced enhancement of TMX toxicity was seen; on the contrary, most patients experienced a relief of anxiety. Mean serum levels of insulin-like growth factor 1 (IGF-1), which is a growth factor for breast cancer, significantly decreased on therapy, and this decline was significantly higher in responders than in patients with SD or progression. This pilot phase II study would suggest that the concomitant administration of the pineal hormone melatonin may induce objective tumour regressions in metastatic breast cancer patients refractory to TMX alone. Modulation of estrogen receptor mRNA expression by melatonin in MCF-7 human breast cancer cells Molis TM; Spriggs LL; Hill SM Department of Anatomy, Tulane University School of Medicine, New Orleans, Louisiana 70112. Mol Endocrinol (UNITED STATES) Dec 1994, 8 (12) p1681-90. Melatonin, the hormonal product of the pineal gland, has been shown to inhibit the development of mammary tumors in vivo and the proliferation of MCF-7 human breast cancer cells in vitro by mechanisms not yet identified. However, previous studies have demonstrated that melatonin significantly decreased estrogen-binding activity and the expression of immunoreactive estrogen receptor (ER) in MCF-7 breast cancer cells. To determine the mechanism(s) by which melatonin regulates ER expression in MCF-7 cells, the relationship between the level of steady state ER mRNA and the rate of ER gene transcription were examined in response to melatonin. Physiological concentrations of melatonin decreased steady state levels of ER mRNA expression in a dose- and time-specific manner. This decrease was not dependent upon the presence of estrogen since similar decreases in steady state ER mRNA levels were seen in MCF-7 cells cultured in both complete and estrogen-depleted media. The decreased expression of ER mRNA in response to melatonin appears to be directly related to the suppression of transcription of the ER gene. This regulation is independent of the synthesis of new proteins, as cycloheximide was unable to block the melatonin-induced decrease of steady-state ER mRNA levels. The down-regulation of ER by melatonin appears to not be mediated via a direct interaction with the ER and subsequent feedback on its own expression, since melatonin treatment did not alter the transcriptional regulatory ability of the fully activated wild type ER or a constitutively active hormone-binding domain-deleted ER variant. In addition, the stability of the ER transcript was unaffected by melatonin. Thus, it appears that the antiproliferative actions of this pineal indoleamine are mediated, at least in part, through the suppression of the transcription of the ER gene in MCF-7 human breast cancer cells. Differences between pulsatile or continuous exposure to melatonin on MCF-7 human breast cancer cell proliferation. Cos S; Sanchez-Barcelo EJ Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, Santander, Spain. Cancer Lett (IRELAND) Sep 30 1994, 85 (1) p105-9. We studied the different in vitro antiproliferative actions of melatonin on MCF-7 cells, depending on whether the cells are exposed to hormone concentrations which remain constant in culture media (Group I, 10(-9) M; Group II, 10(-11) M melatonin) or varying at 12 h intervals, thus simulating a diurnal rhythm: Group III, 12 h in 10(-9) M melatonin/12 h without melatonin (10(-9) M/0 12/12 h); Group IV, 10(-11) M/0 12/12 h; Group V, 10(-9) M/10(-11) M 12/12 h. After 5 days of culture, cell proliferation appeared significantly inhibited in Groups I and III, but not in Groups II and IV. However, the highest antiproliferative effect was obtained by sequential exposure to 10(-9) M/10(-11) M melatonin (Group V), which mimics the physiological rhythm of serum melatonin concentration. Breast cancer, blindness and melatonin Coleman MP; Reiter RJ Unit of Descriptive Epidemiology, International Agency for Research on Cancer, Lyon, France. Eur J Cancer (ENGLAND) 1992, 28 (2-3) p501-3. The hypothesis is advanced that blindness from an early age may lead to a reduced risk of breast cancer through altered patterns of melatonin secretion by the pineal gland. The available experimental evidence in animals and in vitro is consistent with this hypothesis. The hypothesis can be tested in humans by a simple observational study in which the breast cancer risk in blind women is compared with that of all women. The effect of age at onset, duration and degree of blindness could also be assessed, after adjustment for known risk factors for breast cancer. Melatonin might prove to be a natural oncostatic agent of practical value in cancer prevention. (33 Refs.) Seasonal changes in serum melatonin in women with previous breast cancer Holdaway IM; Mason BH; Gibbs EE; Rajasoorya C; Hopkins KD Department of Endocrinology, Auckland Hospital, New Zealand. Br J Cancer (ENGLAND) Jul 1991, 64 (1) p149-53, A seasonal variation in the month of initial detection of breast cancer has been previously observed in pre-menopausal women, and it has been proposed that this may be due to cyclic changes in tumour growth mediated by the effects of melatonin on ovarian function. To investigate this possibility serum melatonin concentrations have been measured every 2 h for 24 h at the summer and winter solstice in 20 pre-menopausal women with previous breast cancer and nine controls. Twelve women had detected their tumour in winter and eight in summer. Overall melatonin secretion assessed by either amplitude of the nocturnal melatonin pulse or the area under the 24 h melatonin curve (AUC) was not different between breast cancer women or controls. However, the amplitude and AUC fell in winter in breast cancer patients (summer to winter 93.6 to 77.5 pg ml-1, P less than 0.002 and 743 to 634 AUC units, P less than 0.005 for amplitude and AUC respectively), whereas the winter minus summer values were significantly positive in controls compared with cancer patients. The abnormal fall in winter values in the women with previous breast cancer was confined to the group of women who had been winter detectors (mean summer to winter levels 94.9 to 72.6 pg ml-1, P less than 0.01 and 775 to 637 AUC units, P less than 0.05 for amplitude and AUC respectively) whereas there was no significant seasonal alteration in these measurements in summer detectors. The acrophase of the nocturnal pulse of serum melatonin was significantly advanced in both groups of women with previous breast cancer (change in acrophase winter to summer from 0210 h to 0140 h in summer detectors, P less than 0.01, 0330 h to 0210 h in winter detectors, P less than 0.05) with a similar although nonsignificant trend in control women. The abnormal reduction of serum melatonin seen in wintertime in winter detectors of breast cancer could promote tumour growth at this season and so contribute to the decreased survival previously observed in this group compared with summer detectors. The relatively normal seasonal profile of melatonin observed in summer detectors could allow increased ovarian steroidogenesis in spring/summer with a resulting increase in tumour growth and consequent rise in tumour detection rate at this time. |