Dietary Supplement
Ionic Minerals Research
The following research abstracts
are presented to reflect the findings of possible benefits from
minerals as a dietary supplement and nutritional supplement.
For more information on individual minerals, please visit the
ionic minerals page.
Prostate cancer:
Diagnosis and Treatment
JP Lattanzi, AL Hanlon, GE Hanks
International Journal of Radiation Oncology
Biology Physics, 1997, Vol 38, Iss 3, pp 569-573
Lattanzi JP, Fox Chase Canc Ctr, Dept Radiat Oncol,
7701 Burholme Ave, Philadelphia,PA 19111 USA
Purpose: This study identifies
two early prostate cancer populations within the T1/T2AB, Gleason
2-7, pretreatment prostate specific antigen (PSA) 4-15 ng/ml
grouping. By demonstrating different outcomes we may be able
to more appropriately select a subgroup for whom adjuvant therapy
trials or altered treatment techniques are indicated. Materials
and Methods: One hundred forty-six patients with T1/T2AB, Gleason
score 2-7, PSA 4-15 ng/ml prostate cancer were treated with
external beam radiotherapy alone from November 1987 to October
1993. The median pretreatment PSA was 8.6 and the mean 8.7.
Minimum follow-up was 2 years with a median of 38 months (mean
42 months, range 24-87). The median age was 70 years (range
58-83) and the median central axis dose delivered was 7240 cGy
(mean 7273, range 6541-7895 cGy). Eleven patients received conventional
radiotherapy while 135 were treated using conformal techniques.
As there is evidence that a low PSA nadir is an early marker
for long term biochemical control, time to post treatment PSA
< 1 ng/ml was actuarially analyzed by Gleason score, pretreatment
PSA, radiation dose, stage, and the presence of perineural invasion.
Pretreatment PSA was the only patient characteristic predictive
of achieving a PSA level < 1.0 ng/ml. Biochemical relapse
free (bNED) control (non rising PSA) was then compared for patients
above and below the approximate median pretreatment PSA level
of 8 ng/ml. BNED control rates and the time to PSA <1.0 ng/ml
were estimated using Kaplan-Meier methodology, and differences
in bNED control and PSA <1.0 ng/ml according to PSA level
were evaluated using the log-rank test. Results: Results from
actuarial analysis revealed that pretreatment PSA was the only
significant variable predictive of a PSA <1.0 ng/ml. Ninety-eight
percent of patients with pretreatment PSA <8 achieved a PSA
level <1.0 ng/ml within 3 years compared to 78% for patients
with a PSA >8 ng/ml (p = 0.0003). BNED control for the two
groups separated at a pretreatment PSA of 8 ng/ml confirms a
favorable outcome, 88% bNED control at 5 years for <8 ng/ml
and 74% for a pretreatment PSA greater than or equal to 8 ng/ml
(p = 0.007 for overall curve comparison). Conclusion: For early
prostate cancer patients (T1/T2AB, Gleason 2-7, pretreatment
PSA 4-15) there is a significant break in bNED control following
external beam radiation at a pretreatment PSA level of 8 ng/ml.
Patients with pretreatment PSA <8 have a very favorable bNED
response with radiation alone while those with a pretreatment
PSA 8-15 have a significant decrease in bNED response. The 27%
failure rate at 5 years in the PSA 8-15 ng/ml patients may justify
altered treatment techniques or clinical trials of adjuvant
androgen deprivation in this group. (C) 1997 Elsevier Science
Inc.
R Sharma, M Duclos, PJ Chuba,
F Shamsa, JD Forman
International Journal of Radiation Oncology
Biology Physics, 1997, Vol 38, Iss 3, pp 575-582
prostate cancer; intravesical contrast; three-dimensional
treatment planning Pergamon-Elsevier Science Ltd,
The Boulevard, Langford Lane, Kidlington, Oxford, England OX5
1GB
Purpose: To assess the impact
of intravesical contrast during computed tomography (CT) simulation
on prostate tumor volume definition and dose distribution. Methods
and Materials: Sixteen patients with localized adenocarcinoma
of the prostate underwent CT-based virtual simulation in preparation
for definitive radiotherapy, Patients were immobilized with
a foam cradle and an initial CT was performed after oral but
without intravesical contrast (noncontrast scan), A second scan
was performed following administration of intravesical contrast
(contrast scan), Beam apertures were designed on the noncontrast
scans and digitized into the contrast scan file, Beam apertures
were also designed on the contrast scans, Isodose plans were
generated for several beam apertures and arrangements. Results:
There was enhanced visualization of the prostate at the cephalad
portion of the field for 15 of the 16 cases, The mean differences
between the noncontrast and contrast volumes was significant
(p = 0.0001), The mean percent underdosage to the prostate ranged
from 3.9% to 18.6%, depending upon the target volume and beam
arrangement. Conclusion: This study demonstrates the necessity
of using intravesical contrast for defining the location of
the prostate during CT simulation, The underestimation of the
extent of the prostate when omitting intravesical contrast leads
to significant underdosage, The value of intravesical contrast
is most evident when small (prostate only) conformal fields
are used. (C) 1997 Elsevier Science Inc.
J Ghosh, CE Myers
Biochemical and Biophysical Research Communications,
1997 Vol 235, Iss 2, pp 418-423
Ghosh J, Univ Virginia, Ctr Canc, POB 334, Charlottesville,VA
22908 USA
Arachidonic acid (5,8,11,14-eicosatetraenoic
acid), a member of the omega-g poly-unsaturated fatty acids,
was found to be an effective stimulator of human prostate cancer
cell growth in vitro at micromolar concentrations, Selective
blockade of the different metabolic pathways of arachidonic
acid (e.g. Ibuprofen for cyclooxygenase, SKF-525A for cytochrome
P-450, baicalein and BHPP for 12-lipoxygenase, AA861 and MK886
for 5-lipoxygenase, etc.) revealed that the growth stimulatory
effect of arachidonic acid is inhibited by the 5-lipoxygenase
specific inhibitors, AA861 and MK886, but not by others. Addition
of the eicosatetraenoid products of 5-lipoxygenase (5-HETEs)
showed stimulation of prostate cancer cell growth similar to
that of arachidonic acid, whereas the leukotrienes were ineffective,
Moreover, the 5-series of eicosatetraenoids could reverse the
growth inhibitory effect of MK886. Finally, prostate cancer
cells fed with arachidonic acid showed a dramatic increase in
the production of 5-HETEs which is effectively blocked by MK886.
These experimental observations suggest that arachidonic acid
needs to be metabolized through the 5-lipoxygenase pathway to
produce 5-HETE series of eicosatetraenoids for its growth stimulatory
effects on human prostate cancer cells. (C) 1997 Academic Press.
Tjandrawinata RR, Dahiya R, HughesFulford
M
Br J Cancer 1997 APR;75(8):1111-1118
HughesFulford M, Vet Affairs Med Ctr, Lab Cell Growth 151F,
4150 Clement St, San Francisco,CA 94121 USA
Prostaglandins are synthesized
from arachidonic acid by the enzyme cyclo-oxygenase. There are
two isoforms of cyclo-oxygenases: COX-I (a constitutive form)
and COX-2 (an inducible form). COX-2 has recently been categorized
as an immediate-early gene and is associated with cellular growth
and differentiation. The purpose of this study was to investigate
the effects of exogenous dimethylprostaglandin E-2 (dmPGE(2))
on prostate cancer cell growth. Results of these experiments
demonstrate that administration of dmPGE(2) to growing PC-3
cells significantly increased cellular proliferation (as measured
by the cell number), total DNA content and endogenous PGE(2)
concentration. DmPGE(2) also increased the steady-state mRNA
levels of its own inducible synthesizing enzyme, COX-2, as well
as cellular growth to levels similar to those seen with fetal
calf serum and phorbol ester. The same results were observed
in other human cancer cell types, such as the androgen-dependent
LNCaP cells, breast cancer MDA-MB-134 cells and human colorectal
carcinoma DiFi cells. In PC-3 cells, the dmPGE(2) regulation
of the COX-2 mRNA levels was both time dependent, with maximum
stimulation seen 2 h after addition, and dose dependent on dmPGE(2)
concentration, with maximum stimulation seen at 5 mu g ml(-1).
The non- steroidal anti-inflammatory drug flurbiprofen (5 mu
M), in the presence of exogenous dmPGE(2), inhibited the up-
regulation of COX-2 mRNA and PC-3 cell growth. Taken together,
these data suggest that PGE(2) has a specific role in the maintenance
of human cancer cell growth and that the activation of COX-2
expression depends primarily upon newly synthesized PGE(2),
perhaps resulting from changes in local cellular PGE(2) concentrations.
Wiseman LR, Spencer CM
Drug Aging 1997 JUN;10(6):473-485LA - English
Wiseman LR, Adis Int Ltd, 41 Centorian Dr,
Private Bag 65901, Auckland 10, NEW ZEALAND
The antineoplastic agent mitoxantrone
in combination with a corticosteroid (either prednisone or hydrocortisone)
hasshown clinical efficacy as palliative treatment for a proportion
of patients (about 35 to 40%) with hormone-resistant advanced
prostate cancer; a disease which predominantly affects elderly
men and for which few systemic treatment options are available.
Palliative end-points including pain relief decreased analgesic
use and reduced prostate specific antigen levels (a marker of
tumour response) are reached in a greater percentage of patients
receiving combination therapy than corticosteroid alone. In
addition, there are generally greater improvements in quality-of-life
parameters in mitoxantrone recipients. However, combined treatment
offers no survival advantage over corticosteroid monotherapy.Neutropenia
is the most common toxicity associated with mitoxantrone therapy
and may necessitate dosage reduction in some patients. Otherwise,
mitoxantrone generally has a more favourable tolerability profile
than has been established for other cytotoxic agents such as
doxorubicin with regard to acute adverse events (e.g. Nausea/vomiting,
anorexia, constipation, alopecia, malaise/fatigue, oedema) and
cardiac toxicity.In conclusion, administration of mitoxantrone
plus a corticosteroid can provide palliation for some elderly
patients with hormone-resistant advanced prostate cancer, and
is thus a valuable first-line treatment for this indication.
Lalani EN, Laniado ME, Abel PD
Cancer Metastasis Rev 1997 JUN;16(1-2):29-66
Lalani EN, Hammersmith Hosp, Royal Postgrad Med Sch, Dept
Histopathol, du Crane Rd, London W12 0NN, ENGLAND
Prostate cancer is an enigmatic
disease. Although prostatic-intraepithelial neoplasia appears
as early as the third decade and as many as 80% of 80 year old
men have epithelial cells in their prostate that fit the morphological
criteria for cancer, only about 10% of men will ever have the
clinical disease and less than 3% will die from it. There have
been no significant proven interventions which have al tered
the natural history of the disease since hormone down regulation
was introduced in the 1940s and new research has been poorly
supported. There is however an urgent need to develop new criteria
to distinguish those patients with localised disease who will
benefit from intervention from those that do not require it
or who will have occult extra prostatic metastases. Similarly,
there is an urgent need to develop new treatments for those
in wham the disease is extra- prostatic and therefore incurable
by conventional treatments. This review covers the latest developments
in epidemiology, cellular and molecular biology including new
areas such as ion channels in the field of prostate cancer.
Yablonsky F, AU - Nicolas V,
Riffaud JP, Bellamy F
J Urol 1997 JUN;157(6):2381-2387
Yablonsky F, Labs Debat, Grp Fournier, 153 Rue Buzenval,
F
92380 Garches, FRANCE
The effect of a Pygeum africanum
extract (Tadenan(R)) (Pa), used in the treatment of micturition
disorders associated with BPH, has been examined on the proliferation
of rat prostatic stromal cells stimulated by different growth
factors. EGF, bFGF, and IGF-I but not KGF are mitogenic for
prostatic fibroblasts in culture. Pygeum africanum inhibits
both basal and stimulated growth with IC50 values of 4.5, 7.7
and 12.6 mu g./ml. For EGF, IGF-I and bFGF, respectively, compared
to 14.4 mu g./ml. For untreated cells, the inhibition being
stronger towards EGF. Pygeum africanum inhibited the proliferation
induced by TPA or PDBu in a concentration-dependent manner with
IC50 values of 12.4 and 8.1 mu g./ml. Respectively. The antiproliferative
effects of Pa were not ascribed to cytotoxicity. These results
show that Pygeum africanum is a potent inhibitor of rat prostatic
fibroblast proliferation in response to direct activators of
protein kinase C, the defined growth factors bFGF, EGF and IGF-I,
and the complex mixture of mitogens in serum depending on the
concentration used. PKC activation appears to be an important
growth factor-mediated signal transduction for this agent. These
data suggest that therapeutic effect of Pygeum africanum may
be due at least in part to the inhibition of growth factors
responsible for the prostatic overgrowth in man.
Figg WD, Kroog G, Duray P, Walther
MM, Patronas N, Sartor O, Reed E
Cancer 1997 MAY 15;79(10):1964-1968
Figg WD, NCI, Med Branch, Bldg 10, Room 5A01,
9000 Rockville Pike, Bethesda,MD 20892 USA
Background: Combined androgen
blockade plus (CAB) (medical or surgical castration plus antiandrogen
therapy) is considered by many to be the optimal endocrine maneuver
for patients with metastatic prostate carcinoma. When progression
occurs after CAB, the discontinuation of the antiandrogen is
recommended. The authors present a patient that had a clinical
complete response to flutamide withdrawal plus hydrocortisone
that, at last follow-up, had been maintained for more than 46
months. METHODS. A 71-year-old man with a positive family history
of prostate carcinoma presented in 1989 with urinary frequency
and a suspicious digital rectal examination. He was found to
have a poorly differentiated adenocarcinoma (Gleason 4+4). He
was started on CAB and his prostate specific antigen (PSA) concentration
declined from 96 ng/mL to the normal range and was maintained
for the next 24 months. In 1991 his PSA began to rise, and reached
64 ng/mL by 1993. The patient was enrolled on a clinical trial
that discontinued the flutamide administration and hydrocortisone
was initiated. RESULTS. Physical examination at the time of
enrollment was unremarkable. His PSA declined to below the limits
of detection after this maneuver and at last follow-up had been
maintained there for more than 46 months. In 1995, the patient
underwent a repeat biopsy of the prostate and all six tissue
cores were negative for carcinoma. At last follow-up in December
1996, the patient had no evidence of disease and was being followed
routinely; however, the authors were continuing treatment with
testicular suppression (leuprolide) plus hydrocortisone. CONCLUSIONS.
The authors believe the residual androgens and steroids produced
by the adrenal cortex play a meaningful role in prostate carcinoma
cell proliferation. Based on this case and data from trials
supporting the activity of flutamide withdrawal plus adrenal
suppression, it appears reasonable to evaluate prospectively
the discontinuation of antiandrogen versus antiandrogen withdrawal
plus adrenal suppression in individuals failing CAB. (C) 1997
American Cancer Society.
ShraderBogen CL, Kjellberg JL,
McPherson CP, Murray CL
Cancer 1997 MAY 15;79(10):1977-1986
ShraderBogen CL, Healthsyst Minnesota, Inst Res
Educ, 3800 Pk Nicollet Blvd, 2 S,
Minneapolis,MN 55416 USA
Background: Of the estimated
317,000 men in the United States diagnosed with prostate carcinoma
in 1996, 57% will have localized disease, and their 5-year relative
survival rate will be 98%. Limited information exists on patient-
reported quality of life (QOL) and the incidence and severity
of treatment-related side effects. The purpose of this study
was to identify and compare patients' self- reported QOL and
treatment side effects 1-5 years after radical prostatectomy
or radiotherapy. METHODS. Data collection for this cross-sectional
study included a mailed, self-administered survey with three
parts: a demographic survey, the Functional Assessment of Cancer
Therapy-General (FACT-G), and a newly developed Prostate Cancer
Treatment Outcome Questionnaire (PCTO-Q). The FACT-G measured
the effect of prostate carcinoma on overall QOL in the two treatment
groups. The PCTO-Q assessed the patients' perceptions of the
incidence and severity of specific changes in bowel, urinary,
and sexual functions. The test-retest reliability of the PCTO-Q
in a pilot study was 91.2%. RESULTS. Two hundred seventy-four
eligible men completed the questionnaires; 132 (48%) reported
having undergone prostatectomy and 142 (52%) reported having
undergone radiotherapy. After age adjustment, the radiotherapy
group reported more bowel dysfunction (P = 0.001), whereas the
prostatectomy group reported more urinary problems (P = 0.03)
and more sexual dysfunction (P = 0.001). Scores for the FACT-G
were similar in the two treatment groups. CONCLUSIONS. Men undergoing
treatment for clinically localized prostate carcinoma continue
to experience difficulty long after treatment. In this study,
the prostatectomy group fared worse in regard to sexual and
urinary functions, whereas the radiotherapy group experienced
more bowel dysfunction. Survivor-reported QOL and treatment
outcomes can assist physicians in counseling patients in the
selection of the preferred course of treatment. (C) 1997 American
Cancer Society.
Catalona WJ Smith DS Ornstein
DK
JAMA 1997 MAY 14;277(18):1452-1455
Catalona WJ, Washington Univ, Sch Med, Dept Surg,
Div Urol Surg, 4960 Childrens Pl,
St Louis,MO 63110 USA
Objective: To determine the detection
rate of prostate cancer in a screening population of men with
prostate- specific antigen (PSA) concentrations of 2.6 to 4.0
ng/mL and a benign prostate examination, to assess the clinicopathological
features of the cancers detected, and to assess the usefulness
of measuring the ratio of free to total PSA to reduce the number
of prostatic biopsies. Design.-A community-based study of serial
screening for prostate cancer with serum PSA measurements and
prostate examinations. Setting.-University medical center. Subjects.-A
total of 914 consecutive screening volunteers aged 50 years
or older with serum PSA levels of 2.6 to 4.0 ng/mL who had a
benign prostate examination and no prior screening tests suspicious
for prostate cancer, 332 (36%) of whom underwent biopsy of the
prostate. Main Outcome Measures.-Cancer detection rate, clinical
and pathological features of cancers detected, and specificity
for cancer detection using measurements of percentage of free
PSA. Results.-Cancer was detected in 22% (73/332) of men who
underwent biopsy. All cancers detected were clinically localized,
and 81% (42/52) that were surgically staged were pathologically
organ confined. Ten percent of the cancers were clinically low-volume
and low-grade tumors, and 17% of those surgically staged were
low-volume and low- grade or moderately low-grade tumors (possibly
harm less). Using a percentage of free PSA cutoff of 27% or
less as a criterion for performing prostatic biopsy would have
detected 90% of cancers, avoided 18% of benign biopsies, and
yielded a positive predictive value of 24% in men who underwent
biopsy. Conclusions.-There is an appreciable rate of detectable
prostate cancer in men with serum PSA levels of 2.6 to 4.0 ng/mL.
The great majority of cancers detected have the features of
medically important tumors. Free serum PSA measurements may
reduce the number of additional biopsies required by the lower
PSA cutoff.
