effect of aspartame on oncogene and suppressor gene expressions in
mice, Katalin Gambos, Istvan Ember, et al, University of Pecs,
Hungary, In Vivo 2007 Jan; scores of their relevant past studies since
1977: Murray 2007.04.14
http://groups.yahoo.com/group/aspartameNM/message/1414

[ Rich Murray:

If the reality is that the three components of aspartame are complexly
toxic in large doses for months and years for many groups of humans,
then surely the inevitable exponential evolution of science will make
many facets of the problems increasingly evident, and much more
quickly.

This report is one expression of the increasing confidence and
capability of a few teams in one nation,
dedicated, as all science and spirituality must be, to all peoples.

Many such independent teams have published comparable detailed
research in the last two years
specifically about aspartame toxicity, with remarkably little world
media attention.

These new studies are conscientiously summarized in links at the end
of this long review.

Without changing words, I have added spacing to increase the clarity
and readability
of the dense text in many of these abstracts. ]

In Vivo. 2007 Jan-Feb; 21(1): 89-92.
The effect of aspartame administration on oncogene and suppressor gene
expressions.
Gombos K, katalin_gombos@...
Varjas T,
Orsos Z,
Polyak E,
Peredi J,
Varga Z,
Nowrasteh G,
Tettinger A,
Mucsi G,
Ember I.
Faculty of Medicine, Institute of Public Health University of Pecs,
Pecs, Hungary.

BACKGROUND:
Aspartame (L-phenylalanine N-L-alpha-aspartyl-1-methyl ester)
is an artificial sweetener with widespread applications.

Previously published results have shown that among rats
receiving aspartame a significant increase
of lymphoreticular neoplasms, brain tumours and transitional cell
tumours occurred.

The aim of our short-term experiment was to investigate
the biological effect of aspartame consumption by determining
the expressions of key oncogenes and a tumour suppressor gene.

MATERIALS AND METHODS:
After one week per os administration of various doses of aspartame
to CBA/CA female mice, p53, c-myc,
Ha-ras gene expression alteration were determined in individual
organs.

RESULTS:
The results showed an increase in gene expressions concerning
all the investigated genes especially in organs with a high
proliferation rate:
lymphoreticular organs, bone-marrow and kidney.

CONCLUSION:
Aspartame has a biological effect even at the recommended daily
maximum dose.
PMID: 17354619

In Vivo. 2006 Jul-Aug; 20(4): 539-41.
An in vivo model for testing genotoxicity of environmental
fibre-associated nitroarenes.

* Varga C,
* Szendi K,
* Ember I.

Department of Environmental Health, Institute of Public Health
Medicine, University of Pecs, Hungary. chemsafety@...

The environmental carcinogens nitroarenes are frequently adsorbed by
asbestos fibres.
An effective dose of 1-nitropyrene was studied in vivo.
The mutagenic pattern of excreted urine of orally and
intraperitoneally exposed rats
was tested by the Ames mutagenicity assay.
The characteristics of detected mutagenicity proved to be different in
the two routes of exposure.
TA 100 mutagenicity was only detected following i.p. exposure,
while TA 98 revertant frequencies were increased significantly only
after deconjugation, in both groups.
Since environmental asbestos exposure involves carcinogenic effects of
adsorbed polycyclic aromatic hydrocarbons,
this animal model provides a useful tool for testing fibre-associated
nitroarenes,
in both mechanistic and risk assessment studies.
PMID: 16900786

Orv Hetil. 2004 Mar 7; 145(10): 507-14.
[Molecular epidemiology of cancers and precancerous conditions]
[Article in Hungarian]

* Ember I, istvan.ember@...
* Kiss I,
* Sandor J,
* Varga C,
* Gyongyi Z,
* Nemeth K,
* Feher K,
* Lukacs P,
* Dombi Z.

Pecsi Tudomanyegyetem, Altalanos Orvostudomanyi Kar, Kozegeszsegtani
Intezet, Pecs.

For many years the molecular biology has been one of the most
promising fields of science and its several methods have been used in
practice.
These new methods of molecular biology made impression on epidemiology
and developed a new discipline, called molecular epidemiology.
The molecular and predictive epidemiology play more and more important
roles in the prevention of cancers.
Early biomarkers could identify the high risk population to have the
possibilities of primary preventive interventions.
It uses both molecular biological methods and the elements of
epidemiology.
Its specificity is not high enough to establish the diagnosis but it
can be used to follow the "minimal residual disease" and with markers
of individual susceptibility, to assess the risk of tumors.
As to the practice there are many problems because of the limited
therapeutic possibilities, but the molecular and predictive
epidemiology becomes an important part of medicine in the future.
PMID: 15085589

In Vivo. 2006 Jan-Feb; 20(1): 141-6.
Effect of the chalcone analog E,E-bis(2-hydroxybenzylidene)
acetone on the
7,12-dimethylbenz[a]anthracene-induced Ha-ras gene activity in vivo.

* Perjesi P, pal.perjesi@...
* Ember I,
* Bozak RE,
* Nadasi E,
* Rozmer Z,
* Varjas T,
* Hicks RJ.

Institute of Pharmaceutical Chemistry, University of Pe'cs, School
of
Medicine, Rokus str. 2, H-7623, Pecs, Hungary.

The chalcone analog E,E-bis(2-hydroxybenzylidene)acetone (HBA) was
found to
display strong NAD(P)H:quinone reductase (NQO1) inducer potency in
Hepa 1c1c7
cells. In order to determine whether this promising chemopreventive
activity
would extend to anticarcinogenic properties, the effect of HBA on the
7,12-dimethylbenz[a]anthracene (DMBA)-induced expression of the Ha-ras
gene in
isolated RNA from liver, lung, kidney, spleen, thymus, lymph nodes and
bone
marrow of CBA/Ca inbred mice was investigated.
DMBA is a well-known chemical carcinogen, which can act as initiator
by causing
point mutations in certain oncogenes and tumor suppressor genes.
According to
the previous results, elevated Ha-ras expression has been noted even
24 h after
DMBA treatment. Administration of HBA simultaneously with DMBA
resulted in a
decrease of the DMBA-induced Ha-ras gene expression in all the
investigated
tissues. This observation suggests metabolic interaction of HBA and
DMBA.
Administration of HBA 24 h prior to the DMBA treatment reduced the Ha-
ras gene
expression in all the tissues but the liver,
where a slight elevation could be detected. This latter
effect could be the result of a possible CYPIA inducer and pro-oxidant
effects
of HBA. The pro-oxidant effect of HBA can be taken into consideration
based on
its previously demonstrated GSH-reactivity and the present results
obtained by
investigation of the time-course of Fenton reaction-initiated
degradation of
2-deoxyribose in the presence of HBA.
PMID: 16433043

In Vivo. 2005 May-Jun;19(3):559-62.
Carcinogenic potential of trans-2-hexenal is based on epigenetic
effect.

* Nadasi E, edit.nadasi@...
* Varjas T,
* Pajor L,
* Ember I.

Department of Public Health and Preventive Medicine, Faculty of
Medicine,
University of Pecs, 7624 Pecs, Szigeti u. 12, Hungary.

BACKGROUND: Trans-2-hexenal (2-hexenal) is an alpha,beta-
unsaturated
carbonyl compound protecting plants against harmful substances. Since
humans
have a permanent intake of 2-hexenal via vegetable products, this
genotoxic and
mutagenic compound is considered to play a role in human
carcinogenicity.
MATERIALS AND METHODS: Ha-ras and p53 gene expression changes and
tumor
development were investigated in mice and rats after 2-hexenal
administration.
RESULTS: 2-Hexenal exposure did not result in gene expression
alterations 24, 48
or 72 hours after administration while 10 out of the 72 mice and rats
included
in the long-term study developed a malignancy by the end of the 18-
month follow-up.
CONCLUSION: Our results suggest that, although 2-hexenal showed no
effect on
the expression of the investigated onco-and suppressor genes,
it has a marked carcinogenic potential, which may be
explained only by an epigenetic effect of the compound.
PMID: 15875776


In Vivo. 2005 Mar-Apr;19(2):465-70.
Oncogene amplification and overexpression of oncoproteins in
thyroid
papillary cancer.

* Varkondi E, varkondi@...
* Gyory F,
* Nagy A,
* Kiss I,
* Ember I,
* Kozma L.

Co-operative Research Centre, Semmelweis University, Budapest, H-1367
Budapest 5. Pf 131; Hungary.

BACKGROUND: Several oncogene aberrations have been found in papillary
thyroid cancer, the incidence of which has increased after the
accident in
Chernoby. The occurrence and prognostic significance of these
aberrations may
have importance in therapeutic strategies.
MATERIALS AND METHODS: Tumour tissues from 24 patients were
investigated
by Dot-blot DNA hybridisation for c-myc, Ha-ras amplification and p53
deletion,
and by immunohistochemical method
for cyclin D1, p53 and p21 overexpression.
RESULTS: Overexpression of p53 protein was detected in 66.6%,
with p21 expression (25%) without any influence on tumour phenotype.
Cyclin D1 overexpression was found in 50% to be associated with p21,
in inverse relation to Iymphocytic infiltration.
Overexpression of estrogen receptor was shown in 4 cyclin D1-positive
samples (17%).
CONCLUSION: Our results suggest that cyclin D1 overexpression is
associated
with poor prognosis.
The co-expression of cyclin D1 and p21 causes a CDK-independent,
estrogen receptor-mediated effect of the cyclin D1 also described in
breast cancer.
PMID: 15796211

Anticancer Res. 2004 Nov-Dec;24(6):3997-4001.
Early effects of transplatin on oncogene activation in vivo.

* Nemeth A, arpadnemeth@...
* Nadasi E,
* Bero A,
* Olasz L,
* Ember A,
* Kvarda A,
* Bujdoso L,
* Arany I,
* Csejtei A,
* Faluhelyi Z,
* Ember I.

Department of Public Health, Faculty of Medicine, University of Pecs,
Hungary.

The aim of the study was to investigate the early effect of
Transplatin (the
stereo-isomer of Cisplatin) on oncogenes in inbred CBA/Ca mice.
Cisplatin is
commonly used for the treatment of squamous cell carcinomas of the
head and
neck. Cisplatin has a strong oncogene activation effect compared to
the
structural analogue Transplatin. Body weight equivalent amounts of a
human dose
of Transplatin were administered intra-peritoneally to 6- to 8-week-
old, inbred,
female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment,
RNA was
isolated from the target organs and the expressions of c-myc, Ha-ras
and p53
genes were examined. Investigation of early changes showed no
significant
overexpression compared to Cisplatin, which had a significant effect
on oncogene
expression in the "short-term" in vivo test system.
PMID: 15736445

Magy Onkol. 2004;48(2):111-5. Epub 2004 Sep 7.Click here to read
[Health economics analysis of colorectal screening]
[Article in Hungarian]

* Boncz I, boncz.i@...
* Sebestyen A,
* Dozsa C,
* Pal M,
* Sandor J,
* Palasti J,
* Betlehem J,
* Ember I.

Diagnosztikai es Menedzsment Intezet, Pecsi Tudomanyegyetem,
Egeszsegugyi
Foiskolai Kar, Pecs, Hungary.

AIM: To assess the screening rate, the cost of screening and
treatment, and
to calculate the expected epidemiological and economic gain and
cost-effectiveness of mass-screening programme.
METHODS: The data derive from the financial database
of the National Health Insurance Fund of Hungary from 2001.
The cost of treatment includes the cost of outpatient care, the acute
and
chronic inpatient care, the subsidies of medicines' prices and the
expenditure
on disability to work (including sickness-pay).
The expected benefits of the screening programme were modeled with
different
screening strategy and mortality decrease for a 10 years interval.
RESULTS: The cost of treatment of colorectal cancer was around 9.98
billion Hungarian forints
(34 817 250 USD, 38 871 666 EUR) in 2001.
In the age-group 45-65 with 10% mortality decline 718 lives (net
present value, NPV: 515),
with 20% mortality decline 1462 (NPV: 1050) lives can be saved during
a 10 years screening programme.
The cost of one l ife saved varies between 4.0 million Hungarian
forints (13968 USD, 15595
EUR)/life saved and 16.3 million Hungarian forints (56.952 USD, 63.584
EURO)/life saved
according to the mortality decline and screening strategy.
The cost of one life year saved varies between 307 909 Hungarian
forints (1074 USD, 1200 EUR)/life year saved
and 1.25 million Hungarian forints (4381 USD, 4891 EUR)/life years
saved.
CONCLUSION: The implementation of organized colorectal screening can
lead to cost saving in Hungary.
The cost-effectiveness of colorectal screening seems to be acceptable
for purchaser, but many
methodological and organizational issues should be discussed in
details.
PMID: 15351803

Orv Hetil. 2003 Apr 13;144(15):713-7.
[Health economics analysis of cervical cancer screening]
[Article in Hungarian]

* Boncz I,
* Sebestyen A,
* Pal M,
* Sandor J,
* Ember I.

Orszagos Egeszsegbiztositasi Penztar, Szakmapolitikai es Koordinalo
Foosztaly, Budapest.

INTRODUCTION: To reduce the high mortality rate of cervical cancer
there are
organized, nation-wide mass-screening programmes. AIM: To assess the
screening
rate, the cost of screening and treatment and to calculate the
expected
epidemiological and economic gain and cost-effectiveness of mass-
screening
programme.
METHODS: The data derive from the financial database of the National
Health Insurance Fund of Hungary from 2001. To assess the screening
rate the
authors used the code "No. 29601 cytological examination for
screening" of out-patient care.
The cost of treatment includes the cost of out-patient care, the acute
and chronic inpatient care,
the subsidies of medicines' prices and the expenditure on disability
to work
(including sickness-pay). The expected benefits of the screening
programme were
modelled with changing the screening interval.
RESULTS: The screening rates for
1999, 2000 and 2001 were 14.5%, 16.2% and 15.6% respectively,
while the 3 year screening rate for 1999-2001 were 35.7%.
The cost of treatment of cervical cancer were around 1 billion
Hungarian forint in 2001. The cost of one life saved according to the
current
screening strategy was 16.6 million Hungarian forints (57.792 USD)
with a
successful screening programme, while with a less successful program
it was 33.8
million Hungarian forint (118.093 USD). The cost of one life year
gained
according to the current screening strategy was 0.7 million Hungarian
forints
(2.513 USD) with a successful screening programme,
while with a less successful program it was 1.5 million Hungarian
forint (5.134 USD).
CONCLUSION: It is important to increase the screening rate. With
increasing the
screening interval for women aged between 25-65 from 1 year to 2 or 3
years, it
improves the cost-effectiveness of screening programme.
PMID: 12774432

Anticancer Res. 2004 Jul-Aug;24(4):2557-61.
Failure of alkylating agents to improve induction chemotherapy of
oropharyngeal squamous cell cancer.

* Olasz L, lajos.olasz@...
* Nyarady Z,
* Nemeth A,
* Kiralyfalvi L,
* Ember I.

Department of Oral and Maxillofacial Surgery, University Pecs,
Dischka Gy. u
5., Pecs H-7621, Hungary.

BACKGROUND: This prospective semi-randomized study was undertaken
to assess
the effects and effectiveness of alkylating drugs in a preoperative
setting.
PATIENTS AND METHODS: During a 6-year period preceding February 2000,
80 patients with Stage II-IVa (AJCC 2002) squamous cell cancer of the
oral cavity were treated.
Thirty patients (Group N) received a combination of
bleomycin, vincristine and methotrexate (BVM). In the alkylating
group, thirty
patients (Group A/M) received BVM and mitolactol (dibromodulcitol),
while twenty
patients (Group A/C) received BVM and cisplatin. Patients underwent
surgery
within 3 weeks after chemotherapy. Clinical response rate and tumour-
free
survival were investigated.
RESULTS: Clinical complete response was 30%-36%
(Group N-A). Partial response was 57%-56% (Group N-A). Side-effects
were
moderate and reversible. Nausea, anaemia and leucopenia were observed
in the
alkylating (A) group, while other side-effects (alopecia, mucositis,
gastritis)
were similar in both groups. The observation time was 36 months.
Regional
disease-free survival showed a significant difference, favouring the
non-alkylating (N) group (p=0.03). A higher metastasis rate was
observed in the
alkylating (A) group.
CONCLUSION: Cisplatin and mitolactol in combination with
BVM showed higher local control and lower disease-free survival than
BVM alone.
That was mostly due to a higher rate of regional metastatis formation
in the alkylating-treated patients.
This may be a late side-effect caused by the immunosuppressive and
myelosuppressive
effect of alkylating agents.
PMID: 15330214

Anticancer Res. 2004 Nov-Dec; 24(6): 3965-70.
Polymorphisms of glutathione-S-transferase and arylamine N-
acetyltransferase
enzymes and susceptibility to colorectal cancer.
Kiss I, istvan.kiss@...
Nemeth A,
Bogner B,
Pajkos G,
Orsos Z,
Sandor J,
Csejtey A,
Faluhelyi Z,
Rodler I,
Ember I.
Department of Public Health, Faculty of Medicine, Pecs University of
Sciences,
Pecs, Hungary.

BACKGROUND:
Glutathione-S-transferases (GSTs) and N-acetyltransferases (NATs) are
involved
in the metabolism of a wide range of carcinogenic chemicals.

Allelic polymorphism of these enzymes is associated
with variations in enzyme activity,
hence it may affect the concentration of activated carcinogenic
chemicals in the body.

Previous studies suggest a possible cancer risk-modifying effect of
these
allelic polymorphisms,
but the results are still controversial.

We evaluated the effect of GSTM1, GSTT1, GSTP1, NAT1 and NAT2 enzymes
on
individual susceptibility to colorectal cancer, with particular
attention to
possible interactions between the studied genotypes.

MATERIALS AND METHODS
Five hundred colorectal cancer patients and 500 matched cancer-free
controls
were included in the study.

The allelic polymorphisms of GSTM1, GSTT1 and GSTP1, NAT1 and NAT2
enzymes
were determined by PCR-based methods, from peripheral blood
leukocytes,
and allelic distributions were compared between colorectal cancer
patients and
controls.

RESULTS:
The GSTM1 0 allele (OR: 1.48, 95% CI: 1.15-1.92)
and rapid acetylator genotypes
of NAT2 (OR: 1.52, 95% CI: 1.17-1.98)
were associated with an elevated risk.

No statistically significant correlation between NAT1, GSTT1, GSTP1
genotypes
and colorectal cancer was found.

Remarkably increased risk was associated with the GSTM1 0 allele--NAT2
rapid
acetylator genotype combination (OR: 2.39, 95% CI: 1.75-3.26)
and with the GSTM1 0 allele--NAT2
and NAT1 rapid acetylator triple combination (OR: 3.28, 95% CI:
2.06-5.23).

Carrying 4 or 5 putative "high-risk" alleles substantially increased
the risk of
colorectal cancer
(OR: 3.69, 95% CI: 2.33-5.86).

CONCLUSION:
The genotype of certain metabolizing enzymes affects the risk for
colorectal cancer.

This effect is particularly important when certain allelic
combinations are studied.

In the near future, individual level risk assessment may be reached by
further
increasing the number of studied polymorphisms, combining them with
traditional
epidemiological risk factors.
PMID: 15736440

Orv Hetil. 2006 Oct 1;147(39):1877-83.
[Questions of dermatoinfectology in the practice]
[Article in Hungarian]

* Hunyadi J, hunyadi@...
* Tettinger A,
* Szabo I,
* Kuhnyar A.

Debreceni Egyetem, Orvos- es Egeszsegtudomanyi Centrum, Bor- es
Nemigyogyaszati Klinika.


The importance of bacterial, viral and fungal diseases has
significantly
increased during the past decades. The reasons are numerous, but the
most
important ones are as follows: appearance of new variance of
microbes,
appearance and spread of antibiotic resistant bacterial strains, and
increasing
number of patients with various degree of immunodeficiency. For such
reasons we
consider extremely important to overview and upgrade our current
knowledge and
practice regarding to these diseases. This manuscript will discuss the
hottest
practical questions of dermato-infectology.
PMID: 17111649


Clin Cancer Res. 2006 May 1;12(9):2745-51.Click here to read
Preferential nuclear and cytoplasmic NY-BR-1 protein expression in
primary
breast cancer and lymph node metastases.

* Varga Z, zsuzsanna.varga@...
* Theurillat JP,
* Filonenko V,
* Sasse B,
* Odermatt B,
* Jungbluth AA,
* Chen YT,
* Old LJ,
* Knuth A,
* Jager D,
* Moch H.

Institute of Surgical Pathology, Department Pathology, University
Hospital
of Zurich, Zurich, Switzerland.

PURPOSE: NY-BR-1 is a recently isolated differentiation antigen,
which is
expressed in normal mammary tissue and in breast cancer. However,
current data
are based on RT-PCR analysis and nothing is known about the presence
of NY-BR-1
on a protein level. We previously generated a monoclonal antibody to
NY-BR-1 to
study the protein expression of NY-BR-1. METHODS: In our
immunohistochemical
study, NY-BR-1 was analyzed in normal tissues, various tumor types,
124 primary
breast cancers, and 37 paired lymph node metastases. RESULTS: Among
normal
tissues, NY-BR-1 was present solely in ductal epithelium of the
breast. In
tumors, carcinoma in situ and invasive carcinoma of the breast were NY-
BR-1
positive whereas other tumors and normal tissues were negative.
Sixty percent of invasive breast carcinomas were NY-BR-1 positive,
displaying
cytoplasmic and/or nuclear immunoreactivity. This coexpression was
verified by
confocal microscopy. Although the monoclonal antibody identified
intratumor
al heterogeneity, a majority (72%) of NY-BR-1-positive carcinomas
revealed
immunoreactivity in >50% of the tumor cells. NY-BR-1 expression was
more
frequent in estrogen receptor-positive and lymph node-negative
primary
carcinomas (P < 0.05 each) and was more common in grade 1 (77%) than
in grade 2
(63%) or grade 3 (50%) carcinomas (P < 0.05). This suggests that NY-
BR-1
expression is lost with tumor progression. Forty-nine percent of lymph
node
metastases were NY-BR-1 positive. CONCLUSION: This study supports the
notion
that NY-BR-1 is a differentiation antigen of the breast, which is
present in
normal and tumorous mammary epithelium. The organ-specific expression
of NY-BR-1
and its high prevalence in metastases indicate that it could be a
valuable
target for cancer immunotherapy.
PMID: 16675566


Anticancer Res. 2003 Nov-Dec;23(6C):4831-5.
Early effects of different cytostatic protocols for head and neck
cancer on
oncogene activation in animal experiments.

* Nemeth A,
* Nadasi E,
* Gyongyi Z,
* Olasz L,
* Nyarady Z,
* Ember A,
* Kvarda A,
* Bujdoso L,
* Arany I,
* Kiss I,
* Csejtey I,
* Ember I.

Dept. of Public Health, Faculty of Medicine, University of Pecs,
H-7643
Szigeti u. 12, Hungary. arpadnemeth@...

In vivo investigations on oncogenes and onco-suppressor genes may
provide
new findings on the potential carcinogenic effects of various
cytostatic
protocols inducing secondary tumours of the head and neck. Further
surgeries are
often necessary due to regional recurrence after the Cisplatin-
supplemented BVM
(Bleomycin, Vincristine, Methotrexate) protocol in the treatment of
human head
and neck tumours.
Our earlier studies have illustrated the carcinogenic and mutagenic
potential of Cisplatin.
The effect of Cisplatin on
the alteration of different onco- and suppressor genes has also been
proven.
Our present study aimed at investigating the early effects of the BVM
and the CFu
(Cisplatin, 5-Fluorouracil) protocols on early oncogene and tumour
suppressor
gene expressions in mice. Body weight equivalent amounts of
cytostatics were
administered intraperitoneally to 6- to 8-week-old, inbred, female CBA/
Ca mice.
Twenty-four, 48 and 72 hours after the treatment, RNA was isolated
from th
e target organs and the quantitative expression of c-myc, Ha-ras and
p53 genes
were examined. The protocols caused detectable changes. A "short-term"
in vivo
test, the 24-hour examination of gene expression, is suitable for
detecting
early effects of carcinogen exposure. The alterations of gene
expression, caused
by the Cisplatin-containing protocol, draw attention to the probable
role of
Cisplatin in the development of regional recurrence and to the
possibility of
prevention.
PMID: 14981932

Magy Onkol. 2003;47(2):177-83. Epub 2003 Sep 16.Click here to read
[Investigation of regional clusters of environmentally induced
cancers]
[Article in Hungarian]

* Sandor J,
* Szerencse P,
* Szucs M,
* Nemeth A,
* Kiss I,
* Ember I.

Human Kozegeszsegtani Intezet, Pecsi Tudomanyegyetem, Altalanos
Orvostudomanyi Kar, Pecs 7643, Hungary. janos@...

BACKGROUND: The environment is source of carcinogen effects, which
cannot be
monitored as precisely as it would be required. Due to this fact, it
is worth to
screen for areas with higher than expected number of cancers that is
for
clusters. The significance of cluster suspicion is highly variable and
the
investigations for clusters could need significant resources.
Therefore
step-wise protocols are recommended, which evaluate before proceedings
the
possibility of exclusion of cluster existence,
or of requirement for further epidemiological investigations.
Sometimes, the results establish actions to
reorganise the environmental control.
OBJECTIVES: The relationship between
cancer incidence and dangerous waste disposal sites was investigated
in Tolna
county (Hungary) and the usefulness of cluster studies was
demonstrated by the results.
METHODS: The incidence data based on histological investigations and
the location of 7 dangerous waste disposal sites were analysed by
geographic
al information system.
RESULTS: The incidences were not elevated around 6 sites.
The cancer risk seemed to be high by site in settlement S., because of
high
standardised incidence ratio (SIH=1.41) and empirical Bayes adjusted
SIH
(SIHEB=1.38). The risk increase proved to be significant in z-test and
mid-p
test by 10% and 15% type I error. Since the risks showed
nonhomogeneous spatial
distribution in the county and the number of high-risk settlements was
2.3 to
6.6, the cluster in S. cannot be rejected as false positive
observation. The
chromium contaminated wastes have been stored in S. for several
decades at river-side. Assuming that
the exposure was spred by the river and the villages in the 5-km
vicinity of the
river were exposed, the SIHs were aggregated for every 15-km
intervals. The
distance from S. was inversely related to the aggregated SIHs.
CONCLUSIONS: The sites proved to be noncarcinogenic sources
apart from the site S. for which the results suggested the high-risk
status.
The environmental pollution by site in S. could explain the increased
incidence. Consequently, additional studies are indicated in S. to
improve the
reliability of cluster evaluation. The study also demonstrated that
the cluster
investigation can be inserted into public health practise to improve
the
efficiency of cancer control.
PMID: 12975666

Environ Health Perspect. 2002 Nov;110(11):A662-1.Click here to read
The lack of environmental justice in Central and Eastern Europe.

* Varga C,
* Kiss I,
* Ember I.

PMID: 12417491

Anticancer Res. 2002 Jul-Aug;22(4):2109-16.
The possible relationship between onco/suppressor gene expression
and
carcinogen exposure in vivo: evaluation of a potential biomarker in
preventive
and predictive medicine.

* Ember I,
* Gyongyi Z,
* Kiss I,
* Ghodratollah N,
* Arany I.

Department of Public Health, Faculty of Medicine, University of
Sciences,
Pecs, Hungary. ember@...

An understanding of the molecular changes occuring during exposure
to a
carcinogen enhances the possibility of cancer prevention. Molecular
genetic-biological screening methods offer the potential for early
diagnosis of
high-risk groups, and identification of specific signals, as a major
step in
primary prevention. Recent investigations have suggested that oncogene
or
oncosuppressor gene expression investigation at the RNA level is a
proper and
early molecular epidemiological biomarker of carcinogen exposure and a
tool for
risk assessment. This is one way by which the high-risk groups could
be
recognized. At the protein level, the investigation of gene expression
is very
useful in molecular diagnosis and in molecular pathology.
PMID: 12174891


Magy Onkol. 2001;45(5):424-429.Click here to read
[Investigation of oncogene amplification or deletion, and
oncoprotein
expression in papillary thyroid cancer]
[Article in Hungarian]

* Varkondi E,
* Gyori F,
* Nagy A,
* Kiss I,
* Ember I,
* Kozma L.

Department of Pathology, Health Science Center, Debrecen University,
Debrecen, H-4004, Hungary.

AIM: Assessment of occurrence and possible prognostic significance of
c-myc
and Ha-ras amplification, p53 deletion and overexpression of cyclin
D1, p53 and
p21 in papillary thyroid cancer.
MATERIALS AND METHODS: Formalin-fixed,
paraffin-embedded tumor tissue from 24 patients were investigated. Dot-
blot DNA
hybridization was used to detect oncogene amplification or deletion.
The expression of oncoproteins was determined by immunohistochemical
method.
RESULTS: In our samples neither Ha-ras amplification
nor p53 deletion were found. Low c-myc amplification (mean: 2.55)
occured in 4
cases (17%). p53 protein was detected in 16 samples (66.6%), with p21
expression
(chi(2)=7.02, p<0.01) in 6 cases (25%). The p53 expression did not
influence the
tumor fenotype. Cyclin D1 overexpression was found in 12 cases (50%),
it was
often associated with p21 expression (chi2=10.1, p<0.001) and in
inverse
relation to the tumor lymphocytic infiltration (chi(2)=5.35, p<0.05).
Increased
expression of estrogen receptor was shown in 4 cyclin D1 positive
samples (17%).
CONCLUSIONS: The p53 detected in our study is likely not to be mutant
protein in all cases
because its presence was associated with p21 expression that the
mutant protein
cannot induce and also it did not mean more aggressive tumor
phenotype.
The connection of cyclin D1 overexpression with the lymphocytic
infiltration
of the tumor suggests that the increased expression of cyclin D1 means
poor
prognosis. The coexpression of cyclin D1 and p21 raises the modulative
character
of the p21 protein, thought to be a tumor suppressor originally, but
we find a
CDK-independent, estrogen receptor mediated effect of cyclin D1 more
likely,
which has been described in breast cancer and is also proved by the
coexpression
of cyclin D1 and estrogen receptor detected here.
PMID: 12050691

Anticancer Res. 2002 Jan-Feb;22(1A):225-30.
Effect of rancid corn oil on some onco/suppressor gene expressions
in vivo.
A short-term study.

* Perjesi P,
* Pinter Z,
* Gyongyi Z,
* Ember I.

Department of Medical Chemistry, University Medical School of
Pecs, Hungary.

Autooxidation of polyunsaturated fatty acids (PUFAs) of edible
oils results
in the formation of fatty acid hydroperoxides that can undergo further
chemical
transformations to yield a variety of re-arranged and chain-cleavage
products.
Since the oxidation products of PUFAs have been reported to have
cytotoxic and mutagenic effects, the consumption of rancid oils and
fats
represents a possible health hazard for the population. Storage of
corn oil at
room temperature and in the refrigerator for a forty-eight month
period resulted
in two different qualities of oil samples, which were characterized by
UV,
titrimetric (peroxide value, acid value) and GC-MS methods. Earlier it
was
demonstrated that the increase of expression of certain oncogenes and
tumor
suppressor genes is a method of choice for the early detection of
carcinogen
exposure. Treatment of CBA/Calpha inbred mice with the two oil samples
showed
significantly increased expression of the Ha-ras gene in all the
investigated
organs (liver, lung, kidney, thymus and spleen) of the rancid corn oil-
treated
animals. Expression of the c-myc and the p53 genes was also increased
after the
rancid corn oil-treatment in all the organs but the thymus of the
mice. The
results suggest that rancid oils, rich in omega-6 unsaturated fatty
acids, could be involved
not only in tumor promotion but in initiation as well.
PMID: 12017293


Anticancer Res. 2001 Nov-Dec;21(6A):3937-40.
Long-term effects of 1-nitropyrene on oncogene and tumor
suppressor gene
expression.

* Gyongyi Z, zoli@...
* Nadasi E,
* Varga C,
* Kiss I,
* Ember I.

Department of Preventive Medicine, Faculty of Medicine, University of
Pecs,
Hungary.

Late changes in the expression of oncogenes and tumor suppressor
genes
following carcinogenic exposure were examined in lung, liver and
kidney.
1-Nitropyrene (1-NP), which is a high-risk exposure factor in urban
and
industrial zones, was used as a carcinogenic agent. c-myc, Ha-ras and
p53 gene
expression was investigated after administration of a single dose of 1-
NP to
sensitive CBA/Ca mice in lung, liver and kidney for one year. One week
after a
single dose 1-NP administration, the expression of p53 was elevated in
the liver,
but, decreased in the lung and kidney.
There was no increase in the expression of c-myc or Ha-ras genes at
that time.
One month after the administration of the 1-NP, the expression of p53
was
increased in the kidney while the expression of Ha-ras and p53 was
elevated in
the liver. There was no significant difference in gene expression
between the
treated and control animal groups at any of the investigated periods
except for
the above-mentioned organs and
at the end point of the investigation. According to the literature, 1-
NP and
its metabolites remain at high concentrations in the kidney, liver and
lung. The
concentration of the carcinogenic agent and the expression of the
studied genes
did not seem to correlate with each other in this experiment.
PMID: 11911274

Eur J Epidemiol. 2001;17(5):443-7.Click here to read
Association between gastric cancer mortality and nitrate content
of drinking
water: ecological study on small area inequalities.

* Sandor J, janos@...
* Kiss I,
* Farkas O,
* Ember I.

Department of Public Health, University of Pecs, Hungary.

The carcinogenic feature of N-nitroso compounds has been well
established.
Similarly, the transformation of ingested nitrate to N-nitroso
compounds in the
stomach has been thoroughly documented, nevertheless nitrates'
carcinogenic
effect has not been proved convincingly in human. The present study
was aimed to
investigate a population of small villages provided by drinking water
with high
and widely variable nitrate content (72 mg/l median, 290.7 mg/l 95-
percentile
concentration). Empirical Bayes estimates for settlement-specific
age-, sex-,
and year-standardised mortality ratios of gastric cancer (GC) were
related to
the settlement level average nitrate concentrations in drinking water
controlling for confounding effects of smoking, ethnicity and
education.
The log-transformed average nitrate concentration showed significant
positive association with stomach cancer mortality
in linear regression analysis (p = 0.014).
The settlements were aggregated according to the nitrate concentration
into 10-percentile groups and the standardised mortality ratios
(SMRs) were calculated. Those groups with higher than 88 mg/l average
nitrate
concentration showed substantial risk elevation and the log-
transformed exposure
variables proved to be significant predictors of mortality (p = 0.032)
at this
level of aggregation also. The association seemed to be fairly strong
(r2 =
0.46). Although this investigation constituting an ecological study
has certain
limitations, it supports the hypothesis that the high level of nitrate
in
drinking water is involved in the development of GC.
PMID: 11855578

Anticancer Res. 1999 Mar-Apr;19(2A):1181-5.
Different H2 haplotypes have a strong influence on oncogene
action.

* Ember I, ember@...
* Kiss I,
* Nowrasteh G.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

The H2 complex has an important role in determining susceptibility
to viral
and chemical leukemogenesis in inbred mice. This also applies to
transplantable
leukemias, within the syngeneic system. In this respect H2K is
sensitive, H2d is
relatively sensitive, and H2b is absolutely resistant to leukemia
induction and
transplantation. In our present study we investigated the effect of
Cyclophosphamide, (a known chemical leukemogen) on onco/suppressor
gene
expression in CBA/Ca mice, very shortly after treatment with chemical
carcinogen
without any manifestation of tumour/leukemia symptoms. Here we
describe, in a
"short-term" experiment, the gene expression of Ha-ras, c-myc and p53
which was
similar to the leukemia induction in a "long-term" experiment. H2K
showed marked
elevation in terms of onco/suppressor gene expression. H2b expression
was modest
and H2d turned out to be more or less silent. The results obtained
from a short
term gene expression investigation shows similarity to
those obtained earlier from long term leukemia inducing experiments.
PMID: 10368672

In Vivo. 1998 Sep-Oct;12(5):489-94.
In vivo effects of CHOP protocol on onco and suppressor gene
expression:
follow-up study.

* Ember I,
* Kiss I,
* Raposa T,
* Nowrasteh G,
* Matolcsy A.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

In vivo investigation of onco/suppressor gene effects may provide
new
findings concerning chemical carcinogenesis. In earlier studies we
pointed out
the carcinogenic potential of COPP and ABVD chemotherapeutical
protocols in
"long-term" experiments. In another follow up study we proved the
connection
between the early gene expression changes and the late consequences of
COPP and
ABVD treatment during, a one year latency period. CHOP protocol is
containing
both proved carcinogenic cyclophosphamide and highly mutagenic
doxorubicyn. CHOP
protocol in "short-term" experiments shows strong effect on Ha-ras
oncogene expression.
PMID: 9827356

Anticancer Res. 2007 Jan-Feb;27(1A):279-82.
Prognostic factors in Hungarian breast cancer patients.

* Nadasi E,
* Anga B,
* Sandor J,
* Megyesi J,
* Kelemen D,
* Mottolese M,
* Natali PG,
* Hegedus G,
* Arany I,
* Ember I.

University of Pecs, Department of Public Health and Preventive
Medicine,
Szigeti u 12, 7624 Pecs, Hungary. edit.nadasi@...

BACKGROUND: Breast cancer is the most common cancer among women, with
variable outcomes, justifying a continuous search for new parameters
to predict
accurate prognosis and indicate suitable adjuvant therapy for
patients.
MATERIALS AND METHODS: Fourty-four stage I-III breast cancer specimens
were
investigated immunohistochemically for the expression of
cyclooxygenase-2 enzyme
(COX-2), hormone receptors, tumor suppressor gene p53, oncogene HER2
and
proliferation marker Ki-67. Additionally, twelve specimens were also
investigated for the
presence of the phosphorylated extracellular signal-regulated kinase
(pERK).
RESULTS: It was demonstrated that expressions of biological markers
were related
to each other (ER to p53 and Ki-67, COX-2 to ER, PgR, Ki-67 and p53,
Ki-67 to
p53 and PgR, p53 to PgR).
CONCLUSION: Our data indicate that concomitant
immunohistochemical evaluation of cyclooxygenase-2, hormone receptors,
p53 and
Ki-67 may be of clinical value in determining an accurate prognosis.
PMID: 17352244

Ann Oncol. 2007 Jan 27; [Epub ahead of print] Click here to read
The organisation and results of first screening round of the
Hungarian
nationwide organised breast cancer screening programme.

* Boncz I,
* Sebestyen A,
* Dobrossy L,
* Pentek Z,
* Budai A,
* Kovacs A,
* Dozsa C,
* Ember I.

Department of Health Policy, National Health Insurance Fund
Administration,
Vaci ut 73/A., 1139 Budapest, Hungary.

BACKGROUND: The aim of this paper is to give an overview of
organisational
issues of the Hungarian nationwide organised breast cancer screening
programme
and to provide the results of the first screening round of the
programme for the
years 2002-2003.
PATIENTS AND METHODS: Data were derived from the financial
database of the National Health Insurance Fund Administration covering
the
period 2000-2003. Women who underwent mammography screening were
included into
the study.
RESULTS: Uptake of the organised screening programme in 2002-2003 was
45.09%, while the recall rate was 7.23%. Malignant cases represented
65.38% of
total surgeries and 0.36% of total number of screened women yielding a
cancer
detection rate 3.6 per 1000 screened women. Malignant cases of 10.78%
were
identified as ductal carcinoma in situ, while 89.22% was invasive
cancer. Benign
to malignant ratio was 0.54 : 1.
CONCLUSION: There is therefore an urgent need
to closely monitor performance and to review programme
policies and procedures with the aim of increasing both the
participation rate
and the proportion of women eligible to attend screening.
PMID: 17259642

Orv Hetil. 2006 Aug 27;147(34):1655-7.
[Can we call the preventive part of genomic medicine as genomic
epidemiology?]
[Article in Hungarian]

* Ember I.

PMID: 17017682


Magy Onkol. 2005;49(2):109-15. Epub 2005 Oct 24.Click here to read
[Results of monitoring the year 2002 of the Hungarian breast
cancer
screening program]
[Article in Hungarian]

* Boncz I,
* Hoffer G,
* Sebestyen A,
* Dozsa C,
* Ember I.

Orszagos Egeszsegbiztositasi Penztar, Budapest. boncz.i@...

AIM: The aim of the study is to analyse the regional and time range
characteristics of the breast cancer screening programme and the
utilization of
health services related to the programme.
METHODS: The data derive from the
database of the National Health Insurance Fund Administration
containing routinely collected financial data.
The patients include all the women having mammography screening in the
year of 2002
(N=314,395).
In the time range analysis the starting point (T0) was the time of
the mammography screening identified with the outpatient code
"42400 mammography screening".
We calculated the average delay between the time of mammography
screening (time=T0), further diagnostic (time=T1) and therapeutic
(time=T2) procedures.
For the calculation of the average period spent from the time of
mammography screening we used the median value instead of arithmetic
mean.
RESULTS: According to our data 17,303 women had ultrasound examination
in axilla
(T1 median value: 20 days) and 23,249 women
had ultrasound examination in breast (T1 median value: 26 days).
Among the women having mammography examination in 2002, 906 had
chemotherapy
(T2 median value: 83 days), while 1364 patients had radiotherapy
(T2 median value: 136 days).
The T2 median value of subtotal and total mastectomy was 43-47 days
and 50-53 days respectively,
while the T2 median value of breast operations because of non-
malignant causes was 57 days after
mammography screening.
The total annual cost of organised breast cancer screening programme,
including the cost of mammography examination, the cost of further
diagnostic
examination and surgical, radio- and chemotherapy treatment of
recalled women,
was 2,242 billion Hungarian forints (8,968 million euros) in 2002.
CONCLUSION: We observed significant regional differences, which result
in
large discrepancies in the equity. We can assume that these
differences can be
reduced by better organisation and the more consistent application of
professional guidelines.
PMID: 16249805

Orv Hetil. 2005 Sep 18;146(38):1963-70.
[The attendance of the first screening round (2002-2003) of the
Hungarian
organized breast cancer screening program and its effect on the number
of
diagnostic and screening mammography]
[Article in Hungarian]

* Boncz I,
* Sebestyen A,
* Dobrossy L,
* Pentek Z,
* Kovacs A,
* Csaba D,
* Budai A,
* Ember I.

Orszagos Egeszsegbiztositasi Penztar, Budapest. boncz.i@...

AIM: Organised, nationwide screening for breast cancer with
mammography in
the age group 45-65 years with 2 years screening interval started in
Hungary in
January 2002. The aim of this study is to analyze the attendance rate
of breast
screening programme, including the analysis of the ratio of screening
and
diagnostic mammography examinations.
DATA AND METHODS: The data derive from the
financial database of the National Health Insurance Fund
Administration (NHIFA)
covering the period 2000-2003. The ratio of women was calculated in
the age
group 45-65 years having either a screening mammography or a
diagnostic
mammography. The analysis was carried out for the years 2000-2001
(mainly
opportunistic screening) before and 2002-2003 after the implementation
of
nationwide organized programme.
RESULTS: In the years 2000-2001 7,26% of the women aged 45-65 had an
opportunistic screening mammography while in 2002-2003 33,95% of the
target
population had screening mammography within the or
ganized programme. During the same periods 19,67% (2000-2001) and
22,05%
(2002-2003) of women aged 45-65 had a diagnostic mammography. Thus the
total
(screening and diagnostic) coverage of mammography increased from
25,85%
(2000-2001) to 53,46% (2002-2003).
CONCLUSIONS: The attendance of the Hungarian
organized breast cancer screening programme - compared to the previous
period
before the implementation of the organized screening programme - is
promising,
although to achieve the expected results in mortality decrease a
further
improvement of the uptake is necessary.
PMID: 16238249

Anticancer Res. 2001 Sep-Oct;21(5):3377-80.
Changes in expression of onco- and suppressor genes in peripheral
leukocytes--as potential biomarkers of chemical carcinogenesis.

* Gyongyi Z,
* Ember I,
* Kiss I,
* Varga C.

Department of Preventive Medicine, Faculty of Medicine, University
of Pecs,
Hungary. zoli@...

An animal model was developed to investigate the expression of two
oncogenes
(c-myc, Ha-ras) and a suppressor gene (p53) as early markers of the
effects of
carcinogenic exposure and/or tumourigenesis. Inbred Long-Evans rats
were treated
with 7,12-dimethylbenz(a)anthracene and the transient/permanent gene
expressions
were measured after 24 and 48 hours by dot blotting in potential
target tissues
(lung, liver, lymph nodes, kidneys, spleen) and in peripheral blood
leukocytes.
The aim of the study was to test blood leukocytes, as surrogate
tissue, showed
similar expression patterns of the selected genes following
carcinogenic
exposure. c-myc did not prove to be an applicable early biomarker due
to the
lack of or low level of its expression. However, remarkable of early
elevations
were detected in the expression signals of Ha-ras and p53.
PMID: 11848497

Anticancer Res. 2001 Mar-Apr;21(2B):1321-5.
Copy number of cancer genes predict tumor grade and survival of
pancreatic
cancer patients.

* Nagy A,
* Kozma L,
* Kiss I,
* Ember I,
* Takacs I,
* Hajdu J,
* Farid NR.

Department of Pathology, University Medical School of Debrecen,
Hungary.

Pancreatic cancer is on the increase. While means of early
diagnosis are
being sought, it continues to present late. Prognostication is based
on patient
and tumor characteristics, including expression or mutation of cancer-
related
genes. Few studies have examined the impact of the amplification of
these genes
on the outcome of pancreatic cancer. We have now used a non-
radioisotopic
slot-blot technique to relate gene copy numbers of p53, c-myc and K-
ras to tumor
grade and survival. Outcomes were corrected for patient
characteristics, tumor
location and TNM staging.
The Kaplan-Meier test for likelihood of survival showed
that increase in copy number of the two oncogenes and loss of p53
were
associated with non-significant reduction in survival. When these
variations in
cancer gene copy numbers were, however, examined by logistic
regression analysis
in the context of patient and tumor characteristics, survival was
negatively
related to K-ras amplification (p = 0.0291). Tumor grade, but not
survival
was positively related to loss of p53 gene copy (p = 0.0131)
as well as c-myc amplification (p = 0.0248). Thus using a simple
non-radioisotopic technique for the detection of cancer gene copy
number in
association with patients and disease characteristics, we could
predict survival
on the one hand and tumor behavior on the other. Such information
could be used
to plan initial and follow-up therapy.
PMID: 11396207

Anticancer Res. 2001 Jan-Feb;21(1B):707-10.
C-myc amplification and cluster analysis in human gastric
carcinoma.

* Kozma L,
* Kiss I,
* Hajdu J,
* Szentkereszty Z,
* Szakall S,
* Ember I.

Department of Preventive Medicine, University Medical School of
Debrecen,
4012 Debrecen, P.O. Box 9, Hungary.

The tumour samples ot 23 patients (9 male, 14 female, aged 28-85)
were
randomly selected for the study. DNA was isolated from paraffin
embedded tissue
for quantitative dot-blot hybridization, in order to determine the
amplification
values for the c-myc and K-ras oncogenes. The clinical and
histological
parameters studied were as follows: grade, TNM staging system,
Lauren's
histological type, localization and the severity of the disease.
Amplified c-myc
was found in 6 cases. Amplification was concomitant with c-myc
overexpression
detected with immunohistochemical staining. The amplification--9.1-
fold on the
average (ranging from 2.12 to 18.2) was significantly associated with
the
presence of distant metastasis (corr. coeff.: 0.5623, p < 0.01), but
with none
of the other parameters. No case with K-ras amplification was
recorded. The
result of the multivariate cluster analysis proved that age was the
decisive factor
in the segregation process. This age-related distribution (69 vs. 40,
p < 0.001),
however, did not coincide with either the incidence of distant
metastasis or c-myc amplification.
PMID: 11299830

Eur J Cancer Prev. 2000 Dec;9(6):439-42.Click here to read
Comparison of early onco/suppressor gene expressions in
peripheral
leukocytes and potential target organs of rats exposed to the
carcinogen
1-nitropyrene.

* Ember I,
* Kiss I,
* Gyongyi Z,
* Varga CS.

Department of Preventive Medicine, Faculty of Medicine, University of
Pecs,
Hungary. ember@...

An in-vivo model has been developed to study early expressions of
c-myc,
Ha-ras oncogenes and p53 suppressor gene as biomarkers of carcinogenic
exposure
and/or tumorigenesis. In order to validate the in-vivo expression
changes as
biomarkers, rats were treated with the outdoor air pollutant
carcinogen 1-nitropyrene.
The gene expression levels were measured after 24 and 48 h in
potential target tissues (lung, liver, lymph nodes, kidneys, spleen)
and in
peripheral blood leukocytes. Another main objective was to prove the
applicability of leukocytes as a surrogate tissue, having a similar
expression
pattern of the selected genes upon carcinogenic exposure. The c-myc
oncogene was
not suitable as an early biomarker because of the lack or low level of
its
expression. However, in the case of the other oncogene Ha-ras and the
suppressor
gene p53, remarkable and early changes were detected in the expression
signals.
Similar expression patterns could only be detected in leukocytes and
the
spleen; therefore we continue this validation study by using other
types and
routes of exposure.
PMID: 11201684

Eur J Cancer Prev. 2000 Dec;9(6):429-32.Click here to read
Allelic polymorphism of GSTM1 and NAT2 genes modifies dietary-
induced DNA
damage in colorectal mucosa.

* Kiss I,
* Sandor J,
* Ember I.

Department of Public Health, Medical Faculty, University of Sciences
Pecs,
Hungary. op@...

Typically, cancer is caused by the interaction of genetic and
environmental
factors. In colorectal carcinogenesis, diet and nutritional habits are
the most
important external risk determinants. Allelic polymorphisms of
certain
metabolizing enzymes may have an influence on cancer risk by modifying
the
concentration of active carcinogenic compounds in the body. In the
present study
we investigated the interaction between nutritional and genetic
susceptibility
factors in human colon carcinogenesis. Healthy volunteers were divided
into four
groups, based on allelic polymorphisms of N-acetyltransferase 2 and
glutathione-S-transferase M1 enzymes. Comet assay was used to
determine the
level of DNA strand breaks in exfoliated colorectal mucosal cells,
following a
2-day vegetarian diet, and after switching to a 2-day 'high-meat'
diet. The
'high-meat' diet statistically significantly increased the amount of
single-strand breaks in rapid acetylators and among individuals with a
GSMT1 + genotype,
while it caused only a slight and not significant increase in the
other groups.
Our study emphasizes the importance of using susceptibility markers
in
cancer epidemiology, since environmental effects are strongly modified
by these
genetic factors.
PMID: 11201682

Anticancer Res. 2000 May-Jun;20(3A):1695-701.
The prognostic value of the presence of mutations at the codons
12, 13, 61
of K-ras oncogene in colorectal cancer.

* Pajkos G,
* Kiss I,
* Sandor J,
* Ember I,
* Kishazi P.

MI Central Hospital, 2nd Department of Internal Medicine-Oncology,
Budapest,
Hungary.

The predictive and prognostic value of the c-K-ras mutation is
still
unequivocal despite extensive and intensive studies. Investigation of
the
occurrence of mutations in 88 colorectal cancer patients' specimens
using the
polymerase chain reaction (PCR) is reported: age: 61.9 years (27-80),
gender: 48 male, 42 female, Dukes' stages:
43 at B, 35 at C, 10 at D, primary of tumour: 52 colon, 36 rectal
adenocarcinoma.
Mutation of one of the three ras-codons was detectable in the 54
cases, more frequently at the Dukes' stage C (p < 0.05). The ras-
mutation
correlated to a more elevated death-rate in the Dukes' B and C stages
(p < 0.01). Mean survival time and time to progression were
significantly longer at
the Dukes' stage B if mutation was not detected (p < 0.01). The
genetic
alteration occurred significantly more frequently at tumours of the
right-side
colon, than the left side (p < 0.02) or rectum (p < 0.05). However, in
the age
group of 41-50 years, it was more significantly ident
ified in the cases of rectal cancer (p < 0.01). At the age of 51-60
years
mutations were detected in men at a higher rate (p < 0.05). The
mutation of the
codon 13 appeared more frequently in the cases of local recurrences (p
< 0.05).
The occurrence of the ras-oncogene is a sign of an extremely malignant
potential of tumour.
This fact manifested itself
in the time to progression and mean survival time of patients at the
same
clinical or pathological stage. The higher frequency of genetic
alterations at
the proximal colon may be the reason for more unfavourable prognosis
of the
disease localised to this site. Reconstructing the molecular events,
the
presence of the ras mutation proved to be an important element for
prognosis of
the disease and should be a basis of potentially individualised
therapeutic
intervention.
PMID: 10928094

Anticancer Res. 2000 May-Jun;20(3A):1563-6. Links
1-Nitropyrene induces elevated expression of oncogenes and tumor
suppressor
genes 24 hours after treatment in CBA/Ca mice.

* Ember I,
* Pusztai Z,
* Gyongyi Z,
* Kiss I.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

In an earlier experiment we found that 1-nitropyrene treatment
causes an
increase in the expression of certain onco/suppressor genes in
different organs of CBA/Ca mice.
In order to further study the kinetics and significance of these gene
expression
changes, we determined the effect of 1-nitropyrene treatment on the
expression
of c-myc, p53, Ha-ras, N-ras, and Ki-ras genes, 24 hours after
treatment.
Expression of the ras family did not change during the studied
interval, while
elevated expression of c-myc and p53 genes was observed in the spleen,
bone
marrow and lymph nodes (only c-myc in the latter). The results suggest
a
different pattern for the involvement of the ras genes in 1-
nitropyrene-caused
carcinogenesis, and also underlines the differences in the organ
specificity of
chemical carcinogens in humans and in experimental animals. In the
present
study, we also confirmed the in vivo applicability of early gene
expression
changes as biomarkers of carcinogenic exposure.
PMID: 10928071

Anticancer Res. 2000 Jan-Feb;20(1B):519-22.
Colorectal cancer risk in relation to genetic polymorphism of
cytochrome P450 1A1, 2E1, and glutathione-S-transferase M1
enzymes.

* Kiss I,
* Sandor J,
* Pajkos G,
* Bogner B,
* Hegedus G,
* Ember I.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

Chemical carcinogens generally require metabolic activation in
order to be
able to bind to DNA and contribute to cancer causation. Most of the
human
metabolizing enzymes are genetically polymorphic, and these
polymorphisms may
affect the enzyme activity or inducibility. In our present study we
investigated
the connection between genetic polymorphism of cytochrome P450 1A1,
2E1 (phase I
enzymes) and glutathione-S-transferase M1 (a phase II enzyme) and
colorectal
cancer occurrence in a Hungarian population. The CYP 2E1 c2 allele
proved to be
in significant association with colorectal cancer (OR: 1.91, 95% CI:
1.05-3.52),
the CYP 1A1 Val allele was also overrepresented among colon cancer
patients (OR:
1.57, 95% CI: 0.90-2.74), and the frequency of GSTM1 homozygous 0
genotype showed only
minor difference (OR: 1.19, 95% CI: 0.75-1.35). Combined analysis of
the
polymorphisms showed that individuals carrying all the three "high-
risk" alleles
have a strikingly increased risk for sporadic colorectal cancer
(OR: 4.62, 95% CI: 1.23-25.68).
PMID: 10769717

Anticancer Res. 2000 Jan-Feb;20(1A):475-81.
Effect of E-2-(4'-methoxybenzylidene)-1-benzosuberone on the
7,12-dimethylbenz[alpha]anthracene-induced onco/suppressor gene action
in vivo.
I: A 24-hour experiment.

* Perjesi P,
* Bayer Z,
* Ember I.

Department of Medical Chemistry, University Medical School of Pecs,
Hungary.

The cyclic chalcone analogue, E-2-(4'-methoxybenzylidene)-1-
benzosuberone
(MBB), was found to show outstanding in vitro antineoplastic activity
against
P388, L1210, Molt 4/C8 and CEM cells as well as against a panel of
human tumor
cell lines. In order to determine whether this promising
antineoplastic activity would extend to anticarcinogenic properties,
the effects of MBB on the
7,12-dimethylbenz[alpha] anthracene (DMBA)-induced expression of
c-myc, Ha-ras and p53 genes in isolated RNA from liver, lung, kidney,
spleen,
thymus, lymph nodes and bone marrow of CBA/Ca inbred mice was
investigated.
DMBA is a well-known chemical carcinogen, which can act as an
initiator by causing
point mutations in certain oncogenes and tumor suppressor genes.
Elevated
expression of oncogenes after treatment with DMBA and other
carcinogenic
chemicals has been noted previously. Administration of MBB
simultaneously with DMBA,
24 hours prior to or 24 hours after the DMBA treatment
characteristically modified the DMBA-induced expression
of the three genes in the 24-hour experiments.
The most pronounced suppression effect of MBB could be observed in
almost all the investigated tissues when it was administered
simultaneously with DMBA.
These "short-term" in vivo results support our previous conclusion
that
MBB can serve as a model molecule for subsequent structural
modifications in searching for
new effective anticarcinogenic agents.
PMID: 10769699

Eur J Cancer Prev. 1999 Aug;8(4):331-4.
The usefulness of in vivo gene expression investigations from
peripheral
white blood cells: a preliminary study.

* Ember I,
* Kiss I,
* Raposa T.

Institute of Preventive Medicine, University Medical School of Pecs,
Hungary. ember@...

Alterations of onco/tumour suppressor genes are involved in the
formation of
human hematological malignancies. Previously, in animal models, we
demonstrated
the applicability of in vivo gene expression investigations to monitor
the
effects of certain carcinogenic chemicals. In our present study we
determined
the expression of onco/suppressor genes from isolated peripheral white
blood
cells of patients with chronic myeloid leukaemia (CLL) and non-Hodgkin
lymphoma
(NHL). Gene expressions were determined by isolation of total RNA
and slot blot hybridization with chemiluminescently labeled gene
probes
(Ha-ras, c-myc and p53).
Expression levels were compared before and after treatment with a
combined cytostatic protocol, containing cyclophosphamide,
doxorubicin,
vincristine and prednisolone (CHOP). Both the CLL and NHL group of
patients
exhibited significantly higher expression of the investigated genes
than healthy
controls. One month after the cytostatic treatment, we found conside
rably fewer individuals with overexpressed oncogenes than before the
treatment.
Our study proved that onco/tumour suppressor gene expressions could be
used as
biomarkers of certain hematological malignancies, and to monitor the
therapeutical effect of cytostatic drugs.
PMID: 10493309

Orv Hetil. 1999 Jul 25;140(30):1673-9.
[Prognostic value of the presence of the mutation of the codons
12, 13 and
61 in K-ras oncogene in colorectal cancer]
[Article in Hungarian]

* Pajkos G,
* Kiss I,
* Sandor J,
* Ember I,
* Kishazi P.

II. Belgyogyaszat-Onkologia, BM Kozponti Korhaz es Intezmenyei,
Budapest.

Despite of extensive and intensive investigations, the predictive
and
prognostic value of c-K-ras mutation is not unequivocal. There has
been reported
about investigation the occurrence of mutations in the 88 colorectal
cancer
patient's specimen using polymerase chain reaction. Age: 61.9 years
(27-80),
gender 8 male, 42 female. Dukes' stages: 43 at the B, 35 at C, 10 at
D. Primary
of tumour: 52 colon, 36 rectal adenocarcinoma. Mutation out of one of
the three
ras-codons was detectable in the 54 cases, more frequently at the
stage Dukes' C
(p < 0.05). The ras-mutation concerned to more elevated death-rate in
the stages
Dukes' B and C (p < 0.01). Mean survival time to progression was
significantly
longer at the stage Dukes' B if mutation had not been detected (p <
0.01). The
occurrence of the rate of genetic alteration was significantly more
frequent at
tumours of right-side colon, than left side (p < 0.02) or rectum (p <
0.05) one's.
However, at the age of 41-50 years it was significantly more
presented
at the cases of rectal cancer (p < 0.01). At the age
of 51-60 years mutations were detected among men at higher rate (p <
0.05). The
cases of local recurrences concerned by mutation at the codon of 13 (p
< 0.05).
Occurrence of ras-oncogene is the sign of extremely malignant
potential of
tumour. This fact manifested itself in the time to progression and
mean survival
time of patients at same clinical or pathological stage. The higher
frequency of
genetic alterations at the proximal colon may be the reason of more
unfavourable
prognosis of the disease localised to this site. Reconstructing the
molecular
events, the presence of ras mutation can serve as a basis for
prognosis of the
disease and permit of potentially individualised therapeutic
intervention.
PMID: 10461447 [

Anticancer Res. 1999 Mar-Apr;19(2A):1181-5.
Different H2 haplotypes have a strong influence on oncogene
action.

* Ember I,
* Kiss I,
* Nowrasteh G.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary. ember@...

The H2 complex has an important role in determining susceptibility
to viral
and chemical leukemogenesis in inbred mice. This also applies to
transplantable
leukemias, within the syngeneic system. In this respect H2K is
sensitive, H2d is
relatively sensitive, and H2b is absolutely resistant to leukemia
induction and
transplantation. In our present study we investigated the effect of
Cyclophosphamide, (a known chemical leukemogen) on onco/suppressor
gene
expression in CBA/Ca mice, very shortly after treatment with chemical
carcinogen
without any manifestation of tumour/leukemia symptoms. Here we
describe, in a
"short-term" experiment, the gene expression of Ha-ras, c-myc and p53
which was
similar to the leukemia induction in a "long-term" experiment. H2K
showed marked
elevation in terms of onco/suppressor gene expression. H2b expression
was modest
and H2d turned out to be more or less silent. The
results obtained from a short term gene expression investigation
shows
similarity to those obtained earlier from long term leukemia inducing
experiments.
PMID: 10368672

Orv Hetil. 1999 Jan 3;140(1):21-8.
[Epidemiologic study of regional inequalities]
[Article in Hungarian]

* Sandor J,
* Kiss I,
* Benyi M,
* Brazay L,
* Ember I.

Human Kozegeszsegtani Intezet, Pecsi Orvostudomanyi Egyetem.

The technological achievements of the recent years and the need
for more
advanced control of the processes within the health sector have
supported the
geographical epidemiology to become a distinct branch of epidemiology.
The
combined application of the simple standardized rates, statistical
tests and
different corrected risk parameters is able to describe the health
status for
geographically defined, small populations. Several statistical
processes have
been elaborated to estimate the number of the false positive results
and to evaluate
the role of chance in predicting the observed geographical pattern.
These data
completed with the usual risk measures quantify the risk difference
within a
broader region and determine the actual risk levels for the
investigated small
areas. The routine data processing system operating as a part of the
public
health surveillance identifies the high risk areas (the clusters) and
without
leaving the framework of routine data handling investigates
the association between basic exposure data and health risks
producing
additional data about the nature of the aggregation of health related
events.
All the spetially varying etiological factors (environmental effects,
social
status, traditions, regional features of the health sector etc.) are
ready to
elicit regional alterations in the health status. The aim of the
geographical
information system is to cover the consequences of the uneven
distribution of
these factors. Since these kind of etiological factors play
significant role
in the generation of the most important public health problems in
Hungary,
and it is known that the small area
inequalities are profound for these health impairments, the more
extensive
application of geographical information systems is expected to improve
the
efficiency of the control for public health problems and the
performance of
preventive medicine.
PMID: 9989108

Anticancer Res. 1998 Nov-Dec;18(6A):4489-92.
Short-term effects of 1-nitropyrene on chromosomes and on oncogene/
tumor
suppressor gene expression in vivo.

* Pusztai Z,
* Selypes A,
* Ember I.

Department of Public Health, University Medical School of Pecs,
Hungary.

In order to establish an animal model testing the effects of 1-
nitropyrene
in vivo at the oncogene level, we investigated the early biological
effects of
1-nitropyrene in mice. The treatment of 6-8 week-old CBA/Ca mice with
a single
30 mumol/kg body weight dose of 1-nitropyrene
caused a significant increase in chromosome aberrations 48 hours after
exposure.
The aberrations were mainly of the euploid type. We also found
elevated
expression of the Ha-ras oncogene in the isolated total cellular RNA
from the
liver, lung, kidney, spleen and thymus. The highest increase was seen
in the
lung and it was also high in the spleen and in the thymus. There was a
higher
increase in the males than in the females in all organs. In this study
we
confirmed that early genetic alterations such as oncogene expression,
can be
examined not only in vitro, but also in vivo experiments.
PMID: 9891514

Eur J Cancer Prev. 1998 Oct;7(5):417-9.
Detection of elevated oncogene expressions in brain tumours and
their
macroscopically healthy surrounding tissues.

* Kiss I,
* Dezsenyl E,
* Kiss T,
* Csecsei G,
* Ember I.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.
PMID: 9884889

In Vivo. 1998 Sep-Oct;12(5):489-94.
In vivo effects of CHOP protocol on onco and suppressor gene
expression:
follow-up study.

* Ember I,
* Kiss I,
* Raposa T,
* Nowrasteh G,
* Matolcsy A.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

In vivo investigation of onco/suppressor gene effects may provide
new
findings concerning chemical carcinogenesis. In earlier studies we
pointed out
the carcinogenic potential of COPP and ABVD chemotherapeutical
protocols in
"long-term" experiments. In another follow up study we proved the
connection
between the early gene expression changes and the late consequences of
COPP and
ABVD treatment during, a one year latency period. CHOP protocol is
containing
both proved carcinogenic cyclophosphamide and highly mutagenic
doxorubicyn. CHOP
protocol in "short-term" experiments shows strong effect on Ha-ras
oncogene
expression.
PMID: 9827356

Eur J Cancer Prev. 1998 Apr;7(2):167-8.
Oncogene and tumour suppressor gene expression changes in persons
exposed to
ethylene oxide.

* Ember I,
* Kiss I,
* Malovics I.

PMID: 9818781


Ember I, Kiss I, Faluhelyi Z.
Gene expression changes as potential biomarkers of tumour
bearing status in humans.
Eur J Cancer Prev. 1998 Aug;7(4):347-8. No abstract available.
PMID: 9806124


In Vivo. 1998 Mar-Apr;12(2):201-7.
Early effect of cyclophosphamide on oncogene expression in vivo.

* Ember I,
* Kiss I,
* Vermes E.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

Cyclophosphamide (CP) is a widely used chemotherapeutic drug, with
proven
carcinogenic effects. Secondary tumours induced by CP are kidney
tumours in
humans and haemopoietic malignancies in rodents. Previous experiments
have shown
its effect on H-ras, c-myc and p53 gene expression in long term in
vivo
experiments. Our model was developed to analyse the events in the
first 24 hours after the administration of
CP in short term experiments. The expression of Ha -ras, c-myc and p53
was
investigated in the target organs during and up to 24 hours after the
administration, at 0.25, 0.5, 1, 6, 12 and 24 h. Since the majority
of
CP-induced tumours are leukemias and lymphomas in the CBA/Ca mouse
model, RNA
was obtained from the thymus and the spleen. The results show that p53
is
strongly expressed in the thymus during the focused period. On the
other hand,
the samples were subjected to in situ hybridisation and compared with
the
results of in situ hybridisation of lung and liver samples.
Comparing the results of total RNA and in situ hybridisation should
prove
useful if the total RNA signal is too weak or not detectable at all.
The in situ
hybridisation picture showed many positive cells without high
expression of
oncogenes. Further flow-cytometric studies are necessary to provide a
full
explanation of the mechanism of CP induced changes.
PMID: 9627803

Cancer Detect Prev. 1998;22(3):241-5.
Oncogene and suppressor gene expression as a biomarker for
ethylene oxide
exposure.

* Ember I,
* Kiss I,
* Gombkoto G,
* Muller E,
* Szeremi M.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

Ethylene oxide is a proven genotoxic chemical, and there is lots
of evidence
suggesting its carcinogenic effects in humans. The unexpected massive
appearance
of a certain tumorous cluster in personnel exposed to ethylene oxide
in a
Hungarian county hospital focused attention on the effects of this
toxic gas.
Since we had developed an animal model for the investigation of
alterations in
onco/suppressor gene expression due to external carcinogenic agents,
and this
model had already been used to evaluate the carcinogenic effects of
cytostatic
drugs in humans, an analysis of the effects of ethylene oxide exposure
seemed to
offer further information on the usefulness of gene expression as a
biomarker.
The main purpose of our study was to
determine whether or not ethylene oxide exposure causes an elevated
expression
of onco/suppressor genes in the white blood cells of exposed people.
Two
different exposed groups and one control group were included in the
study.
The N-ras and p53 genes were chosen for the investigations of gene
expression.
N-ras is known to be activated in several tumor types,
and p53 is also involved in carcinogenesis and plays an important role
in the cellular answer mechanism to exogenous toxic effects.
RNA was isolated from the white blood cells, slot blotted onto
nitrocellulose membranes, and hybridized with chemoluminescently
labeled gene
probes. The results were detected on X-ray films and scanned into a
computer,
and relative risk for elevated gene expression was calculated in each
group.
Elevated N-ras and detectable p53 expressions were observed more
frequently in
both exposed groups compared with the control group
(relative risks--N-ras: 1.57 [0.77-3.22] and
2.34 [1.21-4.52]; p53: 6.67 [2.35-18.92] and
6.06 [2.10-17.49]).
PMID: 9618046

Anticancer Res. 1998 Mar-Apr;18(2A):1149-52.
Effect of ABVD therapeutic protocol on oncogene and tumor
suppressor gene
expression in CBA/Ca mice.

* Ember I,
* Kiss I,
* Ghodratollah N,
* Raposa T.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

The in vivo investigation of onco/suppressor gene effects may
provide new
information on chemical-environmental carcinogenesis. We previously
described
the elevation of onco/suppressor gene expression due to CHOP and COPP
chemotherapeutical protocols in a CBA/Ca mouse model. Below we
describe the
results of the onco/suppressor gene expression studies after treatment
with
ABVD, a non-cyclophosphamide containing protocol. Expression of c-myc,
Ha-ras,
and p53 genes was investigated 1/2, 1, 3, 6, 12, 24 hours, 2 6 30
days, 6, and
12 months after treatment with a single dose of ABVD protocol.
RNA was isolated from the thymus, spleen, liver, bone
marrow, kidneys, and hybridzed with chemiluminescently labelled probes
of
Ha-ras, c-myc, and p53 genes. Significant changes of gene expression
was found
in the spleen and thymus, even after 30 minutes. The female spleen
seemed to be
more sensitive than the male one, but no sex difference was observed
in the
thymus. No significant alteration was detected in the other
investigated organs.
PMID: 9615780

Anticancer Res. 1998 Mar-Apr;18(2A):1149-52.
Effect of ABVD therapeutic protocol on oncogene and tumor
suppressor gene
expression in CBA/Ca mice.

* Ember I,
* Kiss I,
* Ghodratollah N,
* Raposa T.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

The in vivo investigation of onco/suppressor gene effects may
provide new
information on chemical-environmental carcinogenesis. We previously
described
the elevation of onco/suppressor gene expression
due to CHOP and COPP chemotherapeutical protocols in a CBA/Ca mouse
model. Below we describe the results of the onco/suppressor gene
expression
studies after treatment with ABVD, a non-cyclophosphamide containing
protocol.
Expression of c-myc, Ha-ras, and p53 genes was investigated 1/2, 1, 3,
6, 12, 24
hours, 2 6 30 days, 6, and 12 months after treatment with a single
dose of ABVD
protocol. RNA was isolated from the thymus, spleen, liver, bone
marrow, kidneys,
and hybridzed with chemiluminescently labelled probes of Ha-ras, c-
myc, and p53
genes. Significant changes of gene expression was found in the spleen
and
thymus, even after 30 minutes. The female spleen seemed to be more
sensitive
than the male one, but no sex difference was observed in the thymus.
No
significant alteration was detected in the other investigated organs.
PMID: 9615780

Anticancer Res. 1998 Jan-Feb;18(1A):445-7.
Effect of 7,12-dimethylbenz(a)anthracene on onco/suppressor gene
action in
vivo: a short-term experiment.

* Ember I,
* Kiss I,
* Pusztai Z.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

Dimethylbenz[a]anthracene is a pluripotent carcinogenic chemical,
which acts
as an initiator by causing point mutations in certain oncogenes and
tumor
suppressor genes. Changes in their expression may be another possible
area of
investigation the carcinogenic effect of DMBA. Elevated expression of
oncogenes
was previously has been shown after treatment with carcinogenic
compounds. In
the present study, expression of c-myc, c-Ha-ras and p53 24 hours
after a single
dose treatment of DMBA in the spleen and in the liver of Long-Evans
rats was
investigated. Control animals were injected with the solvent corn oil
only. We
could not find any significant change on the transcriptional level of
the
investigated oncogenes in the liver. In the spleen, the overexpression
of Ha-ras
was 2-fold and c-myc was 3-fold higher in the DMBA-treated rats
than in the corresponding control group.
Since DMBA is a typical environmental carcinogen,
the results of animal experiments may serve as a basis for
application of gene expression investigations as a screening method in
humans.
PMID: 9568117

In Vivo. 1997 Sep-Oct;11(5):399-402.
In vivo effects of COPP protocol on onco- and suppressor gene
expression in
a 'follow up study'.

* Ember I,
* Kiss I,
* Raposa T.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

In vivo investigation of onco or suppressor genes may provide new
information concerning chemical carcinogenesis. In earlier studies we
illustrated the carcinogenic potential of COPP chemotherapeutical
protocol in
"long term" experiments. Elevated expression of oncogenes was shown as
soon as
24 hours after treatment in CBA/Ca inbred mice, in "short term"
experiments. Now
we present the results of the follow-up study dealing with the
carcinogenic
effect of COPP. The genes most frequently involved were N-ras and p53,
with the thymus being the target organ of COPP.
PMID: 9427043

Anticancer Res. 1997 Sep-Oct;17(5A):3593-7.
In vivo effects of cyclophosphamide on oncogene and suppressor
gene
expression in a "follow up" study.

* Ember I,
* Kiss I.

Department of Preventive Medicine, University Medical School of Pecs,
Hungary.

Cyclophosphamide is a chemotherapeutical drug, with proved
carcinogenic side
effects. Our previous experiments showed its effect on the expression
of certain
oncogenes and tumor suppressor genes. In order to further explore the
effects of
cyclophosphamide at the gene level an in vivo mouse model was
developed. We
compared the effects of cyclophosphamide with that of cyclosporine,
which is a
non genotoxic human carcinogenic chemical. After different time
periods of
intraperitoneal cyclophosphamide or cyclosporine injection, RNA was
isolated
from whole organs of experimental animals,
and expression of onco/suppressor genes was determined by slot blot
hybridisation.
In our model we have
proved that gene expression changes caused by cyclophosphamide can be
detected
even six months after treatment without tumor development. Our results
support
the hypothesis that gene expression investigations could be useful
biomarkers in
monitoring the effects of environmental carcinogenic compounds.
PMID: 9413208

Acta Chir Hung. 1997;36(1-4):119-21.
Is the presence of distant metastasis associated with c-myc
amplification in
gastric cancer?

* Hajdu J,
* Kozma L,
* Kiss I,
* Szentkereszty Z,
* Szakall S,
* Ember I.

1st Department of Surgery, University Medical School of Debrecen,
Hungary.

The expression of the c-myc oncogenes has already been reported in
human
gastric carcinoma. Overexpression can be the consequence of oncogene
amplification and often correlates with different prognostic factors.
Authors
investigated the value of c-myc oncogene amplification
in 23 patients (9 male, 14 female, aged 28-85 yrs) with
gastric cancer and its correlation to the following clinical and
histopathological parameters: grade, TNM stage, Lauren's type,
localisation and
severity of disease. DNA was isolated from formalin-fixed, paraffin
embedded
tissue for quantitative dot-blot hybridisation. Amplified c-myc was
found in 6
out of 23 cases. Its values ranged from 2.12 up to 18.2 (average
9.1).
Significant association was found between the presence of c-myc
amplification
and distant metastasis (corr. coeff.: 0.5623, p < 0.01). High scores
of the
other parameters also correlated with c-myc, albeit not significantly.
The
result of cluster analysis, based on the similarity of the parameter
values for the individual patients proved that the age was the
decisive
factor in creating two groups. The distribution of patients into these
groups
did not seem to coincide with the presence of c-myc amplification or
distant
metastasis, inspite of the proved correlation between them.
PMID: 9408311

Cancer Lett. 1997 Jan 1;111(1-2):127-31.
Investigation of c-myc and K-ras amplification in renal clear
cell
adenocarcinoma.

* Kozma L,
* Kiss I,
* Nagy A,
* Szakall S,
* Ember I.

Department of Pathology, University Medical School of Debrecen,
Hungary.

Tumour DNA samples isolated from 36 patients with renal clear cell
carcinoma
were investigated for c-myc and K-ras amplification, using a
quantitative
dot-blot hybridization. The characteristic clinical and histological
parameters
involved in the statistical analysis were age, sex, histological grade
of the
tumour, the TNM staging system, tumour size and weight, vascular
invasion and
the quality of life. The goal of the study was to estimate the
prevalence as
well as the prognostic value of the amplification of the oncogenes in
question.
Amplified c-myc (2.47-fold on the average) was found in three
specimens (8.3%),
showing slight correlation with intravasation (P > 0.05, n.s.).
K-ras amplification (2.93-fold) detected in six
tumours (16.6%) was shown to significantly correlate with both
histological
grade (2.2 vs. 1.8, P < 0.05) and tumour size (15 vs. 8 cm, P < 0.05).
In cases
with amplified K-ras also lymph node involvement was somewhat more
frequent (P >
0.05, n.s.). No coamplification of these oncogenes was observed.
The results of the study suggest that K-ras amplification may account
for a more rapid progression of the disease.
PMID: 9022137

Orv Hetil. 1995 Aug 27;136(35):1875-83.
[The function of the p53 gene suppressor in carcinogenesis]
[Article in Hungarian]

* Sandor J,
* Ambrus T,
* Ember I.

Pecsi Orvostudomanyi Egyetem Nepegeszsegtani Intezet.

The alteration of the p53 gene or protein seems to be the most
frequent
alteration in the human malignancies. It plays a significant role in
the
regulation of the physiological cell division. The genetic impairments
caused by
a series of exogenous or endogenous agents induce the activation of
the p53 which
results in the G1-S arrest to ensure the opportunity for repair to
correct the
alteration or in apoptosis when the repair is not able to cope with
the
mutation. Eventually, the p53 is anticarcinogenic because of its genom
guarding
function. The investigation of the behavior of this gene and protein
is fruitful
in solving problems of preventive, diagnostic and therapeutic work.
PMID: 7675427

Anticancer Res. 1995 Jul-Aug;15(4):1285-8.
Effect of different cytostatic protocols on oncogene expression in
CBA/Ca
mice.

* Ember I,
* Raposa T,
* Varga C,
* Kiss I.

Department of Public Health, University Medical School of Pecs,
Hungary.

In vivo investigations on oncogene action may provide new findings
on the
toxicology of potential carcinogens. In this study we investigated the
early
effects of different cytostatic protocols on early oncogene expression
in CBA/Ca
mice. Most of the examined protocols showed detectable early changes,
especially
those containing cyclophosphamide. The most frequently involved
oncogenes were
N-ras, c-myc, and c-myb.
PMID: 7654010

In Vivo. 1995 Jan-Feb;9(1):65-9.
Carcinogenic effects of cytostatic protocols in CBA/Ca mice.

* Ember I,
* Raposa T,
* Varga C,
* Herceg L,
* Kiss I.

Department of Public Health, University Medical School of Pecs,
Hungary.

An in vivo mouse model was developed in order to study the
characteristics
of secondary tumor induction by cytostatic drug combinations used in
human
anticancer treatment. In this model we have proved the carcino-
leukemogenic
effects of widely used chemotherapeutical drug combinations (CHOP,
COPP,
COPBLAM, VAM). The carcinogenic hazards of cyclophosphamide and other
alkylating
drugs could also be demonstrated in our model.
PMID: 7545447

Cancer Lett. 1994 Jun 30;81(2):165-9.
Investigation of c-myc oncogene amplification in colorectal
cancer.

* Kozma L,
* Kiss I,
* Szakall S,
* Ember I.

Department of Pathology, University Med. School of Debrecen, Hungary.

Tumour DNA samples of 20 patients with colorectal carcinoma were
tested for
c-myc amplification, using a quantitative dot-blot hybridization.
Statistical
analysis involving clinical and histological parameters like degree
of
differentiation, Dukes' stage, TNM staging system, age, sex and
severity of
disease, was applied to estimate the prognostic value of c-myc
amplification.
The amplification of the investigated oncogene--1.61-fold on the
average--was
found to significantly correlate with the presence of distant
metastasis (corr.
coeff.: 0.506, P < 0.05) and the severe course of the disease (corr.
coeff.:
0.468, P < 0.05). This result supports the hypothesis that tumour
cells with
c-myc amplification represent a more malignant and aggressive
phenotype.
It is also worth noting that both c-myc amplification
and formation of distant metastasis are late events in the
progression
of colorectal cancer, which accounts for the more severe course of the
disease.
PMID: 8012933

Anticancer Res. 1994 May-Jun;14(3A):1095-6.
Early effects of cyclosporin A on in vivo oncogene expression.

* Ember I,
* Kiss I,
* Dezsenyi E,
* Kertai P.

Department of Public Health, University Medical School of Pecs,
Hungary.

Cyclosporine is a widely used immunosuppressant drug, but
development of
secondary malignancies has been observed after Cyclosporine
containing
treatments. In our study we investigated the early effect of
Cyclosporin A on
oncogene expression. 6, 12, 18 and 24 hours after 80 mg/bwkg
Cydosporin A
treatment, RNA was isolated from different organs, slot blotted onto
Hybond N+
membrane and hybridized with chemiluminescently labelled oncogene
probes. As a
positive control, rehybridisation with beta-actin probe was used. X-
ray films
were exposed for 15 minutes, developed, evaluated with densitometer,
and the results were expressed as a ratio to the positive control.
There was no effect of Cyclosporine A on the expression of c-sis and
il-2 receptor genes.
The expression of N-ras, c-myc, c-ptc/ret and c-myb oncogenes was
elevated in the
thymus, lymph nodes, spleen and liver, either transitionally or
continuously.
We could not detect any elevated gene expressions in the kidney, lung
and bone marrow.
PMID: 8074456

Cancer Lett. 1993 Feb;68(2-3):185-92.
Studies on acute myelomonocytic leukemia in LBF1 rats.

* Kozma L,
* Kiss A,
* Ember I,
* Kertai P.

Department of Pathology, University Medical School of Debrecen,
Hungary

Granulocytic leukemia was induced in Long-Evans (LE) rats by using
the
Huggins and Sugiyama method. After serial passage the cells became
transformed.
The newly transformed cells could be transplanted to LBF1 hybrid rats
and
observed more readily. A quantity of 10(8) cells/100 g body weight was
injected intravenously
and after 2-3 weeks myelomonocytic leukemia developed.
By examining the bone marrow, spleen and lymph nodes,
cytochemical tests verified this transformation. Transplanting
10(2)-10(4) cells under the renal capsule, a quickly growing solid
tumor was
observed, which caused metastasis to the parathymical lymph nodes and
peritoneum. The investigation of oncogene expression for the myc and
ras
families revealed the presence of myc p62 and ras p21 oncoproteins in
the tumor
cells by using monoclonal antibodies in immunohistochemical tests.
LBF1 rats
proved to be good models in obtaining solid tumor growth and
myelomonocytic
leukemias, equivalent to human M4-M5 type leukemia.
PMID: 8443791


Cancer Lett. 1991 Dec 1;60(3):199-203.
Comparative studies on genotoxic and carcinogenic effects of
different
cytostatic protocols. I. In vivo cytogenetic analyses in CBA mice.

* Varga C,
* Ember I,
* Raposa T.

Department of Hygiene and Epidemiology, University Medical School of
Debrecen,
Hungary.

In vivo rodent cytogenetics may provide an important basis for an
animal
model for the assessment of the carcinogenic potential of antitumor
drugs in
man. In this paper, genotoxic alterations (i.e. sister chromatid
exchanges and
micronuclei) caused by different cytostatic protocols in CBA/Ca mice
are
described. The strongest sister chromatid exchange inducing effects
were shown
by the ABVD (doxorubicin-dacarbazine-bleomycinvinblastine) group and
combinations containing cyclophosphamide. Compounds which affect the
mitotic
spindle induced only micronuclei, but not sister chromatid exchanges.
PMID: 1756509

67: Arany I, Ember I, Rady P.
Abstract Subcellular distribution of hexokinase in leukemic and
stimulated lymphoid cells of mice.
Haematologia (Budap). 1988;21(2):109-14.
PMID: 3417182

68: Arany I, Jozsa Z, Ember I.
Abstract Further studies on migration and colonization of leukemic
lymphoblasts
in AKR and HSS inbred mice.
Cancer Biochem Biophys. 1987 May;9(2):149-54.
PMID: 3621139

69: Szollosi J, Matyus L, Tron L, Balazs M, Ember I, Fulwyler MJ,
Damjanovich S. Related Articles, Links
Abstract Flow cytometric measurements of fluorescence energy
transfer
using single laser excitation.
Cytometry. 1987 Mar;8(2):120-8.
PMID: 3582060

70: Telek B, Ember I, Kiss A, Pecze K.
No abstract [Significance of terminal deoxynucleotidyl transferase
in
lymphoproliferative diseases]
Orv Hetil. 1986 Dec 28;127(52):3183-6. Hungarian.
PMID: 3468473

71: Ember I, Olah E, Balogh E, Arany I, Rady P, Matyus L,
Thomazy V, Kertai P.
Abstract Transplantation of chemically induced mouse leukaemia into
newborn F344 rats.
Haematologia (Budap). 1986;19(3):207-17.
PMID: 3781355

72: Bardocz S, Rady P, Ember I, Karsai T, Kertai P.
Abstract Effect of 12-O-tetradecanoylphorbol-13-acetate on polyamine
metabolism in mice sensitive and resistant to lung-adenoma.
Carcinogenesis. 1983 Oct;4(10):1349-50.
PMID: 6616764

73: Ember I, Szollosi J, Thomazy V, Arany I, Rady P, Kertai P.
No abstract A rapid method of following the spontaneous regression
of
experimental leukemias.
Experientia. 1982 Oct 15;38(10):1234-5.
PMID: 7140926

74: Szollosi J, Ember I, Tron L, Kertai P.
Abstract A follow-up study of the progression or spontaneous
regression
of leukemia in mouse strains.
Cytometry. 1982 Sep;3(2):110-5.
PMID: 6958443

75: Papp Z, Ember I, Juhasz E, Tasnady Z, Karsai T, Elodi P.
No abstract Acid-soluble glycoproteins in amniotic fluid and cystic
fibrosis of the foetus.
Clin Genet. 1977 Jun;11(6):431-2.
PMID: 880743
///////////////////////////////////////////////////////////


aspartame (methanol, formaldehyde) toxicity research summary: Rich
Murray 2007.04.14
http://groups.yahoo.com/group/aspartameNM/message/1404

One liter aspartame diet soda, about 3 12-oz cans,
gives 61.5 mg methanol,
so if 30% is turned into formaldehyde, the formaldehyde
dose of 18.5 mg is 37 times the recent EPA limit of
0.5 mg per liter daily drinking water for a 10-kg child:
www.epa.gov/teach/chem_summ/Formaldehyde_summary.pdf
2007.01.05 [ does not discuss formaldehyde from methanol
or aspartame ]
http://www.epa.gov/teach/teachsurvey.html comments
teach@...

"Of course, everyone chooses, as a natural priority,
to actively find, quickly share, and positively act upon
the facts about healthy and safe food, drink, and
environment."

Rich Murray, MA Room For All rmforall@...
505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505

http://groups.yahoo.com/group/aspartameNM/messages
group with 79 members, 1,414 posts in a public, searchable archive
http://RMForAll.blogspot.com

http://groups.yahoo.com/group/aspartameNM/message/1340
aspartame groups and books: updated research review of
2004.07.16: Murray 2006.05.11


http://groups.yahoo.com/group/aspartameNM/message/1395
Aspartame Controversy, in Wikipedia democratic
encyclopedia, 72 references (including AspartameNM # 864
and 1173 by Murray), brief fair summary of much more
research: Murray 2007.01.01


Dark wines and liquors, as well as aspartame, provide
similar levels of methanol, above 120 mg daily, for
long-term heavy users, 2 L daily, about 6 cans.

Within hours, methanol is inevitably largely turned into
formaldehyde, and thence largely into formic acid -- the
major causes of the dreaded symptoms of "next morning"
hangover.

Fully 11% of aspartame is methanol -- 1,120 mg aspartame
in 2 L diet soda, almost six 12-oz cans, gives 123 mg
methanol (wood alcohol). If 30% of the methanol is turned
into formaldehyde, the amount of formaldehyde, 37 mg,
is 18.5 times the USA EPA limit for daily formaldehyde in
drinking water, 2.0 mg in 2 L average daily drinking water.

http://groups.yahoo.com/group/aspartameNM/message/1286
methanol products (formaldehyde and formic acid) are main
cause of alcohol hangover symptoms [same as from similar
amounts of methanol, the 11% part of aspartame]:
YS Woo et al, 2005 Dec: Murray 2006.01.20


http://groups.yahoo.com/group/aspartameNM/message/1143
methanol (formaldehyde, formic acid) disposition:
Bouchard M et al, full plain text, 2001: substantial
sources are degradation of fruit pectins, liquors,
aspartame, smoke: Murray 2005.04.02

"According to model predictions, congruent with the data in the
literature [Dorman et al., 1994; Horton et al., 1992], a certain
fraction of formaldehyde is readily oxidized to formate,
a major fraction of which is rapidly converted to CO2 and exhaled,
whereas a small fraction is excreted as formic acid in urine.

However, fits to the available data in rats and monkeys of Horton et
al. [1992] and Dorman et al. [1994] show that, once formed, a
substantial fraction of formaldehyde is converted to unobserved forms.

This pathway contributes to a long-term unobserved compartment.

The latter, most plausibly, represents either the formaldehyde that
[directly or after oxidation to formate] binds to various endogenous
molecules [Heck et al., 1983; Røe, 1982] or is incorporated in the
tetrahydrofolic-acid-dependent one-carbon pathway to become the
building block of a number of synthetic pathways
[Røe, 1982; Tephly and McMartin, 1984].

That substantial amounts of methanol metabolites or by-products are
retained for a long time is verified by Horton et al. [1992] who
estimated that 18 h following an iv injection of 100 mg/kg of
14C-methanol in male Fischer-344 rats,
only 57% of the dose was eliminated from the body.

>From the data of Dorman et al. [1994] and Medinsky et al. [1997],
it can further be calculated that 48 h following the start
of a 2-h inhalation exposure to 900 ppm of 14C-methanol vapors
in female cynomolgus monkeys,
only 23% of the absorbed 14C-methanol was eliminated from the body.

These findings are corroborated by the data of Heck et al. [1983]
showing that 40% of a 14C-formaldehyde inhalation dose remained
in the body 70 h postexposure.

In the present study, the model proposed rests on acute exposure
data, where the time profiles of methanol and its metabolites were
determined only over short time periods
[a maximum of 6 h of exposure and a maximum of 48 h postexposure].

This does not allow observation of the slow release from the long-term
components.

It is to be noted that most of the published studies on the detailed
disposition kinetics of methanol regard controlled short-term
[iv injection or continuous inhalation exposure over a few hours]
methanol exposures in rats, primates, and humans
[Batterman et al., 1998; Damian and Raabe, 1996;
Dorman et al., 1994; Ferry et al., 1980; Fisher et al., 2000;
Franzblau et al., 1995; Horton et al., 1992; Jacobsen et al., 1988;
Osterloh et al., 1996; Pollack et al., 1993; Sedivec et al., 1981;
Ward et al., 1995; Ward and Pollack, 1996].

Experimental studies on the detailed time profiles following
controlled repeated exposures to methanol are lacking."


http://groups.yahoo.com/group/aspartameNM/message/1385
Coca-Cola carcinogenicity in rats, Ramazzini Foundation,
F Belpoggi, M Soffritti, Annals NY Academy Sciences
2006 Sept, parts of 17 pages: Murray 2006.12.02

http://groups.yahoo.com/group/aspartameNM/message/1382
Fiorella Belpoggi & Morando Soffritti of Ramazzini
Foundation prove lifetime carcinogenicity of Coca-Cola,
aspartame, and arsenic, Annals of the NY Academy of
Sciences: Murray 2006.11.28


http://groups.yahoo.com/group/aspartameNM/message/1406
brain cell tangles and neuron death similar to Alzheimers
via low dose formaldehyde from methanol,
Chunlai Nie, Rongqiao He et al, China, 2007.01.23 BMC
Neuroscience 28 pages, 63 references: Murray 2007.01.24

http://groups.yahoo.com/group/aspartameNM/message/1369
Bristol, Connecticut, schools join state program to limit
artificial sweeteners, sugar, fats for 8800 students,
Johnny J Burnham, The Bristol Press: Murray 2006.09.22

http://groups.yahoo.com/group/aspartameNM/message/1341
Connecticut bans artificial sweeteners in schools,
Nancy Barnes, New Milford Times: Murray 2006.05.25


http://groups.yahoo.com/group/aspartameNM/message/1376
soft drinks and adolescent hyperactivity, mental distress,
conduct problems, Lars Lien, Nanna Lien, Sonja Heyerdahl,
Mayne Thoresen, Espen Bjertness 2006 Oct., A J Pub Health:
Murray 2006.10.21

http://groups.yahoo.com/group/aspartameNM/message/1375
healthy diet, vitamins, and fish oil help reduce
depression and violence, studies by Joseph Hibbeln,
Bernard Gesch, and Stephen Schoenthaler, articles by
Felicity Lawrence in UK Guardian Unlimited and Pat
Thomas in The Ecologist: Murray 2006.10.21

http://groups.yahoo.com/group/aspartameNM/message/1353
carcinogenic effect of inhaled formaldehyde, Federal
Institute of Risk Assessment, Germany -- same safe level
as for Canada: Murray 2006.06.02

http://groups.yahoo.com/group/aspartameNM/message/1352
Home sickness -- indoor air often worse, as our homes
seal in pollutants [one is formaldehyde, also from the 11%
methanol part of aspartame],
Megan Gillis, WinnipegSun.com: Murray 2006.06.01


http://groups.yahoo.com/group/aspartameNM/message/1366
toxicity in rat brains from aspartame, Vences-Mejia A,
Espinosa-Aguirre JJ et al 2006 Aug: Murray 2006.09.06

http://groups.yahoo.com/group/aspartameNM/message/1373
aspartame rat brain toxicity re cytochrome P450 enzymes,
especially CYP2E1, Vences-Mejia A, Espinosa-Aguirre JJ
et al, 2006 Aug, Hum Exp Toxicol: relevant abstracts re
formaldehyde from methanol in alcohol drinks:
Murray 2006.09.29

http://groups.yahoo.com/group/aspartameNM/message/1271
combining aspartame and quinoline yellow, or MSG and
brilliant blue, harms nerve cells, eminent C. Vyvyan
Howard et al, 2005 education.guardian.co.uk,
Felicity Lawrence: Murray 2005.12.21

http://groups.yahoo.com/group/aspartameNM/message/1277
50% UK baby food is now organic -- aspartame or MSG
with food dyes harm nerve cells, CV Howard 3 year study
funded by Lizzy Vann, CEO, Organix Brands,
Children's Food Advisory Service: Murray 2006.01.13

http://groups.yahoo.com/group/aspartameNM/message/1279
all three aspartame metabolites harm human erythrocyte
[red blood cell] membrane enzyme activity, KH Schulpis
et al, two studies in 2005, Athens, Greece, 2005.12.14:
2004 research review, RL Blaylock: Murray 2006.01.14


http://groups.yahoo.com/group/aspartameNM/message/1349
NIH NLM ToxNet HSDB Hazardous Substances Data Bank
inadequate re aspartame (methanol, formaldehyde,
formic acid): Murray 2006.08.19

http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~HwoSfJ:1
HSDB Hazardous Substances Data Bank: Aspartame

ASPARTAME CASRN: 22839-47-0
METHANOL CASRN: 67-56-1
FORMALDEHYDE CASRN: 50-00-0
FORMIC ACID CASRN: 64-18-6


http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol
98 mg/L ( becomes formaldehyde in body ): EU Scientific
Committee on Foods 2001.07.12: Murray 2004.01.22


http://www.HolisticMed.com/aspartame mgold@...
Aspartame Toxicity Information Center Mark D. Gold
12 East Side Drive #2-18 Concord, NH 03301 603-225-2100

http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

http://groups.yahoo.com/group/aspartameNM/message/957
safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
Murray 2003.01.12 EU Scientific Committee on Food,
a whitewash

http://groups.yahoo.com/group/aspartameNM/message/1045
http://www.holisticmed.com/aspartame/scf2002-response.htm
Mark Gold exhaustively critiques European Commission
Scientific Committee on Food re aspartame ( 2002.12.04 ):
59 pages, 230 references
///////////////////////////////////////////////////////////


http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 2002.01.17
Jerry D Smith, Chris M Terpening,
Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following
Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center,
Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic
disorder that is often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia
syndrome for two to 17 years are described.
All had undergone multiple treatment modalities with
limited success.
All had complete, or nearly complete,
resolution of their symptoms within months after
eliminating monosodium glutamate (MSG)
or MSG plus aspartame from their diet.
All patients were women with multiple comorbidities
prior to elimination of MSG.
All have had recurrence of symptoms whenever MSG
is ingested.

Siegfried O. Schmidt, MD Asst. Clinical Prof.
siggy@...
Community Health and Family Medicine, U. Florida,
Gainesville, FL Shands Hospital West Oak Clinic
Gainesville, FL 32608-3629 352-376-5071
///////////////////////////////////////////////////////////

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity: Thrasher & Kilburn: Shaham: EPA:
Gold: Wilson: CIIN: Murray 2002.12.12

Thrasher (2001): "The major difference is that the
Japanese demonstrated the incorporation of FA and its
metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and
fetal tissues at 48 hours was 26.9% of the administered
dose." [ Ref. 14-16 ]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde.
[100 references]
Thrasher JD, Kilburn KH. toxicology@...
Sam-1 Trust, Alto, New Mexico, USA. full text
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html

http://www.drthrasher.org/formaldehyde_1990.html full text
Jack Dwayne Thrasher, Alan Broughton, Roberta Madison.
Immune activation and autoantibodies in humans with
long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.
PMID: 2400243
///////////////////////////////////////////////////////////