Search PubMed for publications by Dr Michael Wargovich
Norman HA, Butrum RR, Feldman E, Heber D, Nixon D,
Picciano MF, Rivlin R, Simopoulos A, Wargovich MJ, Weisburger EK, and Zeisel SH.
The Role of Dietary Supplements during Cancer Therapy. J Nutr 133:3794S-3799S,
2003.
This guide was compiled after recommendations by
the American Institute for Cancer Research (AICR) Cancer Resource Advisory
Council. It encompasses the AICR position on current issues in nutrition for
cancer survivors during treatment and is intended to provide advice about
dietary supplements for cancer survivors who are still being treated. Current
scientific findings about the safety and effectiveness of some commonly used
dietary antioxidants and nonantioxidant supplements during chemotherapy are
presented and assessed. Use of dietary supplements during cancer treatment
remains controversial. Patients are cautioned that vitamin and mineral
supplements as therapies are not substitutes for established medicine. The
current recommendation for cancer patients is to only take moderate doses of
supplements because evidence from human clinical studies that confirm their
safety and benefits is limited. A daily multivitamin containing supplements at
the levels of the Dietary Reference Intakes can be used safely as part of a
program of healthy nutrition. In addition, the AICR Cancer Resource Advisory
Council concluded that further scientific research is needed to provide a set of
firm guidelines for the use of vitamin and mineral supplements by cancer
patients during treatment.
Lewis RC, Bostick RM, Xie D, Deng Z, Wargovich MJ, Fina MF, Roufail WM,
Geisinger KR.
Polymorphism of the cyclin D1 gene, CCND1, and
risk for incident sporadic colorectal adenomas. Cancer Res. 2003 Dec 1; 63(23): 8549-53.
Cyclin D1, encoded by the CCND1 gene and activated by the adenomatous polyposis
coli-beta-catenin-T-cell factor/lymphoid enhancing factor pathway, induces G(1)
to S-phase cell cycle transition, promoting cell proliferation. A recently
described codon 242, exon 4, G to A single nucleotide polymorphism (A870G)
produces a longer half-life cyclin D1. To investigate whether CCND1 genotype
influences risk for colorectal adenoma, we genotyped CCND1 by PCR/RFLP on 161
incident sporadic adenoma cases and 213 controls ages 30-74 years in a North
Carolina colonoscopy-based case-control study. At least one polymorphic A allele
was found in 68% of cases and 60% of controls. Having an A allele was associated
with increased risk for adenoma: the age- and sex-adjusted odds ratio (OR) was
1.5 [95% confidence interval (CI) 1.0-2.4], a finding that was stronger for
those whose adenomas were multiple (OR 2.9, 95% CI 1.4-6.0), larger (>or=1 cm;
OR 2.4, 95% CI 1.2-4.8), had moderate to severe dysplasia (OR 2.1, 95% CI
1.1-3.8), or were in the right side of the colon (OR 3.6, 95% CI 1.3-10.0).
Joint risk factor multivariate analyses revealed stronger positive associations
among those who were older (>57 years; OR 2.8, 95% CI 1.4-5.5), male (OR 2.8,
95% CI 1.3-5.7), currently smoked (OR 2.7, 95% CI 1.3-5.7), or currently drank
alcohol (OR 2.2, 95% CI 1.2-4.2) if they had an A allele and stronger inverse
associations among those who used nonsteroidal anti-inflammatory drugs (OR 0.4,
95% CI 0.2-0.9) or had higher calcium intakes (OR 0.4, 95% CI 0.2-0.9) if they
had no A allele. These data support the hypothesis that the CCND1 A870G
polymorphism may increase risk for colorectal neoplasms.
Wargovich MJ, Chang P, Velasco M, Sellin J.
Expression of cellular adhesion proteins and abnormal glycoproteins in human
aberrant crypt foci. Applied Immunohistochemistry and Molecular Morphology, 12:
350-355, 2004.
Aberrant crypt foci (ACFs) may be the earliest
recognizable histologic precursor lesion for colon cancer. ACF may develop from
a complex of events, including the development of cryptal hyperproliferation,
defects in the rate of apoptosis, and abnormalities in cellular adhesion. In
this study, we hypothesized that human ACF would exhibit discrete differences in
cell adhesion proteins compared with normal mucosa of biologic markers
associated with colon cancer. ACFs were isolated from resected colon mucosa from
45 patients undergoing surgery for colon cancer. We evaluated the protein
expression of 3 biologic markers that may be related to the progression of
aberrant crypt foci to tumors: carcinoembryonic antigen, E-cadherin, and sialyl
Tn antigen. In general, ACFs located near cancers in the right colon were more
often hyperplastic than dysplastic; this was more noticeable in the left colon.
Carcinoembryonic antigen expression was found to be more intense in apical
portions of ACF crypts, with sialyl Tn antigen moderately increased, whereas
E-cadherin diffusely stained throughout crypts within ACFs. There are
significant biologic changes in potential tumor markers that accompany the early
transformation of the normal glandular epithelium, some of which are expressed
very early in the colon at the stage of appearance of ACF.
Kim KP, Whitehead C, Piazza G, and Wargovich, MJ.
Combinatorial Chemoprevention: Efficacy of Lovostatin and Exisulind on the
Formation and Progression of Aberrant Crypt Foci Induced by Azoxymethane in F344
Rats. Anticancer Research, 24(3a):1805-1811, 2004.
BACKGROUND: There are several advantages to
combinatorial chemoprevention strategies over monotherapeutic approaches. Both
the HMG-CoA reductase inhibitor (HRI) lovastatin (LOV) and the selective
apoptotic antineoplastic drug (SAAND) exisulind (EXS) have shown remarkable
chemopreventive effects in previous studies, in cell lines and limited studies
in rodents. Here, experiments were designed to assess the potential use of these
two compounds in combinatorial chemoprevention therapy, using two bio-assays in
which inhibition of the carcinogen-induced preneoplastic lesions, aberrant crypt
foci (ACF), was used to quantitate efficacy. MATERIALS AND METHODS: ACF were
induced by the carcinogen azoxymethane (AOM) in F344 rats by two sequential
weekly i.p. injections at a dose of 15 mg/kg. F344 rats were fed seven
experimental diets containing LOV @ 50 parts per million (ppm), EXS @ 100, 250
and 1000 ppm and combination diets containing EXS at 100, 250 and 1000 ppm, each
combined with LOV @ 50 ppm. Quantification of ACF number and type (singlet,
doublet, triplet and four or more) was performed on whole mounts of rat colons
stained with 1.0% methylene blue. RESULTS: During the initiation protocol,
administration of LOV @ 50 ppm alone and the combination of LOV @ 50 ppm with
EXS @ 1000 ppm significantly decreased the mean number of ACF when compared to
the positive control by 49% and 47%, respectively; however EXS @ 250 ppm
displayed tumor promoting effects by significantly increasing the mean number of
ACF by 64%. The post-initiation protocol administration of EXS @ 100, 250 and
1000 ppm and the combinations of LOV @ 50 ppm with EXS @ 100 and 250 ppm
significantly increased the mean number of ACF when compared to the positive
control by 44%, 48%, 55%, 49% and 40%, respectively. CONCLUSION: LOV shows
greater promise than EXS in fulfilling the role as a supplemental
chemopreventive agent in combinatorial chemopreventive strategies for cancers
such as colon cancer. EXS did not augment this activity, failing to enhance
chemopreventive therapy in this animal model.
Zander M, Wargovich MJ, Hebert JR. Methodologic
Considerations in the Study of Diet as Part of Complementary and Alternative
Medicine Modalities, Alt Therap Health Med, 10 (6) 2-7, 2004.
Diet is an essential component of most comprehensive
health systems. Food figures prominently in the consciousness of most
individuals, and the sensations of taste and smell are fundamentally important
in human emotion. Complex configurations of dietary sanctions and strictures
exist in virtually every human society, providing additional force to the power
of diet. A wide variety of epidemiologic and laboratory-based studies have
implicated a number of specific dietary factors in health and disease, with the
former producing much in the way of equivocal evidence on most diet-health
relationships and the latter often focusing so narrowly as to call into question
the relevance of findings to human health. Assessing the role of diet as an
important component of complementary and alternative medical treatment and
preventive strategies will require a broad understanding of methodologic issues.
Careful consideration of what is required to answer substantive questions in
this intriguing and important area also will serve to advance the study of
complementary and alternative modalities more generally.
Zander MES, Davenport DNM, Wargovich MJ.
Potential NSAID-like and Chemopreventive Effects of Ginseng and Ginkgo biloba.
Int J Cancer Prevention, 1 (3); 77-87, 2004.
Boyapati SM, Bostick RM, McGlynn KA,. Fina M,
Roufail WM, Geisinger KR, Hebert JA, Coker A, and Wargovich MJ. Folate
intake, MTHFR C677T polymorphism, alcohol consumption, and risk for sporadic
colorectal adenoma (United States). Cancer Causes Control 15: 493-501, 2004. Volate S, Davenport
DM, Issa A, Wargovich MJ. Modulation of aberrant crypt foci,
inflammation and apoptosis by dietary herbal supplements Carcinogenesis, 26:
1450-156, 2005.
It is estimated that one-third of Americans use
dietary herbal supplements on a regular basis. Diets rich in bioactive
phytochemicals are associated with reduced risk of certain cancers, notably,
colon cancer. Herbal supplements have not been directly tested as sources of
bioactive cancer preventives. Hence, this study compares the ability of four
herbal flavonoids (quercetin, curcumin, rutin and silymarin) and one whole
herb mixture (ginseng powder) to suppress aberrant crypt foci (ACF) in an
azoxymethane (AOM)-induced rat colon cancer model. Second, this study
examines the effect of these herbal compounds on apoptosis and the
mechanisms by which these compounds evoke apoptosis. The results of this
study show that diets containing quercetin, curcumin, silymarin, ginseng and
rutin decreased the number of ACFs by 4-, 2-, 1.8-, 1.5- and 1.2-fold,
respectively compared with control. Histological analysis of the colon
mucosa revealed that all the herbal supplements, except silymarin, induced
apoptosis, with quercetin being the most potent (3x increase compared with
control). Furthermore, ginseng and curcumin were region-specific in inducing
apoptosis. The ability of quercetin and curcumin to modulate ACFs correlates
well with their ability to induce apoptosis. Western blot analysis of
caspase 9, Bax (proapoptotic) and Bcl-2 (antiapoptotic) proteins from the
colon scraping suggests that quercetin and curcumin induce apoptosis via the
mitochondrial pathway. Taken together, the results of this study suggest
that these herbal supplements may exert significant and potentially
beneficial effects on decreasing the amount of precancerous lesions and
inducing apoptosis in the large intestine. Zander MES,
Wargovich MJ. Effects of Ginseng and Ginkgo biloba on the Efficacy of
5-Flurouracil in Colon Cancer Cells. J Cancer Integ Med 3:19-25, 2005. Robertson DJ, Burke
CA, Scwhender B, Wargovich MJ, Greenberg, ER, Sandler RS, Ahnen D, Rothstein
R, Mott L, Baron JA. Histamine receptor antagonists and incident
adenomas. Aliment Pharmacol Ther., 22: 123-128, 2005.
BACKGROUND: Prior studies suggest that
histamines may modulate the development of colorectal neoplasia. AIM: To
assess whether histamine receptor antagonist use was associated with adenoma
formation. METHODS: Patients (n = 2366) were drawn from three adenoma
chemoprevention trials. All underwent baseline colonoscopy with removal of
adenoma(s) and were deemed free of remaining lesions; they were followed
with surveillance colonoscopy. Medication use was assessed by questionnaire.
Adjusted risk ratios for adenoma formation related to histamine receptor
antagonist use (histamine H1 and H2 receptor, H1RA and H2RA) were determined
using log linear models. RESULTS: In pooled analyses, H1RA exposure was not
associated with subsequent adenoma risk (RR = 1.10; 95% CI 0.97-1.25) or
multiple adenoma formation (RR = 0.85; 95% CI 0.67-1.07). H2RA use also was
not associated with adenoma (RR = 0.90; 95% CI 0.77-1.06), or multiple
adenoma (RR = 0.77; 95% CI 0.57-1.04) in the pooled analyses, but H2RA users
in the first trial had a decreased risk of adenoma (RR = 0.70; 95% CI
0.48-1.03) and multiple adenoma (RR = 0.31; 95% CI 0.12-0.79). CONCLUSION:
H2RA use was associated with reduced risk for adenoma in one trial, but not
in the pooled analyses. Further study would be warranted before undertaking
randomized trials of H2RAs for adenoma chemoprevention.
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