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Biomedical subjects

L A Cohen

Publications and source records attributed to L A Cohen.

At least 19 recordsLinked to original sources
PubMed2003

Effect of soy protein isolate and conjugated linoleic acid on the growth of Dunning R-3327-AT-1 rat prostate tumors.

BACKGROUND: Epidemiologic and animal model studies suggest that consumption of soy isoflavones may be associated with reduced risk of prostate cancer (PC). In addition, animal model studies suggest that conjugated linoleic acid (CLA), a natural positional isomer of linoleic acid, inhibits tumor growth in various models, including models of PC. METHODS: Based on the above-mentioned data, the objective of the present study was to test the hypothesis that supplementation of the diet with combinations of isoflavone-rich soy protein isolate and CLA would act to inhibit the growth of androgen-independent R-3327-AT-1 rat prostate tumor cells inoculated ectopically into male Copenhagen rats. RESULTS: The results of this study indicate that neither an isoflavone-rich soy protein isolate (SPI), nor CLA inhibit the in vivo growth and development of prostate tumor cells when administered in the diet either singly or in combination. Moreover, at the highest concentrations SPI and CLA (i.e., 20% SPI, 1% CLA), there was a statistically significant increase in tumors volume over controls. Administration of SPI at 10% in the diet also enhanced tumor growth, whereas at 5%, SPI exerted no measurable effect. CLA administration alone had no observable effects on AT-1 tumor growth. CONCLUSION: These results, in an established rat model, suggest caution in using isoflavone-rich SPI in human studies involving advanced hormone-refractory prostate cancer until further investigation of these effects are completed.

Animals↗
PubMed2001

LAS, a novel selective estrogen receptor modulator with chemopreventive and therapeutic activity in the N-nitroso-N-methylurea-induced rat mammary tumor model.

The N-nitroso-N-methylurea-induced rat mammary tumor model was used to conduct two types of studies: a prevention study designed to test the ability of the novel selective estrogen receptor modulator lasofoxifene (LAS) to inhibit the development of mammary tumors, and a treatment study designed to test the inhibitory effect of LAS on the growth of established tumors. The prevention study indicated that LAS markedly delayed the emergence of N-nitroso-N-methylurea-induced tumors to an extent similar to that obtained by the established antiestrogen tamoxifen (TAM). At the highest dose administered, both TAM and LAS reduced tumor incidence by 75% and total tumor number by 90% relative to the controls. LAS also reduced the multiplicity of tumors, i.e., the mean number of tumors per rat, and resulted in substantially smaller total tumor burden. In the treatment study, LAS significantly inhibited tumor growth compared with the controls. In addition, whereas none of the untreated tumors regressed completely over the experimental period, 40% of LAS-treated tumors regressed by >50% at the highest dose (10 mg/kg daily). The results of this study in a rat mammary tumor model indicate that LAS has both chemopreventive and chemotherapeutic effects quantitatively comparable with those of TAM.

Animals↗
PubMed2001

Effects of a lycopene-rich diet on spontaneous and benzo[a]pyrene-induced mutagenesis in prostate, colon and lungs of the lacZ mouse.

Consumption of lycopene has been associated with reduced risk of prostate cancer. We have investigated the effects of lycopene, fed as a lycopene-rich tomato oleoresin (LTO) at two doses, on in vivo mutagenesis in prostate, colon, and lungs of lacZ mice. Both short-term benzo[a]pyrene (BaP)- induced and long-term spontaneous mutagenesis were monitored. Non-significant inhibition of spontaneous mutagenesis in prostate and colon was observed at the higher dose of LTO, and the observation of inhibition in colon was facilitated by an unusually high spontaneous mutagenesis rate. BaP-induced mutagenesis was slightly inhibited by LTO in prostate. However, enhancement of BaP-induced-mutagenesis was observed in colon and lung. These results indicate that any antimutagenic effects of LTO may be organospecific.

Animals↗
PubMed2001

Feeding thiol-containing compounds, derived from vegetables, fails to inhibit N-methylnitrosourea-induced mammary tumorigenesis.

Various thiol-containing compounds have been shown to inhibit chemically-induced tumors in animal models. Two thiol-containing compounds derived from vegetables, namely 1,2 dithiol-3-thione (DTT) and S-methylmethane thiolsulfonate (MMTS), were tested for their chemopreventive activity in the N-methylnitrosourea (NMU)-induced rat mammary tumor model. Each compound was incorporated into the grain-based Teklad 7001 diet and fed to the rats one week prior to initiation with NMU until termination 18 weeks post NMU. DTT was fed at 166 and 500 ppm and MMTS at 200 and 800 ppm. Neither compound exerted a significant inhibitory effect on any index of tumor development including incidence, total tumor, tumor multiplicity, volume or latency. Serum levels of DTT assessed at termination in the 500 ppm DTT group ranged from 10-30 microg/ml. MMTS was undetectable in serum from either MMTS-fed group. The results of this study, using the direct acting carcinogen, NMU, suggest that the chemopreventive effect of thiol-containing compounds may be confined to animal models using carcinogens that require host activation.

Administration, Oral↗
PubMed2000

Preventive potential of wheat bran fractions against experimental colon carcinogenesis: implications for human colon cancer prevention.

Epidemiological studies suggest an inverse relationship between the intake of dietary fiber, particularly fiber from cereal grains, and colon cancer risk. Animal model assays have demonstrated that the protective effects of dietary fiber on colon cancer development depend on the nature and source of the fiber. Wheat bran (WB) appears to inhibit colon tumorigenesis more consistently than do oat bran or corn bran. This study was designed to determine whether specific WB fractions such as WB fiber, WB lipids, or phytic acid differentially affect colon carcinogenesis in a well-established colon cancer model. In addition, the modulating effect of specific fractions of WB on the activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-1 and COX-2 enzymes were assessed in colon tumors as those have been shown to play a role in tumor progression. At 5 weeks of age, groups of male F344 rats were assigned to one of six diets: a high-fat diet containing 10% WB (control diet) and experimental high-fat diets containing 10% dephytinized WB (WB-P), 10% defatted WB (WB-F), 10% dephytinized and defatted WB (WB-PF), 10% WB-PF fortified with 2% bran oil and/or with 0.4% phytate. At 7 weeks of age, all eats except those in the vehicle-treated groups were given two weekly s.c. injections of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight/week. They continued to receive their respective diets until 50 weeks after carcinogen treatment and were then killed. Colon tumors were analyzed for iNOS, COX-1, and COX-2 expression and enzymatic activities. Colon tumors were evaluated histopathologically and classified as adenomas and adenocarcinomas. We found that removal of phytic acid (WB-P) or lipids (WB-F) from WB had no significant effect on colon tumor incidence (% animals with tumors) or multiplicity (tumors/ animal), whereas removal of both phytate and lipids from WB (WB-PF) significantly increased colon tumor multiplicity and volume. Interestingly, WB-PF fortified with excess bran oil or with bran oil plus phytate significantly inhibited colon tumor incidence, multiplicity, and volume; but supplementation of WB-PF with phytate alone had no significant effect on colon tumorigenesis in rats suggesting that lipid fraction of WB possesses tumor-inhibitory properties. Moreover, feeding WB-PF diet significantly increased iNOS, total COX and COX-2 enzyme activities, and iNOS protein expression in colon tumors as compared with wheat bran control diet. Feeding the WB-PF that was fortified with excess bran oil alone or with bran oil plus phytate significantly suppressed the activities of iNOS and COX-2 as well as the expression of iNOS and COX-2 in colon tumors compared with that in rats fed the WB diet or WB-PF diet. The study demonstrates for the first time that the lipid fraction of wheat bran has strong colon tumor inhibitor properties. The exact mechanism(s) by which the lipid fraction of WB inhibits colon carcinogenesis in addition to alteration of iNOS and COX activities remains to be elucidated. Additional studies are warranted to identify biologically active constituents of lipid fraction of WB and their relative role in colon tumor inhibition.

Adenocarcinoma↗
PubMed2000

Effect of intact and isoflavone-depleted soy protein on NMU-induced rat mammary tumorigenesis.

Experiments in animal models of carcinogenesis suggest that soy consumption decreases tumor number and incidence. Genistein, an isoflavone which is present in soy at high concentrations, has been considered to be the primary antitumor constituent in soy. In the present study, the N-nitroso-N-methylurea (NMU)-induced mammary tumor model was used as a means to determine whether the chemopreventive effect of soy was attributable specifically to its high content of isoflavones. Five groups of rats (30/group) were fed the following modified AIN-93G diets: group 1, 20% intact soy protein (SP); group 2, 10% SP; group 3, 20% isoflavone-depleted soy protein (IDSP); group 4, 10% IDSP; group 5, the casein-based AIN-93G diet. The SP contained 1.07 and IDSP 0.073 mg genistein/g isolate, respectively. Experimental diets were initiated 1 week prior to NMU administration (at 50 days of age) and continued for another 18 weeks. No significant differences were found among the five groups when assessed in terms of tumor incidence, latency, multiplicity or volume. A trend towards inhibition was observed in both the 20 and 10% SP and IDSP groups when assessed in terms of total tumors/group, tumor volume and latency, but this trend did not achieve statistical significance. The results of this model study do not support the hypothesis that the isoflavone components of soy protein, or soy protein itself, inhibit chemically induced mammary tumor development.

Adenocarcinoma↗
PubMed1999

Oral enzyme therapy and experimental rat mammary tumor metastasis.

Although there has been much interest over the years in the medical use of orally administered proteolytic enzymes, there is considerable controversy about their efficacy against advanced stages of cancer. In light of this, the goal of the present study was to assess the inhibitory effects of different doses of an orally administered porcine pancreas preparation on the growth and metastasis of the R13762 transplantable rat mammary tumor. Five groups of 12 F-344 female retired breeders were inoculated orthotopically with a 2mm3 tumor implant and placed on the following diets: (1) AIN-76A diet + 20% porcine pancreas preparation (PPP); (2) AIN-76A + 20% PPP + 10 mg Mg citrate/rat/day; (3) AIN-76A + 2% PPP; (4) AIN-76A + 2% PPP + 10 mg Mg citrate and (5) AIN-76A only (control). Primary tumor development was monitored for 40 days and following sacrifice, lungs were excised, stained and metastatic foci quantitated. Metastatic foci were sorted into 3 groups based on their radii: small (<1mm), medium (1-3mm) and large (>3mm), and volumes calculated. The oral enzyme preparation had no effect on primary tumor growth or on body weight change over the duration of the study. The percent (incidence) of rats with pulmonary metastases among the five groups were not significantly different. However, among the three size categories of pulmonary foci, decreased incidence was found only in the large (>3mm) volume subset of the 2% PPP group supplemented with Mg++. When assessed in terms of mean number of pulmonary foci/rat, the 20% PPP group exhibited the highest and controls the lowest frequency with the important exception of the 2% PPP + Mg++ group (large volume) which exhibited the lowest frequency of all treatment groups. In general, the presence of Mg++ resulted in marked decreases in mean number of pulmonary foci/rat compared to groups fed PPP without the Mg++ supplement. Similar results were obtained when foci were quantitated in terms of metastatic volume rather than frequency. The results of this laboratory animal study suggest that to show effective inhibition of metastatic dissemination of the R13762 tumor by PPP, lower doses of PPP and larger numbers of animals, to account for the high variability in the model, will be required.

Administration, Oral↗
PubMed1999

S-allylcysteine, a garlic constituent, fails to inhibit N-methylnitrosourea-induced rat mammary tumorigenesis.

Epidemiological and experimental studies suggest that consumption of garlic may protect against several types of cancer. Moreover, a plausible hypothesis has been proposed that the biological effects of garlic can be attributed to the enhancing action of a variety of organosulfur compounds, present in garlic, on hepatic phase II carcinogen detoxification enzymes. We have used the N-methylnitrosourea (NMU)-induced rat mammary tumor model to test the chemopreventive effects of a water-soluble organosulfur constituent derived from aged garlic, S-allylcysteine (SAC). Rats were fed diets supplemented with 666 and 2,000 ppm SAC beginning seven days before initiation with NMU (55 days of age) to termination (18 wk post-NMU), at which time mammary tumors were enumerated. At neither dose did SAC exert an inhibitory effect on any index of tumor development, including incidence, latency, multiplicity, or volume, compared with untreated controls. Weight gains in all groups were similar. Assay of serum SAC levels in supplemented groups indicated that SAC concentrations were beneath the limits of detection of the high-performance liquid chromatography system used. These results contradict previous animal model studies indicating that SAC acts as an inhibitory agent in experimental mammary tumorigenesis; reasons for this discrepancy include the possibility that SAC may exhibit nonlinear dose effects.

Adenocarcinoma↗
PubMed1999

Effect of dietary lycopene on N-methylnitrosourea-induced mammary tumorigenesis.

Epidemiological studies suggest protective effects of lycopene-rich foods on several types of cancer, including prostate and gastrointestinal tract. Moreover, an inverse association between serum lycopene concentrations and several types of cancer has been reported. However, few studies have focused on breast cancer, and they have shown little association between lycopene consumption and cancer risk. In this report, we used the N-methylnitrosourea (NMU)-induced rat mammary tumor model to compare the effects of pure lycopene with a lycopene-rich tomato carotenoid oleoresin (TCO) on NMU-induced mammary tumorigenesis. Rats were fed diets supplemented with 250 and 500 ppm crystalline lycopene or TCO beginning seven days before initiation with NMU (55 days of age) to termination (18 wk after NMU). Neither pure lycopene nor lycopene in the form of a mixed carotenoid oleoresin exerted an inhibitory effect on tumor incidence, latency, multiplicity, volume, or total tumors per group compared with unsupplemented controls. Weight gains in all groups were similar. Assay of serum lycopene concentrations in lycopene-supplemented groups indicated that median levels of 7,12,60, and 87 ng/ml were attained in blood of groups supplemented with 250 and 500 ppm lycopene and 250 and 500 ppm TCO, respectively. The results of this animal study are consistent with epidemiological reports indicating that lycopene does not protect against breast cancer.

Animals↗
PubMed1999

Inhibition by dietary menhaden oil of cyclooxygenase-1 and -2 in N-nitrosomethylurea-induced rat mammary tumors.

Studies in laboratory animals and epidemiological surveys suggest a relationship between the type and amount of dietary fat and mammary cancer. One mechanism proposed to explain this relationship is modulation by dietary fat, of mammary tumor eicosanoid levels through action at the rate limiting enzyme in eicosanoid synthesis, cyclooxygenase (COX). Until recently there have been no studies which have examined COX gene expression in human breast or rodent mammary tissues. In this study we have demonstrated the presence of two immunoreactive isoforms of cyclooxygenase (COX-1 and -2), and the modulating effects of n-3 fatty acids on their expression, in N-nitrosomethylurea (NMU)-induced rat mammary tumors. Three different high fat diets were compared namely, corn oil (CO) 23%; CO 18% menhaden oil (MO) 5%; CO, 5%/MO 18%; low fat corn oil (5%) served as a control. It was found that immunoreactive COX-2 protein levels were approximately 3x higher than COX-1 levels in NMU-induced mammary tumors. Moreover, the high menhaden oil diet (rich in n-3 fatty acids) significantly suppressed both COX-1 (-28%) and COX-2 (-36%) protein levels when compared to the high corn oil diet. No differences were found among the other treatment groups when compared pair-wise or with low-fat control. The mechanism(s) by which n-3 fatty acids suppress COX-1 and COX-2 remain to be determined.

Animals↗
PubMed1998

International, multicentre, placebo-controlled study to evaluate the effectiveness of ondansetron vs. metoclopramide in the prevention of post-operative nausea and vomiting.

Ondansetron 4 mg was compared with metoclopramide 10 mg for prevention of post-operative nausea and emesis in in-patients undergoing major gynaecological surgery in this double-blind, randomized, placebo-controlled, multicentre study. A total of 1044 patients received a single intravenous (i.v.) injection of study medication immediately before induction of anaesthesia. Nausea and emesis were assessed over the 24 h post-operative period. Significantly more patients who received ondansetron experienced no emetic episodes (44%) compared with those who received metoclopramide (37%, P = 0.049) or placebo (25%, P < 0.001). No nausea was experienced by significantly more patients who received ondansetron (32%) than with patients who received metoclopramide (24%, P = 0.009) or placebo (16%, P < 0.001). In addition, fewer emetic episodes, less severe nausea and a reduced need for rescue antiemetics were also observed with ondansetron (P < 0.05 vs. metoclopramide and placebo). Metoclopramide and placebo-treated patients were also 1.5 times (95% Cl 1.5-4.2) and 2.5 times (95% Cl 1.1-2.0) more likely, respectively, to experience nausea post-operatively. Overall, ondansetron was the most effective antiemetic in this patient population.

Adolescent↗
PubMed1998

Maryland veterans' knowledge of risk factors for and signs of oral cancers and their use of dental services.

OBJECTIVES: The purpose of this study was to evaluate outpatient veteran'í knowledge about risk factors for and signs of oral cancers, and their utilization of dental services. DESIGN: Patients receiving primary health care services were surveyed during August 1997. SETTING: Primary health care services at three medical centres within the VA Maryland Health Care System (VAMHCS). SUBJECTS: A total of 135 outpatient veterans were interviewed. INTERVENTION: Questionnaire administered by trained interviewers. MAIN OUTCOME MEASURES: Fifteen percent of the sample were eligible for dental care at the VA, while over 40% of those veterans participating in the study were unaware of their VA eligibility for dental services. Fifty six percent of the total sample received dental services from a private dentist, while 13% reported they had no provider of dental care. Of those not eligible for dental care at the VA (n = 115), the majority (67%) received dental care from a private dentist. Current use of tobacco and alcohol was reported by 27% of the sample. Nonsmokers were more likely to visit the dentist in the previous year than smokers (OR = 2.39, 95% C.I. 1.11,5.12). Although 84% correctly identified tobacco use as a risk factor, only 39% correctly identified regular alcohol use as a risk factor. CONCLUSIONS: Veterans at higher risk for oral cancers were less likely to have visited the dentist in the previous year, and, overall, were ill informed and misinformed about these cancers.

Alcohol Drinking↗
PubMed1998

Lycopene uptake and tissue disposition in male and female rats.

Epidemiologic and clinical studies suggest that tomato consumption may reduce the risk of cancer. Lycopene, a hydrocarbon carotenoid, is the major carotenoid in tomatoes and, as a potent singlet oxygen quencher, has been considered by some to be the biologically active agent responsible for the reduction of cancer risk associated with tomato consumption. However, little is known concerning lycopene absorption or biological activity in rodent models of cancer. Therefore, the present study was designed to provide information regarding the uptake and tissue disposition of lycopene and related carotenoid after feeding a diet containing a carotenoid mixture extracted from tomatoes (Betatene). Betatene was added to the diet at 2.3, 0.9, 0.45, 0.23, 0.09 and 0 (mM/kg diet) and fed to male and female Fischer-344 rats for a period of 10 weeks. Using reverse phase HPLC methods, it was found that approximately 55% of administered lycopene was excreted in the feces. In both males and females, lycopene concentrations were highest in the liver (120-42 microg/g wet wt.); physiologically significant levels were detected in prostate (97-47 ng/g), lung (227-134 ng/g), mammary gland (309-174 ng/g) and serum (285-160 ng/ml). Tissue concentrations were related to dose with the exception of serum, and differences between males and females were minimal. Other carotenoids present in Betatene (i.e., phytoene, phytofluene, z-carotene and beta-carotene) were also absorbed and stored in the liver. These results indicate that lycopene, when incorporated into the semipurified AIN-76A diet, is absorbed in both male and female rats in a dose-related manner and can be detected at nanogram levels in a variety of target organs.

Animals↗