Rye whole grain and bran intake compared with refined wheat decreases urinary C-peptide, plasma insulin, and prostate specific antigen in men with prostate cancer

Rye whole grain and bran intake has shown beneficial effects on prostate cancer progression in animal models, including lower tumor take rates, smaller tumor volumes, and reduced prostate specific antigen (PSA) concentrations. A human pilot study showed increased apoptosis after consumption of rye bran bread. In this study, we investigated the effect of high intake of rye whole grain and bran on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Seventeen participants were provided with 485 g rye whole grain and bran products (RP) or refined wheat products with added cellulose (WP), corresponding to ~50% of daily energy intake, in a randomized controlled, crossover design. Blood samples were taken from fasting men before and after 2, 4, and 6 wk of treatment and 24-h urine samples were collected before the first intervention period and after treatment. Plasma total PSA concentrations were lower after treatment with RP compared with WP, with a mean treatment effect of -14% (P = 0.04). Additionally, fasting plasma insulin and 24-h urinary C-peptide excretion were lower after treatment with RP compared with WP (P < 0.01 and P = 0.01, respectively). Daily excretion of 5 lignans was higher after the RP treatment than after the WP treatment (P < 0.001). We conclude that whole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion.     

Plasma enterolactone or intestinal Bifidobacterium levels do not explain adenoma formation in multiple intestinal neoplasia (Min) mice fed with two different types of rye-bran fractions

The study was designed to evaluate whether two types of rye-bran fractions result in distinct bifidogenic effect or enterolactone production in multiple intestinal neoplasia (Min) mice and whether these parameters are associated with intestinal tumorigenesis in this animal model. The experimental diets were a non-fibre diet (control), a rye-bran diet, and diets containing either the soluble extract or the insoluble fraction prepared from rye bran. The main result on adenoma formation in these experiments was the observation that the soluble extract increased number (P=0.012) and size (P=0.008) of adenomas in the distal small intestine when compared with the non-fibre group. All rye-supplemented diets supported similarly the in vivo growth of Bifidobacterium (10(8)-10(9) colony forming units/g) in Min mice, whereas the non-fibre diet lowered intestinal Bifidobacterium below the level of detection. The results show that water solubility does not affect the bifidogenicity of rye bran. Mean plasma enterolactone concentration was highest in the rye-bran group (30.0 nmol/l; P=0.002), which along with the soluble-extract group (16.2 nmol/l; P=0.024) differed significantly from the non-fibre diet group (7.5 nmol/l). Thus, the mice fed with the rye bran were the best enterolactone producers. In conclusion, rye bran and rye fractions influence adenoma formation in Min mice to a varying degree but plasma enterolactone levels or the production of bifidogenic bacteria do not mediate the effect.     

Lignan precursors from flaxseed or rye bran do not protect against the development of intestinal neoplasia in ApcMin mice

Phytoestrogens, like isoflavonoids and lignans, have been postulated as possible colorectal cancer protective constituents. To investigate this hypothesis, two high-fiber sources rich in lignan precursors, i.e., rye bran and flaxseed, were tested for their ability to modulate intestinal tumor development in ApcMin mice. Test diets consisted of a control diet (a Western-style diet, adjusted for fiber and/or phytate content) supplemented with 5% flaxseed or 30% rye bran. Chemical analysis of diets and blood samples confirmed the enhanced systemic exposure of mice fed the test diets to the major lignan precursors, i.e., secoisolariciresinol and matairesinol. No statistically significant difference was observed in the incidence and multiplicity of small intestinal and colon tumors at terminal sacrifice between mice fed the control diet or the diet supplemented with 5% flaxseed. With the rye bran diet a statistically significant enhancement of the number of small intestinal tumors in female mice was observed. The number of colon tumors, however, was comparable between the control and rye bran-fed mice of either sex. Furthermore, no activating point mutations in the K-ras oncogene nor positive immunohistochemical staining for the p53 gene were observed in a set of 48 colon tumors. In conclusion, our results demonstrate that increased intake of lignan precursors from flaxseed or rye bran, administered in a Western-style diet, does not protect against intestinal tumor development in an appropriate animal model for intestinal neoplasia such as the ApcMin mice.     

A High-Fat Diet Containing Lard Accelerates Prostate Cancer Progression and Reduces Survival Rate in Mice: Possible Contribution of Adipose Tissue-Derived Cytokines

To examine the effects of high-fat diet (HFD) containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP) and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.     

Intermittent Calorie Restriction Delays Prostate Tumor Detection and Increases Survival Time in TRAMP Mice

Prostate cancer is the most frequently diagnosed cancer in men. Whereas chronic calorie restriction (CCR) delays prostate tumorigenesis in some rodent models, the impact of intermittent caloric restriction (ICR) has not been determined. Here, transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were used to compare how ICR and CCR affected prostate cancer development. TRAMP mice were assigned to ad libitum (AL), ICR (2 wk 50% AL consumption followed by 2 wk pair feeding to AL consumption), and CCR (25% AL consumption) groups at 7 wk of age and followed until disease burden necessitated euthanasia or mice reached terminal endpoints (48 or 50 wk of age). Body weights fluctuated in response to calorie intake (P < 0.0001). ICR mice were older at tumor detection than AL (P = 0.0066) and CCR (P = 0.0416) mice. There was no difference for age of tumor detection between AL and CCR mice (P = 0.3960). Similar results were found for survival. Serum leptin, adiponectin, insulin, and IGF-I were all significantly different among the groups. These results indicate that the way in which calories are restricted impacts both time to tumor detection and survival in TRAMP mice, with ICR providing greater protective effect compared to CCR.     

Effects of dietary fatty acids on DU145 human prostate cancer cell growth in athymic nude mice

The purpose of this study was to examine the effects of diets containing different unsaturated fatty acids (FAs) on DU145 human prostate cancer cell growth in nude mice. In Experiment 1, groups of 25 mice were fed 23% (wt/wt) fat diets containing 18% corn oil (CO)‐5% linseed oil (18: 2n‐6 FA‐rich), 18% linseed oil (LO)‐5% CO (18: 3n‐3 FA‐rich), or 18% menhaden oil (MO)‐5% CO (20: 5 and 22: 6n‐3 FA‐rich), and seven days later they were injected subcutaneously with 1 × 10⁶ DU145 cells. The diets were continued for six weeks. The growth rates and final weights of tumors from the 18% CO‐5% LO and 18% LO‐5% CO mice were similar; there was a 30% reduction in tumor growth in the 18% MO‐5% CO group (p < 0.001). The tumor phospholipid FA patterns suggested that the inhibitory effect of the high‐MO diet was due, at least in part, to a reduction of arachidonic acid available for prostaglandin biosynthesis. In Experiment 2, groups of 25 mice were injected with 5 × 10⁵ or 1×10⁶ DU145 cells directly into the prostate gland and fed a high‐fat linoleic acid (n‐6 FA)‐rich or a low‐fat diet for 10 weeks. At necropsy, macroscopic cancers and microscopic intraprostatic tumors were evaluated. When the initial tumor load was 1 × 10⁶ cells, all but 7 of the 50 mice had developed large macroscopic tumors; the mean tumor weight in the high‐fat group was twice that in the low‐fat group (p = 0.047). A stimulatory effect of dietary n‐6 FA on DU145 prostate cancer cell growth may require a critical initial tumor cell mass.     

Dietary lignins are precursors of mammalian lignans in rats

The mammalian lignans enterolactone (ENL) and enterodiol, commonly found in human plasma and urine, are phytoestrogens that may contribute to the prevention of breast cancer and coronary heart disease. They are formed by the conversion of dietary precursors such as secoisolariciresinol and matairesinol lignans by the colonic microflora. The identification of lignins, cell-wall polymers structurally related to lignans, as precursors of mammalian lignans is reported here for the first time. In study 1, rats were fed rye or wheat bran (15% diet) for 5 d. Untreated brans and brans extracted with solvents to remove lignans were compared. ENL was estimated in urine samples collected for 24 h by time-resolved fluoroimmunoassay. ENL urinary excretion was reduced from 18.6 to 5.3 nmol/d (n=8; P<0.001) when lignans were removed from rye bran and from 30.5 to 6.2 nmol/d (P<0.001) when they were removed from wheat bran. These results suggest that lignins, embedded in the cell wall and retained in the bran during solvent extraction, account for 26-32% of the ENL formed from cereal brans. In study 2, rats were fed a deuterated synthetic lignin (0.2% diet) together with wheat bran (15%) for 3 d. The detection of deuterated ENL by LC-tandem MS in urine (20 nmol/d) clearly confirms the conversion of lignin into mammalian lignans. More research is warranted to determine the bioavailability of lignins in the human diet.     

A γ-tocopherol-rich mixture of tocopherols maintains Nrf2 expression in prostate tumors of TRAMP mice via epigenetic inhibition of CpG methylation

Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a pivotal role in maintaining cellular redox homeostasis and eliminating reactive toxic species. Nrf2 is epigenetically suppressed due to CpG hypermethylation in prostate tumors from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. We previously showed that dietary feeding of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) suppressed prostate tumorigenesis in TRAMP mice associated with higher Nrf2 protein expression. We hypothesized that γ-TmT may maintain Nrf2 through epigenetic inhibition of promoter CpG methylation. In this study, 8-wk-old male TRAMP mice were fed 0.1% γ-TmT or a control diet for 16 wk. The methylation in the Nrf2 promoter was inhibited in the prostate of the γ-TmT group compared with the control group. Protein expressions of DNA methyltransferase (DNMT), including DNMT1, DNMT3A, and DNMT3B, were lower in the prostate of the γ-TmT group than in the controls. TRAMP-C1 cells were treated with 30 μmol/L of γ-TmT or blank medium for 5 d. The methylation in the Nrf2 promoter was inhibited in the γ-TmT-treated cells compared with the untreated cells at d 5, and mRNA and protein expressions of Nrf2 and NAD(P)H:quinone oxidoreductase 1 were higher. Interestingly, only DNMT3B was inhibited in the γ-TmT-treated cells compared with the untreated cells. In the aggregate, our findings demonstrate that γ-TmT could inhibit CpG methylation in the Nrf2 promoter in the prostate of TRAMP mice and in TRAMP-C1 cells, which might lead to higher Nrf2 expression and potentially contribute to the prevention of prostate tumorigenesis in this TRAMP model.     

Long-term effects of fermentable fibers on rat colonic pH and epithelial cell cycle

The long-term effects of fermentable fibers on colonic luminal pH and the epithelial cell cycle were compared in 50 male Sprague-Dawley rats fed either a defined basal fiber-free diet or the basal diet supplemented with 10% pectin, cellulose or guar or with 20% oat bran. After 8 mo, in vivo pH measurements revealed that acidification of luminal contents occurred in the cecum and in mid and distal colons of rats fed fiber-supplemented diets when compared with the fiber-free controls (P less than 0.05). Pectin and guar produced the greatest acidification of luminal contents, the largest increase in cecal surface area and the highest percentage of colonic cells in S-phase, as measured by flow cytometry. In the proximal colon of the pectin group 9.2 +/- 0.5% of cells were in S-phase (6.3 +/- 0.8% with the fiber-free group) (P less than 0.05) and in the distal colon of the guar group 10.9 +/- 1.4% were in S-phase (7.1 +/- 0.5% with the fiber-free group) (P less than 0.05). Even though the most fermentable fibers produced the greatest mitogenic response, there was no site-specific correlation between pH and mucosal cell growth except in the cecum. This suggests that fibers may act as colon cell growth factors by some mechanism other than extracellular pH changes.     

Decreased growth of human prostate LNCaP tumors in SCID mice fed a low-fat, soy protein diet with isoflavones

Epidemiological studies suggest that high intake of dietary fat is a risk factor for the development of clinical prostate cancer. Soy protein has also been proposed to play a role in the prevention of prostate cancer, and one of the isoflavones in soy protein, genistein, inhibits the growth of human prostate cancer cell lines in vitro. This study was designed to evaluate whether altering dietary fat, soy protein, and isoflavone content affects the growth rate of a human androgen-sensitive prostate cancer cell line (LNCaP) grown in severe-combined immunodeficient (SCID) mice. SCID mice were randomized into four dietary groups: high-fat (42.0 kcal%) + casein, high-fat (42.0 kcal%) + soy protein + isoflavone extract, low-fat (12.0 kcal%) + casein, and low-fat (12.0 kcal%) + soy protein + isoflavone extract. After two weeks on these diets, the mice were injected subcutaneously with 1 x 10(5) LNCaP tumor cells and placed in separate cages (1 mouse/cage) to strictly control caloric intake. Isocaloric diets were given 3 days/wk, and tumor sizes were measured once per week. The tumor growth rates were slightly reduced in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In addition, the final tumor weights were reduced by 15% in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In this xenograft model for prostate cancer, there were statistically significant effects on tumor growth rate and final tumor weight attributable to a low-fat + soy protein + isoflavone extract diet.     

血管内皮生长因子与卵巢癌细胞凋亡的关系

目的:探讨血管内皮生长因子(VEGF)在卵巢癌中的表达及其与细胞凋亡的关系。方法:分别采用免疫组织化学SP法和TUNEL检测VEGF在45例卵巢癌中的表达及细胞凋亡情况。结果:45例卵巢癌中VEGF阳性表达率为86.7%(39/45)。卵巢癌组织中60%(27/45)细胞凋亡为阳性,40%(18/45)细胞凋亡为阴性。卵巢癌细胞凋亡阴性组中VEGF强阳性表达率88.9%(16/18)高于细胞凋亡阳性组40.7%(11/27),P=0.039。结论:VEGF抑制肿瘤细胞凋亡,促进肿瘤生长、局部侵袭及远处转移。     

DC-CTL免疫细胞对卵巢上皮癌细胞的靶向性治疗研究

目的：探讨经树突状细胞（ DC）诱导的细胞毒性T淋巴细胞（ CTL）免疫细胞靶向性的抑制卵巢上皮癌细胞的机制,为临床上DC-CTL治疗卵巢癌提供理论基础。方法无胸腺BALB／C／nu／nu裸小鼠48只,分为4组,每组12只,裸鼠人卵巢癌SKOV3移植瘤模型成功后用未经DC诱导的CTL免疫细胞和经DC诱导的CTL免疫细胞进行治疗,比较各组裸鼠移植瘤体积和重量、抑瘤率、移植瘤miRNAlet-7表达和HMGA2蛋白表达的差异。结果 DC-CTL组和CTL组裸鼠的移植瘤体积和移植瘤重量低于模型对照组（F值分别为8．175、6．823,均P＜0．05）,DC-CTL组裸鼠的移植瘤体积和移植瘤重量低于CTL组,且差异具有统计学意义（t＝13．244,P＜0．05）;DC-CTL组裸鼠的抑瘤率（69．57±10．81）％高于CTL组（42．35±8．15）％,且差异具有统计学意义（t＝6．965,P＜0．05）;DC-CTL组和CTL组裸鼠的移植瘤miRNAlet-7表达均高于模型对照组（F＝7．528,P＜0．05）, DC-CTL组裸鼠的移植瘤miRNAlet-7表达（1．69±0．40）高于CTL组（1．17±0．39）,且差异具有统计学意义（t＝2．964,P＜0．05）;DC-CTL组和CTL组裸鼠的HMGA2蛋白表达的ISH评分均低于模型对照组（F＝6．419,P＜0．05）,DC-CTL组裸鼠的HMGA2蛋白表达的ISH评分（15．31±1．72）低于CTL 组（17．18±1．86）,且差异具有统计学意义（t ＝3．143,P＜0．05）。结论经DC诱导的CTL免疫细胞能够明显抑制裸鼠卵巢癌移植瘤的生长,其机制可能为促进let-7表达和抑制HMGA2蛋白表达有关。     

Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice.

The objectives of our studies are to characterize the ability of dietary soybean components to inhibit the growth of prostate cancer in mice and alter tumor biomarkers associated with angiogenesis. Soy isoflavones (genistein or daidzein) or soy phytochemical concentrate inhibit the growth of prostate cancer cells LNCaP, DU 145 and PC-3 in vitro, but only at supraphysiologic concentrations, i.e., 50% inhibitory concentration (IC(50)) > 50 micromol/L. G2-M arrest and DNA fragmentation consistent with apoptosis of prostate cancer cells are also observed at concentrations causing growth inhibition. In contrast, the in vitro proliferation of vascular endothelial cells was inhibited by soy phytochemcials at much lower concentrations. We evaluated the ability of dietary soy phytochemical concentrate and soy protein isolate to inhibit the growth of the LNCaP human prostate cancer in severe combined immune-deficient mice. Mice inoculated subcutaneously with LNCaP cells (2 x 10(6)) were randomly assigned to one of the six dietary groups based on the AIN-76A formulation for 3 wk. A 2 x 3 factorial design was employed with two protein sources (20%, casein vs. soy protein) and three levels of soy phytochemical concentrate (0, 0.2 and 1.0% of the diet). Soy components did not alter body weight gain or food intake. Compared with casein-fed controls, the tumor volumes after 3 wk were reduced by 11% (P = 0.45) by soy protein, 19% (P = 0.17) by 0.2% soy phytochemical concentrate, 28% by soy protein with 0.2% soy phytochemical concentrate (P < 0.05), 30% by 1.0% soy phytochemical concentrate (P < 0.05) and 40% by soy protein with 1.0% soy phytochemical concentrate (P < 0.005). Histologic examination of tumor tissue showed that consumption of soy products significantly reduced tumor cell proliferation, increased apoptosis and reduced microvessel density. The angiogenic protein insulin-like growth factor-I was reduced in the circulation of mice fed soy protein and phytochemical concentrate. Our data suggest that dietary soy products may inhibit experimental prostate tumor growth through a combination of direct effects on tumor cells and indirect effects on tumor neovasculature.     

EGCG对人前列腺癌裸鼠移植瘤生长和间隙连接蛋白43表达的影响

目的研究表没食子儿茶素没食子酸脂（EGCG）对前列腺癌裸鼠移植瘤生长和间隙连接蛋白43（Cx43）表达的影响,探讨EGCG防治前列腺癌的作用机制。方法分别采用四甲基偶氮唑蓝法、膜联蛋白／碘化丙锭双标流式细胞术和划痕标记荧光染料传输技术,体外观察不同浓度的EGCG（10、20、40mg/L）对人前列腺癌PC-3细胞的生长抑制率、凋亡率、细胞间间隙连接通讯功能（GJIC）的变化。采用PC-3细胞建立裸鼠皮下移植瘤动物模型,随机分为对照组和不同剂量的EGCG组（10、20、40mg/kg）,14d后称量移植瘤体重并计算抑瘤率,DNA原位缺口末端标记法和免疫组织化学分别检测凋亡指数（AI）和肿瘤微血管密度（MVD）,半定量逆转录聚合酶链反应检测移植瘤组织cx43mRNA的表达水平。结果20mg/L和40mg／L的EGCG均能明显抑制PC-3细胞的生长[（22．33±4．62）％,（38．67±5．67）％VS（3．47±0．31）％,P〈0．01]和诱导细胞凋亡[（7．84±1．37）％,（24．53±2．28）％V8（2．17±0．70）％,P〈0．01],并增强细胞间的GJIC功能。不同剂量的EGCG均能抑制裸鼠前列腺癌移植瘤生长,促进肿瘤细胞凋亡,减少肿瘤血管生成。（20、40mg/kg）EGCG能显著上调移植瘤组织Cx43mRNA的表达（0．58±0．08,0．80±0．07V80．42±0．04,P〈0．01）。EGCG对前列腺移植瘤的抑制作用、诱导细胞凋亡和上调Cx43表达的效应均随剂量的增加而增强,呈剂量依赖性（P〈0．05）。结论EGCG能上调Cx43在裸鼠前列腺癌组织中的表达和增强Cx43介导的间隙连接通讯功能,从而有效抑制前列腺癌移植瘤的生长。     

Immunization with recombinant DNA and modified vaccinia virus Ankara (MVA) vectors delivering PSCA and STEAP1 antigens inhibits prostate cancer progression

Despite recent advances in early detection and improvement of conventional therapies, there is an urgent need for development of additional approaches for prevention and/or treatment of prostate cancer, and the use of immunotherapeutic modalities, such as cancer vaccines, is one of the most promising strategies. In this study, we evaluated the prophylactic efficacy of an active immunization protocol against prostate cancer associated antigens mPSCA and mSTEAP1 in experimental prostate cancer. Two antigen delivery platforms, recombinant DNA and MVA vectors, both encoding either mPSCA or mSTEAP1 were used in diversified DNA prime/MVA boost vaccination protocol. Antitumour activity was evaluated in TRAMP-C1 subcutaneous syngeneic tumour model and TRAMP mice. DNA prime/MVA boost immunization against either mPSCA or mSTEAP1, delayed tumour growth in TRAMP-C1 cells-challenged mice. Furthermore, simultaneous vaccination with both antigens produced a stronger anti-tumour effect against TRAMP-C1 tumours than vaccination with either mPSCA or mSTEAP1 alone. Most importantly, concurrent DNA prime/MVA boost vaccination regimen with those antigens significantly decreased primary tumour burden in TRAMP mice without producing any apparent adverse effects. Histopathological analysis of prostate tumours from vaccinated and control TRAMP mice revealed also that mPSCA/mSTEAP1 based-vaccination was effective at reducing the severity of prostatic lesions and incidence of high-grade poorly differentiated prostate cancer. Suppression of the disease progression in TRAMP mice was correlated with decreased proliferation index and increased infiltration of T-cells in prostate tissue. Active immunization against PSCA and STEAP1 using DNA prime/MVA boost strategy is a promising approach for prevention and/or treatment of prostate cancer.     

Comparison of calcium supplementation or low-fat dairy foods on epithelial cell proliferation and differentiation

Epidemiological evidence suggests that dietary calcium and vitamin D intake are inversely related to incidence of colon cancer. Previous studies have demonstrated that supplementation of the diet with calcium in the form of calcium tablets or low-fat dairy foods alters colonic epithelial cell proliferation from a higher- to a lower-risk pattern. The present study compared relative effects of administration of calcium carbonate at approximately 900 mg/day (calcium) with those of a low-fat dairy food diet providing about the same amount of calcium (dairy) in a cross-over "head-to-head" study of 40 subjects at risk for colonic neoplasia. Dietary intake of macronutrients was similar in the two study periods, except for a slight increase in protein intake during dairy calcium supplementation. Rectal epithelial cell proliferation was studied in flat endoscopically normal-appearing mucosa at baseline and at the end of each of the two study periods and showed a significant reduction in epithelial crypt cell labeling index from 12.5% to 9.1% (calcium) or 9.3% (dairy) as well as in proliferating cells in the upper 40% of the crypt from 0.09 to 0.03 in the calcium- and low-fat dairy-supplemented intervention groups. No significant changes in two epithelial cell differentiation markers, cytokeratin AE1 and acidic mucins, were found. Furthermore, there were no differences in epithelial cell apoptosis or expression of the proapoptotic gene product BAK. These data indicate that increased dietary calcium given as supplements or in the diet in low-fat dairy foods lowers epithelial cell proliferation indexes from a higher- to a lower-risk pattern. Because supplemental calcium has been shown to reduce the recurrence of colonic adenomatous polyps in patients at increased risk for colonic neoplasia, our data suggest that supplemental low-fat dairy foods may also be effective.     

Antitumor effects of ursolic acid in a mouse model of postmenopausal breast cancer

Over the past two decades, bioactive natural compounds have been shown to be a plausible adjunct to the treatment of breast cancer, the second leading cause of cancer death among American women. This study was designed to investigate the effects of ursolic acid (UA), a pentacyclic triterpene found in many foods and herbs, in a model of postmenopausal breast cancer. Ovariectomized C57BL/6 mice (n = 40) were randomized to receive control diet (AIN-93G) or diet supplemented with UA at 1 of 3 doses (wt/wt): 0.05%, 0.10%, or 0.25% (≈54, 106, or 266 mg/kg body weight/day, respectively). After 3 wk, syngeneic MMTV-Wnt-1 mammary tumor cells were injected in the mammary fat pad, and mice continued on their respective diets for 5 more wk. All UA doses decreased tumor cell proliferation, as assessed by Ki67 immunostaining; nevertheless, UA at 0.10% was most effective in inhibiting tumor take and decreasing tumor final tumor size. Modulation of Akt/mTOR signaling and induction of apoptosis appeared to mediate these effects on tumor growth. UA potently disrupted cell cycle progression and induced necrosis in a clonal MMTV-Wnt-1 mammary tumor cell line in vitro. This study supports the potential of UA as an antitumorigenic agent.     

White Button Mushroom (Agaricus Bisporus) Exhibits Antiproliferative and Proapoptotic Properties and Inhibits Prostate Tumor Growth in Athymic Mice

White button mushrooms are a widely consumed food containing phytochemicals beneficial to cancer prevention. The purpose of this research was to evaluate the effects of white button mushroom extract and its major component, conjugated linoleic acid (CLA) on prostate cancer cell lines in vitro and mushroom extract in vivo. In all cell lines tested, mushroom inhibited cell proliferation in a dose-dependent manner and induced apoptosis within 72 h of treatment. CLA inhibited proliferation in the prostate cancer cell lines in vitro. DU145 and PC3 prostate tumor size and tumor cell proliferation were decreased in nude mice treated with mushroom extract, whereas tumor cell apoptosis was increased compared to pair-fed controls. Microarray analysis of tumors identified significant changes in gene expression in the mushroom-fed mice as compared to controls. Gene network analysis identified alterations in networks involved in cell death, growth and proliferation, lipid metabolism, the TCA cycle and immune response. The data provided by this study illustrate the anticancer potential of phytochemicals in mushroom extract both in vitro and in vivo and supports the recommendation of white button mushroom as a dietary component that may aid in the prevention of prostate cancer in men.     

Usefulness of oral mucosal epithelial cell apoptosis rate in nutritional assessment

OBJECTIVE: This preliminary study was designed to explore a new method for nutritional assessment by measuring oral mucosal cell apoptosis or proliferation. METHODS: Forty-two consecutive patients with gastrointestinal malignant tumors were hospitalized on the surgical wards and studied prospectively. Patient-Generated Subjective Global Assessment was used to identify malnourished patients. Anthropometric measurements including weight, body mass index, triceps skinfold thickness, and midarm muscle circumference were recorded. The serum proteins measured were retinol-binding protein (RBP), transferrin, prealbumin (PA), and albumin. Simultaneously, the rates of oral epithelial cell apoptosis and proliferation were measured by flow cytometry. Of the 20 malnourished patients, 14 were followed up in a serial study with a 3-d nutritional support therapy. Nutritional indices and oral epithelial cell apoptosis rate were measured after 3 d of nutritional support. RESULTS: Malnutrition was diagnosed in 20 of 42 patients (47.6%). Oral epithelial apoptosis and proliferation rates were significantly decreased (P < 0.01 and P < 0.05, respectively) in malnourished compared with non-malnourished patients, although there were no significant differences between their anthropometric data. Malnourished patients had lower serum levels of RBP, albumin, and PA and rates of oral epithelial cell apoptosis and proliferation. The rate of oral epithelial cell apoptosis positively correlated with serum RBP (R = 0.32, P < 0.05) and PA (R = 0.33, P < 0.05). The rate of oral epithelial cell apoptosis and serum RBP and PA increased significantly in the malnourished patients who received nutritional support for 3 days. CONCLUSIONS: Measuring the rate of oral epithelial cell apoptosis may be another non-invasive technique to determine nutritional assessment and is worthy of further exploration.