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This study is concerned with the problem of generalised Kalman-Yakubovich-Popov (GKYP) lemma and its application to two-dimensional (2D) continuous-discrete systems described by Roesser model. On the basis of the feature of states in the system, a rectangular finite frequency range is characterised by a linear matrix inequality and then combined with S-procedure, the GKYP lemma is developed for 2D continuous-discrete systems in Roesser model. As special cases of this lemma, 2D continuous-discrete case finite frequency bounded realness and positive realness are investigated as well. Furthermore, the finite frequency 2D positive realness control problem via state-feedback controllers are considered based on the developed lemma. Finally, numerical examples are given to illustrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Brevetoxins are a group of natural neurotoxins characterized by polyether ring systems that are found in the blooms of red tide algae. In a conventional water/organic solvent system, without any other additives, deprotonated molecules of brevetoxins do not appear in high abundance in negative mode electrospray mass spectrometry (ES-MS) due to lack of acidic functional groups; thus, they are not well-suited for collision-induced decomposition (CID) experiments in negative mode electrospray. In this study, several anions were tested for their abilities to form anionic adducts by mixing animonium salts of these anions with brevetoxin-2 and brevetoxin-3. Under CID, [M + C1]-, [M + Br]-, [M + OAc]-, [M + HCOO]-, and [M + NO3]- adducts all produced only the respective anions in CII) experiments and thus provided no stnictural infonnation. In contrast, upon CU), both [M + F]- and [M + HCO3]- precursor adducts gave structurally informative fragment peaks that exhibited similarities to those OHM - HI-ions, which indicated that the first step in gas-phase decomposition of these anionic adducts was loss of neutral HF or H2CO3 molecules, respectively, leaving deprotonated brevetoxin (FM — H]-) to undergo consecutive fragmentations. In comparison to bicarbonate, fluoride formed adducts in higher abundance and provided more fragment peaks, thus more structural information, in MS/MS experiments. It is therefore the anion of choice to study brevetoxins in negative mode electrospray mass spectrometay using the anion attachment approach. The detailed fragmentation mechanisms are discussed, and diagnostic product ions are proposed for the brevetoxin-2 side chain (m/z 95, 133, and 151), the brevetoxin-3 side chain (m/z 97, 135, and 153), and the type-B brevetoxin backbone (m/z 725, 739, 741, and 797). To test the developed methodologmr, a sample of brevetoxin-2 subjected to in vitro micinsomal incubation was analyzed, and a reduction product of the substrate was conflnned to have the sIructu of brevetoxin-3. [ABSTRACT FROM AUTHOR]

Brevetoxins are natural neurotoxins that are produced by “red tide” algae. This class of compounds can cause neurotoxic shellfish poisoning and other health problems. Brevetoxin-2 is the most abundant among the nine brevetoxins that have been characterized, whereas brevetoxin-1 is the most toxic. In this study, brevetoxin-1 and brevetoxin-2 were incubated with rat liver hepatocytes and rat liver microsomes, respectively. After clean-up steps were taken to remove the proteins, samples were analyzed by liquid chromatography (LC) coupled with electrospray mass spectrometry (LC-MS). After incubation of brevetoxin-1, two metabolites were found: brevetoxin-1-M1 (molecular weight = 900 Da), and brevetoxin-1-M2 (molecular weight = 884 Da). The increase in molecular weight combined with evidence from tandem mass spectrometry showing an increased tendency for loss of water molecules, along with considerations of established precedents for chemical transformations led to the conclusion that brevetoxin-1-M1 was formed by converting one double bond in the E or F ring of brevetoxin-1 into a diol. The second metabolite (brevetoxin-1-M2) is proposed to be a hydrolysis product of brevetoxin-1 involving opening of the lactone ring with the addition of a water molecule. The incubation study of the other starting compound, brevetoxin-2, found two metabolites in the LC-ES-MS selected ion chromatogram. Brevetoxin-2-M1 (molecular weight = 912 Da) gave a large [M−H]− peak at m/ z 911, and its product ion mass spectrum allowed the deduction that this metabolite was the hydrolysis product of brevetoxin-2 involving conversion of the lactone to a carboxylic acid and an alcohol. The second metabolite (brevetoxin-2-M2, molecular weight = 896 Da) was deduced to have the same structure as that of brevetoxin-3 based on identical chromatographic retention times and similar mass spectra as those obtained for a brevetoxin-3 standard. [ABSTRACT FROM AUTHOR]

Apigenin has been previously shown to induce G2/M cell-cycle arrest in human colon cancer cell lines. The present study assessed the individual and interactive influence of seven apigenin analogs on cell cycle, cell number, and cell viability in human SW480 and Caco-2 colonic carcinoma cells, Cellular concentration of selected apigenin analogs was further assessed by high-performance liquid chromatography to assess cellular availability. The apigenin analogs studied were acacetin, chrysin, kampherol, luteolin, myricetin, naringenin, and quercetin. DNA flow cytometric analysis indicated that treatment with either chrysin or acacetin at 0 to 80 μM for 48 h resulted in cell-cycle arrest at the G2/M phase in a dose-dependent manner in the SW480 cells but not in the Caco-2 cells. The percentage of SW480 cells at G2/M also increased when cells were treated with kampherol, luteolin, or quercetin between 5 and 30 μM, but the percentage of cells in G2/M decreased at doses greater than 40 μM. Cell number was significantly decreased in a time- and dose-dependent manner following the treatments with each analog except for naringenin and myricetin. The interactive effects of these analogs with apigenin were further assessed by combining each analog at doses from 0 to 80 μM with apigenin at 20 μM, a dose at which apigenin was found to double the proportion of SW480 cells in G2/M. When either acacetin, chrysin, luteolin, kampherol, or quercetin at doses between 5 and 30 μM were combined with apigenin at 20 μM, there was an increase of 22% in the proportion of G2/M cells over that observed with 20 μM apigenin alone (P < 0.05). At doses higher than 40 μM, however, the interaction became antagonistic, and the proportion of cells in G2/M decreased below that observed with apigenin alone. Cell viability, as assessed by Trypan blue exclusion assay, significantly decreased by treatments with high doses of each agent or each agent combined with apigenin. Cellular concentration of apigenin, chrysin, or naringenin in SW480 cells significantly increased at doses of 40 μM or greater, but it was not correlated with their impact on G2/M cell-cycle arrest. The induction of cell-cycle arrest by five of seven tested apigenin analogs and the additive induction by the combination of flavonoids at low doses suggest that apigenin-related flavonoids may cooperatively protect against colorectal cancer through conjoint blocking of cell-cycle progression. [ABSTRACT FROM AUTHOR]

Presents a study that examined the detectability and asymptotic reconstructibility of the state of two-dimensional singular discrete circuit systems. Review of related studies on two-dimensional singular systems; Details on a general observer for a detectable singular system; Design of a class of full-order asymptotic observers; Investigation of the properties of state feedback systems that contain observers.

Our previous studies demonstrated that lignan metabolites, enterolactone and enterodiol, inhibited colonic cancer cell growth by inducing cell cycle arrest and apoptosis. This study is focused on the cancer preventive impact of lignan secoisolariciresinol diglucoside (SDG), one of the prominent lignan glycoside, in human colonic cancer SW480 cells. Treatment with SDG at 0-40 µmol/L for 48 hrs resulted in a dose-and time-dependent decrease in cell numbers, which was comparable to enterolactone. These cell growth inhibitions by SDG were not mediated by cytotoxicity, but rather linked to an increased cell cycle arrest at S-phase. Furthermore, HPLC analysis indicated SDG in the media for 48 hrs was much more stable than enterolactone (stability at 95% for SDG in comparison to 57% for enterolactone). The intracellular levels of SDG rather than enterolactone were undeteetable, suggesting that SDG was not readily absorbed or metabolized to its metabolites in this short-term cell culture system. Taken together, these findings provide novel characteristics of dietary lignan precursor on colonic cancer growth inhibition and may enhance our understanding of bioavailability of dietary lignans for cancer prevention. [ABSTRACT FROM AUTHOR]

Background: We have previously demonstrated that cigarette smoke is associated with a significant reduction of retinoic acid in rat lungs and the formation of tracheal precancerous lesions. However, the underlying mechanism of cancer risk induced by vitamin A deficiency is unclear. The purpose of this study was to determine whether the cigarette smoke-induced depletion of vitamin A is related to changes in lung cancer risk-related molecular markers. Results: We investigated the roles of the retinoic acid receptors (RARs) as well as other biomarkers for potential cancer risk in the lungs of rats exposed to cigarette smoke. Twenty-four male weanling rats were fed a purified diet and divided equally into four groups. Three experimental groups were exposed to increasing doses of cigarette smoke from 20, 40 or 60 commercial cigarettes/day for 5 days/week. After 6 weeks, the retinoic acid concentrations in the lung tissue as measured via high performance liquid chromatography (HPLC) significantly decreased (P < 0.01) in cigarette smoke exposed groups. Western Blot analysis revealed that cigarette smoke exposure increased lung protein expression of RAR α in a threshold manner and decreased RAR β and RAR γ expression in a dose-dependent fashion. Protein expressions of cyclin E and proliferating cell nuclear antigen (PCNA) were increased significantly in a dose-dependent manner in cigarette smoke exposed-groups. Additionally, there was a significant increase in protein expression of cJun and cyclin D1 demonstrating a threshold effect similar to that exhibited by RARα, suggesting a potential independent signaling pathway for RARα in lung carcinogenesis. Conclusions: Findings from this study suggest that cigarette smoke-induced lung retinoic acid depletion may involve two independent pathways, RARα- and RARβ-mediated, responsible for the increased cancer risk associated with cigarette smoke-induced vitamin A deficiency. [ABSTRACT FROM AUTHOR]

CXCL3 plays extensive roles in tumorigenesis in various types of human cancers through its roles in tumor cell differentiation, invasion, and migration. However, the mechanisms of CXCL3 in head and neck squamous cell carcinoma (HNSCC) remain unclear. In our study, multiple databases were used to explore the expression level, prognostic value, and related mechanisms of CXCL3 in human HNSCC through bioinformatic methods. We also performed further experiments in vivo and in vitro to evaluate the expression of CXCL3 in a human head and neck tissue microarray and the underlying effect mechanisms of CXCL3 on the tumor biology of HNSCC tumor cells. The result showed that the expression level of CXCL3 in patients with HNSCC was significantly higher as compared with that in normal tissues (P<0.05). Kaplan–Meier survival analysis demonstrated that patients with high CXCL3 expression had a lower overall survival rate (P=0.038). CXCL3 was further identified as an independent prognostic factor for HNSCC patients by Cox regression analysis, and GSEA exhibited that several signaling pathways including Apoptosis, Toll-like receptor, Nod-like receptor, Jak-STAT, and MAPK signaling pathways may be involved in the tumorigenesis of HNSCC. CAL27 cells overexpressing or HNSCC cells treated with exogenous CXCL3 exhibited enhanced cell malignant behaviors, whereas down-regulating CXCL3 expression resulted in decreased malignant behaviors in HSC4 cells. In addition, CXCL3 may affect the expression of several genes, including ERK1/2, Bcl-2, Bax, STAT3, and NF-κB. In summary, our bioinformatics and experiment findings effectively suggest the information of CXCL3 expression, roles, and the potential regulatory network in HNSCC. [ABSTRACT FROM AUTHOR]

Objective: CXCL3, a member of the chemokine family, plays a key role in angiogenesis, tumorigenesis, and cell invasion and migration. However, the role of CXCL3 in oral squamous cell carcinoma (OSCC) remains unclear. The purpose of this study is to explore the expression of CXCL3 in OSCC and to explore the role of CXCL3 in human OSCC HSC-4 cells and its molecular mechanism.Methods: The expression of CXCL3 in human OSCC tissues was assessed using immunohistochemistry and The Cancer Genome Atlas (TCGA) database. In vivo and in vitro experiments investigated the effects of CXCL3 on the proliferation, migration, and invasion of OSCC cells.Results: The expression of CXCL3 in tumors is higher than that in normal tissues and is closely related to stage and lymph node metastasis. In vitro experiments showed that the proliferation and migration ability of HSC-4 cells treated with exogenous recombinant human CXCL3 and HSC-4 cells overexpressing CXCL3 were enhanced. Experiments on xenografts in nude mice showed that overexpression of CXCL3 promotes tumor growth in vivo. GSEA showed that patients with high expression of CXCL3 have varying degrees of enrichment in cytokine-cytokine receptor interaction, apoptosis, Jak-STAT signaling pathway, and MAPK signaling pathway. Subsequent mechanism studies showed that the use of ERK1/2 blocker PD98059 can attenuate the proliferation and migration effects induced by CXCL3.Conclusion: CXCL3 is involved in the occurrence of OSCC and may become a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Abstract: The efficacy of dietary apigenin, a dietary flavonoid, in colon cancer prevention was investigated by evaluating the inhibition of the ornithine decarboxylase (ODC) activity and the formation of aberrant crypt foci (ACF) and by studying the ability of apigenin to block colon carcinogenesis in two mouse models. First, the activity of ODC was measured in colon cancer cells (Caco-2) and in the colon epithelium of CF-1 mice. Apigenin at 10 and 30 μM significantly inhibited the ODC activity of Caco-2 cells by 26% and 57%, respectively. Colonic ODC activity in CF-1 mice was reduced with 0.1% dietary apigenin by 42% compared with the control, but this difference was not statistically significant. Second, ACF formation was evaluated in azoxymethane (AOM)-induced CF-1 mice. Female CF-1 mice at 6 wk of age were i.p. injected with 5 mg/kg body weight (BW) AOM once to induce ACF. ACF formation in CF-1 mice was reduced by 50% (P < 0.05) with 0.1% dietary apigenin fed for 6 wk when compared with the control. Dietary apigenin inhibited ACF only in the distal region of the CF-1 mouse colon. Finally, tumorigenesis studies were conducted using two different mouse models: AOM-induced CF-1 mice and Min mice with mutant adenomatous polyposis coli (APC) gene. Female CF-1 mice at 6 wk of age were i.p. injected with 10 mg/kg BW AOM weekly for 6 (AOM Study I) or 4 (AOM Study II) wk to induce tumors. CF-1 mice were fed diets containing 0.025% or 0.1% apigenin for 23-25 wk. Female Min mice were fed diets for 10 wk beginning at 5 wk of age. In two AOM-treated mouse colon tumor studies 0.025% and 0.1% dietary apigenin modestly reduced tumors in the group fed 0.025% apigenin (25% incidence in comparison with 65% in the controls) in a non-dose response manner. Apigenin failed to inhibit adenoma formation in the Min mouse study. These results suggest that dietary apigenin showed promise in cancer prevention by reducing the ODC activity and ACF formation, however, clear evidence of cancer prevention was not obtained in mouse tumor studies. Further investigation of the potential chemopreventive effect of apigenin in carcinogenesis is warranted. [ABSTRACT FROM AUTHOR]

C‑X‑C motif chemokine ligand 5 (CXCL5) is a CXC‑type chemokine that is a crucial inflammatory mediator and a powerful attractant for granulocytic immune cells. Increasing evidence has indicated that CXCL5 is involved in the tumorigenesis of various malignancies. The present investigation demonstrated that CXCL5 was expressed in both hepatoblastoma HepG2 cells and liver stellate LX‑2 cells, and CXCL5's receptor C‑X‑C chemokine receptor type 2 (CXCR2) was expressed in HepG2 cells by reverse transcription‑polymerase chain reaction (RT‑PCR), western blotting and ELISA assays. Cell counting kit‑8, colony formation and Transwell assays revealed that exogenous CXCL5 expression efficiently promoted proliferation, colony formation and migration of HepG2 cells. To explore the autocrine and paracrine roles of CXCL5 in the oncogenic potential of HepG2 cells, HepG2 cells overexpressing CXCL5 and LX‑2 cells overexpressing CXCL5 were successfully constructed by gene transfection. Similarly, overexpression of CXCL5 in HepG2 also enhanced proliferation, colony formation and migration of HepG2 cells. Furthermore, the condition medium of LX‑2 cells overexpressing CXCL5 affected the proliferation and migration of HepG2 cells. RT‑PCR and western blotting assays were also conducted to explore whether overexpression of CXCL5 in HepG2 modulated the expression of genes. The results revealed that overexpression of CXCL5 regulated the expression of several genes, including N‑myc downregulated gene 3,w B‑cell lymphoma‑2 (Bcl‑2), Bcl‑2‑associated X protein, P53, vascular endothelial growth factor, interleukin (IL)‑18, IL‑1β and cystathionine‑γ‑lyase. In conclusion, the present findings indicate that CXCL5/CXCR2 axis contributes to the oncogenic potential of hepatoblastoma via autocrine or paracrine pathways by regulating expression of genes associated with the progression of carcinoma. [ABSTRACT FROM AUTHOR]

Breast cancer is a very common malignant tumor, whose incidence ranks the first among various types of cancer in women worldwide. An important hallmark of cancer is the activation of oncogenes, which lead to overgrowth of cancer cells. Therefore, it is necessary to identify the critical genes involved in regulating the progression of breast cancer and elucidate the corresponding molecular mechanisms. The present study demonstrated that integrin‑linked kinase (ILK) overexpression promoted cell proliferation and growth in MCF‑7 cells, while ILK knockdown led to growth arrest in MDA‑MB‑231 cells. In addition, activation of the phosphoinositide 3‑kinase (PI3K)/Akt pathway was positively regulated by ILK, suggesting that the regulatory effects of ILK on cell growth and proliferation may be at least in part mediated by PI3K/Akt signaling. These results indicated that ILK promoted cell proliferation and growth in breast cancer cells through activation of the PI3K/Akt pathway, suggesting that ILK may be considered to be a potential therapeutic target for the therapy of breast cancer in the future. [ABSTRACT FROM AUTHOR]

The effects of different dietary fats with variable levels of polyunsaturated fatty acids (PUFAs) on egg quality of Shan Partridge Duck, serum, and yolk lipid parameters were examined in this study. A flock of 585 optimal produced ducks were selected and diets enriched with 0.5%, 1%, or 2% fish oil (F)/flaxseed oil (FL)/rapeseed oil (R)/tallow (T) plus basal diet were supplied through a 28-d period. Supplemental fat source and fat level had no effects on egg qualities. Proportions of yolk total cholesterol (TC), saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) were reduced (P < 0.001), while polyunsaturated fatty acids (PUFAs), ω-6 polyunsaturated fatty acids (n-6 PUFAs), ω-3 polyunsaturated fatty acids (n-3 PUFAs), Docosahexaenoic Acid (DHA), and Eicosapentaenoic Acid (EPA) were increased by fish oil, flaxseed oil, or rapeseed oil. Effects of supplementation increasing DHA and EPA were detected in F, FL, and R. Compared with C, fish oil significantly increased low-density lipoprotein cholesterol (LDL-C) in serum, flaxseed oil significantly reduced TC and increased very low-density lipoprotein cholesterol (VLDL-C), rapeseed oil significantly reduced TC and LDL-C in serum and increased VLDL-C, tallow significantly increased LDL-C. It is concluded that unsaturated fatty acids rich diets (fish oil, flaxseed oil, and rapeseed oil) might increase yolk PUFAs, reduce yolk cholesterol, and change serum lipid parameters without evident effect on egg qualities. [ABSTRACT FROM AUTHOR]

Weight control by exercise and dietary calorie restriction (DCR) has been associated with reduced cancer risk, but the underlying mechanisms are not well understood. This study was designed to compare the effects of weight loss by increasing physical activity or decreasing calorie intake on tumor promoter-induced Ras-MAPK and PI3K-Akt pathways. SENCAR mice were randomly assigned to one of the following five groups: ad libitum-fed sedentary control, ad libitum-fed exercise (AL+Exe), exercise but pair-fed at the amount as controls (PF+Exe), 20% DCR, and 20% DCR plus exercise (DCR+Exe). After 10 weeks, body weight and body fat significantly decreased in the groups of DCR, DCR+Exe, and PF+Exe when compared with the controls. AL+Exe did not induce weight loss due to, at least in part, increased food intake. Plasma IGF-1 levels reduced significantly in DCR and DCR+Exe but not PF+Exe. The protein H-Ras and activated Ras-GTP significantly decreased in TPA-induced skin tissues of DCR-fed mice but not exercised mice. PI3K protein, phosphoserine Akt, and p42/p44-MAPK were reduced, however, in both DCR and PF+Exe groups. Immunohistochemistry demonstrated that the significantly reduced H-Ras occurred in subcutaneous fat cells, while the reduced PI3K and PCNA took place only in the epidermis. Plasma leptin decreased in PF+Exe, DCR, and DCR+Exe, while the caspase-3 activity increased in DCR+Exe only. Genomic microarray analysis further indicated that the expression of 34 genes relevant to PI3K and 31 genes to the MAPK pathway were significantly regulated by either DCR or PF+Exe treatments. The reduced PI3K in PF+Exe mice was partially reversed by IGF-1 treatment. The overall results of this study demonstrated that DCR abrogated both Ras and PI3K signaling, which might inhibit TPA-induced proliferation and anti-apoptosis. Selective inhibition of PI3K by PF+Exe but not AL+Exe seems more attributable to the magnitude of the caloric deficit and/or body fat loss than diet versus exercise comparison. [ABSTRACT FROM AUTHOR]

As the largest group of phytochemicals, dietary phenolics play an important role in human health and disease prevention. Cultural practices have been shown to have the potential for affecting phenolic compounds in food crops. Spring and summer trials were conducted in 2003 to examine the effects of organic fertilization and high tunnel environments on phenolic constituents of lettuce (Lactuca sativa L.) cultivars Red Sails and Kalura. Effects of postharvest storage at 4 °C for 16 days on total phenolics of lettuce harvested from the summer trial were also evaluated. Total phenolics, excluding anthocyanins, were measured spectrophotometrically, and major phenolic constituents were identified and quantified by high-performance liquid chromatography. Chlorogenic acid and quercetin glycosides were found to be predominant in lettuce. 'Red Sails' consistently exhibited significantly higher phenolic concentrations than 'Kalura'. Organic (compost + fish emulsion) and conventional (N-P-K + CaNO3) fertilization did not consistently differentially affect lettuce phenolics in our recently established organic and conventional plots. The high tunnel environment generally reduced phenolic levels in lettuce relative to the open field. However, differences between high tunnel and open field varied with cultivar and season. Effects of production factors on lettuce phenolics were maintained during cold storage. There was a substantial increase in total phenolics during storage, likely correlated with declining lettuce quality. Further studies are warranted to more fully assess the impact of cultivar and production management, including organic fertilization, on lettuce phenolics. [ABSTRACT FROM AUTHOR]

Wheat bran was shown to provide protection against colorectal cancer in human intervention and animal studies. Our recent study showed, however, that antitumor activities of wheat bran from various wheat cultivars differed significantly even when wheat fiber was equal in diets. We hypothesized that phytochemical lignans in wheat bran may account for the differences among wheat cultivars in cancer prevention. The concentration of a major lignan, secoisolariciresinol diglycoside, was determined by HPLC in 4 selected wheat cultivars (i.e., Madison, Ernie, Betty, and Arapahoe). The lignan concentrations and their antitumor activities, previously determined in APC-Min mice, were correlated (r = 0.73, P < 0.02). The cancer preventive mechanisms of 2 prominent lignan metabolites (enterolactone and enterodiol) were further studied in human colonic cancer SW480 cells. Treatment with enterolactone and enterodiol, alone or in combination, at 0–40 μmol/L resulted in dose- and time-dependent decreases in cell numbers. Although the cytotoxicity as measured by trypan blue staining in adherent cells was not affected, DNA flow cytometric analysis indicated that the treatments induced cell cycle arrest at the S-phase. Western blot analysis for cyclin A, a required protein for S/G2 transition, showed that the cyclin A protein levels decreased after treatment with enterodiol or the combination of enterolactone and enterodiol at 40 μmol/L for 72 h. Apoptosis analysis by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay showed an increased percentage of apoptotic cells in the floating cells after enterodiol alone or combined treatments. These results suggest for the first time that lignans may contribute, at least in part, to the cancer prevention by wheat bran observed in APC-Min mice. Inhibition of cancer cell growth by lignan metabolites seems to be mediated by cytostatic and apoptotic mechanisms. [ABSTRACT FROM AUTHOR]

Studies in animal models demonstrated that weight control via physical activity had cancer preventive effect. We found the circulation level of IGF-1 and IGF-1 dependent signaling decreased in weight controlled mice by exercise. To further confirm the mechanistic role of IGF-1, we restored IGF-1 in SENCAR mice that were pair fed with the sedentary control and exercised by treadmill at 0.5 mph for 90 min daily, 5 days per week, for 10 weeks (PE). IGF-1 was restored by i.p. injection at 10 µg/kg B.W. twice per week in the last two weeks. The results indicated that the body weight was significantly decreased in PE mice when compared to the control. Fat composition in IGF-1-injected mice was brought back to the levels of the control, but significantly higher than the PE mice. Total 338 phospholipids from 12 species in the skin tissues were detectable by lipidomics and the percentage of phosphatidylinositol 38:4 was significantly reduced in PE mice but increased in IGF-1-restored mice. Furthermore, IGF-1 injection significantly enhanced some lysophosphatidylcholine species such as 20:3, 20:4, and 20:5 in PE group in comparison with the control. The study showed that some phospholipids that related to signaling pathway, cell proliferation, and/or cell death were selectively reduced by PE treatment and IGF-1 restoration seemed to reverse, at least in part, the impact. [ABSTRACT FROM AUTHOR]

Our previous studies in a mouse skin cancer model via treadmill exercise or dietary calorie restriction (DCR) have suggested a significant reduction of body weight and body fat might prevent cancer by attenuating TPA-induced PI3K signaling. Our recent lipidomics data showed a significant alteration of phospholipid profiles between exercised mice and sedentary control. Among of which, some ?-3 fatty acyl combinations in phosphatidylcholine and phosphatidylethanolamine species increased significantly in exercise and pair-fed mice when compared to the controls. Gene expression as measured by microarray data demonstrated a significant up-regulation of genes related to elongation of very long fatty acids in DCR-fed mice. Furthermore, proteomics analysis including over 600 protein spots in each 2D gel has been recently established in our lab for identification and quantification via matrix-assisted laser desorption/ionization mass spectrometry. A differential expression of certain proteins such as apolipoprotein A 1 and transgelin 2 was found to be significantly reduced in DCR mice. Consideration of the profiling changes in signaling phospholipids, lipid metabolism-related gene and protein expression together may ultimately help us to understand the mechanisms by which weight control may protect against cancer. [ABSTRACT FROM AUTHOR]

Weight control via physical activity with dietary caloric restriction (DCR) has been shown to protect against cancer in animal models. By using TPA-induced cancer promotion model, we and others have found that the circulation level of IGF-1 and IGF-1-dependent signaling were significantly reduced in both DCR-fed and exercised mice with limited calorie intake. To further confirm the role of IGF-1, we restored IGF-1 in SENCAR mice that were assigned to one of the three treatment groups for 10 wks: ad libitum-fed sedentary control, pair-fed at the amount as the control and treadmill exercise at 0.5 mph for 60 min/d, 5 d/wk (PE), and 20% DCR-fed group, IGF-1 was administrated via i.p. injection at 10 ug/kg B.W., twice/wk in the last two wks. As expected, both body weight, plasma IGF-1 levels, and H-ras protein in skin tissues significantly decreased in PE and DCR groups when compared with the controls. However, IGF-1 injection did not significantly affect IGF-1 levels, IGF-1 receptor, and three isomers of NFkB PE and DCR mice. A time course study indicated that 0.5-hr half-time and 6-hr clearance of plasma IGF-1 levels after injection might partially explain these discrepancies. [ABSTRACT FROM AUTHOR]

Carcinogenesis is a complex multi-step process, resulting from genetic alterations leading to aberrant cellular proliferation. Caloric restriction is associated with resistance to this process in many species. To investigate the molecular level events underlying the interaction of diet, exercise and cancer resistance, this study assessed the expression of proliferation/inhibition markers in skin of TPA-treated mice. 4 groups were pretreated 10 weeks: (a) ad-libitum-fed, sedentary; (b) exercised, pair fed with group a; (c) ad-libitum fed, exercised and (d) 20% calorie restriction, sedentary. TPA was applied to shaved skin with tissue harvest 2 hr later. Skin sections were evaluated by IHC for: expression of proteins of cell proliferation (PCNA); a hormone regulator of energy expenditure (leptin); and an effector enzyme vital to apoptosis (caspase 3). Immunoreactivity was graded by cell counts and staining density. Skin PCNA was elevated in group "c" compared to all other groups, p>0.01. Caspase 3-related apoptosis was elevated in group "b" (24 ± 2) vs. other groups (19 ± 2; 18 ±7; 18±10) but did not reach significance. Leptin staining was similar for all groups, p=0.97. We conclude that TPA-treated mouse skin shows important upregulation of cell proliferation proteins after well-fed exercise as expressed by PCNA. This protein is present throughout the cell cycle, and is involved in DNA repair. The elevated apoptotic marker, also in an exercised group, suggests the importance of metabolic studies to insight on aberrant cell death and proliferation. [ABSTRACT FROM AUTHOR]