W E Hardman

Marshall University, Huntington, West Virginia, United States

Are you W E Hardman?

Claim your profile

Publications (69)238.82 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Capsaicin, the pungent ingredient of chili peppers, displays potent anti-neoplastic activity in a wide array of human cancer cells. The present manuscript examines the signaling pathways underlying the apoptotic activity of capsaicin in human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal cells show that capsaicin exerts its biological activity via the transient receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The TRPV family is comprised of six members (TRPV1–6). Capsaicin is a known agonist of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC cells was mediated via the TRPV receptor family; however it was independent of TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6 receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients) and SCLC cell lines but almost absent in normal lung tissues. This correlates with our results that capsaicin induced very little apoptosis in normal lung epithelial cells. The pro-apoptotic activity of capsaicin was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin increased the activity of calpain 1 and 2 by threefold relative to untreated SCLC cells. Such calpain activation, in response to capsaicin, was downstream of the TRPV6 receptor. Taken together, our data provide insights into the mechanism underlying the apoptotic activity of capsaicin in human SCLCs.
    APOPTOSIS 08/2014; 19(8). · 3.95 Impact Factor
  • Source
    W Elaine Hardman
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiology studies indicate that diet or specific dietary components can reduce the risk for cancer, cardiovascular disease and diabetes. An underlying cause of these diseases is chronic inflammation. Dietary components that are beneficial against disease seem to have multiple mechanisms of action and many also have a common mechanism of reducing inflammation, often via the NFκB pathway. Thus, a plant based diet can contain many components that reduce inflammation and can reduce the risk for developing all three of these chronic diseases. We summarize dietary components that have been shown to reduce cancer risk and two studies that show that dietary walnut can reduce cancer growth and development. Part of the mechanism for the anticancer benefit of walnut was by suppressing the activation of NFκB. In this brief review, we focus on reduction of cancer risk by dietary components and the relationship to suppression of inflammation. However, it should be remembered that most dietary components have multiple beneficial mechanisms of action that can be additive and that suppression of chronic inflammation should reduce the risk for all three chronic diseases.
    Nutrition research and practice 06/2014; 8(3):233-240. · 0.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those in the control diet mice. The final average tumor size in the walnut-diet animals was roughly one-fourth the average size of the prostate tumors in the mice that ate the control diet.
    Cancer Investigation 06/2013; · 2.24 Impact Factor
  • Source
    Johannes F Fahrmann, W Elaine Hardman
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: B-Cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. Clinical treatment of CLL is often limited due to drug resistance and severe therapy-induced toxicities. We hypothesized that the omega 3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), would increase the sensitivity of malignant B-lymphocytes to anti-cancer drugs doxorubicin, vincristine and/or fludarabine in vitro and that increased sensitivity is achieved by alterations in cell-cycle progression leading to growth inhibition and/or enhanced cell death. We further postulate that enhanced sensitivity is dependent on the formation of lipid peroxides and to the generation of reactive oxygen species (ROS). METHODS: In the present study, B-CLL-derived leukemic cell lines EHEB and MEC-2 and the B-Prolymphocytic leukemic-derived (PLL) cell line JVM-2 were tested for in vitro sensitivity against doxorubicin, vincristine or fludarabine in the presence or absence of vehicle, arachidonic acid (omega 6), EPA or DHA. Cell cycle analysis and Annexin-V assays were performed to determine cell cycle progression and% apoptotic cells, respectively. Assays for malondialdehyde, a measure of lipid peroxidation, and DCF fluorescence assays, a measure of intracellular ROS, were performed to determine if enhanced sensitivity of cells to the drugs by n-3 was dependent on the formation of ROS. RESULTS: Our results indicated that: 1) EPA and DHA differentially sensitized B-leukemic cell lines EHEB, JVM-2 and MEC-2 to doxorubicin, vincristine and fludarabine in vitro; 2) n-3 alone and with drug treatment increased cell death and induced G2/M arrest in a cell-type specific manner; 3) lipid peroxidation increased in the presence of n-3; 4) there was higher lipid peroxidation in MEC-2 cells in presence of DHA and doxorubicin than with either alone; 5) n-3 increased generation of ROS in MEC-2, and 6) the addition of vitamin-E abrogated the increase in ROS generation and chemo-sensitivity of MEC-2 to doxorubicin by DHA. CONCLUSION: N-3's are promising chemo-sensitizing agents for the treatment of CLL. Selective enhancement of chemo-sensitivity of EHEB, JVM-2 and MEC-2 to drugs by n-3 that is not dependent on increased lipid peroxidation and ROS generation indicates alternative mechanisms by which n-3 enhances chemo-sensitivity.
    Lipids in Health and Disease 03/2013; 12(1):36. · 2.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancer is the third leading cause of cancer-related death in the western world. In vitro and in vivo experiments showed that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can attenuate the proliferation of cancer cells, including colon cancer, and increase the efficacy of various anticancer drugs. However, these studies address the effects of n-3 PUFAs on the bulk of the tumor cells and not on the undifferentiated colon cancer stem-like cells (CSLCs) that are responsible for tumor formation and maintenance. CSLCs have also been linked to the acquisition of chemotherapy resistance and to tumor relapse. Colon CSLCs have been immunophenotyped using several antibodies against cellular markers including CD133, CD44, EpCAM, and ALDH. Anti-CD133 has been used to isolate a population of colon cancer cells that retains stem cells properties (CSLCs) from both established cell lines and primary cell cultures. We demonstrated that the n-3 PUFA, eicosapentaenoic acid (EPA), was actively incorporated into the membrane lipids of COLO 320 DM cells. 25 uM EPA decreased the cell number of the overall population of cancer cells, but not of the CD133 (+) CSLCs. Also, we observed that EPA induced down-regulation of CD133 expression and up-regulation of colonic epithelium differentiation markers, Cytokeratin 20 (CK20) and Mucin 2 (MUC2). Finally, we demonstrated that EPA increased the sensitivity of COLO 320 DM cells (total population) to both standard-of-care chemotherapies (5-Fluorouracil and oxaliplatin), whereas EPA increased the sensitivity of the CD133 (+) CSLCs to only 5-Fluorouracil.
    PLoS ONE 01/2013; 8(7):e69760. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent case-controlled clinical studies show that bronchioalveolar carcinomas (BACs) are correlated with smoking. Nicotine, the addictive component of cigarettes, accelerates cell proliferation through nicotinic acetylcholine receptors (nAChRs). In this study, we show that human BACs produce acetylcholine (ACh) and contain several cholinergic factors including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1, SLC5A7), vesicular acetylcholine transporter (VAChT, SLC18A3) and nACh receptors (AChRs, CHRNAs). Nicotine increased the production of ACh in human BACs and ACh acts as a growth factor for these cells. Nicotine-induced ACh production was mediated by α7-, α3β2-, and β3-nAChRs, ChAT and VAChT pathways. We observed that nicotine upregulated ChAT and VAChT. Therefore, we conjectured that VAChT antagonists, such as vesamicol, may suppress the growth of human BACs. Vesamicol induced potent apoptosis of human BACs in cell culture and nude mice models. Vesamicol did not have any effect on EGF or IGF-II-induced growth of human BAC's. siRNA-mediated attenuation of VAChT reversed the apoptotic activity of vesamicol. We also observed that vesamicol inhibited Akt phosphorylation during cell death, and overexpression of constitutively active Akt reversed the apoptotic activity of vesamicol. Taken together, our results suggested that disruption of nicotine-induced cholinergic signaling by agents such as vesamicol may have applications in BAC therapy.
    Cancer Research 12/2012; · 9.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Targeting the nuclear factor kappa B (NFκB) pathway is proposed as therapy for chronic lymphocytic leukemia (CLL). We hypothesized that an omega-3 fatty acids (n-3) supplement would suppress NFκB activation in lymphocytes of Rai Stage 0-1 CLL patients. The initial dose of 2.4 g n-3/day was gradually increased to 7.2 g n-3/day. After n-3 consumption: 1) plasma n-3 increased; 2) NFκB activation was suppressed in lymphocytes; 3) in vitro sensitivity of lymphocytes to doxorubicin was increased; and 4) expression of 32 genes in lymphocytes was significantly decreased.
    Cancer Investigation 11/2012; · 2.24 Impact Factor
  • Source
    Angiogenesis 03/2012; · 4.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation of primary human microvascular endothelial cells of the lung (HMEC-Ls). Furthermore, MG624 displayed robust anti-angiogenic activity in the Matrigel, rat aortic ring and rat retinal explant assays. The anti-angiogenic activity of MG624 was assessed by two in vivo models, namely the chicken chorioallantoic membrane model and the nude mice model. In both of these experimental models, MG624 inhibited angiogenesis of human SCLC tumors. Most importantly, the administration of MG624 was not associated with any toxic side effects, lethargy or discomfort in the mice. The anti-angiogenic activity of MG624 was mediated via the suppression of nicotine-induced FGF2 levels in HMEC-Ls. MG624 decreased nicotine-induced early growth response gene 1 (Egr-1) levels in HMEC-Ls, and reduced the levels of Egr-1 on the FGF2 promoter. Consequently, this process decreased FGF2 levels and angiogenesis. Our findings suggest that the anti-angiogenic effects of MG624 could be useful in anti-angiogenic therapy of human SCLCs.
    Angiogenesis 12/2011; 15(1):99-114. · 4.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to a high ω-3 diet containing canola oil and fish oil concentrate (FS). High ω-3 diet increased ω-3 and decreased ω-6 fat content of mice tissues. Average weights of prostate and genitourinary bloc were significantly lower in mice consuming high ω-3 diet at adulthood (CO-FS) than mice fed a lifetime high ω-6 diet (CO-CO). There was slower progression of tumorigenesis in dorsalateral prostate of CO-FS than in CO-CO mice. CO-FS mice had slightly lower plasma testosterone level at 24 and 40 weeks, significantly lower estradiol level at 40 weeks and significantly less expressed androgen receptor (AR) in the dorsalateral prostate at 40 weeks than CO-CO mice. Consumption of high ω-3 diet lowered the expression of genes expected to increase proliferation and decrease apoptosis in dorsalateral prostate. Our results suggest that consumption of high ω-3 diet slows down prostate tumorigenesis by lowering estradiol, testosterone and AR levels, promoting apoptosis and suppressing cell proliferation in C3(1)Tag mice.
    Carcinogenesis 10/2011; 33(1):140-8. · 5.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Walnuts contain multiple ingredients that, individually, have been shown to slow cancer growth, including omega-3 fatty acids, antioxidants, and phytosterols. In previous research, consumption of walnuts has slowed the growth of implanted breast cancers. We wanted to determine whether regular walnut consumption might reduce the risk for developing cancer. Homozygous male C(3)1 TAg mice were bred with female SV129 mice consuming either the control AIN-76 diet or the walnut-containing diet. At weaning, the female hemizygous pups were randomized to control or walnut-containing diets and followed for tumor development. Compared to a diet without walnuts, consumption of walnuts significantly reduced tumor incidence (fraction of mice with at least one tumor), multiplicity (number of glands with tumor/mouse), and size. Gene expression analyses indicated that consumption of the walnut diet altered expression of multiple genes associated with proliferation and differentiation of mammary epithelial cells. A comparison with another dietary intervention indicated that the omega 3 content alone did not account for the extent of tumor suppression due to the walnut. The results of this study indicate that walnut consumption could contribute to a healthy diet to reduce risk for breast cancer.
    Nutrition and Cancer 08/2011; 63(6):960-70. · 2.70 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Western diet is high in omega-6 fatty acids and low in omega-3 fatty acids. Canola oil contains a healthier omega 3 to omega 6 ratio than corn oil. Jurkat T leukemia cells were treated with free fatty acids mixtures in ratios mimicking that found in commercially available canola oil (7% α-linolenic, 30% linoleic, 54% oleic) or corn oil (59% linoleic, 24% oleic) to determine the cell survival or cell death and changes in expression levels of inflammatory cytokines and receptors following oil treatment. Fatty acid uptake was assessed by gas chromatography. Cell survival and cell death were evaluated by cell cycle analyses, propidium-iodide staining, trypan blue exclusion and phosphatidylserine externalization. mRNA levels of inflammatory cytokines and receptors were assessed by RT-PCR. There was a significant difference in the lipid profiles of the cells after treatment. Differential action of the oils on inflammatory molecules, following treatment at non-cytotoxic levels, indicated that canola oil mimetic was anti-inflammatory whereas corn oil mimetic was pro-inflammatory. These results indicate that use of canola oil in the diet instead of corn oil might be beneficial for diseases promoted by inflammation.
    Lipids in Health and Disease 06/2011; 10:90. · 2.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study was designed to test how extended exposure of lenses to sera with different ionic strengths influences the distribution of ions and water in the lens. Pig lenses were incubated in cold sera (0 degree C), which were adjusted to variable concentrations of NaCl, and their K+, Na+, Cl-, and water contents were measured. Incubation at 0 degree C inhibits active transport processes and thereby allows equilibration of the mobile ions and water. The hypothesis was that lens water content (volume) would follow the ion-induced protein changes predicted by a model derived from previous osmotic studies on proteins. As expected, exposure of the lens to cold caused a gain of sodium and a partial loss of potassium. However, the potassium concentration in the lens remained several fold higher than that in the bathing solution (about 41 vs. 1.8-4.6 mM/kg H2O), indicating that a portion of the potassium within the cold-exposed lens was not free to diffuse. That the water content of the lens showed a negative rather than a positive relationship with the concentration of NaCl within the lens was explained by the idea that an increase in NaCl within the lens (up to at least 250 mM/kg H2O) causes a decrease in the osmotically unresponsive water volume associated with lens proteins.
    Biochemistry and Cell Biology 01/2011; 69(10-11):742-6. · 2.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of the polyunsaturated omega-3 (n-3) and omega-6 (n-6) fatty acids (FA) on hematopoiesis are complex in that both FA forms are processed into leukotrienes, eicosanoids, and prostaglandins, which can have independent effects. These FA have antagonistic effects in that n-6 FA prostaglandins tend to be pro-proliferative and pro-inflammatory, while the effects of n-3 FA prostaglandins are the opposite. We have previously shown that diets high in n-3 FA reduce the size of the middle to later stage myeloid progenitor compartment in FVB X sv129 F1hybrid mice. To assay the effects of high n-3 FA diets on earlier stages of myelopoiesis, we fed C57BL/6J mice diets high in n-3 FA or levels of n-3/n-6 FA similar to western diets and assayed the effects on myelopoiesis with flow cytometry and colony forming cell assays. Results indicate an expansion of the common myeloid progenitor cell compartment in high n-3 FA diets, which does not persist into later stages where the number of progenitor cells is actually lower in high n-3 FA fed animals. Investigations in vitro with the hematopoietic stem cell line EML-clone 1 indicate that cells cultured with eicosapentaenoic acid (n-3 FA) or arachidonic acid (n-6 FA) have no differences in cell viability but that arachidonic acid more rapidly produces progenitors with low levels of the macrophage developmental marker, F4/80.
    Lipids 01/2011; 46(1):47-57. · 2.56 Impact Factor
  • Source
    Gabriela Ion, Juliana A Akinsete, W Elaine Hardman
    [Show abstract] [Hide abstract]
    ABSTRACT: Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring. Female SV 129 mice were divided into two groups and placed on diets containing either 10% w/w corn oil (which is 50% n-6 PUFA, control diet) or 10% w/w canola oil (which is 20% n-6 PUFA, 10% n-3 PUFA, test diet). After two weeks on the diets the females were bred with homozygous C3(1) TAg transgenic mice. Mother mice consumed the assigned diet throughout gestation and nursing of the offspring. After weaning, all female offspring were maintained on the control diet. Compared to offspring of mothers fed the corn oil diet (CO/CO group), offspring of mothers fed the canola oil diet (CA/CO group) had significantly fewer mammary glands with tumors throughout the experiment. At 130 days of age, the CA/CO group had significantly fewer tumors per mouse (multiplicity); the tumor incidence (fraction of mice with any tumor) and the total tumor weight (per mouse that developed tumor) was less than one half that of the CO/CO group. At 170 days of age, the total tumor weight per mouse was significantly less in the CA/CO group and if a tumor developed the rate of tumor growth rate was half that of CO/CO group. These results indicate that maternal consumption of canola oil was associated with delayed appearance of mammary gland tumors and slowed growth of the tumors that developed. Substituting canola oil for corn oil is an easy dietary change for people to make; such a change to the maternal diet may decrease risk for breast cancer in the daughter.
    BMC Cancer 03/2010; 10:81. · 3.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of RBCs might accurately indicate incorporation of omega 3 fatty acids in the WBCs. In this report we determine and compare the changes in fatty acid compositions of red blood cells and white blood cells in response to consumption of three doses of an omega 3 fatty acid supplement. We found that the fraction of omega 3 fatty acids in both red blood cells and white blood cells increased following consumption of the supplement. There was a linear, dose responsive increase in the fraction of omega 3 fatty acids in red blood cells but the increase in omega 3 in white blood cells was not linear. The magnitude of increase in omega 3 fatty acids was different between the two cell types. Fatty acid analysis of red blood cells is a good measure of compliance with supplement consumption. However, fatty acid analysis of white blood cells is needed to correlate changes in fatty acid composition of white blood cells with other biochemical changes in the white blood cells. ClinicalTrials.gov NCT00899353.
    Lipids in Health and Disease 03/2010; 9:31. · 2.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays anti-proliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo. BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently suppressed the growth of H69 human SCLC tumors in vivo as ascertained by CAM assays and nude mice models. The second part of our study attempted to provide insight into molecular mechanisms underlying the anti-proliferative activity of capsaicin. We found that the anti-proliferative activity of capsaicin is correlated with a decrease in the expression of E2F-responsive proliferative genes like cyclin E, thymidylate synthase, cdc25A and cdc6, both at mRNA and protein levels. The transcription factor E2F4 mediated the anti-proliferative activity of capsaicin. Ablation of E2F4 levels by siRNA methodology suppressed capsaicin-induced G1 arrest. ChIP assays demonstrated that capsaicin caused the recruitment of E2F4 and p130 on E2F-responsive proliferative promoters, thereby inhibiting cell proliferation. Our findings suggest that the anti-proliferative effects of capsaicin could be useful in the therapy of human SCLCs.
    PLoS ONE 01/2010; 5(4):e10243. · 3.53 Impact Factor
  • W. Elaine Hardman
    [Show abstract] [Hide abstract]
    ABSTRACT: The efficacy of ω-3 fatty acids against cancer has been demonstrated in preclinical in vitro and in vivo studies. However, for most clinical trials, it is unlikely that ω-3 supplementation would be used alone but rather it would be combined with standard chemo- or radiation therapy. Thus, it is important to know the effects of ω-3 fatty acids on the efficacy of standard therapies. Preclinical studies using numerous cancer models with multiple chemotherapeutic agents have demonstrated the enhanced efficacy of the standard therapy when ω-3 fatty acids are incorporated in the culture media of cells or in the diet of the animal. These studies will be summarized in this chapter. Keywordsω-3 fatty acids-Cancer-Chemotherapy-Oxidative stress-PUFA
    12/2009: pages 219-229;
  • Source
    Melinda E Varney, W Elaine Hardman, Vincent E Sollars
    [Show abstract] [Hide abstract]
    ABSTRACT: Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.
    Lipids in Health and Disease 04/2009; 8:9. · 2.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to characterize tissue responses attributable to the stage of tumourigenesis in CF-1 mice. The study involved initiating colon carcinogenesis by eight weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH at 12mg/kg body weight), while the control mice received injections of the carrier vehicle. All mice were killed for examination of tissue responses at 24 weeks after the completion of the injections. Each mouse was classified into one of four groups based on the histology of the most advanced colonic lesion. The four groups or stages were: 1 no lesions (non-DMH-treated mice); 2 mice with aberrant crypt foci (ACF); 3 mice with one or more adenomas (AD) and 4 mice with an adenocarcinoma (AC). Significant tissue specific responses were identified and related to the stage of tumourigenesis. For example, mice with AC demonstrated a stage specific and marked hypertrophy of the entire colon and spleen, while demonstrating loss of body weight with no change in weight of the thymus or liver. The colonic crypts from these AC-bearing mice demonstrated hyperproliferation and an upward shift of the proliferative zone, with a concurrent loss of iron, but not of calcium, copper, magnesium or zinc in the liver. Splenomegaly was attributed to transition of the tumour to an invasive state. It is proposed that the AC produces a blood-borne trophic factor which helps explain a field effect on the colonic epithelium far removed from the growing AC. This field effect can help explain how biopsy of the large bowel (usually taken from the rectum in humans) can provide morphokinetic information predictive of the stage of colon carcinogenesis.
    Cell Proliferation 04/2008; 27(12):741 - 753. · 2.27 Impact Factor

Publication Stats

961 Citations
238.82 Total Impact Points

Institutions

  • 2007–2014
    • Marshall University
      • • Department of Pharmacology, Physiology and Toxicology
      • • Department of Biochemistry and Microbiology
      Huntington, West Virginia, United States
  • 1992–2008
    • University of Texas Health Science Center at San Antonio
      • Department of Cellular and Structural Biology
      San Antonio, TX, United States
  • 2002–2006
    • Pennington Biomedical Research Center
      Baton Rouge, Louisiana, United States
  • 1994–1998
    • Wichita State University
      • Department of Public Health Sciences
      Wichita, Kansas, United States