Displaying publications 21 - 34 of 34 in total

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  1. Casey SC, Vaccari M, Al-Mulla F, Al-Temaimi R, Amedei A, Barcellos-Hoff MH, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1:S160-83.
    PMID: 26106136 DOI: 10.1093/carcin/bgv035
    Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.
  2. Nahta R, Al-Mulla F, Al-Temaimi R, Amedei A, Andrade-Vieira R, Bay SN, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1:S2-18.
    PMID: 26106139 DOI: 10.1093/carcin/bgv028
    As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks.
  3. Ochieng J, Nangami GN, Ogunkua O, Miousse IR, Koturbash I, Odero-Marah V, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1:S128-59.
    PMID: 26106135 DOI: 10.1093/carcin/bgv034
    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial-mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis.
  4. Engström W, Darbre P, Eriksson S, Gulliver L, Hultman T, Karamouzis MV, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1:S38-60.
    PMID: 26106143 DOI: 10.1093/carcin/bgv030
    The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.
  5. Robey RB, Weisz J, Kuemmerle NB, Salzberg AC, Berg A, Brown DG, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1(Suppl 1):S203-31.
    PMID: 26106140 DOI: 10.1093/carcin/bgv037
    Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested.
  6. Carnero A, Blanco-Aparicio C, Kondoh H, Lleonart ME, Martinez-Leal JF, Mondello C, et al.
    Carcinogenesis, 2015 Jun;36 Suppl 1(Suppl 1):S19-37.
    PMID: 26106138 DOI: 10.1093/carcin/bgv029
    Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes.
  7. Hamid RA, Nazar R, Pop I
    Sci Rep, 2015;5:14640.
    PMID: 26440761 DOI: 10.1038/srep14640
    The paper deals with a stagnation-point boundary layer flow towards a permeable stretching/shrinking sheet in a nanofluid where the flow and the sheet are not aligned. We used the Buongiorno model that is based on the Brownian diffusion and thermophoresis to describe the nanofluid in this problem. The main purpose of the present paper is to examine whether the non-alignment function has the effect on the problem considered when the fluid suction and injection are imposed. It is interesting to note that the non-alignment function can ruin the symmetry of the flows and prominent in the shrinking sheet. The fluid suction will reduce the impact of the non-alignment function of the stagnation flow and the stretching/shrinking sheet but at the same time increasing the velocity profiles and the shear stress at the surface. Furthermore, the effects of the pertinent parameters such as the Brownian motion, thermophoresis, Lewis number and the suction/injection on the flow and heat transfer characteristics are also taken into consideration. The numerical results are shown in the tables and the figures. It is worth mentioning that dual solutions are found to exist for the shrinking sheet.
  8. Hamid RA, Ungku Ahmad UN
    MyJurnal
    An increasing number of women participate in the work force due to socio-economic development result a big impact to work and family institution. Failure to meet demand for both work and family lead to work-family conflict that may give negative consequences on work and family. An example of major work-related outcome is burnout which can lead to turnover intention. Social support has been identified as an important resources that can reduce work-family conflict and burnout. This paper aims to identify the relationship between work-family conflict and turnover intention and also the mediation effect of burnout on work-family conflict and turnover intention relationship. It is proposed that there will be a positive relationship between work-family conflict and turnover intention and there is an indirect relationship between work-family conflict and turnover intention through the mediation effect of burnout. Social support from work and family is proposed to moderate the relationship between work-family conflict and burnout. Furthermore it is proposed that the strength of relationship between work-family conflict and turnover intention depends on the mediation effect of burnout and moderating effect of social support.
  9. Baharum Z, Akim AM, Taufiq-Yap YH, Hamid RA, Kasran R
    Molecules, 2014 Nov 10;19(11):18317-31.
    PMID: 25389662 DOI: 10.3390/molecules191118317
    The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid-reactive substances (TBARS), and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC50) was 358.3±7.0 µg/mL and total phenolic content was 22.0±1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4%±1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC50)=41.4±3.3 µg/mL]. Given the overall high IC50 for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts.
  10. Hamsin DE, Hamid RA, Yazan LS, Taib CN, Yeong LT
    PMID: 24641961 DOI: 10.1186/1472-6882-14-102
    In our previous studies conducted on Ardisia crispa roots, it was shown that Ardisia crispa root inhibited inflammation-induced angiogenesis in vivo. The present study was conducted to identify whether the anti-angiogenic properties of Ardisia crispa roots was partly due to either cyclooxygenase (COX) or/and lipoxygenase (LOX) activity inhibition in separate in vitro studies.
  11. Hamid RA, Kee TH, Othman F
    Pharmacognosy Res, 2013 Apr;5(2):129-33.
    PMID: 23798889 DOI: 10.4103/0974-8490.110544
    Acanthopanax trifoliatus is a ginseng-like plant, which has been widely used to treat various diseases including inflammatory-related diseases.
  12. Yeong LT, Hamid RA, Yazan LS, Khaza'ai H
    Asian Pac J Cancer Prev, 2013;14(4):2301-5.
    PMID: 23725131
    Ardisia crispa (Family: Myrsinaceae) is an evergreen, fruiting shrub that has been traditionally used as folklore medicine. Despite a scarcity of research publications, we have succeeded in showing suppressive effects on murine skin papillomagenesis. In extension, the present research was aimed at determining the effect of a quinone-rich fraction (QRF) isolated from the same root hexane extract on both initiation and promotion stages of carcinogenesis, at the selected dose of 30 mg/kg. Mice (groups I-IV) were initiated with a single dose of 7,12-dimethylbenz(α)anthracene (DMBA, 100 μg/100 μl) followed by repeated promotion of croton oil (1%) twice weekly for 20 weeks. In addition, group I (anti-initiation) received QRF 7 days before and after DMBA; group II (anti-promotion) received QRF 30 minutes before each croton oil application; group III (anti-initiation/ promotion) was treated with QRF as a combination of group I and II. A further two groups served as vehicle control (group V) and treated control (group VI). As carcinogen control, group IV showed the highest tumor volume (8.79±5.44) and tumor burden (3.60±1.17). Comparatively, group III revealed only 20% of tumor incidence, tumor burden (3.00±1.00) and tumor volume (2.40±1.12), which were significantly different from group IV. Group II also showed significant reduction of tumor volume (3.11), tumor burden (3.00) and tumor incidence (11.11%), along with prominent increase of latency period of tumor formation (week 12). Group I, nonetheless, demonstrated marked increment of tumor incidence by 40% with prompted latency period of tumor formation (week 7). No tumor formation was observed in groups V and VI. This study provided clear evidence of inhibitory effects of QRF during promotion period which was in agreement with our previous findings. The mechanism(s) underlying such effects have yet to be elucidated.
  13. Hamsin DE, Hamid RA, Yazan LS, Taib CN, Ting YL
    PMID: 23298265 DOI: 10.1186/1472-6882-13-5
    Ardisia crispa (Myrsinaceae) is used in traditional Malay medicine to treat various ailments associated with inflammation, including rheumatism. The plant's hexane fraction was previously shown to inhibit several diseases associated with inflammation. As there is a strong correlation between inflammation and angiogenesis, we conducted the present study to investigate the anti-angiogenic effects of the plant's roots in animal models of inflammation-induced angiogenesis.
  14. Sulaiman H, Hamid RA, Ting YL, Othman F
    J Cancer Res Ther, 2012 Jul-Sep;8(3):404-10.
    PMID: 23174723 DOI: 10.4103/0973-1482.103521
    CONTEXT: Ardisia crispa Thunb. A. DC (Myrsinaceae) or locally known as hen's eyes has been used in local folk medicine as a remedy in various illnesses. Previously, it has been reported to inhibit various inflammatory diseases. However, research done on this plant is still limited.
    AIMS: In the present study, the hexane fraction of the A. crispa root (ACRH) was evaluated on the peri-initiation and promotion phases of skin carcinogenesis.
    MATERIALS AND METHODS: This two-stage skin carcinogenesis was induced by a single topical application of 7,12-dimethylbenz(α)anthracene (DMBA) and promoted by repeated treatment with croton oil for 10 weeks in Imprinting Control Region (ICR) mice. Morphological observation would be conducted to measure tumor incidence, tumor burden, and tumor volume. Histological evaluation on the skin tissue would also be done.
    RESULTS: The carcinogen control group exhibited 66.67% of tumor incidence. Although, in the ACRH-treated groups, at 30 mg/kg, the mice showed only 10% of tumor incidence with a significant reduction (P < 0.05) in the values of tumor burden and tumor volume of 2.00 and 0.52 mm(3), respectively. Furthermore, the result was significantly lower than that of the carcinogen and curcumin control. At 100 mg/kg, ACRH showed a comparable result to carcinogen control. On the contrary, at 300 mg/kg, ACRH exhibited 100% tumor incidence and showed a significant elevated (P < 0.05) value of tumor burden (3.80) and tumor volume (14.67 ± 2.48 mm(3)).
    CONCLUSIONS: The present study thus demonstrates that the anti-tumor effect of the chemopreventive potential of ACRH is at a lower dosage (30 mg/kg bwt) in both the initiating and promotion period, yet it exhibits a promoting effect at a higher dosage (300 mg/kg bwt).
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