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  1. Fulltext Tualang honey improves human corneal epithelial progenitor cell migration and cellular resistance to oxidative stress in vitro
    Tan JJ, Azmi SM, Yong YK, Cheah HL, Lim V, Sandai D, et al.
    PLoS One, 2014;9(5):e96800.
    PMID: 24802273 DOI: 10.1371/journal.pone.0096800
    Stem cells with enhanced resistance to oxidative stress after in vitro expansion have been shown to have improved engraftment and regenerative capacities. Such cells can be generated by preconditioning them with exposure to an antioxidant. In this study we evaluated the effects of Tualang honey (TH), an antioxidant-containing honey, on human corneal epithelial progenitor (HCEP) cells in culture. Cytotoxicity, gene expression, migration, and cellular resistance to oxidative stress were evaluated. Immunofluorescence staining revealed that HCEP cells were holoclonal and expressed epithelial stem cell marker p63 without corneal cytokeratin 3. Cell viability remained unchanged after cells were cultured with 0.004, 0.04, and 0.4% TH in the medium, but it was significantly reduced when the concentration was increased to 3.33%. Cell migration, tested using scratch migration assay, was significantly enhanced when cells were cultured with TH at 0.04% and 0.4%. We also found that TH has hydrogen peroxide (H2O2) scavenging ability, although a trace level of H2O2 was detected in the honey in its native form. Preconditioning HCEP cells with 0.4% TH for 48 h showed better survival following H2O2-induced oxidative stress at 50 µM than untreated group, with a significantly lower number of dead cells (15.3 ± 0.4%) were observed compared to the untreated population (20.5 ± 0.9%, p<0.01). Both TH and ascorbic acid improved HCEP viability following induction of 100 µM H2O2, but the benefit was greater with TH treatment than with ascorbic acid. However, no significant advantage was demonstrated using 5-hydroxymethyl-2-furancarboxaldehyde, a compound that was found abundant in TH using GC/MS analysis. This suggests that the cellular anti-oxidative capacity in HCEP cells was augmented by native TH and was attributed to its antioxidant properties. In conclusion, TH possesses antioxidant properties and can improve cell migration and cellular resistance to oxidative stress in HCEP cells in vitro.
    Matched MeSH terms: Neoplasm Proteins/metabolism
  2. Fulltext The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to ethnicity of the patients; Chinese, Malay and Indian
    Liang S, Singh M, Gam LH
    Dis Markers, 2010;28(3):149-65.
    PMID: 20534901 DOI: 10.3233/DMA-2010-0694
    Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was applied in this study to identify changes in the protein profile of cancerous tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort.
    Matched MeSH terms: Neoplasm Proteins/metabolism*
  3. The Potential Use of Anticancer Peptides (ACPs) in the Treatment of Hepatocellular Carcinoma
    Ng CX, Lee SH
    Curr Cancer Drug Targets, 2020;20(3):187-196.
    PMID: 31713495 DOI: 10.2174/1568009619666191111141032
    Peptides have acquired increasing interest as promising therapeutics, particularly as anticancer alternatives during recent years. They have been reported to demonstrate incredible anticancer potentials due to their low manufacturing cost, ease of synthesis and great specificity and selectivity. Hepatocellular carcinoma (HCC) is among the leading cause of cancer death globally, and the effectiveness of current liver treatment has turned out to be a critical issue in treating the disease efficiently. Hence, new interventions are being explored for the treatment of hepatocellular carcinoma. Anticancer peptides (ACPs) were first identified as part of the innate immune system of living organisms, demonstrating promising activity against infectious diseases. Differentiated beyond the traditional effort on endogenous human peptides, the discovery of peptide drugs has evolved to rely more on isolation from other natural sources or through the medicinal chemistry approach. Up to the present time, the pharmaceutical industry intends to conduct more clinical trials for the development of peptides as alternative therapy since peptides possess numerous advantages such as high selectivity and efficacy against cancers over normal tissues, as well as a broad spectrum of anticancer activity. In this review, we present an overview of the literature concerning peptide's physicochemical properties and describe the contemporary status of several anticancer peptides currently engaged in clinical trials for the treatment of hepatocellular carcinoma.
    Matched MeSH terms: Neoplasm Proteins/metabolism*
  4. Styryl-lactone goniothalamin inhibits TNF-α-induced NF-κB activation
    Orlikova B, Schumacher M, Juncker T, Yan CC, Inayat-Hussain SH, Hajjouli S, et al.
    Food Chem Toxicol, 2013 Sep;59:572-8.
    PMID: 23845509 DOI: 10.1016/j.fct.2013.06.051
    (R)-(+)-Goniothalamin (GTN), a styryl-lactone isolated from the medicinal plant Goniothalamus macrophyllus, exhibits pharmacological activities including cytotoxic and anti-inflammatory effects. In this study, GTN modulated TNF-α induced NF-κB activation. GTN concentrations up to 20 μM showed low cytotoxic effects in K562 chronic myelogenous leukemia and in Jurkat T cells. Importantly, at these concentrations, no cytotoxicity was observed in healthy peripheral blood mononuclear cells. Our results confirmed that GTN inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in Jurkat and K562 leukemia cells at concentrations as low as 5 μM as shown by reporter gene assays and western blots. Moreover, GTN down-regulated translocation of the p50/p65 heterodimer to the nucleus, prevented binding of NF-κB to its DNA response element and reduced TNF-α-activated interleukin-8 (IL-8) expression. In conclusion, GTN inhibits TNF-α-induced NF-κB activation at non-apoptogenic concentrations in different leukemia cell models without presenting toxicity towards healthy blood cells underlining the anti-leukemic potential of this natural compound.
    Matched MeSH terms: Neoplasm Proteins/metabolism
  5. Side population cells in anaplastic thyroid cancer and normal thyroid
    Mahkamova K, Latar NM, Aspinall S, Meeson A
    Exp Cell Res, 2019 01 01;374(1):104-113.
    PMID: 30465733 DOI: 10.1016/j.yexcr.2018.11.012
    Comparison of studies of cells derived from normal and pathological tissues of the same organ can be fraught with difficulties, particular with cancer where a number of different diseases are considered cancer within the same tissue. In the thyroid, there are 4 main types of cancer, three of which arise from follicular epithelial cells; papillary and follicular which are classified as differentiated, and anaplastic which is classified as undifferentiated. One assay that can be utilised for isolation of cancer stem cells is the side population (SP) assay. However, SP studies have been limited in part due to lack of optimal isolation strategies and in the case of anaplastic thyroid cancer (ATC) are further compounded by lack of access to ATC tumors. We have used thyroid cell lines to determine the optimal conditions to isolate viable SP cells. We then compared SP cells and NSP cells (bulk tumour cells without the SP) of a normal thyroid cell line N-thy ori-3-1 and an anaplastic thyroid cancer cell line SW1736 and showed that both SP cell populations displayed higher levels of stem cell characteristics than the NSP. When we compared SP cells of the N-thy ori-3-1 and the SW1736, the SW1736 SP had a higher colony forming potential, expressed higher levels of stem cell markers and CXCR4 and where more migratory and invasive, invasiveness increasing in response to CXCL12. This is the first report showing functional differences between ATC SP and normal thyroid SP and could lead to the identification of new therapeutic targets to treat ATC.
    Matched MeSH terms: Neoplasm Proteins/metabolism
  6. Prognostic prospect of soluble programmed cell death ligand-1 in cancer management
    Khairil Anwar NA, Mohd Nazri MN, Murtadha AH, Mohd Adzemi ER, Balakrishnan V, Mustaffa KMF, et al.
    Acta Biochim Biophys Sin (Shanghai), 2021 Jul 28;53(8):961-978.
    PMID: 34180502 DOI: 10.1093/abbs/gmab077
    Aggressive tissue biopsy is commonly unavoidable in the management of most suspected tumor cases to conclusively verify the presence of cancerous cells through histological assessment. The extracted tissue is also immunostained for detection of antigens (tissue tumor markers) of potential prognostic or therapeutic importance to assist in treatment decision. Although liquid biopsies can be a powerful tool for monitoring treatment response, they are still excluded from standard cancer diagnostics, and their utility is still being debated in the scientific community. With a myriad of soluble tissue tumor markers now being discovered, liquid biopsies could completely change the current paradigms of cancer management. Recently, soluble programmed cell death ligand-1 (sPD-L1), which is found in the peripheral blood, i.e. serum and plasma, has shown potential as a pre-therapeutic predictive marker as well as a prognostic biomarker to monitor treatment efficacy. Thus, this review focuses on the emergence of sPD-L1 and promising technologies for its detection in order to support liquid biopsies for future cancer management.
    Matched MeSH terms: Neoplasm Proteins/metabolism*
  7. Fulltext Preventive inositol hexaphosphate extracted from rice bran inhibits colorectal cancer through involvement of Wnt/β-catenin and COX-2 pathways
    Shafie NH, Mohd Esa N, Ithnin H, Md Akim A, Saad N, Pandurangan AK
    Biomed Res Int, 2013;2013:681027.
    PMID: 24260743 DOI: 10.1155/2013/681027
    Nutritional or dietary factors have drawn attention due to their potential as an effective chemopreventive agent, which is considered a more rational strategy in cancer treatment. This study was designed to evaluate the effect of IP₆ extracted from rice bran on azoxymethane- (AOM-) induced colorectal cancer (CRC) in rats. Initially, male Sprague Dawley rats were divided into 5 groups, with 6 rats in each group. The rats received two intraperitoneal (i.p.) injections of AOM in saline (15 mg/kg body weight) over a 2-week period to induce CRC. IP₆ was given in three concentrations, 0.2% (w/v), 0.5% (w/v), and 1.0% (w/v), via drinking water for 16 weeks. The deregulation of the Wnt/β-catenin signaling pathway and the expression of cyclooxygenase (COX)-2 have been implicated in colorectal tumorigenesis. β-Catenin and COX-2 expressions were analysed using the quantitative RT-PCR and Western blotting. Herein, we reported that the administration of IP₆ markedly suppressed the incidence of tumors when compared to the control. Interestingly, the administration of IP₆ had also markedly decreased β-catenin and COX-2 in colon tumors. Thus, the downregulation of β-catenin and COX-2 could play a role in inhibiting the CRC development induced by IP₆ and thereby act as a potent anticancer agent.
    Matched MeSH terms: Neoplasm Proteins/metabolism
  8. Potential hydrophobic protein markers of breast cancer in Malaysian Chinese, Malay and Indian patients
    Liang S, Singh M, Gam LH
    Cancer Biomark, 2010;8(6):319-30.
    PMID: 22072120 DOI: 10.3233/CBM-2011-0221
    Breast cancer is a leading cause of worldwide mortality in females. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of these, the Chinese had the most number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was used to identify protein profile changes in cancerous tissues compared with the normal tissues, the tissues were collected from patients of three different ethnicities, i.e. Chinese, Malay and Indian. Ten differentially expressed hydrophobic proteins were identified. We had evaluated the potential of these proteins as biomarker for infiltrating ducal carcinoma (IDC) and the ethnic-specific expression of these proteins was also determined. The data showed that peroxiredoxin-2, heat shock protein 60, protein disulfide isomerase and calreticulin may serve as ethnic-related potential markers for either one or combination of Chinese, Malay and Indian cohorts as their expression levels were significantly high in the cancerous tissues compared to the normal tissues in the ethnic group tested.
    Publication year=2010-2011
    Matched MeSH terms: Neoplasm Proteins/metabolism*
  9. Fulltext Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort
    Bakker MF, Peeters PH, Klaasen VM, Bueno-de-Mesquita HB, Jansen EH, Ros MM, et al.
    Am J Clin Nutr, 2016 Feb;103(2):454-64.
    PMID: 26791185 DOI: 10.3945/ajcn.114.101659
    BACKGROUND: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.

    OBJECTIVE: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.

    DESIGN: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.

    RESULTS: In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).

    CONCLUSION: Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.

    Matched MeSH terms: Neoplasm Proteins/metabolism
  10. PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells
    Ismail AF, Oskay Halacli S, Babteen N, De Piano M, Martin TA, Jiang WG, et al.
    Biochem. J., 2017 Mar 24;474(8):1333-1346.
    PMID: 28232500 DOI: 10.1042/BCJ20160875
    Urothelial bladder cancer is a major cause of morbidity and mortality worldwide, causing an estimated 150 000 deaths per year. Whilst non-muscle-invasive bladder tumours can be effectively treated, with high survival rates, many tumours recur, and some will progress to muscle-invasive disease with a much poorer long-term prognosis. Thus, there is a pressing need to understand the molecular transitions occurring within the progression of bladder cancer to an invasive disease. Tumour invasion is often associated with a down-regulation of E-cadherin expression concomitant with a suppression of cell:cell junctions, and decreased levels of E-cadherin expression have been reported in higher grade urothelial bladder tumours. We find that expression of E-cadherin in a panel of bladder cancer cell lines correlated with the presence of cell:cell junctions and the level of PAK5 expression. Interestingly, exogenous PAK5 has recently been described to be associated with cell:cell junctions and we now find that endogenous PAK5 is localised to cell junctions and interacts with an E-cadherin complex. Moreover, depletion of PAK5 expression significantly reduced junctional integrity. These data suggest a role for PAK5 in maintaining junctional stability and we find that, in both our own patient samples and a commercially available dataset, PAK5mRNA levels are reduced in human bladder cancer compared with normal controls. Taken together, the present study proposes that PAK5 expression levels could be used as a novel prognostic marker for bladder cancer progression.
    Matched MeSH terms: Neoplasm Proteins/metabolism*
  11. Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects
    Wong MS, Sidik SM, Mahmud R, Stanslas J
    Clin Exp Pharmacol Physiol, 2013 May;40(5):307-19.
    PMID: 23534409 DOI: 10.1111/1440-1681.12083
    Tumour invasion and metastasis have been recognized as major causal factors in the morbidity and mortality among cancer patients. Many advances in the knowledge of cancer metastasis have yielded an impressive array of attractive drug targets, including enzymes, receptors and multiple signalling pathways. The present review summarizes the molecular pathogenesis of metastasis and the identification of novel molecular targets used in the discovery of antimetastatic agents. Several promising targets have been highlighted, including receptor tyrosine kinases, effector molecules involved in angiogenesis, matrix metalloproteinases (MMPs), urokinase plasminogen activator, adhesion molecules and their receptors, signalling pathways (e.g. phosphatidylinositol 3-kinase, phospholipase Cγ1, mitogen-activated protein kinases, c-Src kinase, c-Met kinases and heat shock protein. The discovery and development of potential novel therapeutics for each of the targets are also discussed in this review. Among these, the most promising agents that have shown remarkable clinical outcome are anti-angiogenic agents (e.g. bevacizumab). Newer agents, such as c-Met kinase inhibitors, are still undergoing preclinical studies and are yet to have their clinical efficacy proven. Some therapeutics, such as first-generation MMP inhibitors (MMPIs; e.g. marimastat) and more selective versions of them (e.g. prinomastat, tanomastat), have undergone clinical trials. Unfortunately, these drugs produced serious adverse effects that led to the premature termination of their development. In the future, third-generation MMPIs and inhibitors of signalling pathways and adhesion molecules could form valuable novel classes of drugs in the anticancer armamentarium to combat metastasis.
    Matched MeSH terms: Neoplasm Proteins/metabolism
  12. Fulltext Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)
    Mohd Sakeh N, Md Razip NN, Mohd Ma'in FI, Abdul Bahari MN, Latif N, Akhtar MN, et al.
    Molecules, 2020 Jul 28;25(15).
    PMID: 32731323 DOI: 10.3390/molecules25153403
    Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.
    Matched MeSH terms: Neoplasm Proteins/metabolism
  13. Fulltext Mechanism of Anti-Cancer Activity of Curcumin on Androgen-Dependent and Androgen-Independent Prostate Cancer
    Abd Wahab NA, Lajis NH, Abas F, Othman I, Naidu R
    Nutrients, 2020 Mar 02;12(3).
    PMID: 32131560 DOI: 10.3390/nu12030679
    Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.
    Matched MeSH terms: Neoplasm Proteins/metabolism
  14. Fulltext Malignant melanoma of the gastrointestinal tract presenting as a bleeding gastric ulcer
    Noraidah M, Jasmi AY
    Malays J Pathol, 2003 Jun;25(1):57-61.
    PMID: 16196379
    Malignant melanoma involving the gastrointestinal tract is diagnosed antemortem in only a small percentage of patients with the disease. Presenting symptoms are often non-specific, causing a diagnostic problem. The vast majority of such melanomas are metastatic from a cutaneous primary, however there is evidence that the tumour can arise de novo in the gastrointestinal system. We report a 74-year-old man with malignant melanoma with an unusual presentation simulating a symptomatic gastric ulcer. He presented with epigastric pain, haematemesis and melaena. Explorative laparotomy revealed a large ulcerated tumour with several pigmented satellite nodules in the proximal stomach, multiple ileal nodules and widespread nodal and liver metastases. Proximal gastrectomy and limited small bowel resection was performed. Histology revealed the tumour to be composed of nests of epithelioid cells with melanin pigment. The tumour cells showed immunohistochemical positivity for S100 protein and HMB45 antibodies. This report emphasizes that melanoma should be a diagnostic consideration in patients with gastric ulcer.
    Matched MeSH terms: Neoplasm Proteins/metabolism
  15. Fulltext Isolation, identification and quantification of differentially expressed proteins from cancerous and normal breast tissues
    Othman MI, Majid MI, Singh M, Man CN, Lay-Harn G
    Ann. Clin. Biochem., 2008 May;45(Pt 3):299-306.
    PMID: 18482919 DOI: 10.1258/acb.2007.007104
    Infiltrating ductal carcinoma (IDCA) is the most common type of breast cancer accounting for 85% of all invasive breast cancers.
    Matched MeSH terms: Neoplasm Proteins/metabolism*
  16. Increased protein expression of p16 and cyclin D1 in squamous cell carcinoma tissues
    Eshkoor SA, Ismail P, Rahman SA, Mirinargesi M, Oshkour SA
    Biosci Trends, 2009 Jun;3(3):105-9.
    PMID: 20103831
    Abnormalities of Rb-pathway components are common in the formation of cancer. The immunostaining for cyclin D1 and p16 protein was applied on 1 mm serial tissue microarray (TMA) paraffin sections. Tissue microarray (TMAs) is potentially a good method to find the molecular features of the genes and expressions of them. The aim of this study was to evaluate the protein expressions of cyclin D1 and p16 genes in squamous cell carcinomas (SCCs) of skin and compare with the normal skin tissue. Twenty-five cases of cutaneous SCCs expressed cyclin D1 and p16 proteins. All SCCs samples on the slides showed positive protein expressions of cyclin D1 and p16 genes. Our findings suggested that the increased protein expressions of cyclin D1 and p16 genes might lead to aberrant expressions of these proteins in the affected tumor cells. This study demonstrated that cell cycle controlled deregulation and uncontrolled cell cycle progression might result in the carcinogenesis.
    Matched MeSH terms: Neoplasm Proteins/metabolism*
  17. Fulltext In vitro ultrastructural changes of MCF-7 for metastasise bone cancer and induction of apoptosis via mitochondrial cytochrome C released by CaCO3/Dox nanocrystals
    Kamba AS, Ismail M, Ibrahim TA, Zakaria ZA, Gusau LH
    Biomed Res Int, 2014;2014:391869.
    PMID: 25028650 DOI: 10.1155/2014/391869
    Bones are the most frequent site for breast cancer cells to settle and spread (metastasise); bone metastasis is considered to have a substantial impact on the quality of patients with common cancers. However, majority of breast cancers develop insensitivity to conventional chemotherapy which provides only palliation and can induce systemic side effects. In this study we evaluated the effect of free Dox and CaCO3/Dox nanocrystal on MCF-7 breast cancer using MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide), neural red, and lactate dehydrogenase colorimetric assays while DNA fragmentation and BrdU genotoxicity were also examined. Apoptogenic protein Bax, cytochrome C, and caspase-3 protein were analysed. Morphological changes of MCF-7 were determined using contrast light microscope and scanning and transmission electron microscope (SEM and TEM). The findings of the analysis revealed higher toxicity of CaCO3/Dox nanocrystal and effective cells killing compared to free Dox, morphological changes such as formation of apoptotic bodies, membrane blebbing, and absent of microvilli as indicated by the SEM analysis while TEM revealed the presence of chromatin condensation, chromosomal DNA fragmentation, cell shrinkage, and nuclear fragmentation. Results of TUNEL assay verified that most of the cells undergoes apoptosis by internucleosomal fragmentation of genomic DNA whereas the extent of apoptotic cells was calculated using the apoptotic index (AI). Therefore, the biobased calcium carbonate nanocrystals such as Dox carriers may serve as an alternative to conventional delivery system.
    Matched MeSH terms: Neoplasm Proteins/metabolism*
  18. Fulltext Identification of Potential Chemical Substrates as Fuel for Hypoxic Tumors That May Be Linked to Invadopodium Formation in Hypoxia-Induced MDA-MB-231 Breast-Cancer Cell Line
    Hamad HA, Enezei HH, Alrawas A, Zakuan NM, Abdullah NA, Cheah YK, et al.
    Molecules, 2020 Aug 26;25(17).
    PMID: 32858793 DOI: 10.3390/molecules25173876
    Hypoxia plays a significant role in solid tumors by the increased expression of hypoxia-inducible factor-1α (HIF-1α), which is known to promote cancer invasion and metastasis. Cancer-cell invasion dynamically begins with the degradation of the extracellular matrix (ECM) via invadopodia formation. The chemical substrates that are utilized by hypoxic cells as fuel to drive invadopodia formation are still not fully understood. Therefore, the aim of the study was to maintain MDA-MB-231 cells under hypoxia conditions to allow cells to form a large number of invadopodia as a model, followed by identifying their nutrient utilization. The results of the study revealed an increase in the number of cells forming invadopodia under hypoxia conditions. Moreover, Western blot analysis confirmed that essential proteins for hypoxia and invadopodia, including HIF-1α, vascular endothelial growth factor (VEGF), metallopeptidase-2 (MMP-2), and Rho guanine nucleotide exchange factor 7 (β-PIX), significantly increased under hypoxia. Interestingly, phenotype microarray showed that only 11 chemical substrates from 367 types of substrates were significantly metabolized in hypoxia compared to in normoxia. This is thought to be fuel for hypoxia to drive the invasion process. In conclusion, we found 11 chemical substrates that could have potential energy sources for hypoxia-induced invadopodia formation of these cells. This may in part be a target in the hypoxic tumor and invadopodia formation. Additionally, these findings can be used as potential carrier targets in cancer-drug discovery, such as the usage of dextrin.
    Matched MeSH terms: Neoplasm Proteins/metabolism*
  19. Fulltext Expression of survivin and its clinicopathological correlations in invasive ductal carcinoma of the breast
    Al-Joudi FS, Iskandar ZA, Hasnan J, Rusli J, Kamal Y, Imran AK, et al.
    Singapore Med J, 2007 Jul;48(7):607-14.
    PMID: 17609820
    INTRODUCTION: Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.
    METHODS: In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.
    RESULTS: Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.
    CONCLUSION: This is the fi rst known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.
    Matched MeSH terms: Neoplasm Proteins/metabolism*
  20. Expression of multidrug resistance (MDR) proteins and in vitro drug resistance in acute leukemias
    Fazlina N, Maha A, Jamal R, Zarina AL, Cheong SK, Hamidah H, et al.
    Hematology, 2007 Feb;12(1):33-7.
    PMID: 17364990
    The expression of the multidrug resistance (MDR) proteins may influence the outcome of treatment in patients with acute leukemia. The aim of this study was to determine the IC50 of cytotoxic drugs (cytosine arabinoside, ara-C and daunorubicin, dnr) using the in vitro 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)2H-tetrazolium, inner salt (MTS) assay method. A total of 82 newly diagnosed acute leukemia cases (43 adult myeloid leukaemia, AML cases and 39 acute lymphoblastic leukaemia, ALL cases) and 16 relapsed cases (8 AML cases and 8 ALL cases) were studied. The MTS assay was performed using two cytotoxic drugs, dnr and ara-C. Cells were incubated with different concentrations of drugs for 4 days and the IC50 was extrapolated from the viability curve. In newly diagnosed cases, we found that childhood ALL samples showed higher IC50 values of dnr (0.040 +/- 2.320) compared to adult AML samples (0.021 +/- 0.158). In contrast, newly diagnosed adult AML samples showed higher IC50 values of ara-C (0.157 +/- 0.529) compared to childhood ALL samples (0.100 +/- 2.350). In relapsed cases, two samples of childhood ALL showed IC50 values of dnr (0.910 +/- 1.760) and ara-C (1.310 +/- 2.390), which was higher compared to childhood AML samples (0.129 +/- 0.214 and 0.210 +/- 0.003, respectively). However, there was no correlation between IC50 values of these drugs tested with clinical outcome. In conclusion, we found that MTS assay is an easy, rapid and non laborious method to study in vitro drug resistance in acute leukaemia cases.
    Matched MeSH terms: Neoplasm Proteins/metabolism*
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