Displaying publications 21 - 40 of 77 in total

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  1. Ooi KL, Loh SI, Tan ML, Muhammad TS, Sulaiman SF
    J Ethnopharmacol, 2015 Mar 13;162:55-60.
    PMID: 25554642 DOI: 10.1016/j.jep.2014.12.030
    The juice of the entire fresh herb and infusion of dried sample of Murdannia bracteata are consumed to treat liver cancer and diabetes in Malaysia. However, no scientific evidence of these bioactivities has been reported.
    Matched MeSH terms: Liver Neoplasms/enzymology
  2. Misron NA, Looi LM, Nik Mustapha NR
    Asian Pac J Cancer Prev, 2015;16(4):1553-8.
    PMID: 25743830
    BACKGROUND: COX-2 has been shown to play an important role in the development of breast cancer and increased expression has been mooted as a poor prognostic factor. The purpose of this study was to investigate the relationship between COX-2 immunohistochemical expression and known predictive and prognostic factors in breast cancer in a routine diagnostic histopathology setting.

    MATERIALS AND METHODS: Formalin-fixed paraffin- embedded tumour tissue of 144 no special type (NST) invasive breast carcinomas histologically diagnosed between January 2009 and December 2012 in Hospital Sultanah Bahiyah, Alor Setar, Kedah were immunostained with COX-2 antibody. COX-2 overexpression was analysed against demographic data, hormone receptor status, HER2- neu overexpression, histological grade, tumour size and lymph node status.

    RESULTS: COX-2 was overexpressed in 108/144 (75%) tumours and was significantly more prevalent (87%) in hormone receptor-positive tumours. There was no correlation between COX-2 overexpression and HER2/neu status. Triple negative cancers had the lowest prevalence (46%) (p<0.05). A rising trend of COX-2 overexpression with increasing age was observed. There was a significant inverse relationship with tumour grade (p<0.05), prevalences being 94%, 83% and 66% in grades 1, 2 and 3 tumours, respectively. A higher prevalence of COX-2 overexpression in smaller size tumours was observed but this did not reach statistical significance. There was no relationship between COX-2 expression and lymph node status.

    CONCLUSIONS: This study did not support the generally held notion that COX-2 overexpression is linked to poor prognosis, rather supporting a role in tumorigenesis. Larger scale studies with outcome data and basic studies on cancer pathogenetic pathways will be required to cast further light on whether COX-2 inhibitors would have clinical utility in cancer prevention or blockage of cancer progression. In either setting, the pathological assessment for COX-2 overexpression in breast cancers would have an important role in the selection of cancer patients for personalized therapy with COX-2 inhibitors.

    Matched MeSH terms: Breast Neoplasms/enzymology*
  3. Vincent-Chong VK, Salahshourifar I, Karen-Ng LP, Siow MY, Kallarakkal TG, Ramanathan A, et al.
    ScientificWorldJournal, 2014;2014:897523.
    PMID: 25401159 DOI: 10.1155/2014/897523
    Matrix metalloproteinase 13 (MMP13) plays a central role in the MMP activation cascade that enables degradation of the extracellular matrix and basement membranes, and it is identified as a potential driver in oral carcinogenesis. Therefore, this study aims to determine the copy number, mRNA, and protein expression of MMP13 in oral squamous cell carcinoma (OSCC) and to associate these expressions with clinicopathological parameters. Copy number, mRNA, and protein expression analysis of MMP13 were determined using real-time quantitative PCR and immunohistochemistry methods in OSCC samples. The correlations between MMP13 expressions and clinicopathological parameters were evaluated, and the significance of MMP13 as a prognostic factor was determined. Despite discrepancies between gene amplification and mRNA and protein overexpression rates, OSCC cases showed high amplification of MMP13 and overexpression of MMP13 at both mRNA and protein levels. High level of MMP13 protein expression showed a significant correlation with lymph node metastasis (P = 0.011) and tumor staging (P = 0.002). Multivariate Cox regression model analysis revealed that high level of mRNA and protein expression of MMP13 were significantly associated with poor prognosis (P < 0.050). Taken together, these observations indicate that the MMP13 protein overexpression could be considered as a prognostic marker of OSCC.
    Matched MeSH terms: Mouth Neoplasms/enzymology*
  4. Al-Qubaisi M, Rosli R, Subramani T, Omar AR, Yeap SK, Ali AM, et al.
    Nat Prod Res, 2013;27(23):2216-8.
    PMID: 23767409 DOI: 10.1080/14786419.2013.800979
    Goniothalamin is a biologically active styrylpyrone derivative isolated from various Goniothalamus species. The ability of goniothalamin to induce apoptosis via caspase-3 activation against hepatoblastoma (HepG2) and normal liver cells (Chang cells) was studied using morphological and biochemical evaluations. HepG2 and Chang cells were treated with goniothalamin for 72 h and analysed by TUNEL and Annexin-V/PI staining. Furthermore, the post-mitochondrial caspase-3 was quantified using ELISA. In view of our results, goniothalamin induced apoptosis on treated cells via alteration of cellular membrane integrity and cleavage of DNA. On the other hand, post-mitochondrial caspase-3 activity was significantly elevated in HepG2 cells treated with goniothalamin after 72 h. These findings suggest that goniothalamin induced apoptosis on HepG2 liver cancer cells via induction of caspase-3 with less sensitivity on the cell line of Chang cells.
    Matched MeSH terms: Liver Neoplasms/enzymology
  5. Tee TT, Cheah YH, Hawariah LP
    Anticancer Res, 2007 Sep-Oct;27(5A):3425-30.
    PMID: 17970090
    F16 is a plant-derived pharmacologically active fraction extracted from Eurycoma longifolia Jack. Previously, we have reported that F16 inhibited the proliferation of MCF-7 human breast cancer cells by inducing apoptotic cell death while having some degree of cytoselectivity on a normal human breast cell line, MCF-10A. In this study, we attempted to further elucidate the mode of action of F16. We found that the intrinsic apoptotic pathway was invoked, with the reduction of Bcl-2 protein. Then, executioner caspase-7 was cleaved and activated in response to F16 treatment. Furthermore, apoptosis in the MCF- 7 cells was accompanied by the specific proteolytic cleavage of poly(ADP-ribose) polymerase-1 (PARP-1). Surprisingly, caspase-9 and p53 were unchanged with F16 treatment. We believe that the F16-induced apoptosis in MCF-7 cells occurs independently of caspase-9 and p53. Taken together, these results suggest that F16 from E. longifolia exerts anti-proliferative action and growth inhibition on MCF-7 cells through apoptosis induction and that it may have anticancer properties.
    Matched MeSH terms: Breast Neoplasms/enzymology
  6. Elsadig RE, Reimann K, Yip CH, Lai LC
    Anticancer Res, 2001 Jul-Aug;21(4A):2693-6.
    PMID: 11724341
    Oestrone sulphate is a major source of active oestrogens in the breast. It is converted to oestrone by oestrone sulphatase. Breast cyst fluid (BCF) is a rich source of sex hormones and growth factors. BCF obtained from British women has been shown to inhibit oestrone sulphatase activity in the MCF-7 oestrogen-receptor-positive breast cancer cell line. The aim of the present study was to assess whether BCF obtained from Malaysian women inhibited oestrone sulphatase activity in the MCF-7 and MDA-MB-231 breast cancer cell lines. The cell lines were grown in supplemented Dulbecco's Modified Eagle Medium for 3 days, following which a 3-day incubation with sterilised BCF was carried out. At the end of the treatment period the cell monolayers were assayed for oestrone sulphatase activity and the number of cell nuclei counted on a Coulter Counter. BCF was also fractionated on a Bio-Sil SEC 125-5 column by HPLC and the effects of the fractions collected on oestrone sulphatase activity in the MDA-MB-231 cell line were assessed. All 18 samples of BCF tested inhibited cell growth in the MDA-MB-231 cell line while 8 out of 10 samples inhibited MCF-7 cell growth; 15 out of 18 BCF samples inhibited oestrone sulphatase activity in the MDA-MB-231 cell line whereas 5 out of 10 samples stimulated oestrone sulphatase activity in the MCF-7 cell line. HPLC fractions corresponding to molecular weights of > 158 kDa and 28 kDa were found to inhibit oestrone sulphatase activity in the MDA-MB-231 cell line. Further work is required to fully characterise these substances as they may have roles to play in the prevention of breast cancer.
    Matched MeSH terms: Breast Neoplasms/enzymology*
  7. Ng JH, Nesaretnam K, Reimann K, Lai LC
    Int J Cancer, 2000 Oct 1;88(1):135-8.
    PMID: 10962451
    Oestrogen is important in the development of breast cancer. Oestrogen receptor positive breast cancers are associated with a better prognosis than oestrogen-receptor negative breast cancers since they are more responsive to hormonal treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the breast. It is converted to the potent oestrogen, oestradiol (E(2)) by the enzymes oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase (E(2)DH). Retinoic acid and carotenoids have been shown to have chemopreventive activity against some cancers. The aim of our study was to determine and compare the effects of retinoic acid and palm oil carotenoids on growth of and oestrone sulphatase and E(2)DH activities in the oestrogen receptor positive, MCF-7 and oestrogen receptor negative, MDA-MB-231 breast cancer cell lines. Retinoic acid and carotenoids inhibited MCF-7 cell growth but had no effect on MDA-MB-231 cell growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase activity in the MCF-7 cell line. E(1) to E(2) conversion was inhibited by 10(-7) M carotenoids but was stimulated at 10(-6) M in the MCF-7 cell line. Retinoic acid had no effect on E(1) to E(2) conversion at 10(-7) M but stimulated E(1) to E(2) conversion at 10(-6) M. Retinoic acid and carotenoids had no effect on E(2) to E(1) conversion in the MCF-7 cell line. Retinoic acid stimulated E(1) to E(2) conversion in the MDA-MB-231 cell line but had no effect on oestrone sulphatase activity or E(2) to E(1) conversion in this cell line. Both oestrone sulphatase and E(2)DH activity were not affected by carotenoids in the MDA-MB-231 cell line. In conclusion, retinoic acid and carotenoids may prevent the development of hormone-dependent breast cancers since they inhibit the growth of the MCF-7 cell line.
    Matched MeSH terms: Breast Neoplasms/enzymology*
  8. Lopez JB, Balasegaram M, Thambyrajah V, Timor J
    Malays J Pathol, 1996 Dec;18(2):95-9.
    PMID: 10879229
    This study was undertaken to see if liver function tests (LFT) served a worthwhile purpose in the investigation of hepatocellular carcinoma (HCC). Sera from 80 HCC, 76 benign liver disease (BLD) and 152 healthy adult (HA) subjects were assayed for alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase and lactate dehydrogenase, bilirubin and albumin. Cut-off values were determined from the HA. ALP, GGT, AST and albumin were abnormal in about 90% of the HCC. With the exception of bilirubin, the LFT were abnormal more frequently in HCC than in chronic hepatitis and cirrhosis, the conditions which preceed it. Raised ALP in the presence of normal bilirubin was more often a feature of HCC than BLD although this relationship was not statistically significant. It seems unlikely that LFT serve a useful function in HCC.
    Matched MeSH terms: Liver Neoplasms/enzymology
  9. Yusof YA, Yan KL, Hussain SN
    Anal. Quant. Cytol. Histol., 2003 Dec;25(6):332-8.
    PMID: 14714299
    To determine whether tumor marker pi glutathione transferase (GST-pi) is expressed in hepatocellular carcinoma (HCC) and other chronic liver diseases and to compare its expression with that of alpha-fetoprotein (AFP).
    Matched MeSH terms: Liver Neoplasms/enzymology
  10. Atiomo W, Shafiee MN, Chapman C, Metzler VM, Abouzeid J, Latif A, et al.
    Clin Endocrinol (Oxf), 2017 Nov;87(5):557-565.
    PMID: 28748640 DOI: 10.1111/cen.13436
    OBJECTIVE: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC).

    AIM: To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC.

    DESIGN AND METHODS: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study.

    RESULTS: We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P 

    Matched MeSH terms: Endometrial Neoplasms/enzymology
  11. Ee YS, Lai LC, Reimann K, Lim PK
    Oncol Rep, 1999 6 22;6(4):843-6.
    PMID: 10373668
    Transforming growth factor-beta (TGF-beta) has been shown to inhibit the growth of mammary epithelial cells and may play a protective role in mammary carcinogenesis. In contrast, oestrogens promote the development of breast cancer. Oestrone sulphate (E1S) is a huge reservoir of active oestrogens in the breast being converted to the weak oestrogen, oestrone (E1), by oestrone sulphatase. E1 is reversibly converted by oestradiol-17beta hydroxysteroid dehydrogenase to the potent oestrogen, oestradiol (E2). The aim of this study was to assess the effect of the TGF-beta1 isoform on growth and oestrogen metabolism in the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 human breast cancer cell lines. The results showed that TGF-beta1 significantly inhibited cell growth and stimulated the conversion of E1S to E1 and E1 to E2 in the MCF-7 cell line. In the MDA-MB-231 cell line TGF-beta1 significantly stimulated cell growth and inhibited the interconversions between E1 and E2. In conclusion, the growth inhibitory effect of TGF-beta1 on the MCF-7 cell line would appear to confer a protective effect in breast cancer. However, its ability to increase the amount of E2 would increase the risk of breast cancer. Which of these effects predominates in vivo remains to be explored. The growth stimulatory effect of TGF-beta1 on the MDA-MB-231 cell line probably acts through a mechanism independent of the effect of TGF-beta1 on oestrogen concentrations since this cell line is hormone unresponsive.
    Matched MeSH terms: Breast Neoplasms/enzymology
  12. Abdull Razis AF, Noor NM
    Asian Pac J Cancer Prev, 2013;14(7):4235-8.
    PMID: 23991982
    Glucoraphanin is the main glucosinolate found in broccoli and other cruciferous vegetables (Brassicaceae). The objective of the study was to evaluate whether glucoraphanin and its breakdown product sulforaphane, are potent modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro. The glucosinolate glucoraphanin was isolated from cruciferous vegetables and exposed to human hepatoma cell line HepG2 at various concentrations (0-25 μM) for 24 hours. Glucoraphanin at higher concentration (25 μM) decreased dealkylation of methoxyresorufin, a marker for cytochrome P4501 activity; supplementation of the incubation medium with myrosinase (0.018 U), the enzyme that converts glucosinolate to its corresponding isothiocyanate, showed minimal induction in this enzyme activity at concentration 10 μM. Quinone reductase and glutathione S-transferase activities were unaffected by this glucosinolate; however, supplementation of the incubation medium with myrosinase elevated quinone reductase activity. It may be inferred that the breakdown product of glucoraphanin, in this case sulforaphane, is superior than its precursor in modulating carcinogen- metabolising enzyme systems in vitro and this is likely to impact on the chemopreventive activity linked to cruciferous vegetable consumption.
    Matched MeSH terms: Liver Neoplasms/enzymology
  13. Othman N, Nagoor NH
    Int J Oncol, 2017 Dec;51(6):1757-1764.
    PMID: 29075783 DOI: 10.3892/ijo.2017.4174
    Lung cancer remains a major health problem with a low 5-year survival rate of patients. Recent studies have shown that dysregulation of microRNAs (miRNAs) are prevalent in lung cancer and these aberrations play a significant role in the progression of tumour progression. In the present study, bioinformatics analyses was employed to predict potential miR-608 targets, which are associated with signaling pathways involved in cancer. Luciferase reporter assay identified AKT2 as a novel target of miR-608, and suppression of its protein levels was validated through western blot analysis. Zebrafish embryos were microinjected with cells transfected with miR-608 to elucidate the role of miR-608 in vivo, and immunostained with antibodies to detect activated caspase-3. We present the first evidence that miR-608 behaves as a tumour suppressor in A549 and SK-LU-1 cells through the regulation of AKT2, suggesting that selective targeting of AKT2 via miR-608 may be developed as a potential therapeutic strategy for miRNA-based non-small cell lung cancer (NSCLC) therapy.
    Matched MeSH terms: Lung Neoplasms/enzymology*
  14. Rajadurai P, Fatt HK, Ching FY
    J Gastrointest Cancer, 2018 Jun;49(2):150-157.
    PMID: 28124769 DOI: 10.1007/s12029-017-9921-1
    PURPOSE: Human epidermal growth factor receptor 2 (Erbb2/HER2) overexpression, which was previously detected in invasive breast cancer, has now been implicated in advanced gastric cancer (GC) and gastroesophageal junction cancer (GEC). A study was conducted to determine the rate of HER2 positivity in patients with locally advanced or metastatic GC and GEC in Malaysia and to assess the impact of various demographic and clinical parameters on HER2 positivity.

    METHODS: A total of 228 adult patients with GC or GEC were enrolled from Subang Jaya Medical Centre, Malaysia, for retrospective (210) and prospective study. All patients were subjected to the HER2 immunohistochemistry test using an FDA-approved, standardized test kit. Carcinomas scoring 2+ on immunohistochemistry were further tested with HER2 in situ hybridization (ISH) using an FDA-approved test kit.

    RESULTS: The overall rate of HER2 positivity in the population studied was 24.6% (n = 56). The rate was significantly higher in men than in women (29.6 vs. 16.3%; p = 0.024). HER2 overexpression was significantly more common in diffuse type than in intestinal type of tumors (39.8 vs. 14.9%; p 

    Matched MeSH terms: Stomach Neoplasms/enzymology*
  15. Zainal Abidin SA, Rajadurai P, Hoque Chowdhury ME, Othman I, Naidu R
    Molecules, 2018 06 08;23(6).
    PMID: 29890640 DOI: 10.3390/molecules23061388
    The aim of this study is to investigate the potential anti-cancer activity of l-amino acid oxidase (CP-LAAO) purified from the venom of Cryptelytrops purpureomaculatus on SW480 and SW620 human colon cancer cells. Mass spectrometry guided purification was able to identify and purify CP-LAAO. Amino acid variations identified from the partial protein sequence of CP-LAAO may suggest novel variants of these proteins. The activity of the purified CP-LAAO was confirmed with o-phenyldiamine (OPD)-based spectrophotometric assay. CP-LAAO demonstrated time- and dose-dependent cytotoxic activity and the EC50 value was determined at 13 µg/mL for both SW480 and SW620 cells. Significant increase of caspase-3 activity, reduction of Bcl-2 levels, as well as morphological changes consistent with apoptosis were demonstrated by CP-LAAO. Overall, these data provide evidence on the potential anti-cancer activity of CP-LAAO from the venom of Malaysian C. purpureomaculatus for therapeutic intervention of human colon cancer.
    Matched MeSH terms: Colonic Neoplasms/enzymology
  16. Wang Y, Gao F, Ooi KK, Tai Q, Zhang J, Zhu Y, et al.
    J Environ Pathol Toxicol Oncol, 2019;38(4):297-311.
    PMID: 32464002 DOI: 10.1615/JEnvironPatholToxicolOncol.2019030482
    Early development of liver cancer is usually asymptomatic. The overall survival rate of patients is relatively low due to late diagnosis, despite hepatocellular carcinoma being a common diagnosis. The high mortality rate of liver cancer was due to its overactivated cellular mitochondrial activities, namely thioredoxin reductase enzymatic activities and its downstream activation of nuclear factor kappa B (NF-κB) signaling pathways for cancer cell migration. Our previous study on this candidate compound on A2780 ovarian cancer cells and MCF-7 breast cancer cells, through modulation of cell-cycle checkpoints and respective targeted apoptosis pathways. The current study used HepG2 hepatocellular carcinoma cell lines as a representative in vitro liver cancer cell model. The half maximal inhibitory concentration (IC50) value was obtained via incubation of PTZ compound for 24 h yield of 37.03 μM, whereby it was three-fold more potent than the standard control tested, cisplatin (109.23 μM). The subsequent application of IC50 dosage of PTZ onto HepG2 cells illustrated a growth-static effect via activation of S-phase cell-cycle checkpoints, immediately followed by regulation of apoptosis. Increased cellular concentration of reactive oxygen species eventually generated oxidative damages on mitochondria, hence resulting in the release of cytochrome c protein and suppression of TrxR enzymatic activity, in conjunction with the suppression on invasion of cancer cells via Matrigel invasion chamber. In conclusion, PTZ was hypothesized to act effectively on mitochondria of HepG2 cells; hence it should proceed into detailed drug targeting mechanism research.
    Matched MeSH terms: Liver Neoplasms/enzymology
  17. Kotyla PJ, Engelmann M, Giemza-Stokłosa J, Wnuk B, Islam MA
    Int J Mol Sci, 2021 Feb 28;22(5).
    PMID: 33671049 DOI: 10.3390/ijms22052449
    Recent advances in immunology enabled the characterization of several signal transmitting pathways responsible for proper cytokine and chemokine signaling. Among them, Janus kinases (JAKs) are essential components of receptor activation systems. The discovery of JAK kinases enabled the synthesis of JAK kinase inhibitors (JAKi or Jakinibs), which have proven to be efficacious in the treatment of hematologic malignancies and several rheumatological disorders and continue to be investigated in many clinical indications. Blocking multiple cytokines belonging to several cytokine families with a single small molecule may, however, create a potential risk for the patients. Recently, a higher risk of thromboembolic complications, namely, deep vein thrombosis and pulmonary embolism, has been recognized as the main concern during treatment with Jakinibs. At present, it is not entirely clear whether this increased risk is related to direct cytokine blockade, the presence of concomitant diseases in treated patients or other unknown circumstances that work together to increase the risk of this side effect. In this review, we discuss data on the risk of thromboembolic side effects, with special emphasis on the mechanism that may be responsible for this increased risk. Many indirect data indicate that higher thromboembolic risk may be related to the specificity of JAK inhibitor action, such that preferentially blocking one signaling pathway upsets the balance between pro and anti-thrombotic activities.
    Matched MeSH terms: Neoplasms/enzymology
  18. Liew K, Yu GQS, Wei Pua LJ, Wong LZ, Tham SY, Hii LW, et al.
    Cancer Lett, 2021 Apr 28;504:81-90.
    PMID: 33587980 DOI: 10.1016/j.canlet.2021.02.006
    Despite recent in advances in the management of nasopharyngeal carcinoma (NPC), development of targeted therapy remains challenging particularly in patients with recurrent or metastatic disease. To search for clinically relevant targets for the treatment of NPC, we carried out parallel genome-wide functional screens to identified essential genes that are required for NPC cells proliferation and cisplatin resistance. We identified lymphocyte-specific protein tyrosine kinase (LCK) as a key vulnerability of both proliferation and cisplatin resistance. Depletion of endogenous LCK or treatment of cells with LCK inhibitor induced tumor-specific cell death and synergized cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Further analyses demonstrated that LCK is regulating the proliferation and cisplatin resistance through activation of signal transducer and activator of transcription 5 (STAT5). Taken together, our study provides a molecular basis for targeting LCK and STAT5 signaling as potential druggable targets for the management of NPC.
    Matched MeSH terms: Nasopharyngeal Neoplasms/enzymology
  19. Zhang Y, Yan W, Collins MA, Bednar F, Rakshit S, Zetter BR, et al.
    Cancer Res, 2013 Oct 15;73(20):6359-74.
    PMID: 24097820 DOI: 10.1158/0008-5472.CAN-13-1558-T
    Pancreatic cancer, one of the deadliest human malignancies, is almost invariably associated with the presence of an oncogenic form of Kras. Mice expressing oncogenic Kras in the pancreas recapitulate the stepwise progression of the human disease. The inflammatory cytokine interleukin (IL)-6 is often expressed by multiple cell types within the tumor microenvironment. Here, we show that IL-6 is required for the maintenance and progression of pancreatic cancer precursor lesions. In fact, the lack of IL-6 completely ablates cancer progression even in presence of oncogenic Kras. Mechanistically, we show that IL-6 synergizes with oncogenic Kras to activate the reactive oxygen species detoxification program downstream of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling cascade. In addition, IL-6 regulates the inflammatory microenvironment of pancreatic cancer throughout its progression, providing several signals that are essential for carcinogenesis. Thus, IL-6 emerges as a key player at all stages of pancreatic carcinogenesis and a potential therapeutic target.
    Matched MeSH terms: Pancreatic Neoplasms/enzymology
  20. Liam CK, Ruthranesan M, Lee CH, Pang YK, Chua KT, Lim BK
    Asia Pac J Clin Oncol, 2012 Sep;8(3):267-74.
    PMID: 22897510 DOI: 10.1111/j.1743-7563.2011.01509.x
    To evaluate the response and progression-free survival (PFS) of Malaysian patients with advanced lung adenocarcinoma and unknown epidermal growth factor receptor (EGFR) mutation status treated with gefitinib.
    Matched MeSH terms: Lung Neoplasms/enzymology
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