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Expression of p53, bcl-2 and Ki-67 in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix

Looi ML, Dali AZ, Ali SA, Ngah WZ, Yusof YA

Anal. Quant. Cytol. Histol., 2008 Apr;30(2):63-70.
PMID: 18561741

To assess the expression of p53, bcl-2 and Ki-67 in the progression of cervical neoplasia.

Matched MeSH terms: Uterine Cervical Neoplasms/metabolism*
Fulltext In Vitro Analysis of Metabolites Secreted during Infection of Lung Epithelial Cells by Cryptococcus neoformans

Liew KL, Jee JM, Yap I, Yong PV

PLoS One, 2016;11(4):e0153356.
PMID: 27054608 DOI: 10.1371/journal.pone.0153356

Cryptococcus neoformans is an encapsulated basidiomycetous yeast commonly associated with pigeon droppings and soil. The opportunistic pathogen infects humans through the respiratory system and the metabolic implications of C. neoformans infection have yet to be explored. Studying the metabolic profile associated with the infection could lead to the identification of important metabolites associated with pulmonary infection. Therefore, the aim of the study was to simulate cryptococcal infection at the primary site of infection, the lungs, and to identify the metabolic profile and important metabolites associated with the infection at low and high multiplicity of infections (MOI). The culture supernatant of lung epithelial cells infected with C. neoformans at MOI of 10 and 100 over a period of 18 hours were analysed using gas chromatography mass spectrometry. The metabolic profiles obtained were further analysed using multivariate analysis and the pathway analysis tool, MetaboAnalyst 2.0. Based on the results from the multivariate analyses, ten metabolites were selected as the discriminatory metabolites that were important in both the infection conditions. The pathways affected during early C. neoformans infection of lung epithelial cells were mainly the central carbon metabolism and biosynthesis of amino acids. Infection at a higher MOI led to a perturbance in the β-alanine metabolism and an increase in the secretion of pantothenic acid into the growth media. Pantothenic acid production during yeast infection has not been documented and the β-alanine metabolism as well as the pantothenate and CoA biosynthesis pathways may represent underlying metabolic pathways associated with disease progression. Our study suggested that β-alanine metabolism and the pantothenate and CoA biosynthesis pathways might be the important pathways associated with cryptococcal infection.

Matched MeSH terms: Lung Neoplasms/metabolism*
Do clinical features and survival of single hormone receptor positive breast cancers differ from double hormone receptor positive breast cancers?

Ng CH, Pathy NB, Taib NA, Ho GF, Mun KS, Rhodes A, et al.

Asian Pac J Cancer Prev, 2014;15(18):7959-64.
PMID: 25292095

The significance of the single hormone receptor positive phenotype of breast cancer is still poorly understood. The use of hormone therapy has been found to be less effective for this type, which has a survival outcome midway between double positive and double negative phenotypes. The aim of this study was to investigate differences in patient and tumor characteristics and survival between double-receptor positive (ER+PR+), double receptor negative (ER-PR-) and single receptor positive (ER+PR- and ER-PR+) breast cancer in an Asian setting. A total of 1,992 patients with newly diagnosed stage I to IV breast cancer between 2003 and 2008, and where information on ER and PR were available, were included in this study. The majority of patients had ER+PR+ tumors (n=903: 45.3%), followed by 741 (37.2%) ER-PR-, 247 (12.4%) ER+PR-, and 101 (5.1%) ER-PR+ tumors. Using multivariate analysis, ER+PR- tumors were 2.4 times more likely to be grade 3 compared to ER+PR+ tumors. ER+PR- and ER-PR+ tumors were 82% and 86% respectively less likely to be grade 3 compared with ER-PR- tumors. ER-PR+ tumours were associated with younger age. There were no survival differences between patients with ER+PR+ and ER-PR+ tumors. However, ER+PR- tumors have poorer survival compared with ER+PR+ tumours. ER-PR- tumours had the worst survival. Adjuvant hormonal therapy with tamoxifen was found to have identical survival advantage in patients with ER+PR+ and ER-PR+ tumors whereas impact was slightly lower in patients with ER+PR- tumors. In conclusion, we found ER+PR- tumors to be more aggressive and have poorer survival when compared to ER+PR+ tumors, while patients with ER-PR+ tumours were younger, but had a similar survival to their counterparts with ER+PR+ tumours.

Matched MeSH terms: Breast Neoplasms/metabolism
The estrogen receptor negative-progesterone receptor positive breast carcinoma is a biological entity and not a technical artifact

Ng CH, Pathy NB, Taib NA, Mun KS, Rhodes A, Yip CH

Asian Pac J Cancer Prev, 2012;13(4):1111-3.
PMID: 22799290

The ER-/PR+ breast tumor may be the result of a false ER negative result. The aim of this study was to investigate whether there is a difference in patient and tumor characteristics of the ER-/PR+ phenotype in an Asian setting. A total of 2629 breast cancer patients were categorized on the basis of their age, ethnicity, tumor hormonal receptor phenotype, grade and histological type. There were 1230 (46.8%) ER+/PR+, 306 (11.6%) ER+/PR-, 122 (4.6%) ER-/PR+ and 972 (37%) ER-/PR-. ER-/PR+ tumors were 2.5 times more likely to be younger than 50 years at diagnosis (OR: 2.52; 95% CI: 1.72-3.67). Compared to ER+/PR+ tumors, the ER-/ PR+ phenotype was twice more likely to be associated with grade 3 tumors (OR:2.02; 95%CI: 1.00-4.10). In contrast, compared to ER-/PR- tumors, the ER-/PR+ phenotype was 90% less likely to be associated with a grade 3 tumor (OR: 0.12; 95%CI:0.05-0.26), and more likely to have invasive lobular than invasive ductal histology (OR: 3.66; 95%CI: 1.47-9.11). These results show that the ER-/PR+ phenotype occurs in a younger age group and is associated with intermediate histopathological characteristics compared to ER+/PR+ and ER-/PR- tumors. This may imply that it is a distinct entity and not a technical artifact.

Matched MeSH terms: Breast Neoplasms/metabolism*
Fulltext Gradually implemented new biomarkers for prognostication of breast cancer: complete case analysis may introduce bias

Bhoo Pathy N, Uiterwaal CS, Taib NA, Verkooijen HM, Yip CH

J Clin Epidemiol, 2012 May;65(5):568-71.
PMID: 22269329 DOI: 10.1016/j.jclinepi.2011.09.013

Many recent studies investigated the prognostic value of new biomarkers in breast cancer using data from cancer registries. Some of these studies were conducted using only patients for whom biomarker status was available (or tested). Using human epidermal growth factor receptor 2 (HER2) as an example, we determined whether testing for a recently introduced biomarker was associated with the outcome of women with breast cancer.

Matched MeSH terms: Breast Neoplasms/metabolism
Factors associated with HER2 overexpression in breast cancer: Experience in an Asian developing country

Tan GH, Choo WY, Taib NA, Yip CH

Asian Pac J Cancer Prev, 2009;10(5):837-40.
PMID: 20104975

INTRODUCTION: The HER2 gene is amplified in up to 30% of human breast cancers, leading to overexpression of the HER2 protein on the cell surface. Overexpression of HER2 is associated with a more aggressive cancer and hence a poorer overall survival.
OBJECTIVE: To evaluate the association between clinico-pathological features and HER2 overexpression in breast cancer.
METHODS: This is a retrospective study conducted in the Department of Surgery, University Malaya Medical Centre. The association between HER2 overexpression, determined by immunohistochemistry, and other clinicopathological factors was evaluated in 996 patients with newly diagnosed breast cancer treated from 2005 to 2007 using univariate and multivariate logistic regression.
RESULTS: HER2 overexpression occurred in 30.3% of patients. On bivariate analysis, HER2 overexpression was inversely related to ER expression (p<0.01) and PR expression (p<0.01). This overexpression was associated with a higher tumour grade, lymphovascular positivity and infiltrating ductal carcinoma subtype. On multivariate analysis, HER2 overexpression was significantly associated with higher tumour grade (p= 0.018, CI 1.25-11.04), PR negativity (p= 0.002, CI 0.30-0.77) and lymphovascular positivity (p= 0.042, CI 1.01-2.12).
CONCLUSIONS: HER2 overexpression was observed in 30.3% of Malaysian female breast cancer patients. This group of patients represents a more aggressive subtype of breast cancer with higher tumour grade, PR negativity and lymphovascular positivity. No significant relationship was established between HER2 overexpression and age, race, lymph node, ER, pathology subtype and stage of disease from this study.

Matched MeSH terms: Breast Neoplasms/metabolism*
Fulltext Clinical characteristics of triple-negative breast cancer: experience in an Asian developing country

Tan GH, Taib NA, Choo WY, Teo SH, Yip CH

Asian Pac J Cancer Prev, 2009 Jul-Sep;10(3):395-8.
PMID: 19640180

INTRODUCTION: Triple negative (TN) breast cancers are defined by a lack of expression of oestrogen, progesterone, and HER2 receptors. They tend to have a higher grade, with a poorer outcome compared to non-TN breast cancers.
OBJECTIVE: The aim of this study is to determine the incidence of TN breast cancer in an Asian country consisting of Malays, Chinese and Indians, and to determine the factors associated with this type of breast cancer.
RESULTS: The incidence of TN breast cancer in the University Malaya Medical Center is 17.6%. There is no significant difference amongst the Malays, Chinese and Indians. In bivariate analysis, TN breast cancer was significantly associated with younger age and Grade 3. However, in multivariate analysis using logistic regression, TN breast cancer was only associated with Grade 3.
CONCLUSION: The incidence of TN breast cancer in our study is similar to other studies, and associated with a higher grade.
Study site: University Malaya Medical Centre (UMMC)

Matched MeSH terms: Breast Neoplasms/metabolism
Fulltext Prostate-specific antigen in breast disease

Poh BH, Jayaram G, Sthaneshwar P, Yip CH

Malays J Pathol, 2008 Jun;30(1):43-51.
PMID: 19108411 MyJurnal

The aim of this study is to assess tissue and serum prostate-specific antigen (PSA) in breast lesions; to compare tissue PSA with serum PSA; to compare tissue PSA in benign and malignant lesions and to compare PSA with known prognostic factors in breast carcinoma. Tissue PSA immunoreactivity in twenty women with breast carcinoma was compared with PSA in twenty-three women with benign breast lesions. Tissue PSA was also compared with known prognostic indicators such as tumour size, axillary nodal status, histological type, histological grade, oestrogen receptor status, progesterone receptor status and c-erbB-2 oncoprotein over-expression. Serum free PSAlevels from these women were measured pre- and post-operatively and an attempt was made to correlate serum PSA with tissue PSA expression. 40% and 43% of malignant and benign breast lesions respectively showed tissue PSA immunoreactivity. No significant difference was observed in the tissue PSA expression between these two groups as also between tissue PSA and known prognostic indicators. As serum PSA levels were below the detection limit (< 0.004 ng/ml) in all except two benign cases, no statistical evaluation was done for the latter. Tissue PSA expression did not correlate with other prognostic markers and detectable serum PSA levels were present in too few cases for statistical analysis. Although no definitive conclusion is possible in this preliminary study regarding the role of PSA in breast disease, it stimulates interest in further research in this direction.

Matched MeSH terms: Breast Neoplasms/metabolism*
Fine needle aspiration cytology of neuroendocrine carcinoma of the breast--a case report and review of literature

Kadir AA, Iyengar KR, Peh SC, Yip CH

Malays J Pathol, 2008 Jun;30(1):57-61.
PMID: 19108413

Neuroendocrine carcinomas of the breast are uncommon tumors known to occur in the elderly. While focal neuroendocrine differentiation may be noted in many ductal and lobular carcinomas, the term neuroendocrine carcinoma is to be applied when more than 50% of the tumor shows such differentiation. This case report details the cytological features of a neuroendocrine carcinoma that was encountered in our hospital. The fine needle aspiration (FNA) smears showed discohesive polygonal cells with abundant cytoplasm, many of which contained eosinophilic granules located at one pole. Histology of the mastectomy and axillary lymph nodes specimen from this patient showed features of neuroendocrine carcinoma--solid type, with metastasis, confirmed with immunohistochemistry. The patient is disease free seven months after surgery. This case highlights the need to closely observe cytological details to identify this rare tumor that may otherwise appear to be invasive duct carcinoma--not otherwise specified on FNA. The implications of diagnosing neuroendocrine differentiation for prognosis and management are also discussed.

Matched MeSH terms: Breast Neoplasms/metabolism
Breast cancer in Sabah, Malaysia: a two year prospective study

Leong BD, Chuah JA, Kumar VM, Yip CH

Asian Pac J Cancer Prev, 2007 Oct-Dec;8(4):525-9.
PMID: 18260722

INTRODUCTION: Malaysian women have a 1 in 20 chance of developing breast cancer in their lifetime. Sabah, formerly known as North Borneo, is part of East Malaysia with a population of 3.39 million and more than 30 ethnic groups. We conducted a 2 year prospective epidemiological study to provide unreported data of breast cancer from this part of the world and to recognise which particular group of patients are more likely to present with advanced disease.

METHODS: All newly diagnosed breast cancers seen at the Queen Elizabeth Hospital, Kota Kinabalu, from January 2005 to December 2006 were included in the study. Patient and tumour characteristics, including age, race, education, socioeconomic background, parity, practice of breast feeding, hormonal medication intake, menopausal status, family history, mode of presentation, histology, grade, stage of disease and hormonal receptors status were collected and analysed.

RESULTS: A total of 186 patients were seen. The commonest age group was 40 to 49 years old (32.3%). Chinese was the commonest race (30.6%) followed by Kadazan-Dusun (24.2%). The commonest histology was invasive ductal carcinoma (88.4%). Stages at presentation were Stage 0- 4.8%, Stage I- 12.9%, Stage II- 30.1%, Stage III- 36.6% and Stage IV- 15.6%. The estrogen and progesterone receptor status was positive in 59.1% and 54.8% of cases, respectively. 73.7% of Chinese patients presented with early cancer compared to 36.4% of the other races. Patients who presented with advanced disease were also poor, non-educated and from rural areas. 20.4% of patients defaulted treatment; most of them opted for traditional alternatives.

CONCLUSIONS: Sabahan women with breast cancer present late. Great efforts are needed to improve public awareness of breast cancer, especially among those who have higher risk of presenting with advanced disease.

Matched MeSH terms: Breast Neoplasms/metabolism
Fulltext CD44 expression and axillary lymph node metastasis in infiltrating ductal carcinoma of the breast

Looi LM, Cheah PL, Zhao W, Ng MH, Yip CH

Malays J Pathol, 2006 Dec;28(2):83-6.
PMID: 18376796 MyJurnal

Metastasising ability connotes one of the most important life-threatening properties of malignant neoplasms. Recent studies indicate that CD44 proteins, multifunctional cell adhesion molecules which contribute to "homing" of lymphocytes to lymph nodes as well as cell-cell and cell-matrix interactions, are potential markers of tumour progression. However, whether CD44 expression by human tumours contribute to increased metastatic risk remains controversial. In an attempt to clarify its role in breast cancer, we have investigated the correlation between CD44 expression by breast carcinoma and the presence of axillary lymph node metastases. CD44 expression was detected using a standard immunoperoxidase method on formalin-fixed, paraffin-embedded, primary infiltrating ductal breast carcinoma tissues taken from 60 female patients who underwent mastectomy with axillary node clearance. Tumours were graded according to the modified Bloom and Richardson criteria. 62% of patients had histologically-proven lymph node metastasis. 40% of primary cancers exhibited cytoplasmic membrane immunopositivity for CD44. 46% of primary tumours which have metastasied to axillary lymph nodes were CD44 positive whereas 30% of tumours which have not metastasised expressed CD44. CD44 positivity was expressed by 20% of grade 1, 31% grade 2 and 58% grade 3 tumours. Our results suggest that CD44 may have a role in the progression of breast cancer and emphasise the need to investigate its interaction with other mechanisms of cancer advancement.

Matched MeSH terms: Breast Neoplasms/metabolism*
Breast Cancer Outcomes as Defined by the Estrogen Receptor, Progesterone Receptor, and Human Growth Factor Receptor-2 in a Multi-ethnic Asian Country

Subramaniam S, Bhoo-Pathy N, Taib NA, Tan GH, See MH, Jamaris S, et al.

World J Surg, 2015 Oct;39(10):2450-8.
PMID: 26138872 DOI: 10.1007/s00268-015-3133-2

Breast cancer can be divided into four subtypes based on the expressions of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER2). Each subtype has different clinicopathological features and outcomes.

Matched MeSH terms: Breast Neoplasms/metabolism*
Fulltext PASS-predicted Vitex negundo activity: antioxidant and antiproliferative properties on human hepatoma cells--an in vitro study

Kadir FA, Kassim NM, Abdulla MA, Yehye WA

BMC Complement Altern Med, 2013;13:343.
PMID: 24305067 DOI: 10.1186/1472-6882-13-343

Hepatocellular carcinoma is a common type of tumour worldwide with a high mortality rate and with low response to current cytotoxic and chemotherapeutic drugs. The prediction of activity spectra for the substances (PASS) software, which predicted that more than 300 pharmacological effects, biological and biochemical mechanisms based on the structural formula of the substance was efficiently used in this study to reveal new multitalented actions for Vitex negundo (VN) constituents.

Matched MeSH terms: Liver Neoplasms/metabolism
Inducing G2/M Cell Cycle Arrest and Apoptosis through Generation Reactive Oxygen Species (ROS)-Mediated Mitochondria Pathway in HT-29 Cells by Dentatin (DEN) and Dentatin Incorporated in Hydroxypropyl-β-Cyclodextrin (DEN-HPβCD)

Ashwaq AS, Al-Qubaisi MS, Rasedee A, Abdul AB, Taufiq-Yap YH, Yeap SK

Int J Mol Sci, 2016 Oct 18;17(10).
PMID: 27763535

Dentatin (DEN), purified from the roots of Clausena excavata Burm f., has poor aqueous solubility that reduces its therapeutic application. The aim of this study was to assess the effects of DEN-HPβCD (hydroxypropyl-β-cyclodextrin) complex as an anticancer agent in HT29 cancer cell line and compare with a crystal DEN in dimethyl sulfoxide (DMSO). The exposure of the cancer cells to DEN or DEN-HPβCD complex leads to cell growth inhibition as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To analyze the mechanism, in which DEN or DEN-HPβCD complex causes the death in human colon HT29 cancer cells, was evaluated by the enzyme-linked immunosorbent assay (ELIZA)-based assays for caspase-3, 8, 9, and reactive oxygen species (ROS). The findings showed that an anti-proliferative effect of DEN or DEN-HPβCD complex were via cell cycle arrest at the G2/M phase and eventually induced apoptosis through both mitochondrial and extrinsic pathways. The down-regulation of poly(ADP-ribose) polymerase (PARP) which leaded to apoptosis upon treatment, was investigated by Western-blotting. Hence, complexation between DEN and HPβCD did not diminish or eliminate the effective properties of DEN as anticancer agent. Therefore, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents in the future.

Matched MeSH terms: Colonic Neoplasms/metabolism
Novel docetaxel chitosan-coated PLGA/PCL nanoparticles with magnified cytotoxicity and bioavailability

Badran MM, Alomrani AH, Harisa GI, Ashour AE, Kumar A, Yassin AE

Biomed Pharmacother, 2018 Oct;106:1461-1468.
PMID: 30119220 DOI: 10.1016/j.biopha.2018.07.102

In the present study, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanoparticles were successfully prepared and coated with chitosan (CS). The prepared nanoparticles (NPs) were evaluated for their particle size, zeta potential, particle morphology, drug entrapment efficiency (EE%), and in vitro drug release profile. The anticancer activity of DTX-loaded NPs was assessed in human HT29 colon cancer cell line utilizing MTT assay. The pharmacokinetics of DTX-loaded NPs was monitored in Wistar rats in comparison to DTX solution. The prepared NPs exhibited particle sizes in the range 177.1 ± 8.2-287.6 ± 14.3 nm. CS decorated NPs exhibited a significant increase in particle size and a switch of zeta potential from negative to positive. In addition, high EE% values were obtained for CS coated PCL NPs and PLGA NPs as 67.1 and 76.2%, respectively. Moreover, lowering the rate of DTX in vitro release was achieved within 48 h by using CS coated NPs. Furthermore, a tremendous increase in DTX cytotoxicity was observed by CS-decorated PLGA NPs compared to all other NPs including DTX-free-NPs and pure DTX. The in vivo study revealed significant enhancement in DTX bioavailability from CS-decorated PLGA NPs with more than 4-fold increase in AUC compared to DTX solution. In conclusion, CS-decorated PLGA NPs are a considerable DTX-delivery carrier with magnificent antitumor efficacy.

Matched MeSH terms: Colorectal Neoplasms/metabolism
Correlation between histological grade and c-erbB2 oncoprotein overexpression in infiltrating ductal carcinoma of breast

Looi LM, Cheah PL, Yap SF

Malays J Pathol, 1997 Jun;19(1):35-9.
PMID: 10879240

One hundred and twelve infiltrating ductal carcinoma of breast were studied by the standard avidinbiotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, using a monoclonal antibody to c-erbB-2 oncoprotein. The same tumours were assessed and scored according to the Bloom and Richardson criteria into three histological grades. The distribution of tumours according to grade were: 8 Grade I, 34 Grade II and 70 Grade III. Forty-three (38.4%) tumours showed positive membrane staining for c-erbB-2 oncoprotein. These comprised 7 Grade II and 36 Grade III tumours with c-erbB-2 immunopositivity rates of 20.6% and 51.4% respectively. The oncoprotein was not expressed by Grade I tumours. This study shows a good correlation between c-erbB-2 expression and histological grade, a known prognostic indicator of invasive breast carcinoma. Because the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor gene, its overexpression can be expected to result in more aggressive tumour behaviour. While it may be regarded as another indicator of poor prognosis breast cancers, its value in the selection of carcinomas less responsive to hormonal therapy and those more suitable for immunotherapy than chemotherapy has been mooted but remains to be clarified.

Matched MeSH terms: Breast Neoplasms/metabolism*
The effects of Naja sumatrana venom cytotoxin, sumaCTX on alteration of the secretome in MCF-7 breast cancer cells following membrane permeabilization

Hiu JJ, Yap MKK

Int J Biol Macromol, 2021 Aug 01;184:776-786.
PMID: 34174307 DOI: 10.1016/j.ijbiomac.2021.06.145

Naja sumatrana venom cytotoxin (sumaCTX) is a basic protein which belongs to three-finger toxin family. It has been shown to induce caspase-dependent, mitochondrial-mediated apoptosis in MCF-7 cells at lower concentrations. This study aimed to investigate the alteration of secretome in MCF-7 cells following membrane permeabilization by high concentrations of sumaCTX, using label-free quantitative (LFQ) approach. The degree of membrane permeabilization of sumaCTX was determined by lactate dehydrogenase (LDH) assay and calcein-propidium iodide (PI) assays. LDH and calcein-PI assays revealed time-dependent membrane permeabilization within a narrow concentration range. However, as toxin concentrations increased, prolonged exposure of MCF-7 cells to sumaCTX did not promote the progression of membrane permeabilization. The secretome analyses showed that membrane permeabilization was an event preceding the release of intracellular proteins. Bioinformatics analyses of the LFQ secretome revealed the presence of 105 significantly distinguished proteins involved in metabolism, structural supports, inflammatory responses, and necroptosis in MCF-7 cells treated with 29.8 μg/mL of sumaCTX. Necroptosis was presumably an initial stress response in MCF-7 cells when exposed to high sumaCTX concentration. Collectively, sumaCTX-induced the loss of membrane integrity in a concentration-dependent manner, whereby the cell death pattern of MCF-7 cells transformed from apoptosis to necroptosis with increasing toxin concentrations.

Matched MeSH terms: Breast Neoplasms/metabolism*
Fulltext Monoamine oxidase A is down-regulated in EBV-associated nasopharyngeal carcinoma

Lee HM, Sia APE, Li L, Sathasivam HP, Chan MSA, Rajadurai P, et al.

Sci Rep, 2020 04 09;10(1):6115.
PMID: 32273550 DOI: 10.1038/s41598-020-63150-0

Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we identify for the first time a role for monoamine oxidase A (MAOA) in NPC. MAOA is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines. Depending on the cancer type, MAOA can either have a tumour-promoting or tumour-suppressive role. We show that MAOA is down-regulated in primary NPC tissues and its down-regulation enhances the migration of NPC cells. In addition, we found that EBV infection can down-regulate MAOA expression in both pre-malignant and malignant nasopharyngeal epithelial (NPE) cells. We further demonstrate that MAOA is down-regulated as a result of IL-6/IL-6R/STAT3 signalling and epigenetic mechanisms, effects that might be attributed to EBV infection in NPE cells. Taken together, our data point to a central role for EBV in mediating the tumour suppressive effects of MAOA and that loss of MAOA could be an important step in the pathogenesis of NPC.

Matched MeSH terms: Nasopharyngeal Neoplasms/metabolism*
Fulltext Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3

Lee HM, Lo KW, Wei W, Tsao SW, Chung GTY, Ibrahim MH, et al.

J Pathol, 2017 05;242(1):62-72.
PMID: 28240350 DOI: 10.1002/path.4879

Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1, and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is overexpressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Matched MeSH terms: Nasopharyngeal Neoplasms/metabolism
Fulltext Breast cancer risk factors, survival and recurrence, and tumor molecular subtype: analysis of 3012 women from an indigenous Asian population

Abubakar M, Sung H, Bcr D, Guida J, Tang TS, Pfeiffer RM, et al.

Breast Cancer Res, 2018 09 18;20(1):114.
PMID: 30227867 DOI: 10.1186/s13058-018-1033-8

BACKGROUND: Limited evidence, mostly from studies in Western populations, suggests that the prognostic effects of lifestyle-related risk factors may be molecular subtype-dependent. Here, we examined whether pre-diagnostic lifestyle-related risk factors for breast cancer are associated with clinical outcomes by molecular subtype among patients from an understudied Asian population.
METHODS: In this population-based case series, we evaluated breast cancer risk factors in relation to 10-year all-cause mortality (ACM) and 5-year recurrence by molecular subtype among 3012 women with invasive breast cancer in Sarawak, Malaysia. A total of 579 deaths and 314 recurrence events occurred during a median follow-up period of ~ 24 months. Subtypes (luminal A-like, luminal B-like, HER2-enriched, triple-negative) were defined using immunohistochemical markers for hormone receptors and human epidermal growth factor receptor 2 (HER2) in conjunction with histologic grade. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between risk factors and ACM/recurrence were estimated in subtype-specific Cox regression models.
RESULTS: We observed heterogeneity in the relationships between parity/breastfeeding, age at first full-term pregnancy (FFP), family history, body mass index (BMI), and tumor subtype (p value 30 vs

Matched MeSH terms: Breast Neoplasms/metabolism

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