Displaying publications 1 - 20 of 286 in total

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  1. bin Sabir Husin Athar PP, bte Ahmad Norhan N, bin Saim L, bin Md Rose I, bte Ramli R
    Ann Acad Med Singap, 2008 Sep;37(9):788-3.
    PMID: 18989497
    INTRODUCTION: Metastatic adenocarcinoma from the gastrointestinal tract to the sinonasal tract is rare. The histological morphology of this lesion is indistinguishable from the colonic variant of primary sinus adenocarcinoma or intestinal-type adenocarcinoma (ITAC).

    CLINICAL PICTURE: This is a report of a case of metastatic adenocarcinoma of colorectal origin to the paranasal sinuses in a 52-year-old female who was previously treated for adenocarcinoma of the sigmoid colon. A histologic study of the surgical specimen from the sinonasal cavity demonstrated a tumour identical to the patient's prior primary tumour of the colon. The sinonasal neoplastic tissue showed marked positivity for carcinoembryonic antigen and expressed cytokeratin 20, which differentiates metastatic colonic adenocarcinoma from ITAC.

    TREATMENT/OUTCOME: The patient received palliative radiation but died 3 months after the diagnosis.

    CONCLUSION: Distinguishing metastatic adenocarcinoma from gastrointestinal tract from ITAC can be difficult. In view of the resemblance, immunohistochemical staining can help in differentiating them. It is important to recognise these as metastatic lesions as the treatment is mainly palliative.

    Matched MeSH terms: Adenocarcinoma/metabolism; Adenocarcinoma/radiotherapy; Adenocarcinoma/secondary*
  2. Zulkarnaen M, Tang IP, Wong SL
    Malays J Pathol, 2012 Jun;34(1):53-5.
    PMID: 22870599 MyJurnal
    We present a case of a papillary tumour at the cerebellopontine angle in a 41-year-old man. He presented with left-sided facial and ear pain associated with dizziness, nystagmus and hearing loss. CT scan of the temporal bone showed a destructive tumour at the left cerebellopontine angle. Surgical excision was performed and the diagnosis of the endolymphatic sac tumour was made. Endolymphatic tumour is a low grade adenocarcinoma that originates from the endolymphatic sac. The definitive diagnosis requires a combination of clinical features, radiological finding and pathological correlation.
    Matched MeSH terms: Adenocarcinoma, Papillary/metabolism; Adenocarcinoma, Papillary/pathology*; Adenocarcinoma, Papillary/therapy
  3. Zheng WQ, Zhan RZ
    Anal. Quant. Cytol. Histol., 1998 Feb;20(1):1-6.
    PMID: 9513685
    To clarify the correlation between apoptosis and tumor cell proliferative activity in human breast cancer and to investigate their relevance to p53 protein.
    Matched MeSH terms: Adenocarcinoma/pathology
  4. Zarinah, Z., Maaruf, A.G., Nazaruddin, R., Wong, W.W.W., Xuebing, X.
    MyJurnal
    Some vegetable oils contain natural antioxidants such as beta carotene and vitamin E namely alpha tocopherol. The objective of this study was to screening the value of α-tocopherol, β-carotene, antioxidant capacity, antimicrobial activity and toxicological properties of roasted pili nut oil (RPNO) and unroasted pili nut oil (UPNO). The result showed that RPNO contained higher amount of vitamin E and less amount of beta carotene compared to UPNO. RPNO and UPNO scavenged DPPH radicals by 24.66% and 9.52% at concentration of 140 μg/ml. The total phenolic compound (TPC) in UPNO and RPNO were about 19.96 ± 0.52 mg/kg and 12.43 ± 0.69 mg/kg respectively. It was observed that bacteria species exhibited different sensitivities towards RPNO, UPNO, Gentamycin, Ampicillin and Chloramphenicol. Bacillus cereus 14570 was the most sensitive bacterium and all strains of Staphylococcus aureus tested were resistant against both samples RPNO and UPNO. An in vitro toxicological study based on the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) cytotoxicity assay was also performed. In vitro cytotoxicity indicated that both RPNO and UPNO had no effect against HeLa (cervical cancer cell), MCF-7 (breast cancer cell) and HT-29 (human colon adenocarcinoma cell) cell lines tested.
    Matched MeSH terms: Adenocarcinoma
  5. Zamzuri, Z., Adham, S.Y., Shukrimi, A., Azril, M.A., Amran, R.
    MyJurnal
    Clinically, it is sometimes diffi cult to distinguish an infection of the spine from a metastasis. Spinal tuberculosis is common according to its endemic region and adenocarcinoma of the lung is also rising in the incidence worldwide. Similar presentations, with unknown primary, clinical fi ndings and hematological investigations rarely conclude a true diagnosis. Radiologically, the hallmark of spinal infection is erosion of adjacent vertebral endplates and narrowing of the disc space with or without a paravertebral shadow. Metastasis typically does not involve the disc space with erosion of the adjacent vertebral endplates. It usually presents as a lytic/sclerotic lesion in the vertebral body or “winkle owl” sign. These distinguishing features of infection versus metastasis are not certainties. Biopsy is mandatory whenever in doubt or patient is not responded with provisional treatment. The author presents a case with so-called radiological features of spinal tuberculosis infection, which turns out to be a metastatic adenocarcinoma of the lung.
    Matched MeSH terms: Adenocarcinoma
  6. Zamora-Ros R, Alghamdi MA, Cayssials V, Franceschi S, Almquist M, Hennings J, et al.
    Eur J Nutr, 2019 Dec;58(8):3303-3312.
    PMID: 30535794 DOI: 10.1007/s00394-018-1874-z
    PURPOSE: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study.

    METHODS: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires.

    RESULTS: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97-1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95-1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81-0.99), but this association was based on a sub-analysis with a small number of cancer cases.

    CONCLUSIONS: In this large prospective study, coffee and tea consumptions were not associated with TC risk.

    Matched MeSH terms: Adenocarcinoma, Papillary/epidemiology*
  7. Zamora-Ros R, Cayssials V, Franceschi S, Kyrø C, Weiderpass E, Hennings J, et al.
    Int J Cancer, 2020 Apr 01;146(7):1841-1850.
    PMID: 31342519 DOI: 10.1002/ijc.32589
    Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77-1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80-1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55-2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.
    Matched MeSH terms: Adenocarcinoma, Follicular/epidemiology*; Adenocarcinoma, Follicular/prevention & control
  8. Yusnita Y, Norsiah MD, Rahman AJ
    Malays J Pathol, 2010 Dec;32(2):103-10.
    PMID: 21329181 MyJurnal
    Mitochondrial Subunit ND1 (mtND1) gene is involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). Alteration of the electron transport components by mutations in mtDNA may compromise the normal electron flow. This could lead to an increase of bifurcation and generation of superoxidase radicals and increase oxidative stress in various types of cancer cells. Genomic DNA was extracted from thirty matched primary colorectal tumour tissues and matching non-tumour tissues. Blood samples were obtained from twenty-five normal people. The mtNDI coding region was amplified by step-down PCR. The purified products were then subjected to direct sequencing and subsequently, the DNA sequences obtained were compared with the revised Cambridge Reference Sequence (rCRS) and MITOMAP. From the analysis, the mtND1 gene showed 11 (45.8%) different mutations and also 13 (54.2%) polymorphisms. The heteroplasmic mutation A4123A/G (I273I/V) might have a pathogenic significance as it fulfills various pathogenic criteria. Three mutations, T3394C (Y30H), A3434G (Y43C) and C3497T (A64V) which occur in a highly conserved region were likely to alter the structure and function of the ND1 protein. We suggest that these mutations, and in combination with the polymorphic variance in mtDNA, may cause slight changes that generate subtly higher levels of toxic reactive oxygen species (ROS).
    Matched MeSH terms: Adenocarcinoma/genetics*
  9. Yehya AH, Yusoff NM, Khalid IA, Mahsin H, Razali RA, Azlina F, et al.
    Asian Pac J Cancer Prev, 2012;13(5):1869-72.
    PMID: 22901138
    BACKGROUND: To assess the diagnostic potential of tumor-associated high molecular weight DNA in stool samples of 32 colorectal cancer (CRC) patients compared to 32 healthy Malaysian volunteers by means of polymerase chain reaction (PCR).

    METHODS: Stool DNA was isolated and tumor-associated high molecular weight DNA (1.476 kb fragment including exons 6-9 of the p53 gene) was amplified using PCR and visualized on ethidium bromide-stained agarose gels.

    RESULTS: Out of 32 CRC patients, 18 were positive for the presence of high molecular weight DNA as compared to none of the healthy individuals, resulting in an overall sensitivity of 56.3% with 100% specificity. Out of 32 patients, 23 had tumor on the left side and 9 on the right side, 16 and 2 being respectively positive. This showed that high molecular weight DNA was significantly (p=0.022) more detectable in patients with left side tumor (69.6% vs 22.2%). Out of 32 patients, 22 had tumors larger than 1.0 cm, 18 of these (81.8%) being positive for long DNA as compared to not a single patient with tumor size smaller than 1.0 cm (p<0.001).

    CONCLUSION: We detected CRC-related high molecular weight p53 DNA in stool samples of CRC patients with an overall sensitivity of 56.3% with 100% specificity, with a strong tumor size dependence.

    Matched MeSH terms: Adenocarcinoma/diagnosis*; Adenocarcinoma/genetics
  10. Yaw ACK, Chan EWL, Yap JKY, Mai CW
    J Cancer Res Clin Oncol, 2020 Sep;146(9):2219-2229.
    PMID: 32507974 DOI: 10.1007/s00432-020-03274-y
    PURPOSE: Pancreatic cancer is a lethal form of cancer that can be triggered by prolonged or acute inflammation of the pancreas. Inflammation have been shown to be regulated by a group of key protein molecules known as the inflammasomes. The NLRP3 inflammasome is the most studied inflammasome and have been strongly implicated to regulate cancer cell proliferation. Therefore, this study aimed to examine the regulation of NLRP3 inflammasome under LPS-induced inflammation and its role in modulating cell proliferation in a panel of pancreatic cancer cells.

    METHODS: The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1β, respectively.

    RESULTS: LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1β. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation.

    CONCLUSION: There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.

    Matched MeSH terms: Adenocarcinoma/chemically induced; Adenocarcinoma/drug therapy*; Adenocarcinoma/metabolism
  11. Yatabe Y, Kerr KM, Utomo A, Rajadurai P, Tran VK, Du X, et al.
    J Thorac Oncol, 2015 Mar;10(3):438-45.
    PMID: 25376513 DOI: 10.1097/JTO.0000000000000422
    The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients necessitates accurate, timely testing. Although EGFR mutation testing has been adopted by many laboratories in Asia, data are lacking on the proportion of NSCLC patients tested in each country, and the most commonly used testing methods.
    Matched MeSH terms: Adenocarcinoma/diagnosis; Adenocarcinoma/genetics*; Adenocarcinoma/epidemiology
  12. Yap LF, Velapasamy S, Lee HM, Thavaraj S, Rajadurai P, Wei W, et al.
    J Pathol, 2015 Feb;235(3):456-65.
    PMID: 25294670 DOI: 10.1002/path.4460
    Undifferentiated nasopharyngeal carcinoma (NPC) is a highly metastatic disease that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the contribution of lysophosphatidic acid (LPA) signalling to the pathogenesis of NPC. Here we demonstrate two distinct functional roles for LPA in NPC. First, we show that LPA enhances the migration of NPC cells and second, that it can inhibit the activity of EBV-specific cytotoxic T cells. Focusing on the first of these phenotypes, we show that one of the LPA receptors, LPA receptor 5 (LPAR5), is down-regulated in primary NPC tissues and that this down-regulation promotes the LPA-induced migration of NPC cell lines. Furthermore, we found that EBV infection or ectopic expression of the EBV-encoded LMP2A was sufficient to down-regulate LPAR5 in NPC cell lines. Our data point to a central role for EBV in mediating the oncogenic effects of LPA in NPC and identify LPA signalling as a potential therapeutic target in this disease.
    Matched MeSH terms: Adenocarcinoma/pathology; Adenocarcinoma/physiopathology
  13. Yahaya A, Wa Kammal WS, Abd Shukor N, Osman SS
    Malays J Pathol, 2019 Apr;41(1):59-63.
    PMID: 31025640
    Alpha-fetoprotein (AFP)-producing carcinoma which microscopically mimics hepatocellular carcinoma (HCC) is a rare entity known as hepatoid adenocarcinoma (HC). They usually arise in the stomach, while oesophageal origin is only occasionally encountered. This tumour is highly aggressive and is associated with a poor prognosis. They frequently metastasise to the liver, thus giving rise to diagnostic difficulty, especially in cases where simultaneous oesophageal and liver mass are present. We reported a case of oesophageal hepatoid carcinoma with multiple liver metastasis, that was associated with an increased serum AFP. The distinction between HCC and HC is important because HC is more aggressive and has a poorer prognosis with limited therapeutic options. An extensive diagnostic work-up which include a thorough clinical history, radiological investigations (computed tomography or magnetic resonance imaging) as well as tissue biopsy supported by a panel of immunohistochemical markers are necessary to aid in the diagnosis of HC.
    Matched MeSH terms: Adenocarcinoma
  14. Yaacob NS, Darus HM, Norazmi MN
    Exp. Toxicol. Pathol., 2008 Sep;60(6):505-12.
    PMID: 18579355 DOI: 10.1016/j.etp.2008.05.006
    Studies have shown that ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) can induce differentiation and inhibit proliferation of several cancer cells. The present study was performed to investigate the effects of the PPARgamma ligand, ciglitazone, and the involvement of PPARgamma in modulating the growth of human colorectal cancer cells. Lactate dehydrogenase release assay showed that ciglitazone potently inhibited HT-29 (well-differentiated) and COLO-205 (poorly differentiated) colorectal adenocarcinoma cell growth. Measurement of apoptosis by flow cytometry using a fluorescein-conjugated monoclonal antibody against cytokeratin 18 revealed a high induction of apoptosis by ciglitazone in a time-dependent fashion. The expression of PPARgamma1 but not PPARgamma2 mRNA was significantly downregulated as measured by real-time quantitative PCR, and the PPARgamma protein levels were decreased as determined by Western blot analysis. We conclude that ciglitazone treatment suppressed colon cancer cell growth via induction of apoptosis. However, the anticancer effects of ciglitazone may not depend solely on PPARgamma activation.
    Matched MeSH terms: Adenocarcinoma/drug therapy*; Adenocarcinoma/metabolism; Adenocarcinoma/pathology
  15. Yaacob I, Ahmad Z, Harun Z
    Med J Malaysia, 1990 Sep;45(3):220-4.
    PMID: 1966930
    A review of 119 patients (88 males and 31 females) with carcinoma of the lung seen at the Hospital University Sains Malaysia (HUSM) from 1984 to 1989 was done. The mean age of the patients was 60.3 years with a high proportion (76.6%) of them were between 41 and 70 years. Seventy five percent of patients (84% of men and 26% of women) were smokers. The Chinese have a significantly higher preponderance to carcinoma of the lung. The commonest histological type found was squamous cell carcinoma in men and adenocarcinoma in women. Small cell carcinoma was uncommon. Squamous cell and large cell/undifferentiated type of carcinoma were significantly associated with smoking behaviour of the patients.
    Matched MeSH terms: Adenocarcinoma/etiology; Adenocarcinoma/epidemiology*
  16. Wu H, Nakano T, Daikoku E, Morita C, Kohno T, Lian HH, et al.
    J Med Microbiol, 2005 Dec;54(Pt 12):1117-1125.
    PMID: 16278423 DOI: 10.1099/jmm.0.46158-0
    Helicobacter pylori CagA modifies the signalling of host cells and causes gastric diseases. Although CagA is injected into gastric epithelial cells through the type IV secretion machinery, it remains unclear how CagA is transported towards the machinery in the bacterial cytoplasm. In this study, it was determined that the proton-dependent intracytoplasmic transport system correlates with the priming of CagA secretion from H. pylori. The cytotoxicity of neutral-pH- and acidic-pH-treated H. pylori was examined in the AGS cell line. The amount of phosphorylated CagA in AGS cells incubated with acidic-pH- and neutral-pH-treated H. pylori was determined by enzyme immunoassay and Western blot. The production of CagA and adherence of the treated bacteria were examined by enzyme immunoassay and light microscopy, respectively. To clarify how CagA is transported towards the inner membrane of the treated bacteria, the localization of CagA was analysed by immunoelectron microscopy. The proportion of hummingbird cells in the AGS cell line rapidly increased following the inoculation of acidic-pH-treated H. pylori but increased more slowly with neutral-pH-treated H. pylori, and the phenomenon correlated with the amount of phosphorylated CagA in AGS cells. CagA was densely localized near the inner membrane in the acidic-pH-treated bacterial cytoplasm, but this localization was not observed in the neutral-pH-treated bacterial cytoplasm, suggesting that CagA shifts from the centre to the peripheral portion of the cytoplasm as a result of an extracellular decrease in pH. This phenomenon depended on the presence of UreI, a proton-dependent urea channel, but not on the presence of urea. The pH treatments did not enhance CagA production or the adherence of the bacterium to AGS cells. The authors propose that H. pylori possesses a proton-dependent intracytoplasmic transport system that probably accelerates priming for CagA injection.
    Matched MeSH terms: Adenocarcinoma
  17. Wong YP, Abdul Raub SH, Mohd Dali AZ, Kassim F, Visvalingam V, Zakaria Z, et al.
    Malays J Pathol, 2016 Aug;38(2):93-101.
    PMID: 27568665
    Human papillomavirus (HPV) is a necessary cause of cervical cancer and its precursors. Increased expression of high-risk hrHPV viral oncogenes in abnormal cells might increase the expression of p16INK4a. We aimed to determine the role of p16INK4a in detecting hrHPV-transformed epithelial cells in liquid-based cervical cytology, and compared the results with hrHPV DNA testing by realtime polymerase chain reaction (RT-PCR). Fifty-seven cytological samples were tested for p16INK4a immunomarker and hrHPV DNA. Test performance of both tests was determined by comparing sensitivity, specificity and predictive values using available histological follow-up data as gold standard. Of 57 samples, 36 (63.2%) showed immunoreactivity for p16INK4a and 43 (75.4%) were hrHPV-infected. A fairly low concordance rate (k = 0.504) between p16INK4a immunolabelling and hrHPV DNA status was noted. For prediction of cervical intraepithelial neoplasia (CIN) II and worse lesions, p16INK4a had a sensitivity and specificity of 93.5% and 60%; whereas hrHPV DNA testing had a sensitivity and specificity of 100% and 20%. Dual testing by combining p16INK4a and hrHPV showed sensitivity and specificity of 100% and 33.3%. In conclusion, p16INK4a is useful in predicting severity of the cytological abnormalities. Although p16INK4a is more specific but less sensitive than hrHPV in detecting high-grade cervical lesions, a combination of both tests failed to demonstrate significant improvement in diagnostic sensitivity, specificity and predictive value. Larger-scale prospective studies are required to assess further whether this biomarker should be routinely used as primary screening tool independently or in combination with hrHPV testing to improve diagnostic accuracy in cervical cytology.
    Matched MeSH terms: Adenocarcinoma/diagnosis*; Adenocarcinoma/virology
  18. Wong TH, Amir Hassan SZ
    Med J Malaysia, 2015 Dec;70(6):356-7.
    PMID: 26988209
    This is a case of follicular thyroid carcinoma with extensive lung, bone and brain metastases. Multi-modality treatments including total thyroidectomy, modified radical neck dissection, cranial radiotherapy and Iodine-131 (RAI) therapy were instituted. Post RAI therapy planar whole body scan showed RAI avid metastases in the skull, cervical spine, bilateral lungs and abdomen. With the use of SPECTCT imaging, rare adrenal metastasis and additional rib metastasis were identified. Besides, management strategy was altered due to detection of non-RAI avid brain and lung metastatic lesions.
    Matched MeSH terms: Adenocarcinoma, Follicular
  19. Wong TH, Tan TH, Chin SC, Lee BN
    Med J Malaysia, 2018 06;73(3):181-182.
    PMID: 29962506
    Recently, encapsulated follicular variant of papillary thyroid carcinoma has been reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to emphasize the benign nature of this entity. In our institution, we have assessed 455 patients treated with radioiodine ablation for differentiated thyroid carcinoma and 20 of them were retrospectively found to fulfill the new NIFTP criteria. There was no evidence of metastasis on post radioiodine whole body scans for NIFTP cases and these patients were in remission subsequently. The benign features of these patients' whole body scans and good clinical outcome following treatment further support NIFTP as a low risk thyroid neoplasm.
    Matched MeSH terms: Adenocarcinoma, Follicular/pathology
  20. Wong SHM, Fang CM, Loh HS, Ngai SC
    Anticancer Agents Med Chem, 2023;23(7):817-831.
    PMID: 36380402 DOI: 10.2174/1871520623666221114095733
    AIMS: The aim of this study was to sensitize the resistant breast adenocarcinoma cells towards Tumour Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-induced apoptosis.

    BACKGROUND: Breast cancer is a heterogeneous disease involving complex mechanisms. TRAIL is a potential anticancer candidate for targeted treatment due to its selective killing effects on neoplastic cells. Nonetheless, resistance occurs in many cancers either intrinsically or after multiple treatments.

    OBJECTIVE: Therefore, this research investigated whether the combination of Trichostatin A (TSA) and Zebularine (Zeb) (TZ) followed by TRAIL (TZT) could sensitize the human breast adenocarcinoma cells towards apoptosis.

    METHODS: The breast adenocarcinoma cells, MDA-MB-231, MCF-7 and E-MDA-MB-231 (E-cadherin re-expressed MDA-MB-231) were treated with TSA, Zeb, TZ, TRAIL and TZT. The cells were subjected to hematoxylin and eosin (H & E) staining and FITC-Annexin V/Propidium Iodide apoptosis detection prior to proteome profiling.

    RESULTS: Based on morphological observation, apoptosis was induced in all cells treated with all treatment regimens though it was more evident for the TZT-treated cells. In the apoptosis detection analysis, TZ increased early apoptosis significantly in MDA-MB-231 and MCF-7 while TRAIL induced late apoptosis significantly in E-MDA-MB-231. Based on the proteome profiling on MDA-MB-231, TRAIL R2 and Fas expression was increased. For E-MDA-MB- 231, down-regulation of catalase, paraoxonase-2 (PON2), clusterin, an inhibitor of apoptosis proteins (IAPs) and cell stress proteins validated the notion that E-cadherin re-expression enhances TZT anti-cancer efficacy. Similar trend was observed in MCF-7 whereby TZT treatment down-regulated the anti-apoptotic catalase and PON2, increased the proapoptotic, B cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad) and Bcl-2-associated X (Bax), second mitochondria-derived activator of caspase (SMAC) and HtrA serine peptidase 2 (HTRA2) as well as TRAIL receptors (TRAIL R1 and TRAIL R2).

    CONCLUSION: TZ treatment serves as an efficient treatment regimen for MDA-MB-231 and MCF-7, while TRAIL serves as a better treatment option for E-MDA-MB-231. Therefore, future studies on E-cadherin's positive regulatory role in TRAIL-induced apoptosis are warranted.

    Matched MeSH terms: Adenocarcinoma*
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