Displaying publications 21 - 40 of 84 in total

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  1. Effect of transforming growth factor-beta1 on oestrogen metabolism in MCF-7 and MDA-MB-231 breast cancer cell lines
    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: Cell Division/drug effects
  2. Inhibition of oestrone sulphatase activity in the MDA-MB-231 breast cancer cell line by breast cyst fluid from Malaysian women
    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: Cell Division/physiology
  3. Stemness and angiogenic gene expression changes of serial-passage human amnion mesenchymal cells
    Fatimah SS, Tan GC, Chua K, Fariha MM, Tan AE, Hayati AR
    Microvasc Res, 2013 Mar;86:21-9.
    PMID: 23261754 DOI: 10.1016/j.mvr.2012.12.004
    Particular attention has been directed towards human amnion mesenchymal stem cells (HAMCs) due to their accessibility, availability and immunomodulatory properties. Therefore, the aim of the present study was to determine the temporal changes of stemness and angiogenic gene expressions of serial-passage HAMCs.
    Matched MeSH terms: Cell Division
  4. Proteasomal degradation of p130 facilitate cell cycle deregulation and impairment of cellular differentiation in high-risk Human Papillomavirus 16 and 18 E7 transfected cells
    Gandhi S, Nor Rashid N, Mohamad Razif MF, Othman S
    Mol Biol Rep, 2021 Jun;48(6):5121-5133.
    PMID: 34169395 DOI: 10.1007/s11033-021-06509-4
    The High-Risk Human Papillomaviruses (HR-HPVs) 16 and 18 are known to cause cervical cancer, which is primarily attributed to E6 and E7 oncoproteins. In addition, recent studies have focused on the vital role of the p130 pocket protein as an oncosuppressor to limit the expression of E2F transcription factors required for cell cycle progression. In view of this, the current study was conducted to investigate the mechanism by which transfection with HPV16/18 E7 leads to the deregulation of the host cell cycle, altering the localisation of p130, and expression of differentiation genes in Human Keratinocytes (HaCaT) cells. Co-immunoprecipitation, Western blot analysis, immunofluorescence microscopy, flow cytometry, quantitative-Polymerase Chain Reaction (qPCR), and the inhibition of p130 by MG132 inhibitor were employed to investigate the loss of p130 and its disruption in HPV 16/18 E7-transfected HaCaT cells. The HPV16- and HPV18-transformed cells, known as CaSki and HeLa, respectively, were also used to complement the ectopic expressions of E7 in HaCaT cells. Normal keratinocytes displayed higher level of p130 expression than HPV-transformed cells. In addition, the immunofluorescence analysis revealed that both HPV 16/18 E7-transfected HaCaT and HPV-transformed cells exhibited higher level of cytoplasmic p130 compared to nuclear p130. A significant increase in the number of S/G2 phase cells in HPV-transformed cells was also recorded since E7 has been shown to stimulate proliferation through the deactivation of Retinoblastoma Protein (pRB)-dependent G1/S checkpoint. Furthermore, the findings recorded the down-regulation of keratinocyte differentiation markers, namely p130, keratin10, and involucrin. The proteasomal degradation of the exported p130 confirmed the cellular localisation pattern of p130, which was commonly observed in cancerous cells. The findings provide strong evidence that the localisation of nuclear p130 nuclear was disrupted by HPV16/18 E7 led to the deregulation of the cell cycle and the impairment of cellular differentiation ultimately lead to cellular transformation.
    Matched MeSH terms: Cell Division/physiology
  5. Tissue engineering techniques in tendon and ligament replacement
    Goh JC, Ouyang HW, Toh SL, Lee EH
    Med J Malaysia, 2004 May;59 Suppl B:47-8.
    PMID: 15468812
    Matched MeSH terms: Cell Division/physiology
  6. Using tissue engineering techniques for osteochondral repair and regeneration
    Goh JC, Shao XX, Hutmacher D, Lee EH
    Med J Malaysia, 2004 May;59 Suppl B:17-8.
    PMID: 15468797
    Matched MeSH terms: Cell Division/physiology
  7. In vitro differences of hydroxyapatite from different resources in simulated body fluid
    Hashim N, Sabudin S, Ibrahim S, Zin NM, Bakar SH, Fazan F
    Med J Malaysia, 2004 May;59 Suppl B:103-4.
    PMID: 15468839
    Hydroxyapatite (HA; Ca10(PO4)6(OH)2), is one of the significant implant materials used in Orthopaedics and Dental applications. However, synthetically produced HA may not be stable under ionic environment, which it will unavoidably encounter during its applications. In this paper, the in vitro effects of three HA materials derived from different resources, i.e. commercial HA (HAC), synthesised HA from pure chemicals (HAS) and synthesised HA from kapur sireh; derived traditionally from natural limestone (HAK), were studied. The HA disc samples were prepared and immersed in simulated body fluid (SBF) for 31-day period. The evaluation conducted focuses on the changes of the pH and the Calcium ion (Ca-ion) and Phosphate ion (P-ion) concentrations in the SBF solution, as well as the XRD and SEM data representing the reactions on the HA materials. From the XRD, it was found that HAK has the smallest crystallite sizes, which in turn affect the pH of the SBF during immersion. The Ca and P-ion concentrations generally decrease over time at different rates for different HA. Upon 1-day immersion in SBF, apatite growth was observed onto all three surfaces, which became more pronounced after 3-day immersion. However, the appetites formed were observed to be different in shapes and sizes. The reasons for the difference in the apatite-crystals and their subsequent effects on cells are still being investigated.
    Matched MeSH terms: Cell Division/drug effects*
  8. In vitro response of human breast cancer cell lines to the growth-inhibitory effects of styrylpyrone derivative (SPD) and assessment of its antiestrogenicity
    Hawariah A, Stanslas J
    Anticancer Res, 1998 Nov-Dec;18(6A):4383-6.
    PMID: 9891496
    Previous studies have shown that a styrylpyrone derivative (SPD) from a local tropical plant had antiprogestin and antiestrogenic effects in early pregnant mice models (Azimahtol et al. 1991). Antiprogestins and antiestrogens can be exploited as a therapeutic approach to breast cancer treatment and thus the antitumor activity of SPD was tested in three different human breast cancer cell lines that is: MCF- 7, T47D and MDA-MB-231, employing, the antiproliferative assay of Lin and Hwang (1991) slightly modified. SPD (10(-10) - 10(-6) M) exhibited strong antiproliferative activity in estrogen and progestin-dependent MCF-7 cells (EC50 = 2.24 x 10(-7) M) and in hormone insensitive MDA-MB-231 (EC50 = 5.62 x 10(-7) M), but caused only partial inhibition of the estrogen- insensitive T47D cells (EC50 = 1.58 x 10(-6) M). However, tamoxifen showed strong inhibition of MCF-7 cells (EC50 = 1.41 x 10(-6) M) and to a lesser extent the T47D cells (EC50 = 2.5 x 10(-6) M) but did not affect the MDA-MB-231 cells. SPD at 1 microM exerted a beffer antiestrogenic activity than 1 microM tamoxifen in suppressing the growth of MCF-7 cells stimulated by 1 nM estradiol. Combined treatment of both SPD and tamoxifen at 1 microM showed additional inhibition on the growth of MCF-7 cells in culture. The antiproliferative properties of SPD are effective on both receptor positive and receptor negative mammary cancer cells, and thus appear to be neither dependent on cellular receptor status nor cellular hormone responses. This enhances in vivo approaches as tumors are heterogenous masses with varying receptor status.
    Matched MeSH terms: Cell Division/drug effects
  9. Effects of insulin-like growth factors I and II on oestrone sulphatase activity in human breast cancer cell lines
    Hwa IA, Reimann K, Lim PK, Lai LC
    Int J Mol Med, 1999 Aug;4(2):175-8.
    PMID: 10402485
    Oestrogens play an important role in the development of breast cancer. A very important source of active oestrogens in the breast is oestrone sulphate which is converted to oestrone by oestrone sulphatase. The aim of this study was to assess the effects of IGF-I and IGF-II on oestrone sulphatase activity in, as well as cell growth of, MCF-7 and MDA-MB-231 human breast cancer cell lines. Cells were grown in supplemented DMEM and treated with varying concentrations of IGFs. At the end of the treatment period, intact cell monolayers were washed and assayed for oestrone sulphatase activity and the number of cell nuclei determined on a Coulter Counter. Oestrone sulphatase activity was significantly stimulated by IGF-I and II at concentrations of 100 ng/ml and 200 ng/ml in MCF-7 cells. IGF-I had no effect on oestrone sulphatase activity in MDA-MB-231 cells over the range of concentrations tested. Significant inhibition of oestrone sulphatase was observed in MDA-MB-231 cells at higher concentrations of IGF-II (50 ng/ml, 100 ng/ml and 200 ng/ml). Both IGF-I and IGF-II at higher concentrations (100 ng/ml and 200 ng/ml) significantly inhibited MCF-7 and stimulated MDA-MB-231 cell growth. Since IGF-I and II have effects on cell growth and oestrone sulphatase activity in breast cancer cell lines they may play a role in the development and progression of human breast cancer.
    Matched MeSH terms: Cell Division/drug effects
  10. Fulltext Determination of suitable microspore stage and callus induction from anthers of kenaf (Hibiscus cannabinus L.)
    Ibrahim AM, Kayat FB, Hussin ZE, Susanto D, Ariffulah M
    ScientificWorldJournal, 2014;2014:284342.
    PMID: 24757416 DOI: 10.1155/2014/284342
    Kenaf (Hibiscus cannabinus L.) is one of the important species of Hibiscus cultivated for fiber. Availability of homozygous parent lines is prerequisite to the use of the heterosis effect reproducible in hybrid breeding. The production of haploid plants by anther culture followed by chromosome doubling can be achieved in short period compared with inbred lines by conventional method that requires self pollination of parent material. In this research, the effects of the microspore developmental stage, time of flower collection, various pretreatments, different combinations of hormones, and culture condition on anther culture of KB6 variety of Kenaf were studied. Young flower buds with immature anthers at the appropriate stage of microspore development were sterilized and the anthers were carefully dissected from the flower buds and subjected to various pretreatments and different combinations of hormones like NAA, 2,4-D, Kinetin, BAP, and TDZ to induce callus. The best microspore development stage of the flower buds was about 6-8 mm long collected 1-2 weeks after flower initiation. At that stage, the microspores were at the uninucleate stage which was suitable for culture. The best callus induction frequency was 90% in the optimized semisolid MS medium fortified with 3.0 mg/L BAP + 3.0 mg/L NAA.
    Matched MeSH terms: Cell Division/drug effects; Cell Division/physiology
  11. Cytotoxicity and Toxicological Studies of Artocarpus altilis Extracts, Inducing Apoptosis and Cell Cycle Arrest via CASPASE-3 and CASPASE-8 Pathways Against Human Breast MCF-7 Cells
    Jalal T, Natto HA, Wahab RA
    Comb Chem High Throughput Screen, 2021 Mar 01.
    PMID: 33653245 DOI: 10.2174/1386207324666210302095557
    In recent biomedical research, the area of cancer and infectious diseases has a leading position in the utilization of medicinal plants as a source of drug discovery. Malaysia has a diversity and a large number of underutilized fruits that are rich in phenolic compounds. Artoarpus altilis consider an underutilized fruit that is rich in phenolic compounds. Methanol extracts of A. altilis have been previously found to contain a high content of antioxidant phytochemicals. The purpose of the study was to evaluate the cytotoxicity and toxicological effect of methanol fruit extracts against MCF-7 cells. To determine the least concentration that might kill or suppress the growth of the cancer cells was in a concentration-dependent manner approach. The variation in the cytotoxic activity among the extracts was indicated by determining the IC50 of each extract against cells at 72 h. The IC50 of the samples was measured using a trypan blue exclusion assay. The methanol extract of the pulp part showed the least inhibition concentration of 15.40±0.91 μg/mL on MCF-7 cells. In the study, the molecular mechanism of methanol extracts-induced apoptosis and cell cycle arrested in human cancer cells were investigated in a time-dependent-manners approach by using flow cytometry. The treated cells were stained with nexin to detect early and late apoptosis and with propidium iodide (PI) for cell cycle arrest associated with the DNA fragmentation, various cell arrests occurred at G1/S, S, and G2/M phases. Lastly, the gene expression analysis by (RT-qPCR) method was carried out by analyzing the expression of the gene of interest for the quantification of mRNA levels. Results after cells treated with IC50 were revealed by upregulating anti-apoptotic genes/downregulated of pro-apoptotic BCL-2 gene expressions were triggered the treated cells into CASPASE-3, intrinsic and extrinsic pathways. These findings suggest that the methanol extracts of three parts of A. altilis fruit have potential anticancer activity against MCF-7 cells mainly the pulp part of the fruit.
    Matched MeSH terms: Cell Division
  12. Four quadrant fine needle aspiration cytology for the detection of benign proliferative breast lesions accompanying breast carcinoma
    Jayaram G, Gupta M, Lamba S
    Malays J Pathol, 1993 Dec;15(2):137-42.
    PMID: 8065175
    Forty-eight patients with breast carcinoma were subjected to four quadrant fine needle aspiration (FNA) cytology examination of the ipsilateral and contralateral breast in an attempt to detect any accompanying benign proliferative lesion. Mastectomy of ipsilateral and open biopsy of contralateral breast provided material for histopathological study. Cytological evidence of epithelial proliferation was found in 8 (16.6%) cases which included atypical lobular hyperplasia (ALH), lobular neoplasia in-situ (LNIS), atypical ductal hyperplasia (ADH), and proliferative disease without atypia (PDWA). In lobular proliferative lesions, cytological smears showed configurations of cells that resembled filled up or expanded lobular units. The cytology was not distinctive enough to distinguish the sub-types of lobular proliferations. Likewise, the presence of ductal alterations could be suggested by cytological study but the distinction of proliferative disease without atypia (PDWA) from atypical ductal hyperplasia (ADH) was not possible on a cytological basis.
    Matched MeSH terms: Cell Division/physiology
  13. Four quadrant fine needle aspiration cytology of non-palpable benign proliferative breast lesions
    Jayaram G, Lamba S, Kakar A
    Malays J Pathol, 1993 Dec;15(2):131-6.
    PMID: 8065174
    Seventy-eight symptomatic females without palpable breast lumps were subjected to bilateral four quadrant fine needle aspiration cytology. Cytological evidence of an epithelial proliferative lesion was seen in 44 of these cases. Based on the cytological evidence of proliferation, the site for open biopsy was determined. Histopathological study of the breast biopsies in these patients showed proliferative disease without atypia (PDWA) in 40 cases, atypical ductal hyperplasia (ADH) in two, atypical lobular hyperplasia (ALH) in one and ADH with ALH in one case. Cytology was thus useful in establishing the presence of proliferative activity, commenting on the extent of proliferation, and thereby roughly mapping out the area of the breast most suitable for biopsy. On cytological grounds, it was not possible to distinguish the atypical hyperplastic lesions from the proliferative diseases without atypia.
    Matched MeSH terms: Cell Division/physiology
  14. Effects of Clitoria ternatea leaf extract on growth and morphogenesis of Aspergillus niger
    Kamilla L, Mansor SM, Ramanathan S, Sasidharan S
    Microsc Microanal, 2009 Aug;15(4):366-72.
    PMID: 19575837 DOI: 10.1017/S1431927609090783
    Clitoria ternatea is known for its antimicrobial activity but the antifungal effects of leaf extract on growth and morphogenesis of Aspergillus niger have not been observed. The extract showed a favorable antifungal activity against A. niger with a minimum inhibition concentration 0.8 mg/mL and minimum fungicidal concentration 1.6 mg/mL, respectively. The leaf extract exhibited considerable antifungal activity against filamentous fungi in a dose-dependent manner with 0.4 mg/mL IC50 value on hyphal growth of A. niger. The main changes observed under scanning electron microscopy after C. ternatea extract treatment were loss of cytoplasm in fungal hyphae and the hyphal wall and its diameter became markedly thinner, distorted, and resulted in cell wall disruption. In addition, conidiophore alterations were also observed when A. niger was treated with C. ternatea leaf extract.
    Matched MeSH terms: Cell Division/drug effects
  15. Endothelialisation of poly (carbonate-siloxane-urea) urethane
    Kannan RY, Sales KM, Salacinski HJ, Butler PE, Seifalian AM
    Med J Malaysia, 2004 May;59 Suppl B:107-8.
    PMID: 15468841
    Matched MeSH terms: Cell Division/physiology
  16. Computational prediction of Mycoplasma hominis proteins targeting in nucleus of host cell and their implication in prostate cancer etiology
    Khan S, Zakariah M, Palaniappan S
    Tumour Biol., 2016 Aug;37(8):10805-13.
    PMID: 26874727 DOI: 10.1007/s13277-016-4970-9
    Cancer has long been assumed to be a genetic disease. However, recent evidence supports the enigmatic connection of bacterial infection with the growth and development of various types of cancers. The cause and mechanism of the growth and development of prostate cancer due to Mycoplasma hominis remain unclear. Prostate cancer cells are infected and colonized by enteroinvasive M. hominis, which controls several factors that can affect prostate cancer growth in susceptible persons. We investigated M. hominis proteins targeting the nucleus of host cells and their implications in prostate cancer etiology. Many vital processes are controlled in the nucleus, where the proteins targeting M. hominis may have various potential implications. A total of 29/563 M. hominis proteins were predicted to target the nucleus of host cells. These include numerous proteins with the capability to alter normal growth activities. In conclusion, our results emphasize that various proteins of M. hominis targeted the nucleus of host cells and were involved in prostate cancer etiology through different mechanisms and strategies.
    Matched MeSH terms: Cell Division
  17. Fulltext Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase-Dependent and p53-Independent Pathway in Breast Cancer Cell Lines
    Khazaei S, Abdul Hamid R, Ramachandran V, Mohd Esa N, Pandurangan AK, Danazadeh F, et al.
    Evid Based Complement Alternat Med, 2017;2017:1468957.
    PMID: 29250124 DOI: 10.1155/2017/1468957
    Breast cancer is the second leading cause of cancer death among women and despite significant advances in therapy, it remains a critical health problem worldwide. Allium atroviolaceum is an herbaceous plant, with limited information about the therapeutic capability. We aimed to study the anticancer effect of flower extract and the mechanisms of action in MCF-7 and MDA-MB-231. The extract inhibits the proliferation of the cells in a time- and dose-dependent manner. The underlying mechanism involved the stimulation of S and G2/M phase arrest in MCF-7 and S phase arrest in MDA-MB-231 associated with decreased level of Cdk1, in a p53-independent pathway. Furthermore, the extract induces apoptosis in both cell lines, as indicated by the percentage of sub-G0 population, the morphological changes observed by phase contrast and fluorescent microscopy, and increase in Annexin-V-positive cells. The apoptosis induction was related to downregulation of Bcl-2 and also likely to be caspase-dependent. Moreover, the combination of the extract and tamoxifen exhibits synergistic effect, suggesting that it can complement current chemotherapy. LC-MS analysis displayed 17 major compounds in the extract which might be responsible for the observed effects. Overall, this study demonstrates the potential applications of Allium atroviolaceum extract as an anticancer drug for breast cancer treatment.
    Matched MeSH terms: Cell Division
  18. Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model
    Khurana RK, Kumar R, Gaspar BL, Welsby G, Welsby P, Kesharwani P, et al.
    Mater Sci Eng C Mater Biol Appl, 2018 Oct 01;91:645-658.
    PMID: 30033299 DOI: 10.1016/j.msec.2018.05.010
    The current studies envisage unravelling the underlying cellular internalisation mechanism of the systematically developed docetaxel (DTH) polyunsaturated fatty acid (PUFA) enriched self-nanoemulsifying lipidic micellar systems (SNELS). The concentration-, time- and cytotoxicity-related effects of DTH-SNELS on triple negative breast cancer (TNBC) MDA-MB-231 and non-TNBC MCF-7 cell lines were assessed through Presto-blue assay. Subsequently, rhodamine-123 (Rh-123) loaded SNELS were employed for evaluating their internalisation through flow cytometry and fluorescence microscopy, establishing it to be "clathrin-mediated" endocytic pathway. Apoptosis assay (65% cell death) and cell cycle distribution (47% inhibition at G2/M phase) further corroborated the cytotoxicity of DTH-SNELS towards cancerous cells. Biodistribution, histopathology and haematology studies indicated insignificant toxicity of the optimized formulation on vital organs. Preclinical anticancer efficacy studies using 7,12-dimethylbenzantracene (DMBA)-induced model construed significant reduction in breast tumor-volume. Overall, extensive in vitro and in vivo studies indicated the intracellular localization and cytotoxicity, suggesting DTH-SNELS as promising delivery systems for breast tumor therapeutics including TNBC.
    Matched MeSH terms: Cell Division
  19. Expression of Bcl-2 family members and presence of Epstein-Barr virus in the regulation of cell growth and death in classical Hodgkin's lymphoma
    Kim LH, Nadarajah VS, Peh SC, Poppema S
    Histopathology, 2004 Mar;44(3):257-67.
    PMID: 14987230 DOI: 10.1111/j.0309-0167.2004.01829.x
    AIMS: To examine the expression of the Bcl-2 family of proteins (Bcl-2, Bcl-x, Bcl-xL and Bax) in classical Hodgkin's lymphoma (cHL) and to correlate the expression of these proteins with proliferation, apoptosis and the presence of Epstein-Barr virus (EBV).

    METHODS AND RESULTS: Expression of the Bcl-2 family of proteins was detected by immunohistochemistry, proliferation was determined by Ki67 labelling and apoptosis by TUNEL in-situ hybridization. EBV was detected by Epstein-Barr virus early RNA (EBER) in-situ hybridization. Expression of Bcl-2, Bcl-x, Bcl-xL and Bax was detected in the Hodgkin/Reed-Sternberg (H/RS) cells in 43.7% (27/62), 87.5% (56/64), 67.2% (41/61) and 74.6% (47/63) of the cHL cases, respectively. EBER was detected in 53% (35/66) of the cases, whereas Ki67 was observed in 86.7% (52/60) of the cases. Apoptotic H/RS cells were observed infrequently, and only 43.2% (11/26) of the cases showed an apoptotic index of > or = 10% in the H/RS cells. A statistically significant inverse relationship was observed between the expression of Bcl-2 and the presence of EBV (P = 0.003). Bcl-xL showed an inverse correlation with apoptosis in the H/RS cells (P = 0.004).

    CONCLUSIONS: The higher Bcl-xL expression (67.2%) compared with Bcl-2 expression (43.5%) observed in cHL as well as the statistically significant inverse relationship between Bcl-xL and apoptosis suggests that Bcl-xL plays an important role in the survival of H/RS cells. Expression of Bax may be neutralized by other anti-apoptotic members of the family such as Bcl-2 and/or Bcl-xL.
    Matched MeSH terms: Cell Division
  20. The role of CD30, CD40 and CD95 in the regulation of proliferation and apoptosis in classical Hodgkin's lymphoma
    Kim LH, Eow GI, Peh SC, Poppema S
    Pathology, 2003 Oct;35(5):428-35.
    PMID: 14555388
    AIMS: CD30, CD40 and CD95 are members of the tumour necrosis factor receptor superfamily. Ligation to their respective ligands (CD30L, CD40L, CD95L) will generate a diverse set of signalling cascades. We aim to study the expression pattern of CD30, CD40 and CD95 in classical Hodgkin's lymphoma (cHL) and to correlate the expressions with proliferation and apoptosis in the Hodgkin/Reed-Sternberg (H/RS) cells of cHL with or without associated Epstein-Barr virus (EBV) infection.

    METHODS: A total of 66 cHL cases were retrieved from the archives. Expressions of CD30, CD40, CD95 and proliferation by Ki-67 expression were detected with an immunohistochemical staining method. Apoptosis index was assessed by in situ TUNEL staining technique on 30 randomly selected cases and the presence of EBV was determined by EBER in situ hybridisation.

    RESULTS: Expression of CD30, CD40 and CD95 in the H/RS cells was observed in a high proportion of the cases (100, 93.9, 90.5%, respectively). There was no significant association or correlation of the expression of these molecules with the presence of EBV. Expression of CD40 was associated with expression of the proliferation marker Ki-67 (P=0.044), whereas strong (intermediate and high) expression of CD30 showed a significant correlation with proliferation in the EBV-negative cases only (P=0.025). No correlation was observed for the expression of CD30 and CD40 with apoptosis of the H/RS cells. The childhood cases showed weaker CD95 expression in the H/RS cells than the adult cases, and the expression of CD95 was weaker than that of CD40 in the childhood group.

    CONCLUSIONS: Our results showed that CD30, CD40 and CD95 are highly expressed in the H/RS cells of the majority of cases of cHL. The expression patterns seem to be independent of EBV and do not correlate with apoptosis of the H/RS cells.

    Matched MeSH terms: Cell Division/physiology
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