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  1. Peh SC, Looi LM, Pallesen G
    Histopathology, 1997 Mar;30(3):227-33.
    PMID: 9088951
    The Epstein-Barr virus (EBV) has been implicated as a contributing factor in the development of Hodgkin's disease. Western cases of Hodgkin's disease have shown the presence of EBV in Hodgkin and Reed-Sternberg cells in approximately 50%. We studied a total of 100 consecutive cases of Hodgkin's disease from Malaysia, with the aim to elucidate its association with EBV in a multi-ethnic Asian population. Of 34 patients (34%) less than 15 years of age (childhood), 25 had classical Hodgkin's disease (eight nodular sclerosis, 16 mixed cellularity, one lymphocyte depleted) and nine had lymphocyte predominance Hodgkin's disease. Of the 66 from patients aged 15 years and above, 33 had nodular sclerosis, 24 mixed cellularity, two lymphocyte depleted, one unclassifiable and six lymphocyte predominance Hodgkin's disease. The ethnic distribution of classical Hodgkin's disease was: Malay 23, Chinese 32 and Indian 30 (Malay:Chinese:Indian = 1:1.4:1.3), and the ethnic distribution in the 15 cases of lymphocyte predominance Hodgkin's disease was: Malay four, Chinese 10 and Indian one. Taking into account the ethnic distribution of the general population and of hospital admissions, there appears to be a significant predilection of classical Hodgkin's disease cases in ethnic Indian compared to non-Indian patients (chi-squared test, 0.025 > P > 0.01). Eighty-one cases were tested for the presence of EBV by in situ hybridization for EBV encoded RNA, and 57 cases by immunostaining for EBV latent membrane protein 1. In the younger age group, all except one of the 15 cases (nine mixed cellularity, six nodular sclerosis) showed the presence of EBV (93%). In the older age group, EBV was detected (52%) in the following proportion: 6/27 nodular sclerosis, 19/22 mixed cellularity, 1/2 lymphocyte depleted, 1/1 unclassifiable. None of the 14 cases of lymphocyte predominance Hodgkin's disease showed the presence of EBV in the Hodgkin and Reed-Sternberg cells. The findings suggest a strong association of EBV with Hodgkin's disease in Malaysians (41/67, 61%), in particular childhood cases (93%). In adults, the association with EBV is significantly higher in the mixed cellularity subtype (86%) compared with the nodular sclerosis subtype (22%).
    Matched MeSH terms: Tumor Virus Infections/ethnology; Tumor Virus Infections/pathology; Tumor Virus Infections/virology*
  2. Cheah PL, Looi LM
    Malays J Pathol, 1998 Jun;20(1):1-10.
    PMID: 10879257
    Historical cottontail rabbit papillomavirus studies raised early indications of a mammalian DNA oncogenic virus. Today, molecular cloning recognises numerous animal and human papillomaviruses (HPVs) and the development of in vitro transformation assays has escalated oncological research in HPVs. Currently, their detection and typing in tissues is usually by Southern blotting, in-situ hybridization and polymerase chain reaction methods. The complete papillomavirus virion constitutes a protein coat (capsid) surrounding a circular, double-stranded DNA organised into coding and non-coding regions. 8 early (E1-E8) open reading frames (ORFs) and 2 late (L1, L2) ORFs have been identified in the coding region of all papillomaviruses. The early ORFs encode proteins which interact with the host genome to produce new viral DNA while late ORFs are activated only after viral DNA replication and encode for viral capsid proteins. All papillomaviruses are obligatory intranuclear organisms with specific tropism for keratinocytes. Three possible courses of events can follow papillomaviruses entry into cells: (1) viral DNA are maintained as intranuclear, extrachromosomal, circular DNA episomes, which replicates synchronously with the host cell, establishing a latent infection; (2) conversion from latent into productive infection with assembly of complete infective virions; (3) integration of viral DNA into host cellular genome, a phenomenon seen in HPV infections associated with malignant transformation. Human papillomaviruses (HPVs) essentially induce skin and mucosal epithelial lesions. Various skin warts are well known to be HPV-associated (HPVs 1, 2, 3, 7 and 10). Besides HPVs 3 and 10, HPVs 5, 8, 17 and 20 have been recovered from Epidermodysplasia verruciformis lesions. Anogenital condyloma acuminatum, strongly linked with HPVs 6 and 11 are probably sexually transmitted. The same HPVs, demonstrable in recurrent juvenile laryngeal papillomas, are probably transmitted by passage through an infected birth canal. HPVs described in uterine cervical lesions are generally categorized into those associated with high (16, 18), intermediate (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) and low (6, 11, 26, 40, 42, 43, 44, 53, 54, 55, 62, 66) risk of cervical squamous carcinoma. Cervical adenocarcinoma, clear cell carcinoma and small cell neuroendocrine carcinoma have also been linked to HPVs, especially HPV18. Other lesions reported to be HPV-associated are: papillomas, dysplasia and carcinomas in the nasal cavity (HPV 6, 11, 57); squamous papilloma, condyloma acuminatum, and verruca vulgaris of the oral cavity (HPV 6, 11), oral focal epithelial hyperplasia (HPV 13, 32); warty lip lesions (HPV 2): and conjunctival papillomas (HPV 6, 11).
    Matched MeSH terms: Tumor Virus Infections/pathology*; Tumor Virus Infections/virology
  3. Bande F, Arshad SS, Hassan L, Zakaria Z, Sapian NA, Rahman NA, et al.
    BMC Vet Res, 2012 Mar 22;8:33.
    PMID: 22439903 DOI: 10.1186/1746-6148-8-33
    BACKGROUND: Feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) are major causes of morbidity and mortality in domestic and wild felids. Despite the clinical importance of feline retroviruses and the growing interest in cats as pets, information about FeLV and FIV in Malaysia is presently insufficient to properly advise veterinarians and pet owners. A cross-sectional study was carried out from January 2010 to December 2010 to determine the prevalence and risk factors associated with FeLV and FIV among domestic cats in peninsular Malaysia. Plasma samples were harvested from the blood of 368 domestic cats and screened for evidence of FeLV p27 antigen and FIV antibodies, using an immunochromatographic kit. Additionally, data on cat demographics and health were collected using a structured questionnaire, and were evaluated as potential risk factors for FeLV or FIV status.

    RESULTS: Of the 368 cats that were evaluated in this study, 12.2% (45/368; 95% CI = 8.88 - 15.58) were positive for FeLV p27 antigen, 31.3%, (115/368; 95% CI = 26.51 - 35.99) were seropositive to FIV antibodies, and 4.3% (16/368; 95% CI = 2.27 - 6.43) had evidence of both viruses. Factors found to significantly increase the risk for FeLV seropositivity include sex, age, behaviour, sickness, and living in a multi-cat household. Seropositive response to FIV was significantly associated with sex, neuter status, age, behaviour, and health status.

    CONCLUSIONS: The present study indicates that FeLV and FIV are common among domestic cats in peninsular Malaysia, and that factors related to cat demographics and health such as age, sex, behaviour, health status and type of household are important predictors for seropositive status to FeLV or FIV in peninsular Malaysia. High prevalence of FeLV or FIV observed in our study is of concern, in view of the immunosuppressive potentials of the two pathogens. Specific measures for control and prevention such as screening and routine vaccination are needed to ensure that FeLV and FIV are controlled in the cat population of peninsular Malaysia.

    Matched MeSH terms: Tumor Virus Infections/epidemiology; Tumor Virus Infections/veterinary*
  4. Cheah PL, Looi LM, Ng MH, Sivanesaratnam V
    J Clin Pathol, 2002 Jan;55(1):22-6.
    PMID: 11825919
    AIM: Telomerase activity was studied in invasive uterine cervical carcinoma to assess whether it was activated during cervical malignant transformation and to look for a possible association with human papillomavirus (HPV) infection in a set of Malaysian patients.

    METHODS: Histologically confirmed invasive cervical carcinoma and benign cervices were assayed for telomerase activity using a commercial telomerase polymerase chain reaction (PCR) enzyme linked immunosorbent assay kit. The same cases were subjected to PCR detection of HPV using type specific (HPV types 6b, 11, 16, and 18) followed by L1 open reading frame (ORF) consensus primers.

    RESULTS: HPV was detected in 18 (13 HPV-16, one HPV-6b, four only L1 ORF) of 20 invasive cervical carcinoma and one (only L1 ORF) of 19 benign cervices. Raised telomerase activity (A(450 nm) > 0.215) was detected in 11 cervical carcinomas, with A(450 nm) ranging between 0.238 and 21.790 (mean, 3.952) in positive squamous carcinomas, whereas A(450 nm) was only 0.222 in the one positive adenosquamous carcinoma. Five of 11 cervical carcinomas in stage I, three of six in stage II, both in stage III, and the only case in stage IV showed telomerase activation. Increased telomerase activity was noted in five of the 12 lymph node negative, five of the seven lymph node status unknown cases, and the one case with presumed lymph node metastasis. Ten of 18 HPV positive and one of two HPV negative cervical carcinomas showed telomerase upregulation.

    CONCLUSIONS: Telomerase is activated in invasive cervical carcinoma. Although larger studies are needed, there seems to be no clear association between telomerase upregulation and HPV status, although there is a suggestion of increased telomerase activity in squamous carcinomas and late stage disease.

    Matched MeSH terms: Tumor Virus Infections/complications; Tumor Virus Infections/enzymology*; Tumor Virus Infections/genetics
  5. Khairuddin N, Blake SJ, Firdaus F, Steptoe RJ, Behlke MA, Hertzog PJ, et al.
    Immunol Cell Biol, 2014 Feb;92(2):156-63.
    PMID: 24217808 DOI: 10.1038/icb.2013.75
    Small interfering RNAs (siRNAs) to inhibit oncogene expression and also to activate innate immune responses via Toll-like receptor (TLR) recognition have been shown to be beneficial as anti-cancer therapy in certain cancer models. In this study, we investigated the effects of local versus systemic delivery of such immune-stimulating Dicer-substrate siRNAs (IS-DsiRNAs) on a human papillomavirus (HPV)-driven tumour model. Localized siRNA delivery using intratumour injection of siRNA was able to increase siRNA delivery to the tumour compared with intravenous (IV) delivery and potently activated innate immune responses. However, IV injection remained the more effective delivery route for reducing tumour growth. Although IS-DsiRNAs activated innate immune cells and required interferon-α (IFNα) for full effect on tumour growth, we found that potent silencing siRNA acting independently of IFNα were overall more effective at inhibiting TC-1 tumour growth. Other published work utilising IS-siRNAs have been carried out on tumour models with low levels of major histocompatibility complex (MHC)-class 1, a target of natural killer cells that are potently activated by IS-siRNA. As TC-1 cells used in our study express high levels of MHC-class I, the addition of the immunostimulatory motifs may not be as beneficial in this particular tumour model. Our data suggest that selection of siRNA profile and delivery method based on tumour environment is crucial to developing siRNA-based therapies.
    Matched MeSH terms: Tumor Virus Infections/drug therapy*; Tumor Virus Infections/immunology; Tumor Virus Infections/pathology
  6. Khode SR, Dwivedi RC, Rhys-Evans P, Kazi R
    J Cancer Res Ther, 2014 Jul-Sep;10(3):492-8.
    PMID: 25313727 DOI: 10.4103/0973-1482.138213
    Squamous cell carcinoma involving the oral cavity (OC) and oropharynx regions are a major cause of morbidity and mortality world-wide. The recent discovery of a strong association between human papilloma virus (HPV) infection and OC and oropharyngeal (OP) cancer has prompted world-wide research into the exact etiology and pathogenesis of these cancers in relation to the HPV. HPV-positive OC/OP cancers generally present at a relatively advanced stage (by virtue of cervical nodal involvement) and are more commonly seen in younger patients without significant exposure to alcohol or tobacco. These factors are implicated in prognosis, regardless of HPV association. In this article, we review the biology and epidemiology, risk factors, association, molecular analyses, treatment response and prognosis of HPV-related cancers. Role of HPV vaccination in HPV-related OC/OP cancers has also been discussed.
    Matched MeSH terms: Tumor Virus Infections/complications*
  7. Yasmin AM
    Med J Malaysia, 1997 Jun;52(2):105-7.
    PMID: 10968066
    Matched MeSH terms: Tumor Virus Infections/complications
  8. Chow VT, Tham KM, Lim-Tan SK, Sng IT, Bernard HU
    Asia Oceania J Obstet Gynaecol, 1990 Dec;16(4):373-7.
    PMID: 1966000
    The close epidemiological relationships between specific genital human papillomavirus (HPV) types and neoplasia of the cervix uteri have been extensively documented worldwide, including Singapore. Cervical cancer incidence rates in Singapore show variations between the major ethnic groups. To ascertain the corresponding HPV infection rates among the various races in Singapore, we analysed the cervical smears of 225 women by filter in situ DNA hybridization, and compared the data with a previous similar study. Fourteen (6.2%) individuals were HPV-positive, with HPV 16 and HPV 31 being the commonest types. No significant difference between HPV positivity rates in Chinese (5.0%) and in Malays (6.7%) was found, even though Chinese have a higher cervical cancer incidence than Malays. Furthermore, the cervical HPV carriage rate among women with normal cytology was 5.9%. In the light of reports of high genital HPV prevalence rates detected by DNA amplification, these data support the notion that HPV infection is commonly latent and requires the cooperation of other factors for cervical carcinogenesis.
    Matched MeSH terms: Tumor Virus Infections/ethnology*
  9. Ashouri Saheli Z, Shenagari M, Harzandi N, Monfared A
    Trop Biomed, 2019 Sep 01;36(3):766-775.
    PMID: 33597498
    The need for an intensive care protocol, sometimes weekly or biweekly, has led to a significant increase in laboratory costs for kidney recipients. In the present study, an inhouse tetraplex nested PCR assay was developed and validated for the specific detection of BKV, JCV, HCMV and EBV in clinical samples. We determined the Limit of Detection (LOD) and analytical specificity. To demonstrate the diagnostic performance of the assay, a total of 102 archival plasma samples were tested and compared with a commercial uniplex real-time PCR kits. The analytical sensitivity of the in-house tetraplex nested PCR assay was 173 copies/ml, when all four viruses were present in the specimens. These values were 79.2, 58.7, 87.6 and 96.1 copies/ml when only, BKV, JCV, HCMV and EBV respectively, were present. The cross-reactivity assays were shown no detectable signal in the tetraplex PCR results. The estimated diagnostic sensitivities were 92.6% for BKV, 92.3% for JCV and 100% for both HCMV and EBV as compared with commercial kits. Regarding the sensitivity and specificity, it seems that the developed Multiplex Nested PCR assay could be used as a reliable virusassociated renal rejection (VRR) panel in post renal transplant surveillance.
    Matched MeSH terms: Tumor Virus Infections/diagnosis*
  10. Karim N, Pallesen G
    Malays J Pathol, 2003 Jun;25(1):45-7.
    PMID: 16196377
    Epstein-Barr virus (EBV) has consistently been detected in the tumour cells of nasopharyngeal carcinoma and lymphoepithelial-like carcinoma of the salivary glands, and have occasionally been found in similar tumours at other sites. Moreover, recent studies from various parts of the world including the Orient have shown about 10% of gastric carcinomas to be EBV-associated. We studied 50 gastric carcinomas from Malaysia to investigate its association with EBV in the Malaysian population. They comprised 37 intestinal and 13 diffuse type carcinomas from 32 male and 18 female patients, age range from 29 to 86 years with an ethnic distribution of Malay: Chinese: Indian with the ratio of 4: 27: 19. EBV gene and gene-expression were examined in sections of formalin-fixed, paraffin-embedded tissue using commercially available probes for detecting EBV encoded RNAs (EBERs) by in situ hybridization and monoclonal antibodies to EBV latent membrane protein-1 (LMP-1) by standard immunohistochemistry. Five of 50 gastric carcinomas showed EBER intranuclear positivity in all tumour cells but no cases expressed LMP-1. The EBV-associated cases were classified as intestinal type in 4 and diffuse type in one case and all were histologically unremarkable. EBV-positive tumours were found in 3 Chinese and 2 Indian patients with none in the small Malay group. Four EBV-positive tumours were in male patients, with age-range of 65 to 86 years. We conclude that our findings of about 10% of Malaysian gastric carcinomas being EBV-associated is in line with the results from other parts of the world and from other ethnic groups.
    Matched MeSH terms: Tumor Virus Infections/pathology; Tumor Virus Infections/virology*
  11. Nandi JS, Bhavalkar-Potdar V, Tikute S, Raut CG
    Virology, 2000 Nov 10;277(1):6-13.
    PMID: 11062030
    As a simian species, the langurs are not known to harbor simian retroviruses, except for one report on a simian Type D endogenous retrovirus from the spectacled langur (Trachypithecus obscurus) from Malaysia. The present report describes for the first time natural infection of the common Hanuman langur (Semnopithecus entellus) from India by a novel simian retrovirus (SRV). The new SRV is phylogenetically related to but distinct from the three molecularly characterized serotypes, SRV 1-3, of the five known serotypes of SRVs, based on sequence analyses from the 3'orf and env regions of the viral genome. The novel SRV isolated from the Indian Hanuman langur is provisionally named SRV-6.
    Matched MeSH terms: Tumor Virus Infections/veterinary*; Tumor Virus Infections/virology
  12. Capozza P, Lorusso E, Colella V, Thibault JC, Tan DY, Tronel JP, et al.
    Vet Microbiol, 2021 Mar;254:109008.
    PMID: 33582484 DOI: 10.1016/j.vetmic.2021.109008
    Feline leukaemia virus (FeLV) is a retrovirus associated with fatal disease in cats with infection in its progressive form. Although there are numerous reports on the occurrence of FeLV in the feline population worldwide, there is a paucity of data in Asia. In this study, we assessed the circulation of FeLV by ELISA and nested PCR in cats from different countries in Southeast Asia (i.e., Thailand, Malaysia, Singapore, Philippines, Indonesia and Vietnam) and Taiwan during 2017-2018. Forty-seven cats were positive to FeLV by antigen or provirus detection, but 32 samples were considered truly positive on the basis of positive molecular testing. Frequency of occurrence of FeLV proviral DNA ranged from 0% (0/43 positive samples) in Indonesia to 18.5% (22/119 positive samples) in Thailand. A statistically significant association (p < 0.05) was found between country of cats origin, age, lifestyle, abnormal oral mucosa, and FeLV molecular positive results. In-depth studies are needed in other countries in Southeast Asia to elucidate the mosaic of knowledge about FeLV epidemiology.
    Matched MeSH terms: Tumor Virus Infections/epidemiology; Tumor Virus Infections/veterinary*
  13. Cheah PL
    Malays J Pathol, 1994 Jun;16(1):15-7.
    PMID: 16329570
    The surge of information on the aetiological association of the human papillomavirus (HPV) with some epithelial tumours emanating from various centres has prompted the initiation of a large-scale retrospective study at the Department of Pathology, University Hospital Kuala Lumpur to determine the prevalence and importance of this virus in some epithelial tumours of Malaysian patients. A retrospective analysis of 100 cases of large cell non-keratinising carcinoma of the uterine cervix by in-situ hybridisation on archival formalin-fixed, paraffin-embedded tissue has revealed the presence of HPV type 16 in 47% and type 18 in 41% of cases. This gives an overall detection rate of 88% of the two HPV types most commonly encountered in cervical carcinomas. Except for the unusually high frequency of HPV 18 detected in the cases, the overall prevalence is comparable to that reported in studies from most other centres. Although this higher frequency of HPV 18 may be due to geographical variation, the selection of the large cell non-keratinising type of squamous cell cervical carcinoma for study remains a possible reason for this phenomenon. In comparison to cervical carcinomas, HPV appears to be uncommon in penile carcinomas and HPV 6 was detected in only 1 of 23 cases studied.
    Matched MeSH terms: Tumor Virus Infections/complications*; Tumor Virus Infections/epidemiology; Tumor Virus Infections/pathology
  14. Saini R, Tang TH, Zain RB, Cheong SC, Musa KI, Saini D, et al.
    J Cancer Res Clin Oncol, 2011 Feb;137(2):311-20.
    PMID: 20419384 DOI: 10.1007/s00432-010-0886-8
    PURPOSE: The purpose of this study was to evaluate the role of HPV and p53 polymorphisms in oral squamous cell carcinomas (OSCC) affecting Malaysian population.

    METHODS: We analysed frozen samples from 105 OSCC as well as 105 oral specimens derived from healthy individuals. PCR assays targeting two regions of the virus were used. PCR amplification for the analysis of p53 codon 72 arginine/proline alleles was carried out in a separate reaction.

    RESULTS: HPV DNA was detected in 51.4% OSCC samples, while 24.8% controls were found to be HPV positive. HPV was found to be significantly associated with OSCC (P 

    Matched MeSH terms: Tumor Virus Infections/complications*; Tumor Virus Infections/ethnology; Tumor Virus Infections/virology
  15. Ross IN, Madhavan HN, Tan SH, Abdul Rahim K
    Med J Malaysia, 1985 Dec;40(4):301-6.
    PMID: 3025569
    Serological markers were used to determine the infective agents causing acute viral hepatitis in 246 patients. The frequencies of the five viral infections investigated were: non-A, non-B hepatitis - 99 patients (40.2%); hepatitis A - 98 patients (39.8%); hepatitis B - 43 patients (17.5%); cytomegalovirus - 4 patients (1.6%); and Epstein-Barr virus - 2 patients (0.8%). The log mean ages of presentation for the three predominant infections were: hepatitis A - 18 years; hepatitis B - 25 years; and non-A, non-B hepatitis - 30 years (F = 18.8, p =< 0.001). 52% of all cases were Malays (expected 32. 7%); 32% Chinese (expected 54.6%); and 16% Indians (expected 1l.5%) (X2 = 53, p = < 0.001). Hepatitis A virus infection was more common amongst Malays whilst non-A, non-B hepatitis was more frequent amongst Chinese and Indians. 28% of children <16 years) and 50% of adults had serological markers of previous hepatitis B infection. The variation in frequency for the different forms of hepatitis amongst the three main ethnic groups would suggest that socioeconomic and/or cultural factors are important in the propagation of acute viral hepatitis in Malaysia. HBsAg-negative chronic liver disease in our community may be a product of the high incidence of non-A, non-B hepatitis.
    Matched MeSH terms: Tumor Virus Infections/epidemiology
  16. Imai S, Okumoto M, Iwai M, Haga S, Mori N, Miyashita N, et al.
    J Virol, 1994 May;68(5):3437-42.
    PMID: 8151805
    Several groups of wild mice (Mus musculus) were captured from eight different locations in Asia and bred for several generations in a facility free of any laboratory strains of mice carrying mouse mammary tumor virus (MMTV). The distribution of endogenous MMTV proviral sequences in the liver tissues of these mice was investigated by using Southern blot hybridizations. Four categories of mice were identified. Mice originating from Bogor, Indonesia (Cas-Bgr); He-mei, Taiwan (Cas-Hmi/1); and Malaysia (Cas-Mal) were found to carry an endogenous MMTV provirus consisting of the env, gag-pol, and long terminal repeat sequences. Mice captured from Kojuri, Republic of Korea (Sub-Kjr); Nagoya, Japan (Mol-nag); and three Chinese provinces, Shanghai (Sub-Shh), Beijing (Sub-Bjn), and Jiayuguang (Sub-Jyg/1), appeared to carry defective proviruses. Some mice originating from He-mei (Cas-Hmi/2) and Jiayuguang (Sub-Jyg/2) were found to be completely free of endogenous MMTV. Interestingly, however, the Sub-Jyg/2 mice, after several generations of inbreeding, were found, unlike all of the other subspecies that we examined in the present study, to develop mammary tumors at a high incidence (80 to 90%) with a short period of latency. Electron microscopic examination of the mammary glands and mammary tumors of these mice revealed the presence of numerous intracytoplasmic A, immature, budding, and mature B particles. Furthermore, the mammary tumors were found to contain MMTV proviral sequences. It seems, therefore, that Sub-Jyg/2 mice carry an exogenous MMTV which contributes to their developing mammary tumors.
    Matched MeSH terms: Tumor Virus Infections/epidemiology; Tumor Virus Infections/veterinary*
  17. 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: Tumor Virus Infections/metabolism; Tumor Virus Infections/pathology*
  18. Se Thoe SY, Wong KK, Pathmanathan R, Sam CK, Cheng HM, Prasad U
    Gynecol Oncol, 1993 Aug;50(2):168-72.
    PMID: 8397152
    Epstein-Barr virus (EBV) receptors (EBV/C3d receptors) were detected, using the monoclonal antibody HB5, on 23 ectocervical and 5 endocervical biopsies of the uterine cervix. Elevated IgA titers against the viral capsid antigen and early antigen of EBV were also found in the cervical secretions from cervical carcinoma patients (83%), compared with samples from patients with cervical intraepithelial neoplasia (75%), herpes simplex virus-infected patients (0%), and gynecologic patients with nonmalignant conditions (0%). EBV DNA was present in 63% of cervical carcinoma biopsies detected by in situ hybridization. These observations suggest a positive association between EBV and carcinoma of the cervix.
    Matched MeSH terms: Tumor Virus Infections/complications; Tumor Virus Infections/immunology
  19. Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N
    N Engl J Med, 1995 Sep 14;333(11):693-8.
    PMID: 7637746 DOI: 10.1056/NEJM199509143331103
    BACKGROUND: The Epstein-Barr virus (EBV) is consistently detected in patients with nasopharyngeal carcinoma. To determine whether EBV infection is an early, initiating event in the development of this malignant tumor, we screened nasopharyngeal-biopsy samples, most of which were archival, for preinvasive lesions, including dysplasia and carcinoma in situ. Preinvasive lesions were found in 11 samples, which were tested for the presence of EBV.
    METHODS: EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistochemical staining for latent membrane protein 1 (LMP-1). The larger samples were also tested for the EBV genome with the use of Southern blotting. The expression of specific EBV RNAs was determined by the amplification of complementary DNA with the polymerase chain reaction.
    RESULTS: Evidence of EBV infection was detected in all 11 tissue samples with dysplasia or carcinoma in situ. EBERs were identified in all eight samples tested, and LMP-1 was detected in all six of the tested samples. Six of the seven samples tested for the EBV termini contained clonal EBV DNA: Transcription of the latent EBV gene products, EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples. Viral proteins characteristic of lytic lesions were not detected.
    CONCLUSIONS: Preinvasive lesions of the nasopharynx are infected with EBV. The EBV DNA is clonal, indicating that the lesions represent a focal cellular growth that arose from a single EBV-infected cell and that EBV infection is an early, possibly initiating event in the development of nasopharyngeal carcinoma. Preinvasive lesions contain EBV RNAs that are characteristic of latent infection but not the viral proteins that are characteristic of lytic infection. The detection of the EBV-transforming gene, LMP-1, in all the neoplastic cells suggests that its expression is essential for preinvasive epithelial proliferations associated with nasopharyngeal carcinoma.
    Matched MeSH terms: Tumor Virus Infections/complications; Tumor Virus Infections/diagnosis*
  20. Kim LH, Peh SC, Poppema S
    Int J Cancer, 2003 Nov 1;107(2):250-5.
    PMID: 12949802
    Isolation of single cells permits analysis of DNA or RNA from individual cells among heterogeneous populations. This technique is particularly useful in the study of classical Hodgkin's lymphoma (cHL) due to the scarcity of H/RS tumor cells among large numbers of reactive leukocytes. In a previous study, we found a high frequency of dual LMP-1 variant (concurrent presence of deleted and nondeleted variants) in cHL from whole-tissue sections. For the present study, we applied a single-cell isolation technique to determine the LMP-1 oncogene variant in EBV-associated H/RS cells. Five cases of EBV-infected cHL, containing nondeleted (n=1), deleted (n=1) and dual infection (n=3) based on whole-tissue section analysis, were selected for study. Paraffin-embedded tissue sections were stained with antibody to LMP-1 and positively stained H/RS cells isolated using a semiautomated micromanipulator. Each isolated single cell was subjected to PCR for amplification of the LMP-1 gene flanking the 30 bp deletion region and Xho1 restriction site. Cases with either nondeleted variant or the deleted variant showed similar LMP-1 variant expression in isolated single H/RS cells. However, 1 of the 3 cases with dual variants showed only the deleted variant in H/RS cells. The other 2 cases showed mixed patterns of deleted, nondeleted and dual LMP-1 variants in isolated single H/RS cells. All cases showed loss of the Xho1 restriction site, with the exception of the case with nondeleted LMP-1. Results of single-H/RS cell analysis of the Xho1 restriction site concur with those of whole-tissue section amplification. A mixed pattern of LMP-1 variants was observed in isolated H/RS cells, and it is speculated that this is due to the accumulation of mutation and deletion events.
    Matched MeSH terms: Tumor Virus Infections/virology
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