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  1. Cheah PL, Kunaseegaran R, Looi LM
    Malays J Pathol, 2001 Jun;23(1):27-30.
    PMID: 16329544
    Ki-67 expression in diffuse proliferative lupus nephritis, WHO Class IV, was compared against normal controls to establish that cellular proliferation is involved in the production of glomerular hypercellularity. Twenty-three histologically confirmed WHO Class IV lupus nephritis and 23 normal control renal tissue were immunohistochemically stained with a polyclonal antibody to Ki-67 (Dako) using the peroxidase labelled streptavidin bioitin kit (Dako). There were 20 females and 3 males, with 17 Chinese and 6 Malays in the WHO Class IV lupus nephritis group. Ages of patients ranged between 10-56 years with a mean of 31.9 years. The normal controls, 20 males and 3 females, and ethnically 9 Indians, 7 Malays, 2 Chinese, and 5 foreign nationals (4 Indonesians and 1 Bangladeshi), had an age range between 15-33 years (mean = 23.3 years). Sixteen (69.6%) WHO Class IV lupus nephritis and 8 (34.8%) normal controls demonstrated Ki-67 immunoreactivity in at least 1 glomerulus (p<0.05). Of the 256 WHO Class IV lupus nephritis non-sclerosed, glomeruli studied, 37 (14.5%) were Ki-67 immunopositive compared with normal controls where 16 (0.7%) of 2159 glomeruli demonstrated Ki-67 (p< 0.01). Cellular proliferative activity, as evidenced by Ki-67 expression, was significantly increased in WHO Class IV lupus nephritis confirming that cell proliferation contributes to glomerular hypercellularity.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  2. Yip Ch, Bhoo-Pathy N, Daniel J, Foo Y, Mohamed A, Abdullah M, et al.
    Asian Pac J Cancer Prev, 2016;17(3):1077-82.
    PMID: 27039727
    BACKGROUND: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer.

    MATERIALS AND METHODS: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22.

    RESULTS: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy.

    CONCLUSIONS: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.

    Matched MeSH terms: Ki-67 Antigen/metabolism*
  3. Wang PL, Peh SC
    Malays J Pathol, 1997 Jun;19(1):59-64.
    PMID: 10879243
    The International Working Formulation divides non-Hodgkin's lymphoma (NHL) into three grades: low, intermediate and high. This grading system implies rate of tumour growth and hence prognosis. Ki-67 antigen is a proliferation-related nuclear antigen and bcl-2 oncogene product is known to inhibit apoptosis. This study aimed to determine the pattern of expression of Ki-67 antigen and bcl-2 oncoprotein in various grades of NHL. Paraffin-embedded tissues from 42 cases of NHL (7 low, 15 intermediate, 20 high grade) were retrieved from the files of the Department of Pathology, University of Malaya. Ki-67 antigen and bcl-2 oncoprotein were detected using immunohistochemistry. The percentage of positively stained neoplastic cells was determined by semi-quantitative estimation and given scores ranging from 0 to 6. Partition chi square test demonstrated the association of Ki-67 antigen expression and histological grade (p = 0.007). There was no significant difference in Ki-67 antigen expression between intermediate and high grade malignant lymphomas (p = 0.28), whereas significant difference was demonstrated between low and intermediate/high grade tumours (p = 0.003). Bcl-2 oncoprotein expression in the neoplastic cells varied widely within the three histological grades. Statistical analysis showed no association between the expression of bcl-2 oncoprotein and histological grade (p = 0.25). Ki-67 immunostaining is therefore a useful adjunct to histological grading of NHL.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  4. Azizan N, Hayati F, Tizen NMS, Farouk WI, Masir N
    Investig Clin Urol, 2018 07;59(4):232-237.
    PMID: 29984337 DOI: 10.4111/icu.2018.59.4.232
    Purpose: To evaluate the expression of estrogen receptor (ER)-beta and Ki67 in prostate cancer and study their relationship.

    Materials and Methods: We analyzed 101 cases of prostate adenocarcinoma diagnosed from January 2011 to June 2015 in 100 patients. Immunohistochemical staining of ER-beta and Ki67 was analyzed according to Gleason score categorized into prognostic groups of 1 to 5. Double-immunofluorescent staining of ER-beta and Ki67 was performed in a total of 20 cases to study the co-expression and the relationship between these markers within the same tumor.

    Results: A total of 53 of 101 cases (52.5%) were positive for ER-beta expression. There was a positive correlation whereby a high percentage of ER-beta expression was seen in the higher prognostic groups (groups 4 and 5; p=0.007). High Ki67 expression was observed in the higher prognostic group, whereas low Ki67 or negative expression was found in the lower prognostic group (p<0.001). The majority of cases evaluated with double-immunofluorescent staining (14/20) showed co-expression of ER-beta and Ki67 at the individual cell level.

    Conclusions: ER-beta and Ki67 are independent tumor markers in high prognostic groups. Hence, co-expression of ER-beta and Ki67 indicates a more aggressive tumor with a poorer prognosis.

    Matched MeSH terms: Ki-67 Antigen/metabolism*
  5. Yehya AHS, Subramaniam AV, Asif M, Kaur G, Abdul Majid AMS, Oon CE
    World J Gastroenterol, 2022 Aug 28;28(32):4620-4634.
    PMID: 36157930 DOI: 10.3748/wjg.v28.i32.4620
    BACKGROUND: Pancreatic cancer is the most aggressive cancer type. Gemcitabine is the first line chemo-drug used for pancreatic cancer but exerts a broad spectrum of organ toxicities and adverse effects in patients.

    AIM: To evaluate the anti-tumour activity and toxicological effects of Orthosiphon stamineus extract formulation (ID: C5EOSEW5050ESA trademarked as Nuva-staticTM), and gemcitabine combination on pancreatic xenograft model.

    METHODS: Mice were randomly divided into six groups of 6 mice each (n = 6) and given different treatments for 28 d. The study design consisted of a 2 x 3 factorial treatment structure, with gemcitabine (yes/no) by oral (at 1200 and 400 mg/kg per day). Human pancreatic cancer cells were injected subcutaneously into the flanks of athymic nude mice. C5EOSEW5050ESA (200 or 400 mg/kg per day) was administered orally, while gemcitabine (10 mg/kg per 3 d) was given intraperitoneally either alone or in combination treatment. Histopathological analyses of vital organs, tumour tissues, and incidence of lethality were analysed. Analyses of tumour necrosis and proliferation were determined by haematoxylin-eosin staining and immunohistochemistry for Ki-67, respectively.

    RESULTS: No signs of toxicity or damage to vital organs were observed in all treatment groups compared to the untreated group. C5EOSEW5050ESA at 200 mg/kg and gemcitabine combination had no additive antitumor effects compared to a single treatment. Remarkably, a comparably greater response in a reduction in tumour growth, Ki-67 protein expression, and necrosis was demonstrated by 400 mg/kg of C5EOSEW5050ESA and gemcitabine combination than that of the individual agents.

    CONCLUSION: These results highlighted the synergistic activity of C5EOSEW5050ESA with gemcitabine to reduce pancreatic tumour growth in mice compared to a single treatment. Thus, this study provides valuable insights into using C5EOSEW5050ESA as a complementary treatment with gemcitabine for pancreatic cancer.

    Matched MeSH terms: Ki-67 Antigen/metabolism
  6. Wong Y, Abdul-Rahman F, Samsudin AT, Masir N
    Malays J Pathol, 2014 Aug;36(2):125-9.
    PMID: 25194535 MyJurnal
    Follicular lymphoma is characterised by the t(14;18)(q32;q21) chromosomal translocation causing BCL2 protein overexpression. A proportion of follicular lymphomas do not carry the t(14;18) translocation and lacked BCL2 protein expression. We describe a case of a BCL2 protein- and t(14;18)-negative follicular lymphoma that caused diagnostic difficulty. The usefulness of several immunomarkers including Ki67, CD79a and CD21 in aiding the diagnosis is discussed. The patient is a 51-year-old male who presented with gradually enlarging lymphadenopathy. Histopathological examination of the lymph node showed complete architectural effacement by neoplastic follicles containing expanded CD21-positive follicular dendritic cell meshwork. The neoplastic cells expressed pan-B cell markers (CD20, CD79a) and germinal centre marker (BCL6) but not BCL2 and CD10. Of interest are the staining patterns of Ki67 and CD79a. We observed that the Ki67- positive proliferating cells were evenly distributed within the neoplastic follicles without zonation. In addition, CD79a was homogeneously strong within the neoplastic follicles. These staining patterns were distinctly different from that observed in reactive lymphoid follicles. Fluorescent insitu hybridisation (FISH) analysis however showed absence of BCL2 gene rearrangement. Despite the atypical immunophenotype and lack of BCL2 gene rearrangement, the diagnosis of follicular lymphoma was made based on careful observation of the morphology as well as immunoarchitecture of the Ki67, CD79a and CD21 markers.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  7. Mdpaiman N, Md Ali SA, Mdzin R, Meor Kamal MZ, Md Amin WA, Nallusamy M, et al.
    PLoS One, 2014;9(2):e89172.
    PMID: 24586570 DOI: 10.1371/journal.pone.0089172
    Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in 63 (63.6%) of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  8. Yahaya B, Baker A, Tennant P, Smith SH, Shaw DJ, McLachlan G, et al.
    Exp. Lung Res., 2011 Nov;37(9):519-35.
    PMID: 21895444 DOI: 10.3109/01902148.2011.605513
    Understanding the fundamental processes involved in repairing the airway wall following injury is fundamental to understanding the way in which these processes are perturbed during disease pathology. Indeed complex diseases such as asthma and chronic obstructive pulmonary disease (COPD) have at their core evidence of airway wall remodeling processes that play a crucial functional role in these diseases. The authors sought to understand the dynamic cellular events that occur during bronchial airway epithelial repair in sheep. The injury was induced by endobronchial brush biopsy (BBr), a process that causes epithelial débridement and induces a consequential repair process. In addition, the current experimental protocol allowed for the time-dependent changes in airway wall morphology to be studied both within and between animals. The initial débridement was followed by evidence of dedifferentiation in the intact epithelium at the wound margins, followed by proliferation of cells both within the epithelium and in the deeper wall structures, notably in association with the submucosal glands and smooth muscle bundles. Seven days after injury, although the airway wall was thickened at the site of damage, the epithelial layer was intact, with evidence of redifferentiation. These studies, in demonstrating broad agreement with previous studies in small animals, indicate the wider relevance of this system as a comparative model and should provide a solid basis upon which to further characterize the critical cellular and molecular interactions that underlie both effective restitution and pathological repair.
    Matched MeSH terms: Ki-67 Antigen/metabolism
  9. Alomari YM, Sheikh Abdullah SN, MdZin RR, Omar K
    Comput Math Methods Med, 2015;2015:673658.
    PMID: 25793010 DOI: 10.1155/2015/673658
    Analysis of whole-slide tissue for digital pathology images has been clinically approved to provide a second opinion to pathologists. Localization of focus points from Ki-67-stained histopathology whole-slide tissue microscopic images is considered the first step in the process of proliferation rate estimation. Pathologists use eye pooling or eagle-view techniques to localize the highly stained cell-concentrated regions from the whole slide under microscope, which is called focus-point regions. This procedure leads to a high variety of interpersonal observations and time consuming, tedious work and causes inaccurate findings. The localization of focus-point regions can be addressed as a clustering problem. This paper aims to automate the localization of focus-point regions from whole-slide images using the random patch probabilistic density method. Unlike other clustering methods, random patch probabilistic density method can adaptively localize focus-point regions without predetermining the number of clusters. The proposed method was compared with the k-means and fuzzy c-means clustering methods. Our proposed method achieves a good performance, when the results were evaluated by three expert pathologists. The proposed method achieves an average false-positive rate of 0.84% for the focus-point region localization error. Moreover, regarding RPPD used to localize tissue from whole-slide images, 228 whole-slide images have been tested; 97.3% localization accuracy was achieved.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  10. Mohd Ali NA, Nasaruddin AF, Mohamed SS, Wan Rahman WF
    Asian Pac J Cancer Prev, 2020 Sep 01;21(9):2653-2659.
    PMID: 32986365 DOI: 10.31557/APJCP.2020.21.9.2653
    OBJECTIVE: Phyllodes tumour (PT) is a rare fibroepithelial neoplasm of the breast that carries a risk of malignancy. Histopathological examination remains a gold standard for diagnosis. The usage of the immunohistochemical markers of Ki67 and p53 acts as a supplement method, particularly for the malignant PT. We aim here to study the expression of these markers in PT and to see their relation to the tumour grading.

    METHODOLOGY: We conducted a retrospective cross-sectional study on 57 archived formalin-fixed paraffin-embedded tissue blocks of PT from the years 2015 to 2018 from two hospitals in East Coast Malaysia. The histopathological examination and immunohistochemical stain for Ki67 and p53 were analysed.

    RESULTS: There was an association between clinical descriptive data of skin changes, lump size of more than 3 cm, cytological atypia, stromal hypercellularity, mitosis and immunohistochemistry with the clinical diagnosis of PT. Both marked expression of Ki67 and p53 were seen in borderline and malignant PT. Our study showed that in the presence of high mitotic figures, marked expression of Ki67 was only seen in cases of malignant PT.

    CONCLUSION: We found a significant association of Ki67 and p53 expressions, high mitosis and other descriptive histopathological features in malignant PT. Further study with larger sample size is recommended to predict tumour grade and prognosis as well as the disease-free survival of the tumour. 
    .

    Matched MeSH terms: Ki-67 Antigen/metabolism*
  11. Hew CS, Khoo BY, Gam LH
    PLoS One, 2013;8(7):e68524.
    PMID: 23874655 DOI: 10.1371/journal.pone.0068524
    Gynura procumbens (Lour.) Merr. belongs to the Asteraceae Family. The plant is a well-known traditional herb in South East Asia and it is widely used to treat inflammation, kidney discomfort, high cholesterol level, diabetic, cancer and high blood pressure. Our earlier study showed the presence of valuable plant defense proteins, such as peroxidase, thaumatin-like proteins and miraculin in the leaf of G. procumbens. However, the effects of these defense proteins on cancers have never been determined previously. In the present study, we investigated the bioactivity of gel filtration fractionated proteins of G. procumbens leaf extract. The active protein fraction, SN-F11/12, was found to inhibit the growth of a breast cancer cell line, MDA-MB-231, at an EC50 value of 3.8 µg/mL. The mRNA expressions of proliferation markers, Ki67 and PCNA, were reduced significantly in the MDA-MB-23 cells treated with SN-F11/12. The expression of invasion marker, CCL2, was also found reduced in the treated MDA-MB-231 cells. All these findings highlight the anti-cancer property of SN-F11/12, therefore, the proteins in this fraction can be a potential chemotherapeutic agent for breast cancer treatment.
    Matched MeSH terms: Ki-67 Antigen/metabolism
  12. 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: Ki-67 Antigen/metabolism*
  13. Loo SK, Ch'ng ES, Lawrie CH, Muruzabal MA, Gaafar A, Pomposo MP, et al.
    Pathology, 2017 Dec;49(7):731-739.
    PMID: 29074044 DOI: 10.1016/j.pathol.2017.08.009
    DNMT1 is a target of approved anti-cancer drugs including decitabine. However, the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was expressed in the majority of DLBCL cases (n = 209/230, 90.9%) with higher expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001). Nonetheless, of the 209 DNMT1 positive patients, 33% and 42% did not achieve 5-year OS and PFS, respectively, indicating that DNMT1 positive patients showed considerably heterogeneous outcomes. Moreover, DNMT1 was frequently expressed in mitotic cells and significantly correlated with Ki-67 or BCL6 expression (r = 0.60 or 0.44, respectively; p < 0.001). We demonstrate that DNMT1 is predictive of DLBCL patients' survival, and suggest that DNMT1 could be a DLBCL therapeutic target due to its significant association with Ki-67.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  14. Wong CY, Cheong SK, Mok PL, Leong CF
    Pathology, 2008 Jan;40(1):52-7.
    PMID: 18038316
    AIMS: Adult human bone marrow contains a population of mesenchymal stem cells (MSC) that contributes to the regeneration of tissues such as bone, cartilage, muscle, tendon, and fat. In recent years, it has been shown that functional stem cells exist in the adult bone marrow, and they can contribute to renal remodelling or reconstitution of injured renal glomeruli, especially mesangial cells. The purpose of this study is to examine the ability of MSC isolated from human bone marrow to differentiate into mesangial cells in glomerular injured athymic mice.

    METHODS: MSC were isolated from human bone marrow mononuclear cells based on plastic adherent properties and expanded in vitro in the culture medium. Human mesenchymal stem cells (hMSC) were characterised using microscopy, immunophenotyping, and their ability to differentiate into adipocytes, chondrocytes, and osteocytes. hMSC were then injected into athymic mice, which had induced glomerulonephropathy (GN).

    RESULTS: Test mice (induced GN and infused hMSC) were shown to have anti-human CD105(+) cells present in the kidneys and were also positive to anti-human desmin, a marker for mesangial cells. Furthermore, immunofluorescence assays also demonstrated that anti-human desmin(+) cells in the glomeruli of these test mice were in the proliferation stage, being positive to anti-human Ki-67.

    CONCLUSIONS: These findings indicate that hMSC found in renal glomeruli differentiated into mesangial cells in vivo after glomerular injury occurred.

    Matched MeSH terms: Ki-67 Antigen/metabolism
  15. Masir N, Jones M, Lee AM, Goff LK, Clear AJ, Lister A, et al.
    Histopathology, 2010 Apr;56(5):617-26.
    PMID: 20459572 DOI: 10.1111/j.1365-2559.2010.03524.x
    To investigate the relationship between Bcl-2 protein expression and cell proliferation at single-cell level in B-cell lymphomas using double-labelling techniques.
    Matched MeSH terms: Ki-67 Antigen/metabolism
  16. Seow HF, Yip WK, Loh HW, Ithnin H, Por P, Rohaizak M
    Pathol Oncol Res, 2010 Jun;16(2):239-48.
    PMID: 19882362 DOI: 10.1007/s12253-009-9216-3
    Activation of Akt signaling pathway has been documented in various human malignancies, including breast carcinoma. The objective of this study is to determine the incidence of Akt phosphorylation in breast tumours and its relationship with expression of ER-alpha, ER-beta, HER2, Ki-67 and phosphorylated Bcl-2 associated death domain (p-BAD). Immunohistochemical staining was performed to detect these molecules on 43 paraffin-embedded breast tumour tissues with commercially available antibodies. Eighteen (41.9%), 3 (7.0%), 23 (53.5%), 35 (81.4%), 21 (48.8%), 29 (67.4%), and 34 (81.0%) of breast tumours were positive for nuclear ER-alpha, nuclear ER-beta, membranous HER2, cytonuclear p-Akt (Thr308), p-Akt (Ser473), p-BAD and Ki-67, respectively. ER-alpha expression was inversely correlated with HER2 and Ki-67 (P = 0.041 and P = 0.040, respectively). The p-Akt (Ser473) was correlated with increased level of p-BAD (Ser136) (P = 0.012). No relationship of Akt phosphorylation with HER2, ER-alpha or ER-beta was found. The p-Akt (Ser473) immunoreactivity was significantly higher in stage IV than in stage I or II (P = 0.036 or P = 0.009). The higher Ki-67 and lower ER-alpha expression showed an association with patient age of <50 years (P = 0.004) and with positive nodal status (P = 0.033), respectively. Our data suggest that the Akt phosphorylation and inactivation of its downstream target, BAD may play a role in survival of breast cancer cell. This study does not support the simple model of linear HER2/PI3K/Akt pathway in breast cancer.
    Matched MeSH terms: Ki-67 Antigen/metabolism
  17. Kim LH, Peh SC, Poppema S
    Hum Pathol, 2006 Jan;37(1):92-100.
    PMID: 16360421
    Deregulation of several genes involved in cell cycle control has been reported in classic Hodgkin lymphoma (cHL). This study aimed to investigate the expression of tumor suppressor proteins (P16(INK4A), retinoblastoma protein, and p53) in cHL in relation to the proliferation and apoptosis of Hodgkin/Reed-Sternberg (H/RS) cells, correlating with the status of Epstein-Barr virus (EBV). A total of 66 cHL cases and 10 nonneoplastic reactive lymphoid tissues were retrieved from the archives. Immunohistochemistry technique was used for the detection of protein expression. Presence of EBV infection was detected by EBV early RNA in situ hybridization. p16(INK4A) gene deletion status was assessed by fluorescence in situ hybridization technique. Expression of P16(INK4A) was observed in 49.2% of the cases, whereas positive retinoblastoma protein and p53 expressions in the H/RS cells were detected in 89.1% and 81.5% of the cases, respectively. Epstein-Barr virus positivity was detected in 53.0% of the cases. Proliferation marker, Ki-67 expression, was observed in 86.7% of the cases. There was no significant correlation between the expression of the various tumor suppressor proteins and Ki-67. Retinoblastoma protein and p53 were also not associated with the presence of EBV. An inverse relationship was observed between the expression of P16(INK4A) and the presence of EBV. There were no significant homozygous or hemizygous deletions of the p16(INK4A) gene. However, an aberrant copy number of chromosome 9 with the loss of one or more p16(INK4A) loci was detected in all cases assessable by fluorescence in situ hybridization. Loss of function of one or more tumor suppressor proteins may be involved in defective cell regulation of H/RS cells. Epstein-Barr virus may have a role in inhibiting P16(INK4A) expression, thus resulting in a perturbed p16(INK4A)-Rb cell cycle checkpoint.
    Matched MeSH terms: Ki-67 Antigen/metabolism
  18. Koriem KM, Fathi GE, Salem HA, Akram NH, Gamil SA
    Toxicol. Mech. Methods, 2013 May;23(4):263-72.
    PMID: 23193971 DOI: 10.3109/15376516.2012.748857
    Cadmium has been classified as an environmental pollutant and human carcinogen. Pectin is a family of complex polysaccharides that function as hydrating agents and cementing materials for the cellulosic network. The aim of this study was to evaluate the protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats. Forty male Wistar rats were divided into five equal groups. Groups 1 and 2 were injected intraperitoneally (i.p.) saline (1 mg/kg) and pectin (50 mg/kg), respectively, two days/weeks over three weeks period. Groups 3-5 were injected i.p. with 1 mg/kg cadmium two days/week while groups 4 and 5 co-administrated i.p. with 25 and 50 mg/kg pectin, respectively, three days/week over three weeks period. The results of the present work revealed that cadmium-exposed rats showed decrease in serum testosterone, dehydroepiandrosterone sulfate and lactate dehydrogenase. Testicular cholesterol, total protein, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase and reduced glutathione levels were also decreased while testicular malondialdehyde level was increased after cadmium injection. On the other hand, serum luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and γ-glutamyl transpeptidase were increased after cadmium exposure. Cadmium also induced sperms loss. Co-administration of pectin with cadmium restores all the above parameters and sperms to the normal levels where pectin at higher dose was more effective than lower one. These results were supported by histochemical investigations. In conclusion, pectin can counteract the testicular toxicity and oxidative stress induced by cadmium and the effect was dose-dependent.
    Matched MeSH terms: Ki-67 Antigen/metabolism
  19. Alitheen NB, McClure SJ, Yeap SK, Kristeen-Teo YW, Tan SW, McCullagh P
    PLoS One, 2012;7(11):e49188.
    PMID: 23185307 DOI: 10.1371/journal.pone.0049188
    The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a(+), a majority of those emigrating onto the supporting membrane were Bu-1a(-) and IgM(+). Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240) was examined.
    Matched MeSH terms: Ki-67 Antigen/metabolism
  20. 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: Ki-67 Antigen/metabolism
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