Argyrophilic Nuclear Organizer Region Research Articles

Farnesol alleviates diethyl nitrosamine induced inflammation and protects experimental rat hepatocellular carcinoma.

Hepatocellular carcinoma is a well-known internal malignancy with increased worldwide mortality. The increased progression rate is closely associated with chronic liver diseases such as cirrhosis. Chemical carcinogens cause tumor advocacy over free radical metabolites to causes numerous biochemical and molecular changes that bring oxidative stress. In addition, inflammatory cells and its growth factor promotes the progression of liver cancer through deregulates the numerous cellular signaling pathways involved in normal cellular proliferation. Plant derived phytochemicals have a better complimentary potency to defend against a wide array of free radical mediated diseases such as cancer. More recently, we have evaluated the anticancer effect of Farnesol against DEN induced hepatocellular carcinoma in male wistar albino rats. However, the possible mechanism in which Farnesol attributes its anticancer effect against DEN induced liver cancer remains unknown. Hence in the present study, an attempt has been made to reduce the oxidative stress by appraise the antioxidant effect by Farnesol in DEN induced hepatocellular carcinoma. Elevated oxidative stress markers with concomitant decreased cellular antioxidants levels were observed in DEN induced hepatic tissues. Further, proliferating nuclei with increased proliferating cell nucleolar antigen (PCNA) and inflammatory mediator expression were observed in DEN induced rats. Oral supplementation of Farnesol to DEN induced rats significantly decrease the oxidative stress markers and increase the cellular antioxidant status. Moreover, Farnesol treatment decreases the argyrophilic nuclear organizer region and PCNA along with decreased expression of inflammatory mediators suggest that Farnesol treatment restores DEN induced hepatic abnormalities and protects liver from cancer progression.

Proliferative activity of various grades and types of breast carcinoma using AgNOR (Argyrophilic Nuclear Organizer Region) expression and its prognostic significance

A communal disease of the breast is breast cancer which happens mainly in women. Breast cancer is the most common cancer in women in both the developed and less developed world. The potential biological aggressiveness and behavior of breast neoplasm are of prognostic significance in tumor pathology and this can be assessed by measuring the tumor proliferative activity and malignant transformation. One of such markers is AgNOR (Argyrophilic Nuclear Organizer Region). A search of database sites such as PUBMED, Google Scholar, and Web of Science, as well as, other sources of literature available across public libraries was conducted to obtain information related to the topic. This review has presented a critical discussion on histologically assessing the proliferative activity of various grades and types of breast carcinoma using AgNOR expression and its prognostic significance. This exposé is anticipated to enlighten research scientists on specific management and assessing targets of tumors, which may merit prospective research into developing an appropriate mechanism for assessing the proliferative activity of breast cancer to help solve medical issues relating to cancers.

Genistein regulates tumor microenvironment and exhibits anticancer effect in dimethyl hydrazine-induced experimental colon carcinogenesis.

Colon cancer is one of the leading causes of cancer mortality, worldwide. Cancer stem cells are attractive targets for therapeutic interventions since their abnormal growth may trigger tumor initiation, progression, and recurrence. Colon cancer in rats were induced with 1, 2-dimethyl hydrazine (DMH) and treated with genistein, an isoflavone rich in the soy food products, which also possesses various biological activities. Genistein treatment regulates enzymatic and non-enzymatic anti-oxidants in the DMH-induced colonic tissue microenvironment. Alcian blue staining in colonic tissue reveals that mucin secretion was found to be depleted in DMH-induced group of animals. The alterations were normalized in the genistein-treated groups. Also, the mast cell population and collagen deposition were reduced as compared to induced group. Genistein treatment reduces the prognostic marker Argyrophilic nuclear organizer region (AgNOR) and proliferating cell nucleolar antigen (PCNA) in DMH-induced group of rats. DMH administration induces oxidative stress, whereas genistein activates nuclear factor-erythroid 2 related factor 2 (Nrf-2) and its downstream target hemoxygenase-1 (HO-1). Colonic stem cell marker protein CD133, CD44, and β-catenin expressions were found to be increased in DMH-induced group of animals as compared to control group of rats. Genistein treatment suppressed the expression of these stem cell markers suggesting rapid dysfunctional activation and proliferation of colonic stem cell-induced by DMH. The results of this study indicate that genistein administration in rats restored the colonic niche that was damaged by DMH and inhibits colon cancer progression. © 2016 BioFactors, 42(6):623-637, 2016.

Argyrophilic nuclear organizer region and p73 expression in head and neck squamous cell carcinomas: Teammates or adversaries?

Context:Head and neck squamous cell carcinoma (HNSCC) consists of squamous cell carcinomas (SCCs) arising in the upper aerodigestive tract and accounts for 5% of cancers worldwide. In Malaysia, cancers of the nasopharynx, larynx, tongue and oral cavity are among the top twenty most common cancers in men. Argyrophilic nuclear organizer regions (AgNORs) are increased from normal mucosa to premalignant lesions to malignant lesions and have been associated with tumor grade and prognosis of patients. Although p73 is not mutated in human cancers, high levels of p73 expression have been associated with tumor differentiation status and patient prognosis.Aims:To investigate the correlation between AgNORs and p73 immunoexpression.Settings and Design:Fifty-two formalin-fixed, paraffin-embedded HNSCC cases and ten controls were collected from the Hospital.Subjects and Methods:Tissue blocks were sectioned, dewaxed and rehydrated before silver nitrate staining to determine the AgNOR count and immunohistochemical staining to determine the p73 expression. Adopting the scoring system used by Chen et al. for p73 staining, the proportion of positively stained cells in the whole epithelial layer was determined. Staining was considered positive if >10% of epithelial cells were stained.Statistical Analysis Used:Spearman's correlation coefficient was calculated using SPSS 18 software to determine the relationship between the p73 score against tumor differentiation, mean AgNOR counts and tumor grade and between the mean AgNOR count and p73 score.Results:Positive results were found in the immunoexpression of p73. Positive results were seen with the staining of AgNOR; however, in comparison with the entire sample size, a significant correlation between mean AgNOR count and p73 immunohistochemical expression was not obtained.Conclusions:AgNOR count showed a linear and decreasing trend as the p73 score increases. This correlation was statistically insignificant.

Role of cyclin D1 immunoreactivity and AgNOR staining in the evaluation of benign and malignant lesions of the prostate.

Purpose:Prostatic carcinoma is a common and growing public health problem. Histological evaluation is fairly adequate for assessing tumor differentiation, but tumor proliferative activity is difficult to measure. Increasing evidence suggests that the factors controlling cell cycle progression also modulate the rate of ribosome biogenesis. Despite the influence of cyclin D1 and argyrophilic nuclear organizer region (AgNOR) on prostate cancer proliferation, few studies have evaluated the diagnostic importance of these markers. Therefore, the present study was carried out to analyze the diagnostic value of the proliferative markers cyclin D1 and AgNOR in various prostatic lesions and to determine whether any association or relation between these markers and different Gleason grades exists.Methods:A total 50 cases of various prostatic lesions were studied. Tumor grade, AgNOR staining, and cyclin D1 expression were evaluated in all cases. Correlations between the intensity and differential localization of these markers and Gleason grades were evaluated.Results:The mean AgNOR count in cases of prostatic intraepithelial neoplasia was high compared with cases of benign prostatic hyperplasia (BPH) but lower than that of carcinoma cases. The intensity of cyclin D1 expression was high in carcinoma. A total of 14 cases (46.67%) showed strong positivity. No significant correlation was found between the intensity of cyclin D1 expression, AgNOR count, and histologic grades of prostatic carcinoma, whereas a significant correlation was observed between intensity and percentage expression of cyclin D1 in BPH and carcinoma (P<0.01). Nuclear as well as cytoplasmic positivity was seen among various grades of carcinoma.Conclusions:AgNOR count and cyclin D1 may be helpful in distinguishing between BPH and carcinoma of the prostate but may not be used as reliable indicators of the grade of prostatic adenocarcinoma because of overlapping values in various grades. However, further studies on larger samples are required to elucidate the role of these markers in identification of premalignant lesions.

Correlation Between Single Photon Emission Computed Tomography, AgNOR Count, and Histomorphologic Features in Patients With Active Mandibular Condylar Hyperplasia

To analyze the association between nuclear medicine examination (single photon emission computed tomography [SPECT]), histology, and Argyrophilic Nuclear Organizer Region (AgNOR) count in patients with active condylar hyperplasia who have undergone condylectomy. Eight patients with a diagnosis of active condylar hyperplasia and evidence of facial asymmetry, with progressive deformation in time and on SPECT studies, were evaluated. The relationship between the rate of technetium Tc 99 intake, cartilage layer thickness, and cellular activity measured by recounting nucleolar organizers with AgNOR was evaluated. The 4 pathologic layers of condylar hyperplasia (fibrous, mesenchymal, and hypertrophic chondrocyte layers and ossification layer) showed great variability and different thicknesses among the cases analyzed. As age increased, the histologic layer thickness decreased (r = -0.73, P = .04). The age of the patients was inversely related to the number of AgNOR dots (r = -0.65, P = .08). The thickness of both mesenchymal and hypertrophic chondrocyte layers was related to cartilage island depth (r = 0.81, P = .02). Younger patients with condylar hyperplasia had a thicker condylar layer and more cellular activity measured by AgNOR count. The histologic features of this group of patients could not be associated with their SPECT findings.

Tumour Progression: Mechanisms and Modulation, Abstract 295–303, Symposium

Prostatic carcinoma is a common and growing public health problem. Histological evaluation is fairly adequate for assessing tumor differentiation, but tumor proliferative activity is difficult to measure. Increasing evidence suggests that the factors controlling cell cycle progression also modulate the rate of ribosome biogenesis. Despite the influence of cyclin D1 and argyrophilic nuclear organizer region (AgNOR) on prostate cancer proliferation, few studies have evaluated the diagnostic importance of these markers. Therefore, the present study was carried out to analyze the diagnostic value of the proliferative markers cyclin D1 and AgNOR in various prostatic lesions and to determine whether any association or relation between these markers and different Gleason grades exists.A total 50 cases of various prostatic lesions were studied. Tumor grade, AgNOR staining, and cyclin D1 expression were evaluated in all cases. Correlations between the intensity and differential localization of these markers and Gleason grades were evaluated.The mean AgNOR count in cases of prostatic intraepithelial neoplasia was high compared with cases of benign prostatic hyperplasia (BPH) but lower than that of carcinoma cases. The intensity of cyclin D1 expression was high in carcinoma. A total of 14 cases (46.67%) showed strong positivity. No significant correlation was found between the intensity of cyclin D1 expression, AgNOR count, and histologic grades of prostatic carcinoma, whereas a significant correlation was observed between intensity and percentage expression of cyclin D1 in BPH and carcinoma (P<0.01). Nuclear as well as cytoplasmic positivity was seen among various grades of carcinoma.AgNOR count and cyclin D1 may be helpful in distinguishing between BPH and carcinoma of the prostate but may not be used as reliable indicators of the grade of prostatic adenocarcinoma because of overlapping values in various grades. However, further studies on larger samples are required to elucidate the role of these markers in identification of premalignant lesions.

Basaloid squamous carcinoma of the oral cavity: Report of 2 cases and study of AgNOR, PCNA, p53, and MMP expression

Basaloid squamous carcinoma (BSC) is an uncommon aggressive variant of squamous cell carcinoma (SCC) with a predilection for the head and neck. In the English literature, approximately 40 cases of BSC in the oral cavity have been described. In this study, the clinicopathologic features of 2 cases of BSC affecting the buccal mucosa are reported. In addition, we compare the proliferative and invasive potential of BSC cells with that of poorly differentiated SCC cells matched for age, sex, site, and TNM status. Proliferative activity was studied through use of the argyrophilic nuclear organizer region (AgNOR) method and immunohistochemical quantification of proliferating cell nuclear antigen (PCNA). The invasive potential was evaluated through use of the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for matrix metalloproteinases (MMPs). Alterations of p53 were also investigated through use of immunohistochemistry. The tumors showed many clinical and histopathologic similarities to tumors in cases previously reported. The AgNOR and PCNA indices were significantly higher in the 2 cases of BSC than in the cases of SCC. Immunostaining for p53 protein showed a higher percentage of positive cells and more intense staining in the BSC tissues than in the SCC tissues. RT-PCR studies clearly demonstrated that the expression of MMP-1, MMP-2, and MMP-9 was higher in cells from BSCs than in cells from SCCs. Taken together, the data described here are compatible with the concept that BSC has a more aggressive biologic behavior than conventional SCC. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:563-9)

Long-term survival of patients with stage IV gastric carcinoma.

Survival of patients with Stage IV (based on general rules established by the Japanese Research Society for Gastric Cancer) gastric carcinoma often is unfavorable. Among patients with a poor prognosis, a few do survive > 5 years. The authors examined pathologic and biologic features of tumors of long term survivors. The authors analyzed data from 442 patients with Stage IV gastric carcinoma, including 20 surviving for > 5 years after gastrectomy (Group A) and 422 who died of gastric carcinoma within 5 years (Group B). Mutant p53 was immunohistochemically stained using the monoclonal antibody PAb1801. Proliferative activity was estimated by argyrophilic nuclear organizer region (AgNOR) staining and proliferating cell nuclear antigen (PCNA) staining. Group A had smaller and more localized tumors than Group B (P < 0.05 and P < 0.01, respectively). Lymphatic or venous invasion and peritoneal dissemination were less frequent in Group A than in Group B (P < 0.01). Abnormalities of p53 expression were found in 3 of the 14 tumors in Group A (21%), a value significantly lower than the 58 of 118 tumors in Group B (49%; P < 0.05). AgNOR count and percentage of PCNA labeling were not significantly different between Groups A and B. A multivariate analysis showed that lymph node dissection, liver metastasis, gastric resection, venous invasion, and tumor size were independent prognostic factors. Even in patients with Stage IV gastric carcinoma, radical gastrectomy and extensive lymph node dissection can lead to long term survival. The authors believe that combination analysis of pathologic features and p53 overexpression predict length of survival for patients with Stage IV gastric carcinoma.

Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin.

The modulating effects of dietary feeding of two flavonoids, diosmin and hesperidin, both alone and in combination, during the initiation and post-initiation phases on colon carcinogenesis initiated with azoxymethane (AOM), were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks to induced colon neoplasms. Rats were fed the diets containing diosmin (1000 ppm), hesperidin (1000 ppm) or diosmin (900 ppm) + hesperidin (100 ppm) for 5 weeks (initiation treatment) or 28 weeks (post-initiation treatment). The others contained the groups of rats treated with diosmin, hesperidin alone or in combination, and untreated. At the end of the study (32 weeks), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM together with, or followed by, a diet containing diosmin or hesperidin were significantly smaller than those of rats given AOM alone (P <0.001). The combination regimen during the initiation and post-initiation stages also inhibited the development of colonic neoplasms, but the tumor data did not indicate any beneficial effect of diosmin and hesperidin administered together as compared with when these agents were given individually. In addition, feeding of diosmin and hesperidin, both alone and in combination, significantly inhibited the development of aberrant crypt foci. As for cell proliferation biomarkers, dietary exposure of diosmin and hesperidin significantly decreased the 5'-bromodeoxyuridine-labeling index and argyrophilic nuclear organizer region's number in crypt cells, colonic mucosal ornithine decarboxylase activity, and polyamine levels in the blood. These results indicate that diosmin and hesperidin, both alone and in combination, act as a chemopreventive agent against colon carcinogenesis, and such effects may be partly due to suppression of cell proliferation in the colonic crypts, although precise mechanisms should be clarified.

Assessment of Argyrophilic Nucleolar Organizer Region Quantification in Benign and Malignant Bone Tumors

Quantification of argyrophilic nucleolar organizer regions has been proposed as a technique that may aid in diagnosing and predicting the biologic behavior of a variety of neoplasms. A 1-step silver staining technique was used to identify and quantify argyrophilic nuclear organizer regions in a series of 96 bone tumor specimens. Malignant bone tumors had a higher mean argyrophilic nuclear organizer region count (3.05 +/- 0.82) than giant cell tumors (1.39 +/- 0.14, p < 0.001) and benign bone tumors (1.51 +/- 0.42, p < 0.001). Despite these differences in mean counts, an overlap of argyrophilic nuclear organizer region scores was observed in some benign and malignant cases. The argyrophilic nuclear organizer region counts of the osteosarcomas were analyzed to determine whether they correlated with tumor behavior. The mean argyrophilic nuclear organizer region count of specimens from patients in whom metastatic disease developed was not significantly different than that of patients who remained disease free.

Argyrophilic Nuclear Organizer Region Counts and Ki-67 Scores in Human Renal Cell Carcinoma

The proliferative activity of 21 cases of renal cell carcinoma has been investigated by means of monoclonal antibody Ki-67 and Nucleolar Organizer Regions (AgNORs) analysis. The correlation between AgNOR counts and Ki-67 scores was only slightly significant (r = 0.53, r2 = 0.28) as determined by linear regression. Positive correlation was found between Ki-67 scores and tumour histologic grade. However, no correlation was observed between Ki-67 scores and tumour pathologic stage and between AgNOR counts and tumour histologic grade and/or pathologic stage. The results suggest that AgNOR counts cannot replace Ki-67 scores in evaluating the proliferative activity of renal cell carcinoma and that such activity and both histologic grade and pathologic stage seem to be independent parametres.