Journal of Pathology and Translational Medicine

Original Articles

Progressive Increase of Regulatory T Cells and Decrease of CD8+ T Cells and CD8+ T Cells/Regulatory T Cells Ratio during Colorectal Cancer Development: Tae Jung Jang; Korean J Pathol. 2013;47(5):443-451. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.443

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Background

We examined the distribution of CD8+ T cells and regulatory T cells (Tregs), measured the CD8+ T cell/Tregs ratio, investigated the relationship between Tregs and cyclooxygenase-2 (COX-2) expression during colorectal cancer (CRC) development.

Methods

We performed immunohistochemical staining for CD8, forkhead box P3, E-cadherin, and COX-2 in 32 cases of invasive CRC, 10 cases of intramucosal CRC, 27 cases of high-grade tubular adenoma, 22 cases of low-grade tubular adenoma, and 32 cases of non-neoplastic conditions.

Results

We observed a progressive increase in Tregs, and a decrease in CD8+ T cells and the CD8+ T cells/Tregs ratio during CRC development. The alterations were most severe in high-grade tubular adenoma and CRC. COX-2 expression was positively associated with Tregs infiltration. The degree of T cell infiltration differed among tumor compartment and the ratio in the tumor center was the lowest of all areas. The ratio and number of CD8+ T cells in the tumor center and the invasive front of invasive CRC were associated with gender, differentiation, node metastasis and tumor budding.

Conclusions

Alteration in the distribution of both CD8+T cells and Tregs may contribute to the generation of an immune environment suitable for the development and progression of CRC.

Citations

Citations to this article as recorded by

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The Expression of Cyclooxygenase-2 and Survivin in Urinary Bladder Transitional Cell Carcinoma.: Tae Jung Jang, Kyung Seob Lee; Korean J Pathol. 2009;43(3):206-211.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.206

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Abstract PDF

BACKGROUND
The aim of this study was to investigate the expressions of cyclooxygenase-2 (COX-2) and survivin in bladder transitional cell carcinoma (TCC) that has different clinicopathologic characteristics, and we also wanted to determine if a relation exists between the COX-2 and survivin expressions.
METHODS
The expressions of COX-2 and survivin were investigated in 80 bladder TCCs by performing immunohistochemistry.
RESULTS
The normal bladder mucosa did not express COX-2 and survivin. COX-2 immunopositivity and cytoplasmic survivin immunopositivity were seen in 48% and 30% of bladder tumors, respectively. The expressions of COX-2 and survivin were closely related to the differentiation, depth and recurrence of bladder TCC, and there was a significant correlation in topographic distribution of COX-2 and survivin immunopositivity. In addition, COX-2 and survivin were predominantly expressed at the invasive front of tumors.
CONCLUSIONS
This data suggest that COX-2 and survivin may be involved in the progression of bladder TCC, and there is a close correlation between the expressions of COX-2 and survivin.

Citations

Citations to this article as recorded by

Assessment of survivin and p27 expression as potential prognostic markers in urothelial cell carcinoma of urinary bladder in Egyptian patients
Noha Said Helal, Zeinab Omran, Mona Moussa
African Journal of Urology.2022;[Epub] CrossRef
Cyclooxygenase-2 Expression in Urinary Bladder Transitional Cell Carcinoma and its Association with Clinicopathological Characteristics
Hedieh Moradi Tabriz, Golrokh Olfati, Seyed Ali Ahmadi, Sudabeh Yusefnia
Asian Pacific Journal of Cancer Prevention.2013; 14(8): 4539. CrossRef
High survivin expression in premalignant and malignant kidney lesions
Tahany M. Shams, Samaka M. Rehab, Mokhtar Metawea
Egyptian Journal of Pathology.2012; 32(1): 21. CrossRef
Reciprocal correlation between the expression of cyclooxygenase-2 and E-cadherin in human bladder transitional cell carcinomas
Tae Jung Jang, Woo Heon Cha, Kyung Seob Lee
Virchows Archiv.2010; 457(3): 319. CrossRef

Correlation Between Cyclooxygenase-2 Expression and HuR Cytoplasmic Translocation of Breast Cancer.: Sung Im Do, In Gu Do, Gou Young Kim, Sun Lee, Youn Wha Kim, Yong Koo Park, Juhie Lee, Sung Jig Lim; Korean J Pathol. 2008;42(2):75-80.

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Abstract PDF: BACKGROUND
Embryonic lethal abnormal vision (ELAV)-like protein HuR is known to stabilize mRNA through binding AU-rich elements in the 3'-untranslated region. Recent studies show that HuR expression is associated with the expression of several genes including cyclooxygenase-2 (COX-2). HuR exists predominantly in the nucleus, but cytoplasmic translocation of HuR is thought to be more important for its activity. COX-2 is a well-known enzyme that promotes tumor growth.
METHODS
To evaluate the correlation of HuR and COX-2 expression, we analyzed expression of HuR and COX-2 in 91 cases of breast cancer using immunohistochemistry.
RESULTS
Nuclear and cytoplasmic expression of HuR was seen in 76 (83.5%) and 19 (20.9%) of 91 cases respectively. COX-2 immunoreactivity was seen in 54 (59.4%) cases. Cytoplasmic HuR expression showed significant correlation with COX-2 expression (p=0.001). Nuclear HuR showed no correlation with COX-2 expression or other clinicopathological parameters. COX-2 expression is significantly associated with tumor grade (p=0.028). COX-2 (p=0.092) and cytoplasmic (p=0.569) and nuclear HuR (p=0.247) expression showed no correlation with survival.
CONCLUSIONS
These results suggest that cytoplasmic HuR expression is associated with COX-2 expression in breast cancer and cytoplasmic location of HuR might contribute to the stabilization of COX-2 mRNA.

Expression of c-erbB-2 and Cyclooxygenase-2 in Pancreatic Ductal Adenocarcinoma.: Hye Jeong Choi, Hong Jin Kim, Sung Soo Yun, Joon Hyuck Choi; Korean J Pathol. 2007;41(3):171-175.

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Abstract PDF: Background
: Carcinoma of the pancreas is a fatal malignant disease with limited therapeutic options. Cyclooxygenase-2 (COX-2) and c-erbB-2 are known to be involved in the carcinogenesis, differentiation and invasiveness of various neoplasms. We studied the immunohistochemical expressions of c-erbB-2 and COX-2 and the correlation between these expressions and the clinicopathologic parameters and the relation between the expressions.
Methods
: Immunohistochemical staining for c-erbB-2 and COX-2 were performed on the paraffin embedded sections of 36 cases of surgically resected ductal adenocarcinoma of the pancreas and 10 cases of non-neoplastic pancreas tissue.
Results
: The non-neoplastic control group showed a c-erbB-2 expression in the acini (8/10) and ducts (2/10), and a COX-2 expression in the acini (6/10) and ducts (3/10). The overexpression of c-erbB-2 was observed in 58% (21/36) of the carcinoma specimens. No significant correlation was found between c-erbB-2 and age, gender, tumor size, gross type, histologic grade, vascular invasion, perineural invasion, lymph node metastasis, and the TNM stage. The overexpression of COX-2 was observed in 41.7% (15/36) of the carcinoma specimens. The COX-2 expression was significantly high in the lymph node metastasis group (p<0.05), but it was not correlated with the other clinicopathologic parameters. Also there was no significant correlation between the c-erbB-2 and COX-2 expressions.
Conclusions
: In pancreatic ductal adenocarcinomas, c-erbB-2 and COX-2 were frequently overexpressed, and COX-2 overexpression was correlated with lymph node metastasis.

Synergistic Apoptotic Effect of Combination Treatment with Troglitazone and COX-2 Inhibitor in Glioma Cells.: Kyung Ryoul Kim, Min Young Park, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Dong Geun Lee, Myoung Jae Kang; Korean J Pathol. 2007;41(1):1-6.

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Abstract PDF: BACKGROUND
The use of troglitazone (a PPARgamma ligand) and COX-2 inhibitor have been intensively studied for inhibition of tumor growth in cancer treatment, but the anti-tumor effect with a combination of these agents for cancer has not yet been studied. The aim of this study was to determine if low concentrations of troglitazone with COX-2 inhibitor in combination would cause significant cytotoxicity in glioma cells.
METHODS
The effects of co-treatment with troglitazone and COX-2 inhibitor on cell growth and apoptosis were assessed by use of trypan blue exclusion and a DNA fragmentation assay. A western blot was used to analyze the apoptotic signaling for the expression of bcl-2, bax, PARP and p21 proteins.
RESULTS
A low dose of troglitazone (5micrometer) and COX-2 inhibitor (5micrometer) strongly enhanced the cell growth inhibition and apoptosis in glioma cells when compared to a low dose of each drug alone. Western blotting analysis showed a decreased expression of bcl-2 and PARP proteins. In contrast, the bax protein level was increased.
CONCLUSIONS
The combination of troglitazone and COX-2 inhibitor in a low dose elicits synergistic cytotoxicity in glioma cells. Our study also demonstrates that down regulation of bcl-2, fragmentation of PARP protein and increased expression of bax protein were accompanied by co-treatment with troglitazone and the COX-2 inhibitor.

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