Enzymatic activities of uridine and thymidine phosphorylase in normal and cancerous uterine cervical tissues

Kobayashi, Yoichi; Wada, Yasuna; Ohara, Tatsuru; Okuda, Yusuke; Suzuki, Nao; Hasegawa, Kiyoshi; Kiguchi, Kazushige; Ishizuka, Bunpei

doi:10.1111/j.1749-0774.2007.00036.x

Cited by 6 publications

(4 citation statements)

References 19 publications

(35 reference statements)

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“…92 TYPH activity is increased in invasive cervical SCC, with the highest level in lymph node metastases. 93 Based on these analyses, we demonstrated that the data of iTRAQ-based proteomics were not only supported by the qRT-PCR and IHC verification, and bioinformatic evaluation, but also highly consistent with earlier findings. However, due to the high HPV positivity of cervical lesions, namely, almost all specimens of SCC and most of the CIN II-III are positive for high-risk HPV genotypes, the analysis of gene expression for candidate proteins associated with HPV infection was very limited.…”

Section: Discussionsupporting

confidence: 87%

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Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

Song

Tulake

et al. 2017

Tumour Biol.

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It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix (p < 0.05). In addition, the transcription of PCBP2, MCM5, hnRNPA1, TYPH, and CYC was also significantly increased in cervical intraepithelial neoplasia II-III compared to normal cervix. Immunohistochemistry staining further confirmed the overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5 in squamous cell carcinoma and cervical intraepithelial neoplasia II-III compared to normal controls (p < 0.05). Our data suggest that the expression of ASAH1, PCBP2, DDX5, and hnRNPA1, and possibly MCM4, MCM5, CYC, ENO1, and TYPH, is upregulated during cervical carcinogenesis and potentially associated with human papillomavirus infection. Further validation studies of the profile will contribute to establishing auxiliary diagnostic markers for human papillomavirus-based cancer prognosis. KeywordsCervical carcinoma, isobaric tags for relative and absolute quantitation, proteomics, human papillomavirus infection, cervical specimen Date

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Section: Discussionsupporting

confidence: 87%

“…92 TYPH activity is increased in invasive cervical SCC, with the highest level in lymph node metastases. 93…”

Section: Discussionmentioning

confidence: 99%

Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

Song

Tulake

et al. 2017

Tumour Biol.

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“…The isoform HMG-I(Y) is upregulated by HPV type 16 (HPV-16) E6 in mouse cells (30). UPP1 is involved in uridine metabolism, and related enzyme activity is elevated in various tumor tissues (29,34).…”

Section: Resultsmentioning

confidence: 99%

Transcriptional Changes Induced by Bovine Papillomavirus Type 1 in Equine Fibroblasts

Yuan

Nicolson

Marchetti

et al. 2008

J Virol

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Bovine papillomavirus type 1 (BPV-1) and, less commonly, BPV-2 are associated with the pathogenesis of common equine skin tumors termed sarcoids. In an attempt to understand the mechanisms by which BPV-1 induces sarcoids, we used gene expression profiling as a screening tool to identify candidate genes implicated in disease pathogenesis. Gene expression profiles of equine fibroblasts transformed by BPV-1 experimentally or from explanted tumors were compared with those of control equine fibroblasts to identify genes associated with expression of BPV-1. Analysis of the microarray data identified 81 probe sets that were significantly (P < 0.01) differentially expressed between the BPV-1-transformed and control cell lines. Expression of several deregulated genes, including MMP-1, CXCL5, FRA-1, NKG7, TLR4, and the gene encoding the major histocompatibility complex class I (MHC-I) protein, was confirmed using other BPV-1-transformed cell lines. Furthermore, expression of these genes was examined using a panel of 10 sarcoids. Increased expression of MMP-1, CXCL5, FRA-1, and NKG7 was detected in a subset of tumors, and TLR4 and MHC I showed robust down-regulation in all tumors. Deregulated expression was confirmed at the protein level for MMP-1 and MHC-I. The present report identifies genes modulated by BPV-1 transformation and will help identify the molecular mechanisms involved in disease pathogenesis.

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“…Increased levels of dThdPase have been reported in many malignant tumors [5,9,12]. Although there have been a several reports that investigated the dThdPase activity in cervical, endometrial and ovarian carcinoma [19][20][21], it remains to be determined. In this study of gynecological malignant tumors, we found that uterine cervical, endometrial, and ovarian carcinoma also demonstrated higher dThdPase activity than adjacent normal tissue.…”

Section: Discussionmentioning

confidence: 99%

Use of Localization and Activity of Thymidine Phosphorylase in Human Gynecological Tumors for Predicting Sensitivity to Pyrimidine Antimetabolite Therapy: An Observational Study

Kotake¹,

Sasaki²,

Sasaki³

2011

J Cytol Histol

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Background: Thymidine phosphorylase (dThdPase) is the rate-limiting enzyme in the conversion of 5′-deoxy-5-fluorouridine (5′-dFUrd), an intermediate metabolite of capecitabine (Xeloda ®), to 5-fluorouracil (5-FU). We investigated the correlation between dThdPase activity and immunohistochemical staining in gynecological carcinoma and adjacent normal tissues. We hypothesize that the differential dThdPase activity between tumors and adjacent tissue is predictive of response to treatment with pyrimidine antimetabolites. Methods: In 45 samples of carcinoma tissue and 35 of adjacent normal tissue from 45 patients, we measured dThdPase activity as well as immunoreactivity using an anti-dThdPase monoclonal antibody and macrophage and histiocyte-specific antibodies. Results: dThdPase activity in tumor tissue was significantly higher than that in the corresponding adjacent normal tissue in all samples tested (12 uterine cervical, 19 endometrial, and 4 ovarian tumors). Anti-dThdPase immunopositivity was observed in the epithelial tumor cells of 76.9% of uterine cervical cancer samples, 60.0% of endometrial cancer samples and 63.6% of ovarian cancer samples. In stromal tissue, 84.6% of uterine cervical tumors (11/13), 90.0% of endometrial tumors (18/20), and 81.8% of ovarian tumors (9/11) were immunopositive for anti-dThdPase in interstitial cells (mainly macrophages). Macrophages were also strongly reactive in the stromal tissues of uterine cervical, endometrial, and ovarian cancers. The correlation between dThdPase activity and intensity of immunohistochemical staining of epithelial tumor cells with anti-dThdPase monoclonal antibody was statistically significant in endometrial carcinoma (P = 0.008) but borderline in uterine cervical tumors (P = 0.077). We found a good correlation between dThdPase activity and staining of epithelial tumor cells, particularly in the case of endometrial cancer. Conclusions: We show that gynecological carcinomas show increased dThdPase activity, and this activity correlates with dThdPase staining of tumor epithelial cells. Thus, dThdPase staining of biopsy specimens could be useful in predicting the outcome of therapy with pyrimidine metabolites.

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Enzymatic activities of uridine and thymidine phosphorylase in normal and cancerous uterine cervical tissues

Cited by 6 publications

References 19 publications

Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

Transcriptional Changes Induced by Bovine Papillomavirus Type 1 in Equine Fibroblasts

Use of Localization and Activity of Thymidine Phosphorylase in Human Gynecological Tumors for Predicting Sensitivity to Pyrimidine Antimetabolite Therapy: An Observational Study

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