Thymidine phosphorylase expression in tumor stroma of uterine cervical carcinomas: histological features and microvessel density

Tang, Weihua; Wang, Xiaojuan; Utsunomiya, Hirotoshi; Nakamuta, Yasushi; Yang, Qifeng; Zhang, Qinhuei; Zhou, Gengyen; Tsubota, Yuji; Mabuchi, Yoshiya; Li, Li; Kakudo, Kennichi

doi:10.1016/s0304-3835(99)00326-2

Cited by 8 publications

(4 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is difficult to tell whether this discrepancy is due to our use of LCM to dissect out only cancer cells and avoid stroma cells, or to other methodological factors. However, other study's reports using immunohistochemical staining have also reported expression of TP mainly in stroma cells rather than in cancer cells in uterine cervical cancer, 25 in CRC 26 and prostate cancer. 27 Kojima et al reported that only stroma cell-TP expression was associated with microvessel counts in adenocarcinoma of the lung and concluded that TP induction in tumoral stroma, but not in tumor cells, may promote angiogenesis.…”

Section: Discussionmentioning

confidence: 91%

5‐fluorouracil‐related gene expression levels in primary colorectal cancer and corresponding liver metastasis

Kuramochi

Hayashi

Uchida

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

Gene expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) have been shown to be associated with response to 5-fluorouracil-based therapies. Analyzing these gene expression levels in liver metastases is important to obtain the best prediction of therapy. Our aim was to determine how TS, DPD, TP and OPRT gene expression levels in primary colorectal cancer (CRC) were related to those in liver metastases. Formalin-fixed, paraffin-embedded tumor specimens from 31 pairs of primary CRC and corresponding liver metastases were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse-transcription. Quantitation of target gene and internal reference gene was performed using real-time PCR. No significant difference was seen between median mRNA expression levels of TS, DPD, TP and OPRT in primary cancer and those in corresponding liver metastases (median value: TS 1.48 vs. When matched tissue sets were compared on an individual basis, there was a significant correlation for TS mRNA expression between primary cancer and corresponding liver metastases (rs 5 0.52, p 5 0.0026). However, no correlation was seen between matched sets for DPD, TP or OPRT. Significant correlation was seen between DPD and TP expression levels in both primary CRC (rs 5 0.38, p 5 0.03) and liver metastases (rs 5 0.72, p < 0.0001). A good prediction of TS mRNA levels in liver metastases can be obtained by measuring those of primary CRC, although no correlation was seen for DPD, TP and OPRT. ' 2006 Wiley-Liss, Inc.Key words: 5-fluorouracil; colorectal cancer; liver metastases; thymidylate synthase; dihydropyrimidine dehydrogenase Colorectal cancer (CRC) is the fourth most common malignancy and the second leading cause of cancer death in the United States. 1 The most commonly used chemotherapeutic drug for CRC is 5-fluorouracil (5-FU), which has been used for more than 40 years and still remains an important component of many standard treatments. 2 The main mechanism of 5-FU activity involves inhibition of thymidylate synthase (TS), which is the rate-limiting enzyme in the synthesis of thymine nucleotides.A number of genes have been investigated as predictive factors for response to 5-FU-related drugs and as prognostic markers. Leichman et al. 3 had previously shown that high gene expression levels (mRNA levels) of TS identified tumors that would be nonresponsive to 5-FU based therapy. Dihydropyrimidine dehydrogenase (DPD) is responsible for the degradation of the pyrimidines, uracil and thymine, as well as the inactivation of the 5-FU, and has been shown in several studies to be associated with response to 5-FU-based therapies. [4][5][6][7] Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has a role in tumor angiogenesis but also catalyzes the conversion of 5-FU to the more active nucleoside form and has been shown to be an in vitro determinant of 5-FU activity...

show abstract

Section: Discussionmentioning

confidence: 91%

5‐fluorouracil‐related gene expression levels in primary colorectal cancer and corresponding liver metastasis

Kuramochi

Hayashi

Uchida

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Moreover, TP, also known as a platelet‐derived endothelial cell growth factor, has been reported to be significant in the prognosis of several cancers as an angiogenic factor 4,5 . In uterine cervical cancer, the TP expression in cancer cells and/or stromal cells is detected by immunohistochemistry or ELISA, but the clinical significance of these two enzymes in uterine cervical cancer tissues still remains controversial 6–9 . In many previous studies, the TP expression in cancer cells and stromal cells has been separately detected and evaluated using immunohistochemistry or ELISA.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 In uterine cervical cancer, the TP expression in cancer cells and/or stromal cells is detected by immunohistochemistry or ELISA, but the clinical significance of these two enzymes in uterine cervical cancer tissues still remains controversial. [6][7][8][9] In many previous studies, the TP expression in cancer cells and stromal cells has been separately detected and evaluated using immunohistochemistry or ELISA. However, considering that UP/ TP are 5FU metabolic enzymes, it may be important to analyze the UP/TP activities in the whole cancer, including tumor cells and stromal cells.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

In this study, the preliminary analyses were conducted of enzymatic activities of uridine phosphorylase (UP) and thymidine phosphorylase (TP) in normal tissues and cancer tissues of the uterine cervix. The study was performed on 27 patients of cervical cancer, treated first in our hospital. Normal cervical tissues obtained from 15 patients undergoing hysterectomy for benign diseases were used as controls. The supernatant of the homogenated cervical tissues and the stroma (5-FU and ribose-1-P or deoxyribose-1-P) were analyzed by high performance liquid chromatography, and then the UP and TP activities calculated. TP activity was significantly greater than UP activity (P < 0.0001). Both UP and TP showed significantly greater activity in cancer tissues than in normal tissues (P < 0.0001). In the TP activity of the cancer tissues, there was no significant difference among the histological types, while the TP activity tended to be significantly higher in the cases with lymph node metastasis. These results showed that the TP-mediated route seemed important as the 5FU metabolic pathway in the uterine cervical tissues, and TP enzymatic activity might be associated with lymph node metastasis.

show abstract

“…Distinct patterns of TP expression have been previously observed in various human malignancies. Most studies have shown that TP had a higher expression in tumor cells than in adjacent normal, non‐tumoral cells (22–24) while in some cases, TP protein was found to be mainly expressed in stroma cells rather than in cancer cells themselves (25,26). However, lack of TP immunodetection, as shown here for BCC cells, has been exceptionally described in tumor cells (27,28).…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of thymidine phosphorylase/platelet‐derived endothelial cell growth factor in basal cell carcinomas

Stoebner

Gallic

Berthe

et al. 2008

Experimental Dermatology

View full text Add to dashboard Cite

Thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor is associated with tumor angiogenesis. We evaluated the TP mRNA and protein expression in basal cell carcinomas (BCC) and in various skin tumors including numerous BCC histological simulants. Immunohistochemistry was performed on 99 paraffin sections of formalin-fixed skin tumors using monoclonal antibodies (mAb) against TP. TP mRNA levels were measured by real time RT-PCR in whole BCCs (wBCC) and laser capture microdissected (LCM) BCC tumor cells. TP immunostaining was negative in all BCC variants and in most of the benign trichogeneic tumors studied. By contrast, TP was constantly immunodetected in actinic keratosis (AK), squamous cell carcinomas (SCC), syringomatous carcinomas (SC), basosquamous carcinomas (BSC) and melanomas. TP mRNA levels were low and statistically not different in wBCC and normal skin but were strongly downregulated in LCM-BCC as compared with LCM-normal epidermis. We concluded that (i) anti-TP mAb is an useful marker to differentiate BCC from AK, SCC, BSC and SC but not from trichoblastic tumors, (ii) the lack of TP protein expression in BCC tumoral cells is linked to transcriptional regulatory mechanisms, (iii) the low TP mRNA levels in whole BCC may be related to the low intra-tumoral microvessel density, the slow growth and the very low metastatic potential of these tumors.

show abstract

Thymidine phosphorylase expression in tumor stroma of uterine cervical carcinomas: histological features and microvessel density

Cited by 8 publications

References 20 publications

5‐fluorouracil‐related gene expression levels in primary colorectal cancer and corresponding liver metastasis

5‐fluorouracil‐related gene expression levels in primary colorectal cancer and corresponding liver metastasis

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

Decreased expression of thymidine phosphorylase/platelet‐derived endothelial cell growth factor in basal cell carcinomas

Contact Info

Product

Resources

About