Thymidine phosphorylase expression in oral squamous cell carcinoma

Yao, Li; Itoh, Shigeto; Furuta, Isao

doi:10.1016/s1368-8375(01)00113-0

Cited by 11 publications

(5 citation statements)

References 19 publications

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“…TP overexpression was frequently reported in tumor cells in several types of cancers, including OSCC, and is signi cantly related to classic poor prognostic indicators such as increased microvessel density, higher tumor stage, lymph node metastasis, vascular invasion, and poor prognosis (35)(36)(37)(38). However, the clinicopathologic signi cance of tumoral TP expression did not show statistical signi cance in previous retrospective cohort studies for various types of tumors (24,39,40). In the present study, no signi cant association was found between tumoral TP expression and the prognosis of the patients.…”

Section: Discussioncontrasting

confidence: 94%

Implications of TP-positive CAFs as a possible inducer of bone invasion in the pathogenesis of oral squamous cell carcinoma

Gao,

Kim,

Pei

et al. 2024

Preprint

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Objectives Recently, cancer-associated fibroblasts (CAFs) have been suggested as key cellular components of bone invasion in oral squamous cell carcinoma (OSCC). However, the underlying molecular mechanisms, as well as the subtypes related to their bone invasive function, are largely unknown. In this study, we aimed to investigate the implications of thymidine phosphorylase (TP)-positive CAFs (TP+CAFs) in OSCC bone invasion.Materials and Methods TP expression was determined in 116 patients with OSCC using immunohistochemistry. The influence of TP expression on the biological behavior of CAFs was investigated in vitro. The possible impact of TP+CAFs on bone invasion in OSCC was further evaluated using patient-derived xenograft (PDX) mouse models.Results In bone-invasive OSCC tissues, we found that TP+CAFs were mainly distributed on the surface of resorbed bone tissue rather than on the tumor side. High TP+CAFs were significantly associated with higher T-stage (p = 0.002) and bone invasion (p < 0.001), as well as worsened overall survival (p = 0.013) and recurrence-free survival (p = 0.029), in our study cohort. Multivariate analysis using variable clinicopathologic factors—with tumoral TP and TP+CAFs as cofactors—revealed that high TP+CAFs (hazard ratio: 3.140; p = 0.005) had independent impacts on worsened recurrence-free survival. Recombinant human TP promoted the proliferative and invasive abilities of CAFs and increased matrix metalloproteinase-9 mRNA expression in vitro, which is related to bone resorption. In the PDX mouse models, TP+CAFs were found in early bone resorption on the surface of resorbed bony tissues. Moreover, bone resorption occurred more frequently in the PDX models with TP+CAFs than in those without.Conclusion TP+CAFs were significantly associated with bone invasion and the prognosis of OSCC. This study provides information about cellular and molecular targets for the early diagnosis and treatment of bone-invasive OSCC.

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Section: Discussioncontrasting

confidence: 94%

Implications of TP-positive CAFs as a possible inducer of bone invasion in the pathogenesis of oral squamous cell carcinoma

Gao,

Kim,

Pei

et al. 2024

Preprint

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“…Additional results were provided by the present study, such as the positive correlation observed between Ki67 and TP expression in the palm area. This result corroborates correlations between TP expression and cell proliferation markers reported by other investigators in various other tissues [28, 29]. Also, intrasubject analysis revealed a positive correlation for Ki67 expression between palm and back areas.…”

Section: Discussionsupporting

confidence: 92%

Candidate mechanisms for capecitabine‐related hand–foot syndrome

Milano

Étienne-Grimaldi

Mari

et al. 2008

Brit J Clinical Pharma

104

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Hand-foot syndrome (HFS) is a limiting toxicity of the widely used fluorouracil (5FU) prodrug capecitabine.• The pharmacological origin of HFS has not been elucidated.• The expression of capecitabine-metabolizing enzymes thymidine phosphorylase (TP, activating pathway) and dihydropyrimidine dehydrogenase (DPD, catabolic pathway) in the skin of the palm (target tissue for HFS) is unknown. WHAT THIS STUDY ADDS• This pilot study, conducted in healthy volunteers, clearly demonstrated that TP expression is significantly greater in the palm compared with the lower back (control area).• This suggests TP-facilitated enhanced production of 5FU in the palm that could explain the occurrence of HFS.• This result may support strategies to prevent HFS. AIMSThe oral fluoropyrimidine prodrug capecitabine is widely used in oncology. Capecitabine was designed to generate 5FU via the thymidine phosphorylase (TP) enzyme, preferentially expressed in tumoral tissues. Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine. A pilot study on healthy volunteers was conducted in order to test the hypothesis that the occurrence of HFS could be related to tissue-specific expression of drug-metabolizing enzymes in the skin of the palm and sole. To this end, the expression of TP (activating pathway), dihydropyrimidine dehydrogenase (DPD, catabolic pathway) and cell proliferation (Ki67) were measured in the skin of the palm (target tissue for HFS) and of the lower back (control area). METHODSTwo paired 4-mm diameter punch biopsy specimens (palm and back) were taken in 12 healthy volunteers. Immunohistochemical analyses were performed on frozen tissues. RESULTSProliferation rate (Ki67 staining) was significantly higher in epidermal basal cells of the palm compared with the back (P = 0.008). Also, TP and DPD expression were significantly greater in the palm relative to the back (P = 0.039 and 0.012, respectively). TP and Ki67 expression were positively and significantly correlated in the palm. CONCLUSIONSThe high proliferation rate of epidermal basal cells in the palm could make them more sensitive to the local action of cytotoxic drugs. TP-facilitated local production of 5FU in the palm during capecitabine treatment could explain the occurrence of HFS. This observation may support future strategies to limit the occurrence of HFS during capecitabine therapy.

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“…There are very few studies in oral cancers. Our study results were concordance with the studies done by Yao YL et al, 18 and confirmed that relation of MMP9 expression. Therefore, it can be assumed that extensive presence of MMP9 cause breakdown of the basement membrane of the tissue which causes invasion and metastasis of OSSC, which resulted in high metastatic rate and poor prognosis Also There are many other methods (ELISA, PCR) for MMP9 expression which are more specific 19,20 .…”

Section: Fig 2: Shows Maximum Number Of Cases 50% Had Lesion About Hsupporting

confidence: 93%

Untitled

2019

IJPSR

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Introduction: Oral carcinoma is amongst the leading malignancies worldwide, with squamous cell carcinoma (SCC) as the most common type accounting for over 90% of cases. In OSCC, MMPs, (MMP9) which belongs to gelatinase group, promote tumor progression by new blood vessel formation, disturbing tissue morphology which allows tumor growth breaks the basement membrane and enables metastasis and it's overexpression in OSCC have prognostic value. Aims and Objectives: To evaluate the expression of MMP 9 in different grades of OSCC. Material and Methods: In this prospective study, a total number of 30 blocks specimens; 10 of each well, moderately, poorly differentiated were stained with MMP9 antibodies and compared with normal oral mucosa. All the data were documented and analyzed with SPSS 20 version software. Results: Normal 10 tissues with a mean age of 31.30 years and 30 OSCC patients of 51.93 years mean age were studied. In OSCC, 18 male (60%) and 12 female (40%) were participated. Among them, 8% smoking, 15% chewing and 7% both habits were revealed. With the X 2 test, it was revealed that MMP9 in different grades of OSCC was found statistically significant. (P<0.05) in accordance with increasing order of dysplasia. Conclusion: Evaluation of MMP9 expression could be a prognostic marker in OSCC and can be used for cancer biotherapeutics. Which may improve the treatment protocol and prognosis of the patient.

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Thymidine phosphorylase expression in oral squamous cell carcinoma

Cited by 11 publications

References 19 publications

Implications of TP-positive CAFs as a possible inducer of bone invasion in the pathogenesis of oral squamous cell carcinoma

Implications of TP-positive CAFs as a possible inducer of bone invasion in the pathogenesis of oral squamous cell carcinoma

Candidate mechanisms for capecitabine‐related hand–foot syndrome

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