Role of tumor angiogenesis in gallbladder carcinoma: with special reference to thymidine phosphorylase

Harino, Yukari; Imura, Satoru; Kanemura, Hirofumi; Morine, Yuji; Fujii, Masahiko; Ikegami, Toru; Uehara, Hisanori; Shimada, Mitsuo

doi:10.1007/s10147-008-0778-y

Cited by 14 publications

(7 citation statements)

References 20 publications

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“…High TP expression levels are associated with an increased microvessel density in various human tumors [4,5]. It is also reported that TP expression correlates well with tumor malignancy, infiltration, and metastasis and overall poor survival [6,7].…”

Section: Introductionmentioning

confidence: 96%

Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice

Nishijima

Zhao

et al. 2015

Ann Nucl Med

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Objective Thymidine phosphorylase (TP) is a key enzyme in the pyrimidine nucleoside salvage pathway and its expression is upregulated in a wide variety of solid tumors. In mice, we previously observed high and specific accumulation levels of our TP imaging probe, radioiodinated 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU) not only in high-TP-expressing tumors, but also in the liver and small intestine. To clarify the reason for the high accumulation levels of radioiodinated IIMU in the liver and small intestine, we investigated the expression levels of TP in mice in comparison with the biodistribution of radioiodinated IIMU ( 123 I-IIMU).Methods BALB/cCrSlc mice were injected with 123 I-IIMU, and the radioactivity levels [%ID/g (normalized to a mouse of 25 g body weight)] in the tissues of interest were determined 0.5, 1, 3 and 24 h after the injection (n=5, each time point). To determine the expression levels of TP, BALB/cCrSlc and ddy mice (n=3/each strain)were euthanized, and the heart, liver, lung, spleen, kidney, stomach, small intestine, large intestine and brain were collected. The mRNA and protein expression levels of TP in these organs were examined by quantitative reverse transcription-polymerase chain reaction and western blot analyses, respectively. Immunoblotting showed intense immunoreactive bands of the TP protein for the liver and small intestine, whereas no notable bands were detected for other tissues. Similar expression profiles of TP mRNA and protein were observed in ddy mice. ConclusionWe confirmed TP expression in various tissues of mice at the mRNA and protein levels: high TP expression levels were observed in the liver and small intestine. These high TP expression levels are consistent with the high accumulation levels of 123 I-IIMU in these tissues. Our results may provide important information about the physiological accumulation of 123 I-IIMU, which may be useful for the clinical diagnostic imaging of TP.

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Section: Introductionmentioning

confidence: 96%

Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice

Nishijima

Zhao

et al. 2015

Ann Nucl Med

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“…20–22 Most studies, however, include small numbers of patients, and few, if any, include a comprehensive assessment in the same cohort. This study examines expression of key elements of these pathways in GBCA patients treated at centers on three continents.…”

mentioning

confidence: 99%

Regional Differences in Gallbladder Cancer Pathogenesis: Insights from a Comparison of Cell Cycle-Regulatory, PI3K, and Pro-Angiogenic Protein Expression

et al. 2012

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Background The variable incidence of gallbladder cancer (GBCA) suggests regional pathogenetic differences. This study compares cell cycle-regulatory, angiogenesis-related, and PI3K pathway protein expression in GBCAs from three continents. Methods Immunohistochemical expression of several proteins was assessed, correlated with clinicopathologic variables, and compared among centers from Chile (Fundación Arturo López Pérez [FALP]), Japan (Yokohama City University [YCU]), and the United States (Memorial Sloan-Kettering Cancer Center [MSKCC]). Hierarchical clustering was used to partition the data based on protein-expression and treatment center. Results Tissue from 117 patients (MSKCC = 76; FALP = 22; YCU = 19) was analyzed. Mdm2 overexpression was seen only at MSKCC (p < 0.0001). Absence of p21 (p = 0.03) and VEGFR2 (p = 0.018) were more common and p27 expression was less frequent (p = 0.047) in tumors from YCU. Ki-67 labeling index in YCU tumors (median = 10) was two-thirds lower than at other centers. On hierarchical clustering analysis, all YCU patients (p = 0.017) and those with early tumors (p = 0.017) clustered separately from MSKCC. Median disease-specific survival after curative intent (R0) resection was 27 months and was similar among centers (p = 0.9). Median disease-specific survival of patients with early tumors was 28.4 months and was higher at YCU (not reached, p = 0.06). Conclusions Cell cycle-regulatory protein expression patterns of YCU tumors differed from those treated at FALP and MSKCC. The differential clustering of protein expression and survival in patients with early tumors suggest regional differences in pathogenesis and disease biology.

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“…VEGF expression in eCCA was associated with peritoneal recurrence and shorter survival [24]. Moreover, VEGF was significantly associated with angiogenesis but not with patients survival [25] and prognosis [26] in GBC.…”

Section: Btc-associated Angiogenesis and Lymphangiogenesis: From Pmentioning

confidence: 99%

Targeting Angiogenesis in Biliary Tract Cancers: An Open Option

Simone

Brunetti

Lupo

et al. 2017

IJMS

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Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and evidenced that aberrations in several genes enrolled in the pro-angiogenic signaling, such as FGF receptor-2 (FGFR-2), are characteristic of BTCs. New drugs targeting the signaling pathways involved in angiogenesis have been tested in preclinical studies both in vitro and in vivo with promising results. Moreover, several clinical studies tested monoclonal antibodies against VEGF and tyrosine kinase inhibitors targeting the VEGF and the MEK/ERK pathways. Herein, we evaluate both the pathogenic mechanisms of BTCs focused on angiogenesis and the preclinical and clinical data available regarding the use of new anti-angiogenic drugs in these malignancies.

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Role of tumor angiogenesis in gallbladder carcinoma: with special reference to thymidine phosphorylase

Abstract: Expression of the TP gene in gallbladder carcinoma is associated with angiogenesis and may be a new independent prognostic parameter.

Cited by 14 publications

References 20 publications

Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice

Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice

Regional Differences in Gallbladder Cancer Pathogenesis: Insights from a Comparison of Cell Cycle-Regulatory, PI3K, and Pro-Angiogenic Protein Expression

Targeting Angiogenesis in Biliary Tract Cancers: An Open Option

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