Interleukin-1 (IL-1) is a key inflammatory cytokine that has important effects both on endothelial cell (EC) growth and synthetic function. Fibroblast growth factors (FGF's), including endothelial cell growth factor (ECGF), are important regulators of EC growth, and their role in the pannus formation and synovial proliferation seen in chronic arthritis has been emphasized recently. While ECGF mediated EC proliferation is inhibited by IL-1, potential interaction of these peptides on other aspects of EC function has not been described. As both IL-1 and FGF may be important disease mediators in rheumatoid arthritis, we studied their combined effects on EC prostacyclin production. While ECGF alone had no measurable effects, it enhanced rIL-1 alpha induced prostacyclin production in a dose and time dependent fashion. Both pertussis and cholera toxins blocked the augmentation, suggesting a role for G proteins in mediating the synergism. These studies demonstrate that ECGF can alter certain effects of IL-1 on the endothelium, and point to an additional role that this family of growth factors may play in some inflammatory disorders.

The body's weight loss mechanism while in a tumor-bearing state is still unclear. In this study, we investigated expressions of angiogenic factors in the adipose tissue of tumor-bearing and diet-restricted rabbits evaluating the differences between the two groups. We postulated that low nutrition induced vasculogenesis to transport nutrition in the adipose tissues of diet-restricted rabbits, unlike in tumor-bearing rabbits, and that vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) were related to angiogenesis of the adipose tissues. Although we investigated the expressions of VEGF and PD-ECGF immunohistochemically in tumor-bearing and diet-restricted rabbits, there was no significant difference between the two groups. Whether angiogenesis of the adipose tissue in the diet-restricted animals may be observed during the nutritional recovery period should be investigated.

OBJECTIVE

To investigate the mRNA expression of platelet-derived endothelial cell growth factor (PD-ECGF) in superficial bladder cancer and its significance.

METHODS

PD-ECGF mRNA expressions were determined by RT-PCR in 28 cases of superficial bladder cancers and 6 cases of normal bladder mucosa. The relation between PD-ECGF mRNA expression and tumor invasion to lamina propria or recurrence after transurethral resection was also analyzed.

RESULTS

Some degree of PD-ECGF mRNA expression was present in all the samples. The PD-ECGF mRNA level was 3.1-fold higher in pT(1) tumors than in normal bladder mucosa (t = 2.13, P < 0.05) and 2.2-fold higher in pT(1) tumors than in pT(a) tumors (t = 2.66, P < 0.05); G(3) tumors expressed 3.3-fold higher PD-ECGF mRNA than normal bladder mucosa (t = 2.44, P < 0.05) and 2.5-fold higher than G(1 - 2) tumors (t = 3.36, P < 0.01). Eleven cases recurred during the mean follow-up period of 18 months. Three-fold higher PD-ECGF mRNA expression was showed in cases who recurred after transurethral resection than that in cases who did not recur (t = 4.49, P < 0.01). The specificity and sensitivity of predicting tumor recurrence were 82.4% and 81.8% respectively using 0.095 as a cutoff value of PD-ECGF mRNA level in this group of superficial bladder cancer.

CONCLUSIONS

PD-ECGF mRNA expression correlates with tumor dedifferentiation and plays an important role in the early invasion in superficial bladder cancer. To analyze the PD-ECGF mRNA level contributes to the evaluations of tumor differentiation and invasion to lamina propria as well as recurrence prediction in superficial bladder cancer.

A panel of 40 monoclonal antibodies was constructed in response to cationic endothelial cell growth factor (c-ECGF), the cationic peptide mitogen isolated from endothelial mitogen. The monoclonal antibodies were assayed by dot blot for immunoreactivity to various other peptide angiogenic factors. The panel of monoclonal antibodies to c-ECGF exhibited complete cross-reactivity with pituitary fibroblast growth factor and sarcoma-derived growth factor. A group of 28 monoclonal antibodies was found to exhibit reactivity to anionic endothelial mitogen (a-ECGF), brain fibroblast growth factor, endothelial cell growth factor, and retina-derived growth factor. None of the monoclonal antibodies was found to react with epidermal growth factor or platelet-derived growth factor. These data provide an immunological basis for grouping heparin-binding endothelial cell growth factors into anionic and cationic groups.

Objective: To explore the histopathology, monocytes phenotypes and brain mRNA transcription of angiogenic and atherogenic factors preliminarily in spontaneous hypertensive rats (SHRs) fed with high salt diet and subjected to chronic focal hypoperfusion. Methods: A total of 21 SHRs were randomly assigned into SHR with normal diet (SHR-ND group, n=7), SHR fed with high salt (8%) chows (SHR-HSD group, n=14) groups. After induction of high salt diet for 20 weeks, unilateral carotid artery occlusion was applied to one half of SHR-HSD (SHR-HSD-UCAO, n=7) group for 10 weeks to mimic chronic focal cerebral hypoperfusion. The neuropathology, monocytes phenotypes and brain transcription of fibroblast growth factor (FGF-b), platelet-derived endothelial cell growth factor (PD-ECGF), angiogenin (ANG), transforming growth factor-β (TGF-β) and vascular endothelial growth factor A (VEGF-A) among three groups were compared. Results: The systolic blood pressure ((246±12) mmHg vs (220±16) mmHg, P=0.0291, 1 mmHg=0.133 kPa) and diastolic blood pressure ((189±15) mmHg vs (164±12) mmHg, P=0.0143) of SHR-HSD group were elevated significantly compared with those of SHR-ND group. Compared with normotensive Wistar-Kyoto (WKY), SHR-ND, SHR-HSD and SHR-HSD-UCAO groups demonstrated lipohyalinosis, vessel wall thickening, lumen narrowing and multiple enlarged perivascular space and diffuse disarrangement of nerve fiber and myelin vacuolation in corpus callosum pathologically. The ratio of CD11b(+) CD68(+) monocytes in peripheral blood of SHR-HSD group was higher compared with both SHR-ND and SHR-HSD-UCAO groups (P=0.000 8). The mean inflorescence index (MFI) of CD86 and CD206 showd considerable decline in SHR-HSD-UCAO group compared with those of SHR-HSD group (P=0.018 7 and 0.016 8, respectively). The CD86 MFI of CD11b+CD68+ monocytes in SHR-HSD-UCAO group was remarkably higher than that of SHR-ND and SHR-HSD groups (P=0.000 5). Compared with SHR-ND and SHR-HSD groups, the brain mRNA transcription of angiogenic factors including PD-ECGF and ANG were down-regulated (P=0.004 6 and 0.000 2, respectively), while the atherogenic factors including TGF-β and VEGF-A were up-regulated in SHR-HSD-UCAO group (P<0.000 1 and P=0.045, respectively). Conclusion: SHR-HSD-UCAO group shares the pathophysiological characteristics with advanced stage arteriosclerotic cerebral small vessel disease (aCSVD), including neuropathology, imbalanced circulating monocytes phenotypes and down-regulated angiogenic factors.

目的： 探究自发性高血压大鼠（SHR）高盐饮食合并慢性单侧颈内动脉闭塞模型的组织病理、单核细胞功能表型、脑组织动脉硬化相关血管因子转录改变。 方法： 21只6周龄SHR按照简单随机法直接抽样分成正常饮食组（SHR-ND，n=n=n=结果： SHR-HSD收缩压[（246±12）mmHg比（220±16）mmHg，P=P=P=P=P=P=ECGF）（P=P=P<P=结论： 高盐合并局灶性低灌注的SHR可诱导大鼠小动脉硬化、血管周围间隙扩大、脑白质疏松等病理改变，并伴随循环单核细胞免疫表型失衡、促血管新生因子转录下调，SHR-HSD-UCAO值得作为中晚期小动脉硬化型脑小血管病（aCSVD）疾病动物模型进一步探索。.

Keywords: Angiogenesis; Arteriolosclerosis; Cerebral small vessel disease; Disease animal model; High salt.

This article summarizes some of the data that have been accumulated on several growth factors. Biochemical and biological properties of the Epidermal, Fibroblast, Astrocytes and Tumor growth factors (EGF, FGF, AGF, TGF) and those of growth factors derived from Platelets (PDGF), Brain (BDGF, ECGF), Eye (EDGF) and Cartilage (CDGF) are reviewed, as well as the in vitro mechanism of action of EGF and PDGF. The in vivo effects of these growth factors, particularly the experiments achieved to understand the physiological or physiopathological significance are described. The potential interest of these molecules in pharmacology and their use as wound healing agents is discussed.

The revascularization of a skin flap after flap transposition is an important step in flap survival. This study investigates the efficacy of certain angiogenic agents to expedite the neovascularization process and to increase the viability of skin flaps. Eighty-four island skin flaps were designed on the auricles of 42 New Zealand White rabbits to achieve 90% necrosis over a 7-day period. Thirty-six flaps were treated with Endothelial Cell Growth Supplement (ECGS) or Endothelial Cell Growth Factor (ECGF) at several concentrations topically or immersed in Gelfoam. The remaining flaps were used as normal saline controls. Flap viability and peripheral neovascularization were documented by polar planimetry, angiography, and histological analysis. The flap viability of the ECGS-Gelfoam -treated flaps was 100% greater than their normal saline-Gelfoam controls (p = .021). Flap angiograms demonstrated increased vascular ingrowth among the treated flaps compared to the controls. This study suggests that angiogenic agents can expedite flap neovascularization and have the potential to increase flap viability.

This study was designed to observe the effect of tumor conditioned medium (TCM) on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to TCM from breast carcinoma cell line MDA-MB-231, then we measured their proliferation, apoptosis and cell cycle distribution by MTT and flow cytometery (FCM). Following the stimulation of TCM, HUVECs showed higher pro-mitogenic and anti-apoptotic ability than did the negative control group (ECGF-free medium with 20% FBS), but a similar ability to the positive control group (medium with ECGF and 20% FBS). From these results, we can conclude that breast carcinoma cell line MDA-MB-231 could secret soluble pro-angiogenic factors that induce HUVEC angiogenic switching, including cell cycle progression, proliferation and growth. The role and character of these factors remain to be further studied.

OBJECTIVE

We previously demonstrated stimulation of collateral vessel formation in a rabbit model of unilateral limb ischaemia after administration of endothelial cell growth factor (ECGF). To distinguish clearly the effects of ischaemia alone from those of ischaemia combined with angiogenic stimulation in the same animal, a model of bilateral hindlimb ischaemia was used to evaluate further the angiogenic effect of ECGF.

METHODS

Ischaemia was produced in both hindlimbs of 11 rabbits by femoral artery excision. Beginning 10 days later, ECGF (8 mg in 3 ml of saline) was injected in one hindlimb while 3 ml of saline alone was injected in the other every other day for a total of five doses.

METHODS

Calf systolic blood pressure was measured in both limbs on postoperative days, 10, 30, and 50. On day 50, collateral formation was quantitated angiographically, and muscle samples were obtained for quantitation of capillary density and histologic studies.

RESULTS

The mean calf systolic blood pressure in the both hindlimbs was similar on day 10 (36.9 +/- 2.3 versus 38.1 +/- 2.9 mmHg) but was significantly higher in the ECGF-treated limb on day 30 (68.9 +/- 3.1 versus 45.0 +/- 2.9 mmHg) and day 50 (83.0 +/- 3.0 versus 57.0 +/- 1.7; p < 0.0001 for both comparisons). On day 50, collateral vessels were significantly more numerous in the ECGF-treated limb (17.2 +/- 1.6 versus 11.0 +/- 0.8; p < 0.0006), as were capillaries (225.9 +/- 11.4 versus 159.6 +/- 12.9 per mm2; p < 0.002).

CONCLUSIONS

Local administration of ECGF enhanced collateral development leading to significantly improved perfusion in the treated as compared with the untreated limb in the same animal. Exogenous administration of an angiogenic mitogen can upregulate the normal collateral response to ischaemia and may be useful in treating severe limb ischaemia.

OBJECTIVE

To investigate the relationship between mRNA expression of platelet-derived endothelial cell growth factor (PD-ECGF) and invasion of bladder transitional cell carcinoma (BTCC).

METHODS

The mRNA expression of PD-ECGF in BTCC was detected by RT-PCR. The target PCR bands were analyzed by NIH Image 1.62 software.

RESULTS

The mRNA level of PD-ECGF in BTCC was 3.86 times as high as that of normal bladder mucosa (t = 2.36, P < 0.05). The expression level of stage Ta, T1 and T2-4 tumor was 1.33, 4.02 and 7.59 times as high as that of normal bladder mucosa, respectively. That of Grade 3 tumor was 2.27 times as high as that of Grade 1 - 2 tumor (t = 3.52, P < 0.01).

CONCLUSIONS

The mRNA expression of PD-ECGF was positively correlated with the invasiveness and grade of BTCC. The results suggest that the mRNA level of PD-ECGF might be used as an indicator of tumor progression and a guide for clinical treatment of bladder transitional cell carcinoma.

Endothelial cell growth factor (ECGF) is a peptide synthesized in the hypothalamus and platelets, which regulates a process of angiogenesis, stimulating the vascular endothelial cell proliferation of and formation of new capillaries. As previously shown that activation of target cells in response to insulin, growth factors, stimulators of mitogenesis and chemotaxis, followed by phosphorylation of membrane components, occurs via generation of "signal" ATP on plasma membranes of these target cells. ATP was synthesized within 1 min in the preparations enriched with plasma membrane particles obtained from the endothelium of the bovine aorta and human hemangioma and washed in 0.25 M sucrose, the incubated in the medium containing ECGF 150 micrograms/ml, Tris-HCl pH 7.5, ADP, Mg2+, inorganic P during NADH oxidation in the presence of cytochrome c and oxygen. The stimulation of ECGF on ATP formation in the plasma membranes was detected in 9 experiments when kinases inhibitor of 5-fluorosulfonyl benzoyladenosine was used. The ECGF-stimulated ATP production was equal to 6.1-27.4 and 21.6 nmol/min/mg protein in the membranes of the bovine aortic endothelium and human hemangioma, respectively at 30 degrees. Plasma membrane signal ATP appears to serve as a secondary "membrane messenger" for ECGF.

Natural flora is the richest source of novel therapeutic agents due to their immense chemical diversity and novel biological properties. In this regard, eighteen natural products belonging to different chemical classes were evaluated for their thymidine phosphorylase (TP) inhibitory activity. TP shares identity with an angiogenic protein platelet derived endothelial cell growth factor (PD-ECGF). It assists tumor angiogenesis and is a key player in cancer progression, thus an ideal target to develop anti-angiogenic drugs. Eleven compounds 1-2, 5-10, 11, 15, and 18 showed a good to weak TP inhibitory activity (IC50 values between 44.0 to 420.3 μM), as compared to standards i.e. tipiracil (IC50 = 0.014 ± 0.002 μM) and 7-deazaxanthine (IC50 = 41.0 ± 1.63 μM). Kinetic studies were also performed on active compounds, in order to deduce the mechanism of ligand binding to enzyme. To get further insight into receptor protein (enzyme) and ligand interaction at atomic level, in- sillico studies were also performed. Active compounds were finally evaluated for cytotoxicity test against mouse fibroblast (3T3) cell line. Compound 18 (Masoprocol) showed a significant TP inhibitory activity (IC50 = 44.0 ± 0.5 μM). Kinetic studies showed that it inhibits the enzyme in a competitive manner (Ki = 25.6 ± 0.008 μM), while it adopts a binding pose different than the substrate thymidine. It is further found to be non-toxic in MTT cytotoxicity assay. This is the first report on TP inhibitory activity of several natural compounds, some of which may serve as leads for further research towards drug the development.

The endothelial cellular growth factor alpha-ECGF is a candidate drug for the induction of therapeutic neoangiogenesis. Its use in extensive experimental and clinical trials is hampered by the fact that currently published purification procedures allow only small yields, and the absence of pyrogenic impurities is not demonstrated. The rh alpha-ECGF was expressed in E. coli. Isolation of rh alpha-ECGF from E. coli lysates to apparent homogenicity was achieved by a three step purification procedure involving ionic exchange, heparin-sepharose and polymyxin B chromatography. By this method, 200 mg of rh alpha-ECGF was purified from 15 g wet weight E. coli bacteria. The isolated protein of 18 kDa appeared as a single band after SDS gel electrophoresis and subsequent silver-staining. The biological activity was expressed in the chorion-allantois-membrane assay and in the 3H-thymidine proliferation in baby hamster kidney cells. Drug trials with rabbits revealed no increase in body temperature after intravenous injections with 1 mg rh-ECGF.

The loss of retinal pericytes is one of the earliest changes in diabetic retinopathy. In order to study this phenomenon in vitro, an optimal isolation and cultivation system has to be established. Therefore, pericytes from bovine retinae were isolated enzymatically with 0.4% collagenase in phosphate-buffered saline and identical immunologically by positive staining with antibodies against smooth muscle alpha-actin. Routine cultivation of pericytes was performed by using DMEM supplemented with 10% fetal calf serum. Dependent on the in vitro age of cells, the effect of the following reagents on proliferative activity was determined: fetal calf serum, heparin, ECGF, ECGF+heparin, and glucose. Increasing serum concentrations stimulated the proliferation of pericytes, although the degree of stimulation was reduced with increasing in vitro age. Heparin inhibited the growth in a dose-dependent manner; the achieving 50% inhibition was extrapolated to be 25 micrograms/ml. ECGF increased pericyte proliferation significantly, with a maximum at 10 microliters/ml. In addition, ECGF reversed the inhibitory effect of heparin. Furthermore, all tested glucose concentrations (5.5-27.75 mmol/l) did not show any influence on growth rates of pericytes. The results demonstrate that routine cultivation of retinal pericytes is possible. Moreover, they indicate that enhanced blood glucose concentrations, as observed in diabetic patients, are not the only important factor in the loss of retinal pericytes.

Keloids are benign cutaneous tumours characterized by excess deposition of collagen, specifically type I collagen. We report here that collagen biosynthesis, as measured by hydroxyproline synthesis, was markedly inhibited by 65-80% by the combination of endothelial cell growth factor (ECGF) supplement and heparin in keloid fibroblast cultures. Fibroblast cultures that were incubated with ECGF alone also demonstrated a measurable decrease of approx. 50% in collagen synthesis compared with control cultures. The inhibition of collagen synthesis was related to the down-regulation of collagen gene expression. Quantitative measurements of mRNA-cDNA hybrids revealed that the gene expression of collagen type I was decreased by more than 80% by heparin and ECGF. Markedly diminished levels of mRNA encoding collagen type I were also observed in cultures incubated with ECGF alone. The results show that ECGF and heparin elicit a negative regulatory effect on collagen production, and that this inhibition is due largely to the down-regulation of the pro-alpha 1(I) of type I collagen gene. Furthermore, ECGF has a potent suppressive effect, and heparin provides an additive effect to this inhibitory phenomenon.

OBJECTIVE

Thymidine Phosphorylase/ Platelet Derived-Endothelial Cell Growth Factor (TP/PD-ECGF) has an angiogenic and chemotherapeutic effects. The aim of this work was to evaluate TP/PD-ECGF expression in gastric adenocarcinoma and find its correlation with established clinicopathological parameters and patients' survival.

METHODS

Samples studied consisted of fifty-two gastric specimens (27 cases of chronic gastritis and 25 cases of malignant adenocarcinoma). Immunohistochemical staining for TP/PD-ECGF was done and the tumor was considered positive when more than 5% of cells showed positive staining.

RESULTS

TP/PD-ECGF expression was significantly higher in the malignant group when compared to the control group (p = 0.001). Tumor and stromal cell TP/PD-ECGF expression in the malignant group was significantly correlated with size of the tumor, mitotic count, stage grouping, depth of invasion, number of lymph nodes (LN) involved, perineural invasion, lymphoplasmacytic and tumor associated macrophages (TAMs) infiltration and vessel density (VD). Furthermore, stromal expression of TP/PD-ECGF was significantly correlated with postoperative chemotherapy and apoptotic count. Survival analysis revealed that proximal tumor, small size, early stage, negative LN metastasis, absence of perineural invasion, low VD and negative tumor and stromal TP/PD-ECGF expression correlated with better patients' survival.

CONCLUSIONS

TP/PD-ECGF might have an angiogenic function and role in tumor growth, invasion and metastasis. TP/PD-ECGF could enhance the effect of postoperative chemotherapy.

Thymidine phosphorylase (dThdPase) is an enzyme involved in pyrimidine nucleoside metabolism. dThdPase activity is increased in various types of malignant tumors. Recently, we demonstrated that dThdPase is identical to platelet-derived endothelial cell growth factor (PD-ECGF), and has angiogenic activity. We measured the dThdPase activity and the level of thrombomodulin (TM), as a marker for endothelial cells, in ovarian carcinomas, benign tumors and normal ovarian tissues. The average dThdPase activity of ovarian carcinomas (10.86+/-6.98 nmol/100 mu g protein/h) was significantly higher than that of benign tumors (4.66+/-3.91 nmol/100 mu g protein/h) or normal tissues (2.52+/-1.90 nmol/100 mu g protein/h). The expression of dThdPase detected by immunoblot analysis was well correlated with dThdPase activity. In an immunohistochemical study, the expression of dThdPase was more frequently observed in ovarian carcinomas than in benign tumors or normal tissues. dThdPase activity in human ovarian carcinomas was significantly correlated with the expression of TM in human ovarian carcinomas. These findings suggest that dThdPase expression is significantly correlated with angiogenesis in ovarian tumors.

OBJECTIVE

The aim of the study was to assess the correlation between the activity of thymidine phosphorylase (TP) and the platelet derived-endothelial cell growth factor (PD-ECGF) expression in endometrial carcinoma.

METHODS

The study group consisted of 40 tissue samples taken from patients with endometrial carcinoma, who underwent surgery in First Clinic of Gynecology and Oncologic Gynecology of Medical University in Lodz. The control tissue samples were taken from patients who were operated on for non-oncologic reason. The activity of TP was measured by the spectrophotometric method in the cytosol of tumor cells, and the immunohistochemical staining of PD-ECGF was performed in the same tumors. The results of TP activity were compared with the microvessel density (MD) assessed by immunohistochemical analysis and with clinico-pathological features like tumor grade and FIGO stage.

RESULTS

A positive correlation between the enzyme activity and expression of TP/PD-ECGF protein was found. Moreover a significantly higher TP activity was confirmed in malignant tumors from endometrial cancer patients when compared to the controls. A positive correlation between the enzyme activity and MD was also stated, but there was no connection to the grade of tumors and FIGO stage. Since the TP activity proved to be related to PD-ECGF expression and angiogenesis, we can state that TP seems to be an active form of PD-ECGF growth factor in endometrial carcinoma. This is in agreement with the results of many publications on other malignancies. The proper modulation of this activity may be useful in adjuvant therapies.

OBJECTIVE

To explore the expression and clinical significance of thymidine phosphorylase/platelet-derived endothelial cell growth factor (PD-ECGF) in renal cell carcinoma.

METHODS

The expression of PD-ECGF in 76 specimens of renal cell carcinoma from June 2002 to December 2006 was examined by EnVision immunohistochemistry. The correlation of the expression of PD-ECGF with the clinicopathological characteristics and prognosis in renal cell carcinoma patients were analyzed.

RESULTS

Among 76 renal cell carcinoma patients, 41 patients had a high-level expression of PD-ECGF while another 35 patients a low-level expression. The expression of PD-ECGF was positively correlated with tumor stage and histological grade. The 5-year overall survival rate was significant lower in the patients with a high-level expression of PD-ECGF (60.98% vs 94.29%, P = 0.000). Univariate analysis showed that the characteristics with the prognostic significance for survival were tumor stage, lymph node metastasis, distant metastasis, histological grade and the expression of PD-ECGF. Multivariate analysis showed that tumor stage, histological grade and the expression of PD-ECGF were independent prognostic factors (OR: 17.971, 9.702, 6.790, 95%CI: 3.010 - 107.290, 1.835 - 51.305, 1.156 - 39.894).

CONCLUSIONS

The expression of PD-ECGF may play an important role in the development and invasion of renal cell carcinoma. An elevated level of PD-ECGF is probably correlated with the prognosis of renal cell carcinoma.

Neo-angiogenesis seems to play an important role in the progression of ovarian cancer and in formation of distant metastases. Data from literature on role of phosphorylase in neoplasmatic disease and in neo-angiogenesis are controversial. In mammalian cytosole there are two different pirymidine nucleosyde phosphorylases: thymidine (PT) and uridine (PU). Both of them play important role in the metabolism of nucleosides as well as in the recycling of pyrimidine base. Recently thymidine phosphorylase is identified with platelet derived endothelial cell growth factor (PD-ECGF). It has been demonstrated, that PD-ECGF/PT influence on neo-angiogenesis and correlates with degree of neoplasmatic invasion. In literature the data about thymidine phosphorylase activity and its correlation with neoplasmatic angiogenesis in ovarian tumors are controversial. The aim of the study was to evaluate the activity of PT together with the intensity of angiogenesis in epithelial ovarian tumors. 42 patients with ovarian cancer were included into the study. The enzyme activity was measured in ovarian cancer tissue and in the serum in the spectrophotometer. Intratumoral microvessel density (IMD) was evaluated in tumor using immunohistochemical methods. 10 woman with normal ovaries, treated surgically due to non-oncological reasons served as a control. Activity of PT in ovarian tumor and in serum was compared to the control group. Correlation between the intensity of angiogenesis and PT activity in ovarian cancer was also investigated. Significantly higher PT activity was stated both in tumor and serum when compared to the control. Positive correlation between enzyme activity in the serum and neoplasmatic tissue was found. Surprisingly, the negative correlation between neo-angiogenesis and PT activity in ovarian cancer was observed. Neo-angiogenesis is higher in ovarian cancer, when compared to the group of borderline malignancy tumors. Positive correlation between PT activity and staging in ovarian cancer was observed. No correlation between grading and histopathological type of epithelial cancer was observed. PT activity and neo-angiogenesis evaluation might be useful in diagnostics of ovarian cancer.

Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), and has angiogenic activity. It has been reported that a higher level of dThdPase activity is associated with an unfavorable patient prognosis. The activity of dThdPase was investigated in 15 patients who underwent hepatectomy for hepatic metastasis from colorectal carcinoma, and an assessment was made as to whether its expression was correlated with the prognosis. The dThdPase activity was significantly higher in the patients with extrahepatic metastasis after hepatectomy (n = 5) than in those without extrahepatic metastasis (n = 10) (168.2 +/- 50.8 vs 95.1 +/- 35.2 Unit/mg prot., p < 0.05). This dThdPase activity could be a significant prognostic indicator, and was useful in predicting the extrahepatic recurrence after hepatectomy for hepatic metastasis from colorectal carcinoma.

Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF). TP has an angiogenic activity and confers resistance to hypoxia-induced apoptosis on cells. TP expression is correlated with microvessel count, invasion and poor prognosis in many solid tumors. TPI, an inhibitor of TP, suppresses growth and metastasis of tumors by inhibiting the effect of TP.