A new endothelial cell growth factor (f-ECGF) was partially purified from the cultured medium of human fibroblast cells of embryonic lungs. The partially purified f-ECGF induced neovascularization in rabbit cornea. It showed a selective growth stimulatory activity on the endothelial cells in vitro, whereas acidic- and basic-fibroblast growth factors (a- and b-FGFs) showed a broad spectrum of growth stimulation among tissues or cells. f-ECGF did not compete with the binding of a-FGF to the cell surface receptor in HEP-G2 hepatoblastoma cell lines. These results indicated that f-ECGF is a new endothelial cell growth factor distinct from a- and b-FGFs which are known to be potent endothelial cell growth factors.

Bovine brain-derived growth factor (BDGF), whose biochemical properties resemble those of endothelial cell growth factor (ECGF) and brain-derived acidic fibroblast growth factor (acidic FGF), is able to promote colony formation of normal rat kidney fibroblasts (NRK cells) in soft agar. As in the case of transforming growth factor beta (TGF beta), EGF potentiates the anchorage-independent growth promoting activity of BDGF. In the presence of EGF (5 ng/ml), the optimal concentration of BDGF for stimulation of anchorage-independent of NRK cells is approximately 0.5 ng/ml. At higher concentrations, BDGF becomes inhibitory. The anchorage-independent cell growth promoting activity of BDGF differs from that of TGF beta in acid and reducing agent stability.

OBJECTIVE

Platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (TP) has been implicated in cancer angiogenesis, which is critical for tumor growth and metastasis. We investigated the relationship between the tissue concentration of PD-ECGF/TP and the clinicopathologic status in human lung cancer.

METHODS

The concentrations of PD-ECGF/TP in the tumor extracts of 139 primary human lung carcinomas were measured by using a highly specific and sensitive enzyme-linked immunosorbent assay.

RESULTS

PD-ECGF/TP was detected in the extracts from 137 of 139 specimens at concentrations that ranged from 2.0 to 169.5 U/mg protein. PD-ECGF/TP concentrations in patients with adenocarcinoma (n = 73) and squamous cell carcinoma (n = 49) were (mean +/- SD) 30.7+/-22.9 U/mg protein (range, 7.6 to 169.5 U/mg protein) and 32.0+/-19.8 U/mg protein (range, 8.0 to 84.4 U/mg protein), respectively. No significant difference was found in the PD-ECGF/TP concentration between these two types of non-small cell lung cancer (NSCLC). However, a>> 8-fold lower mean concentration of PD-ECGF/TP was found in tissue extracts from small cell lung cancer (SCLC) (n = 17; 3.65+/-2.01 U/mg protein, ranging from undetectable to 6.1 U/mg protein) than in those from adenocarcinomas (p = 0.00005) or squamous cell carcinomas (p < 0.00001).

CONCLUSIONS

The striking difference in PD-ECGF/TP concentrations between SCLC and NSCLC suggests that these two types of lung cancer use alternative pathways for angiogenesis. The present study suggests that inhibitors of PD-ECGF/TP, which have been recently developed and are under laboratory investigation to test their effectiveness as treatments for various types of cancer, may not be effective against SCLC.

OBJECTIVE

Investigation of the effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) on various aspects of tumour growth in a xenograft model, including growth rate, tumourigenicity and oxygenation levels.

METHODS

MDA 231 breast cancer cells overexpressing PD-ECGF/TP protein were made by retroviral transduction. These cells were grown in vitro and in vivo as xenografts. Direct measurement of tumours was used to record growth parameters, while the comet assay with the bioreductive drug RSU 1069 was used to assess tumour cell oxygenation.

RESULTS

We report that MDA 231 breast tumour cell lines expressing an increased range of levels of PD-ECGF/TP have increased tumourigenicity positively related to the level of PD-ECGF/TP when implanted in nude mice. As previously reported, tumours grown from these overexpressing cell lines grew faster than the parental line. These tumours expressed higher levels of TP activity and showed increased immunocytochemical staining for PD-ECGF. In addition, the rate of growth was found to be positively related to the level of PD-ECGF/TP expressed by the tumour cells. When the comet assay was used to compare the oxygenation status of cells between the parental and PD-ECGF/TP overexpressing tumours, the latter were found to have a larger proportion of well oxygenated cells. This is consistent with these tumours having an increased and functionally competent vascular supply in response to the expression of PD-ECGF/TP.

CONCLUSIONS

PD-ECGF/TP appears to be capable of influencing tumourigenicity, angiogenesis and tumour growth in a proportional manner and can directly influence tumour oxygenation levels via its role in formation of functional vasculature.

OBJECTIVE

To explore the relation between the expressions of PD-ECGF and VEGF and the evolution of capillary hemangioma, so as to provide theoretical basis for treatment.

METHODS

Fourty cases with capillary hemangioma, proved by pathologic method, were randomly selected and divided into proliferative (n=22) and involuted groups (n=18), according to the Mulliken standard. 8 specimens from 8 children with prepuce operation were used as control group. All the specimens were fixed, embedded and underwent HE staining. The expression of PD-ECGF, VEGF and CD34 in endothelial cells were detected by immunohistochemistry. The microvessel-density (MVD) was also calculated. The results were analyzed by SPSS12.0.

RESULTS

The positive expression rates of PD-ECGF and VEGF were 95.45% (21/22) and 86.36% (19/22) in proliferative hemangioma, 77.78% (14/18) and 66.67% (12/ 18) in involuted hemangioma, 37.50% (3/8) and 37.50% (3/8) in normal skin. MVD in proliferative and involuted hemangioma and normal skin was 93.68 +/- 20.56, 51.94 +/- 20.73 and 17.50 +/- 5.30, respectively. There was a significant difference in PD-ECGF expression and MVD between the proliferative and involuted groups, or between the hemangioma and control groups (P < 0.05). The VEGF was significantly different between the proliferative and involuted groups, or between the proliferative and control groups (P < 0.05), but not between the involuted and control groups (P>> 0.05). The expression of VEGF, PD-ECGD and MVD showed a positive relationship.

CONCLUSIONS

PD-ECGF and VEGF have a synergetic effect in the proliferation of micro-vessels. PD-ECGF may enhance the activity of thymidine phosphorylase. They play an important role in the proliferation and involution of hemangioma.

To evaluate the predictive role of the oncogene p53, the proliferating marker Ki-67, angiogenic factors platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/dThdPase) and vascular endothelial growth factor (VEGF) in primary hypopharyngeal carcinoma, we immunohistochemically studied a series of 84 primary hypopharyngeal carcinoma patients who were treated at the Department of Otolaryngology of Kurume University Hospital between 1990 and 1997. The correlation of each score according to the intensity and percentage of the labeled cells with the TNM stage, histological grade, metastasis and survival status was analyzed. The positive rate of p53 was 52.4%. The percentages of Ki-67 labeled cells in patients with or without metastasis showed a significant difference (p = 0.011). VEGF also showed a significant difference between the live and death groups (p < 0.05) and also among the differentiation group (p < 0.05). A statistically significant correlation was also seen between the score of Ki-67 and VEGF (r = 0.438, p < 0.001) or the score of Ki-67 and PD-ECGF (r = 0.259, p < 0.001), respectively. In conclusion, the present study suggests that a correlation exists between proliferating and angiogenesis, and VEGF and Ki-67 are thus considered to be possible prognostic discriminators in hypopharyngeal carcinoma.

Thymidine phosphorylase (TPase) is also known as the platelet-derived endothelial cell growth factor (PD-ECGF) and plays a role in angiogenesis. Deoxyribose (dR; a downstream TPase-product) addition to endothelial cells may stimulate FAK and p70/S6k signaling, which can be inhibited by rapamycin. Rapamycin is a specific mammalian target of the rapamycin (mTOR) inhibitor, a kinase that lies directly upstream of p70/S6k. This suggests a role for TPase in the mTOR/p70/S6k pathway. In order to study this in more detail, we exposed cells with and without TPase expression to dR and rapamycin and determined the effect on cell growth. We observed protection in cytotoxicity in Colo320 cells, but not Colo320 TP1 cells. This was in part mediated by activation of p70/S6k and inhibition of autophagy. Further studies are recommended to elucidate the mechanism behind the protective effect of dR.

The platelet-derived endothelial cell growth factor (PD-ECGF) is one of the potent angiogenic factors. Recently, its homology with thymidine phosphorylase (dThdPase), an enzyme involved in pyrimidine nucleoside metabolism, has been shown. In the present study, dThdPase activity was evaluated spectrophotometrically in 43 breast carcinomas and in 19 cases of non-neoplastic breast tissues. The mean dThdPase activity in breast cancer was almost six fold higher than in normal, non-neoplastic breast tissues (1.92 and 0.29 mumol thymine (T) x mg prot.-1 x h-1 respectively). The enzyme activity significantly correlated with axillary lymph node status (p = 0.0076) and with tumor size (p = 0.0099). Besides, the intratumoral microvessel density (MD) was evaluated using the CD 31 mouse anti-human monoclonal antibody, and there was no correlation between the level of enzymatic activity and a number of microvessels. The positive significant correlation of thymidine phosphorylase activity with prognostic factors in breast cancer patients with no relation to the number of microvessels needs further examination to confirm the prognostic significance of the level of dThdPase.

Angiogenesis contributes to the growth and secondary spreading of solid tumors. Platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (TP) has been identified as such an angiogenic factor. In this study, the expression of PD-ECGF/TP and VEGF was evaluated by immunohistochemical staining of tumor specimens from 40 patients with cervical intraepithelial neoplasia (10 with moderate dysplasia; 10 with severe dysplasia; 10 with carcinoma in situ; 10 with invasive carcinoma). The microvessel density was assessed by immunostaining for factor VIII-related antigen in the most highly neovascularized area. In both the nucleus and cytoplasm, the intensity of PD-ECGF/TP expression in carcinoma in situ and invasive carcinoma was significantly stronger than that in moderate dysplasia. However, the intensity of VEGF expression was not significantly different in the various specimens. The microvessel density in mild dysplasia was significantly different from that in carcinoma in situ (p<0.05), and that in invasive carcinoma (p<0.05). There was no significant relationship between the microvessel density and the expression of PD-ECGF/TP or that of VEGF. These results show that the expression of PD-ECGF/TP appears to be involved in the promotion of angiogenesis in cervical intraepithelial neoplasia.

BACKGROUND

It has been recently reported that thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF). dThdPase is known to be one of the angiogenic factors. Expression of dThdPase has been detected both in cancer cells and in stroma cells. However, the role of dThdPase, in cancer cells and in stroma cells regarding, neovascularization in gastric adenocarcinoma is still unclear. In this study, we analyzed the correlation between dThdPase activity and neovascularization in gastric cancer.

METHODS

We obtained fresh samples (tumors and adjacent normal mucosas) from 67 patients with gastric cancer who underwent gastrectomy between 1993 and 1994. The dThdPase activity was analyzed by the ELISA (enzyme-linked immunosorbent assay) method and by the immunohistochemical staining. Microvessel density (MVD) and vascular endothelial growth factor expression of tumors were analyzed by immunohistochemical staining.

RESULTS

The dThdPase activity of tumors (117 +/- 98 U/mg protein) was significantly higher than that of normal mucosas (46 +/- 36 U/mg protein, P < 0.0001). The expression of dThdPase was detected by immunostaining in stroma cells but not in mucosal cells in normal tissues. Based on the immunostaining results, 16 tumors expressed dThdPase both in cancer cells and stroma cells. The mean dThdPase activity and the mean MVD of these 16 tumors were significantly higher than those of 15 tumors with expression of dThdPase only in the stroma cells, and than those of 36 tumors with expression of dThdPase in neither the cancer cells or the stroma cells. The MVD of tumors strongly correlated with the dThdPase activity of tumors detected by the ELISA method (P < 0.0001).

CONCLUSIONS

The total amount of dThdPase produced by cancer cells and stroma cells may influence tumor angiogenesis in gastric cancer.

BACKGROUND

Angiogenesis is one pathogenesis of allergic airway disease.

METHODS

A potent angiogenic factor is platelet-derived endothelial cell growth factor (PD-ECGF), also known as thymidine phosphorylase (TP) in the field of cancer-associated research. Vascular endothelial growth factor (VEGF) is another representative angiogenic factor. Both factors were added to the culture system of human peripheral blood mononuclear cells (PBMC) with IL-4 and anti-CD40 monoclonal antibody (mAb). Total IgE levels in the supernatants and signal transduction of stimulated PBMC were evaluated.

RESULTS

Addition of PD-ECGF enhances in vitro IgE production by PBMC in the presence of IL-4 and anti-CD40 mAb, but VEGF does not enhance IgE production. Although PD-ECGF catalyzes the reversible phosphorolysis of thymidine to 2-deoxy-D-ribose-1-phosphate (2DDR), treatment of 2DDR has no effect on IgE production by human PBMC. Both IL-4 and anti-CD40 mAb induce PD-ECGF by human PBMC. Thymidine phosphorylase inhibitor (TPI), 5-chloro-6-[1- (2-iminopyrrolidinyl) methyl] uracil hydrochloride reduce IgE production via blocking of STAT6- phosphorylation.

CONCLUSIONS

Taken together, these results suggest TP involvement in the enhancement of IgE production and suggest that TPI is a novel strategy against IgE-related allergic disease.

Angiogenesis has an important role in the growth and metastasis of solid tumors. Several angiogenic factors have been identified, one being platelet-derived endothelial cell growth factor (PD-ECGF), which is identical to thymidine phosphorylase (dThdPase). We investigated the activity of dThdPase in 84 samples of 42 human gastric cancers, by liquid chromatography. The dThdPase activity significantly correlated to the microvessel density assessed by immunostaining to CD-31 antigen (P<0.05). Expression of dThdPase has an important role in the promotion of angiogenesis in human gastric cancer.

BACKGROUND

Thymidine phosphorylase (TP) is identical with platelet-derived endothelial cell growth factor (PD-ECGF) which promotes angiogenesis. The aim of this study was to evaluate the cytosol activity of TP in tumor samples from patients with endometrial cancer.

METHODS

The activity of TP was measured by the spectrophotometric method in the cytosol of endometrial tumor samples from 43 patients. Moreover, the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) protein and microvessel density (MD) were examined in the same endometrial tumor samples by immunohistochemical staining. Normal endometrium from 16 women, treated surgically due to nononcological reasons served as a control.A relationship between the cytosol TP activity, PD-ECGF/TP protein expression, MD and clinicopathologic features was investigated.

RESULTS

A significantly higher the cytosol TP activity, PD-ECGF/TP protein expression and MD was stated in malignant tumor samples when compared to the control (samples of normal endometrium). A positive statistically significant correlation between the cytosol enzyme activity and PD-ECGF/TP protein expression and MD was found, but weaker from the remaining ones between PD-ECGF/TP protein expression and MD was observed.Besides no correlation between the cytosol TP activity, PD-ECGF/TP protein expression as well as MD and grading or histopatological type of endometrial cancer was stated.

CONCLUSIONS

The cytosol TP activity in endometrial cancer is significantly higher than in normal endometrium, with no relation as to the stage and grade of tumors, but correlates with the PD-ECGF/TP protein expression and MD may therefore be associated with favorable prognosis in patients treated with chemo- or radiotherapy after surgery.

In the present study, we synthesized a series of pyrimidine acyclic nucleoside phosphonates bearing a number of substituents in C-5 position of uracil moiety and in the N-1-side chain. In addition, we have investigated in particular the novel syntheses of fluorinated derivatives substituted in the N-1-side chain and uracil C-5 position because fluorine-containing substituents are often powerful modifiers of chemical and biological properties. The obtained compounds exhibit a considerable inhibitory potency of thymidine phosphorylase from SD-lymphoma. In contrast, the synthesized phosphonates are not efficient inhibitors of E. coli and human thymidine phosphorylase.

A series of thymine phosphonomethoxyalkyl derivatives were evaluated for their ability to inhibit thymidine phosphorylase (dThdPase) purified from rat spontaneous T-cell lymphoma. A kinetic study of thymidine phosphorolysis catalyzed by dThdPase was performed with thymidine and/or inorganic phosphate as substrates. Data show that the substantial inhibitory effect of these acyclic nucleotide analogues is decreasing in the order of (R)-FPMPT>(S)-FPMPT>or=(R)-HPMPT>(S)-PMPT>(S)-HPMPT>PMET>or=(R)-PMPT. The inhibitory potency (K(i)/(dThd)K(m)) of the most efficient inhibitors from this series against T-cell lymphoma enzyme is 0.0026 for (R)-FPMPT and 0.0048 for (S)-FPMPT. The studied compounds do not inhibit Escherichia coli and human enzyme and possess lower inhibitory potency against rat liver thymidine phosphorylase.

Differences in the secretion of some vascular regulators, endothelin-1 (ET-1), prostacylin (PGI2), thromboxane A2 (TXA2) and nitric oxide (NO) associated with in vitro aging, were investigated in cultured endothelial cells isolated from normal human umbilical veins (HUVECs). HUVECs from different population doubling levels (PDLs) were cultured in a medium MCDB-104 supplemented with FBS and ECGF. Cell saturation density of HUVECs decreased by 5-fold between PDL 7 and 67. PGI2 secretion per cell increased by 6-fold, and TXA2 secretion per cell increased by 18-fold between PDL 7 and 67. The ratio of PGI2 to TXA2 secretion decreased 3-fold between PDL 7 and 40 and remained at the lower level between PDL 40 and 67. The secretion of ET-1 by HUVECs at a young stage of growth (PDL 7) increased linearly with time between 0 and 36 hours of incubation. ET-1 secretion per cell increased between PDL 7 and 67 by 5-fold after 4-hr incubation and by 3-fold after 9-hr incubation. The release of NO was assayed by a newly established, highly sensitive assay system monitoring guanosine 3':5'-cyclic monophosphate (cGMP) formation in a pig kidney epithelial cell line cocultured with HUVECs. The cGMP formation by NO released from HUVECs decreased 3.3-fold between PDL 8 and 50. These results suggest that the vaso-constrictive activity of endothelial cells increases during in vitro aging which may reflect the increased vascular disorders in the aged people.

Decidualized tissues are characterized by the intensive outgrowth of the microvasculature. Several angiogenic factors are assumed to be involved during the drastic change in the vasculature occurring in the process of decidualization. We examined the possible role of platelet-derived endothelial cell growth factor (PD-ECGF), a known angiogenic factor, during the process of early decidualization in humans. The expression of PD-ECGF in human endometrium was demonstrated by Western blot analysis, a marked increase being found in decidualized endometrium. Immunohistochemical staining showed that PD-ECGF immunoreactivity was present mainly in decidualized endometrial stromal cells. We established a primary cell culture of human endometrial stromal cells which were differentiated into decidualized cells in vitro by the addition of progesterone. In this cell culture system, progesterone augmented the expression of PD-ECGF in a dose-dependent fashion. The addition of progesterone also resulted in an increased release of prolactin, a well-known marker for decidualization. These findings suggest that PD-ECGF may play a physiological role as a possible angiogenic factor in the process of decidualization of human endometrium.

The effect of an angiogenic growth factor-endothelial cell growth factor (ECGF)-was tested in the rat transverse rectus abdominis musculocutaneous (TRAM) flap model based on a single inferior vascular pedicle. The animals were divided into three groups (N = 8 per group) after flap elevation. In group A (control), each animal received both local and local intra-arterial injections of 1 ml saline. In group B (local), each received a 2-mg ECGF local injection and 1-ml saline local intra-arterial injection. In group C (local intra-arterial), each received a 1-ml saline local injection and a 2-mg ECGF local intra-arterial injection. All animals were evaluated on postoperative day 7. There was a significant increase in the percentage of the skin paddle survival area of the TRAM flap in both ECGF-treated groups when compared with the control group (group B vs. group A, p < 0.001; group C vs. group A, p < 0.001). This correlated with a significant increase in vascularity in both ECGF-treated groups compared with the control group (group B vs. group A, p = 0.007; group C vs. group A, p = 0.021). The results between groups B and C were not significant. ECGF, when administered via either local or local intra-arterial route, enhances musculocutaneous flap survival through the process of neovascularization.

Four human megakaryocytoid cell lines, namely MOLM-1, MOLM-7, MEG-01 and HEL, were treated with phorbol 12-myristate 13-acetate (PMA) and expression of the platelet-derived growth factor (PDGF) A chain, von Willebrand factor (vWF) and endothelial cell growth factor (ECGF) genes was examined by the reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers. The gene for PDGF A chain is constitutively weakly expressed by MEG-01 cells and strong expression is induced in MEG-01, MOLM-1 and MOLM-7 but not in HEL cells after treatment with PMA for three days. All four cell lines express the vWF gene both constitutively and after exposure to PMA. None of the cell lines constitutively express the gene for ECGF but MEG-01 cells can be induced to do so after treatment with the phorbol diester. Immunohistochemical staining after exposure to PMA showed that the expression of the platelet-associated markers CD41 and CD61 was enhanced in all cell lines indicating possible differentiation along the megakaryocyte lineage. Our results illustrate differential platelet-associated factor gene expression in different megakaryoblastic cell populations in response to treatment with PMA, and suggest that expressions of the PDGF A chain gene and the ECGF gene may be good markers for megakaryocyte maturation.

Studies of the effect of minor H antigen mismatching on the outcome of renal transplantation are scarce and concern mainly single center studies. The International Histocompatibility and Immunogenetics Workshops (IHIW) provide a collaborative platform to execute crucial large studies. In collaboration with 16 laboratories of the IHIW, the role of 15 autosomal, 10 Y-chromosome encoded minor H antigens and 3 CD31 polymorphisms, was investigated in relation to the incidence of renal graft rejection and graft loss in 444 human leukocyte antigens (HLA)-identical sibling renal transplantations. Recipient and donor DNA samples were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, SP110, PANE1, UGT2B17, C19Orf48, LB-ECGF-1, CTSH, LRH-1, LB-ADIR and HY. The correlation between minor H antigen mismatch and the primary outcome graft rejection or graft loss was statistically analyzed. The incidence of rejection was very low and no correlation was observed between one or more minor H antigen mismatch(es) and a rejection episode (n = 36), of which only eight resulted in graft loss. In summary, in our study cohort of 444 renal transplants, mismatching for neither autosomal nor HY minor H antigens correlate with rejection episodes or with graft loss.

A combination of mechanism-based and structure-based design strategies led to the synthesis of a series of 5- and 6-substituted uracil derivatives as potential inhibitors of thymidine phosphorlase/platelet derived endothelial cell growth factor (TP/PD-ECGF). Among those tested, 6-imidazolylmethyl-5-fluorouracil was found to be the most potent inhibitor with a Ki-value of 51 nM, representing a new class of 5-fluoropyrimidines with a novel mechanism of action.

Computational studies have been conducted to built a closed form of TPase and to characterize the transition state of the phosphorylisis reaction catalyzed by TPase. The results obtained point to a crucial role of His-85 and the O2 of thymine in the catalysis. This modelled transition state forms the basis for the design of new TPase inhibitors.

OBJECTIVE

Microvessel density (MVD) has been studied extensively as the only factor reflecting angiogenesis and a prognostic factor in various malignant tumors. Macrophages and platelet-derived endothelial cell growth factor (PD-ECGF) also play important roles in regulating angiogenesis. The present study was conducted to examine the interrelationship of MVD, liver macrophages and PD-ECGF-positive cells in patients with cholangiocellular carcinoma.

METHODS

Thirty-one patients underwent resection of cholangiocellular carcinoma, and samples of the tumors were immunostained with CD34 antibody to evaluate the relationship between MVD and prognosis. Double immunohistochemical labeling for CD68 and PD-ECGF-positive cells was performed and classified as grade 0, grade 1, or grade 2 according to the number of double-positive cells. We also evaluated the relationship between the double-positive cell grading and prognosis or MVD, and furthermore the relationship between cancer cell PD-ECGF immunoreactivity and prognosis or MVD.

RESULTS

Univariate analysis showed that patients with a median MVD exceeding 48/field had asignificantly poorer prognosis (p=0.02). The survival rate of grade 2 patients was significantly worse than that of the other two groups (p=0.011, p=0.0001), and the survival rate of grade 1 patients was significantly worse than that of grade 0 patients (p=0.007). MVD differed significantly among the three grades (p=0.0007, Kruskal-Wallis test), and there was a significant positive correlation between MVD and grade (p=0.0001). No correlation was observed between MVD and the number of cells positive for PD-ECGF alone (p=0.42). Neither the survival rate nor MVD of PD-ECGF (+) patients differed significantly from that of PD-ECGF (-) patients (p=0.08, p=0.6).

CONCLUSIONS

Although the present results are based on a small number of patients, they suggest that liver macrophages at the invasive margin of cholangiocellular carcinoma might contribute to tumor angiogenesis through PD-ECGF secretion, and thus influence the prognosis of patients.

OBJECTIVE

To investigate the differences of mRNA quantitation and protein expression of vascular growth factors including platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) in intestinal tissues in colorectal carcinoma patients with and without schistosomiasis.

METHODS

Thirty colorectal carcinoma patients with schistosomiasis and 30 colorectal carcinoma patients without schistosomiasis were included in this study. The mRNA quantitation and protein expression of PD-ECGF and VEGF in the normal tissue, peri-carcinoma tissue as well as carcinoma tissue obtained from surgical specimens were detected by qRT-PCR and Western blot.

RESULTS

The mRNA relative quantitations of PD-ECGF in normal tissue, peri-carcinoma tissue and carcinoma tissue in the colorectal carcinoma patients with schistosomiasis were 1.726, 1.766 and 2.729 times to those in the colorectal carcinoma patients without schistosomiasis, respectively. The corresponding ones of VEGF were 2.138, 1.831 and 3.376 times, respectively. The protein expression levels of PD-ECGF and VEGF in normal tissue, peri-carcinoma tissue and carcinoma tissue were higher in the colorectal carcinoma patients with schistosomiasis than in the colorectal carcinoma patients without schistosomiasis.

CONCLUSIONS

The expressions of vascular growth factors including PD-ECGF and VEGF are higher in the colorectal carcinoma patients with schistosomiasis than in the colorectal carcinoma patients without schistosomiasis. Therefore, schistosomiasis may be one of the risk factors of colorectal cancer.