The angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-Deoxy-D-ribose, a degradation product of thymidine generated by TP enzymatic activity, inhibits the upregulation of hypoxia-inducible factor (HIF) 1α, BNIP3 and caspase-3 induced by hypoxia. In the present study, we investigated the molecular basis for the suppressive effect of 2-deoxy-D-ribose on the upregulation of HIF-1α. 2-Deoxy-D-ribose enhanced the interaction of HIF-1α and the von Hippel-Lindau (VHL) protein under hypoxic conditions. It did not affect the expression of HIF-1α, prolyl hydroxylase (PHD)1/2/3 and VHL mRNA under normoxic or hypoxic conditions, but enhanced the interaction of HIF-1α and PHD2 under hypoxic conditions. 2-Deoxy-D-ribose also increased the amount of hydroxy-HIF-1α in the presence of the proteasome inhibitor MG-132. The expression levels of TP are elevated in many types of malignant solid tumors and, thus, 2-deoxy-D-ribose generated by TP in these tumors may play an important role in tumor progression by preventing hypoxia-induced apoptosis.

To clarify the relationship between angiogenesis and the early development of colon cancer, expression of platelet-derived endothelial cell growth factor (PD-ECGF), a known angiogenic and endothelial cell chemotactic factor, was examined in 119 human colon premalignant adenomas and colon carcinomas. Localization of PD-ECGF was assessed by immunocytochemistry in 70 nonpolypoid growth (NPG) lesions that represented 29 carcinomas (NPG carcinomas) and 41 adenomas (NPG adenomas) and 49 polypoid growth (PC) lesions that included 15 carcinomas (PG carcinomas) and 34 adenomas (PC adenomas). Simultaneously, the expression of tranforming growth factor alpha (TGF alpha) and epidermal growth factor receptor (EGFR) were examined in serial sections from these lesions. Twenty (68.9%) of 29 NPC carcinomas and 20 (48.7%) of 41 NPC adenomas exhibited positive staining for PD-ECGF, whereas 15 (100%) of 15 PG carcinomas and 27 (79.4%) of 34 PG adenomas expressed PD-ECGF. There was a statistically significant difference in the frequency of PD-ECGF expression between NPG adenomas and PG adenomas (p<0.01). In addition, the incidence of PD-ECGF expression was higher in PG carcinomas than in NPG carcinomas (p<0.05). Positive staining for TGF alpha and EGFR was detected in 14 (48.2%) and 10 (34.5%) of 29 NPG carcinomas, respectively, whereas, 17 (41.5%) and 13 (31.7%) of 41 NPG adenomas expressed TGF alpha and EGFR, respectively. A significant trend for coexpression of PD-ECGF and TGF alpha was detected in either NPG adenomas (p<0.05) or PG adenomas (p<0.01). These data demonstrate that PD-ECGF may be involved in the early stages of colon cancer development during the adenoma-carcinoma transition and additionally that angiogenesis which may be induced by PD-ECGF and/or TGF alpha could play an important role of colon cancer development.

Human and bovine vascular endothelial cells from the umbilical vein and the aorta, respectively, were cultured in the presence of EDGF (a growth factor prepared from bovine retina) on plastic or on extracellular matrix (ECM). Both EDGF and ECM are required to allow the maximal proliferation of human cells and their organization in a typical monolayer. Conversely, bovine aortic endothelial cells grow perfectly in the absence of both factors in 6% fetal calf serum. However, a requirement for EDGF can also be demonstrated in low serum conditions, or in cells at high passage number. ECM had no growth promoting activity by itself. Thrombin acts similarly to EDGF on bovine serum-starved cells. EDGF prolongs the in vitro lifespan of both types of cells. Cells at all stages still synthesize factor VIII antigen as revealed by immunofluorescence. Thus EDGF, like other growth factors from brain, FGF or ECGF, may have an important role in angiogenesis, a critical problem in pathological retinas.

Angiogenesis is an essential step in tumor growth and metastasis, but rather than being controlled by means of a simple mechanism, the control of tumor angiogenesis may be mediated by several angiogenic factors. We investigated the expression of basic fibroblast growth factor (b-FGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in squamous cell carcinoma of the esophagus in order to clarify the mechanism of angiogenesis. Expression of b-FGF and PD-ECGF was immunohistochemically investigated in tissue specimens from the tumors of 79 patients with squamous cell carcinoma of the esophagus who underwent curative esophagectomy without preoperative chemotherapy or radiation therapy, and the relationship between expression of b-FGF/PD-ECGF, microvessel density (MVD), and clinicopathological background factors was assessed. Tumor cells that expressed b-FGF were found in 41 patients (51.9%), and tumor cells that expressed PD-ECGF were found in 57 patients (72.2%). Although the mean vascular density (47.9/mm(2)) of b-FGF-positive tumors was significantly lower than that (67.2/mm(2)) of b-FGF-negative tumors (p=0.014), the difference between the 56.0/mm2 in PD-ECGF-positive tumors and 60.3/mm2 in PD-ECGF-negative tumors was not significant. Although the survival rate of patients with b-FGF-positive tumors was significantly higher than those with b-FGF-negative tumors (p=0.033), there was no significant difference between the survival rates of patients with PD-ECGF-positive and -negative tumors (p=0.580). Expression of b-FGF may be associated with promotion of angiogenesis and a good prognostic factor in squamous cell carcinoma of the esophagus.

The exposure of cardiac cells to OFR generated artificially, showed a marked decrease (p less than 0.01) in cellular utilization of glucose along with a significant decrease in calcium uptake (p less than 0.05). We have also provided evidence for a direct relationship of neutrophil OFR production with the extent of myocardial ischemia in patients of myocardial infarction. Our data provides evidence for implication of OFR in myocardial injury and the pivotal role played by modulators like calcium, ECGF and prostaglandins in potentiating damage to the myocardium.

The activity of pyrimidine nucleoside phosphorylase (PyNPase) was analyzed in thirty-six cases of resected breast cancer and 9 cases of resected benign breast tumor. PyNPase is an enzyme which converts 5'-DFUR to 5-FU in tumor tissue and has been reported to be identical to the platelet-derived endothelial cell growth factor (PD-ECGF) that has angiogenic activity. PyNPase activity was significantly elevated in cancer and metastatic lymph nodes compared to normal lesions of the same breast. PyNPase activity was higher in T2 and T3 breast cancer than of T1 breast cancer. Furthermore, cases of high PyNPase activity (>200 mu g FU/mg protein/h) were significantly more likely to develop distant metastasis (p<0.01) than those of low PyNPase activity. These results suggest an important role of PyNPase activity in the progression of breast cancer.

To clarify the clinical significance of PyNPase (Pyrimidine Nucleoside Phosphorylase)/ PD-ECGF activity in breast cancer, we examined the possible correlation of PyNPase activity to clinicopathological features and prognosis in 195 patients with primary breast cancer between January 1992 through December 1993. The mean PyNPase activity of primary breast cancer, assayed by ELISA method, was 140.6 U/ml, which was between that of benign breast disease (18.2) and recurrent tumors (270.9). In histological type of breast cancer, tumors with solid-tubular carcinoma had significantly higher levels of PyNPase activity. The activity of ER negative or aneuploid tumors was higher than that of ER positive or diploid tumors, respectively. And there was a significant relationship between PyNPase activity and proliferative activity determined by S-phase fraction (SPF) or DNA polymerase alpha. These findings suggested that PyNPase activity was associated with the degree of malignancy. As regards prognosis, in lower SPF (< 16%) group, patients with higher PyNPase activity had significantly lower disease--free survival rates, whereas those with higher activity had a favorable prognosis in the higher SPF >> or = 16%) group. The contradiction might be explained by the possibility that 5-FU derivatives were effective only in patients with high SPF and PyNPase activity, as all patients were treated by a regimen containing 5-FU derivatives. We suggest that PyNPase activity is associated with progression and proliferation of breast cancer, and that it may be useful for prediction of prognosis and therapeutic efficacy of 5-FU derivatives.

Membrane fluidity, transmembrane signaling responses, and proliferative characteristics of endothelial cells were studied to characterize biochemical and molecular changes after treatment with argon laser energy. Bovine aortic endothelial cells grown in monolayers were irradiated at 50, 100, and 200 J with an argon laser (wavelength, 488 and 514 nm). Proliferation, assayed by [3H]thymidine incorporation, was measured daily for 6 days. An initial lag phase was observed for irradiated cells when compared to nonirradiated controls (P less than 0.03), with eventual recovery by the third day. Membrane fluidity, determined by fluorescence anisotropy, was measured 1 hr after irradiation. A decrease in static rotational motion of 1,6-diphenyl-1,3,5-hexatriene (DPH) was noted in irradiated versus nonirradiated cells indicating a decrease in membrane fluidity (P less than 0.02). Dynamic studies of intracellular calcium and pH flux utilizing fluorescent probes demonstrated a preserved response to mitogenic stimulation. An increase in intracellular Ca2+ with a concomitant alkalinization of the intracellular milieu was observed in irradiated and non-irradiated cells in response to stimulation with endothelial cell growth factor (ECGF). These responses resemble those characterized for other mitogens. Argon laser energy applied to aortic endothelial cells decreases membrane fluidity early after irradiation. These alterations probably cause the initial lag observed in their proliferative response; however, the capacity to respond to exogenous mitogenic stimulation is maintained.

It is well established that serum plays an important role in cell proliferation and differentiation. In this study, we have identified a serum factor that induces rapid neurite retraction of morphologically differentiated NG108-15 cells, cultured in serum-free medium containing 1 mM-dibutyryl cyclic AMP. The serum fraction of Mr greater than 30 x 10(3) induces neurite retraction in a manner identical to that of the whole serum. The neurite retraction activity in serum appears to be acid- and heat-stable. The molecular weight of the serum neurite retraction factor (NRF) has been demonstrated to be approximately 70 x 10(3) by gel permeation on LKB-Ultrogel AcA-44. The neurite retraction activity is dose-dependent, and the time required for half-maximal activity (t1/2) is 1.8 min. NRF is present in sera of various species studied, including human, cattle, sheep, rabbit and horse, but not in tissue extracts of kidney, heart, lung skeletal muscle, and brain of the rat. However, rat spleen and liver homogenates, at a protein content of 1 mg ml-1, caused slight neurite retraction. It is noteworthy that NRF is not detectable in cerebral spinal fluid. Our data on the properties of serum NRF indicate that it differs from all of the well-established growth factors, namely, NGF, EGF, PDGF, FGF, NSILA, ECGF and TGF. Further studies on purified NRF will delineate the biological role(s) of this serum factor in the process of maturation and differentiation of developing neurones.

Chromogenic assays, immunoblotting, and Northern blot hybridization methods were employed to assess the effects of various agonists on the production of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) by the lymphatic endothelium (LEC). Fibrin autography showed that plasminogen-dependent fibrinolytic activity occurred at M(r) of 110 kDa, which represents a complex of tPA with PAI-1, and 65- and 55-kDa bands corresponding to tPA and uPA, respectively. The fractionation of lymph collected from ovine lymphatic vessels also produced a prominent lytic band of approximately 110 kDa, suggesting the formation of PA/PAI complexes in lymph. The stimulation of various agonists produced large-scale increases in tPA mRNA, as shown by Northern blot hybridization analyses. The effects of ECGF, histamine, and LPS on the presence of tPA and on enhancing the levels of mRNA reached maximum activity at 4 h and declined to levels below that of controls by 8 h. However, phorbol-treated cells exhibited reduced levels of tPA mRNA at 4 h, but was significantly increased by 8 h. A large-scale increase in PAI-1 mRNA steady-state levels was also stimulated by the agonists used in these studies. Both the 3.4- and 2.4-kb species of PAI-1 mRNA were increased. These observations demonstrated that tPA and PAI-1 are produced and secreted by LEC monolayer cultures and are also present in lymph.

A limiting factor of the long-term function of bioartificial organs is oxygen delivery to the encapsulated tissue. This study determined whether incorporation of endothelial cell growth factor (ECGF) into the alginate core of a hollow fiber bioartificial organ will induce neovascularization around the hollow fiber. Polyethersulfone (PES) and polyvinylidine difluoride (PVDF) hollow fibers were examined. Endothelial cell growth factor was incorporated into sodium alginate, extruded into the lumen of hollow fibers, and cured in calcium chloride. Samples without ECGF were fabricated and used as controls. Hollow fibers were implanted into 16 rats. For each rat, two implants were placed subcutaneously and two intraperitoneally, one with and one without ECGF at each site. Implants were placed on opposite sides of each animal. Implants were removed 65 days later and examined using immunohistochemical methods and light microscopy to determine the extent of neovascularization. A total of 64 implants were used. Most intraperitoneal implants were found free floating but were encased within a 100-microm thick avascular fibrotic reaction. This finding was independent from the presence of ECGF. Hollow fibers without ECGF, implanted subcutaneously, also had an avascular fibrotic reaction surrounding each implant. Subcutaneous implants with incorporation of ECGF within the alginate core had marked neovascularization within the fibrotic overgrowth that surrounded these implants. This was most prevalent in hollow fibers, with the thin separation layer facing the fiber lumen irrespective of limiting pore size. Potent angiogenic factors, such as ECGF, incorporated into diffusion chamber bioartificial organs can promote neovascularization around the subcutaneously implanted hollow fiber and may improve oxygen delivery to the tissue encapsulated within devices based on this technology.

Twenty-five patients with ovarian clear cell carcinoma (CC-Ca) were enrolled in this study, and tumor cell expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) was investigated, and correlated with the microvessel count (MVC) and the impact of complication endometriosis. Expression of VEGF was strongly positive in 16 cases, weakly positive in 6 cases, and negative in 3 cases. Expression of PD-ECGF was strongly positive in 11 cases, weakly positive in 6 cases, and negative in 8 cases. VEGF expression and the MVC were significantly correlated (p<0.01), and there were no correlations among complication by endometriosis, expression of VEGF, expression of PD-ECGF, and MVC.

OBJECTIVE

To investigate the growth mechanisms of large uterine leiomyoma (LULM) on the basis of a clinical morphology examination, by providing immunohistochemical (IHC) characteristics of the expression of growth factors (transforming growth factor-beta (TGFβ) and platelet-derived endothelial cell growth factor (PD-ECGF)) and markers of stemness (CD117/c-kit, Connexin 43, Nestin) and proliferation (Ki-67).

METHODS

The investigators examined surgical specimens from 38 women diagnosed with simple uterine leiomyoma (ULM), who had been divided into two groups: 1) 21 patients with LULM (>6 cm in diameter) (a study group); 2) 17 patients with small ULM (<4 cm in diameter) (a comparison group). Each group was also divided into two age subgroups (younger (<45 years) and older (≥45 years) subgroups (1a (n=12), 1b (n=9), 2a (n=8) and 2b (n=9), respectively. Histological specimens were used to make IHC examination with antibodies against TGFβ, PD-ECGF, CD117/c-kit, Connexin 43, Nestin, and Ki-67.

RESULTS

The growth mechanisms of LULM of simple histological structure were found to be associated with the larger number of growth zones in the tumors, with their enhanced cellular proliferative activity, and with the appearance of cells with signs of stemness, which is combined with the preserved subsequent maturation of tumor cells and determines the benign nature of LULM.

CONCLUSIONS

There were differences in the molecular profile of LULM and small ULM, as well as LULM in perimenopausal and young women by the expression levels of Ki-67, TGFβ, PD-ECGF, CD117, and Connexin 43, which can be used for diagnosis, prediction, and development of targeted therapies.

BACKGROUND

We aimed to find out if there is a correlation between Doppler perfusion index (DPI) and platelet- derived endothelial cell growth factor (PD-ECGF), which is an angiogenic factor with angiopoietic function, in patients with colorectal carcinoma.

METHODS

50 colorectal carcinoma patients (22 cases with liver metastases, 28 cases without liver metastases) and 50 healthy controls were assessed with Doppler ultrasound as a preoperative evaluation. PD-ECGF expression in postoperative specimens of the 50 cases with colorectal carcinoma was assayed by immunohistochemistry and real-time polymerase chain reaction methods.

RESULTS

The mean DPI value was 0.29 ± 0.05 in patients suffering from colon cancer with hepatic metastases and 0.12 ± 0.03 in the healthy control group. The DPI value was significantly higher in patients with liver metastases (p < 0.05). PD-ECGF expression in patients with colorectal liver metastases was significantly higher than that in the group without liver metastases (p < 0.05). A positive correlation was found between DPI value and PD-ECGF expression in patients with liver metastases (p < 0.05).

CONCLUSIONS

DPI and PD-ECGF may be valuable factors when screening hepatic metastases in patients with colorectal cancer and serve as practical measurements in postoperative follow-up.

Expression of smooth muscle alpha-actin and migratory behaviour of cloned cerebral endothelial cells (cEC) which exhibited two distinct phenotypes (type I, type II) were studied. Removal of mitogenic factors (alpha ECGF, ECGS) and heparin from the culture medium resulted in a smooth muscle-like appearance (type II) of the cells, expression of smooth muscle alpha-actin protein and smooth muscle actin mRNA and in an increased migratory activity. In contrast, addition of growth factors and heparin led to a cobblestone-like phenotype (type I) which lacked the expression of smooth muscle alpha-actin but expressed other proteins as determined by 2-D-gel electrophoresis.

Culture of endothelial cell is gotten from human umbilical cord by enzymatic digestion. For the growth of cells in culture, medial RPMI 1640 with 20% mixed human serum (NHS) or 20% fetal calf serum (FCS), endothelial cell growth factor (ECGF) and heparin have been used. Plastic, 0.1% gelatin and fibronectin have been used as a fundament. Immune identification of endothelial cells was culture is performed by monoclonal antibodies on vWF:Ag. Homogeneous cell line in culture might be used as in vitro model in both experimental and practice work.

OBJECTIVE

To establish a simple and convenient method for the culture of human umbilical vein endothelial cells (HUVECs) and study its characterization in vitro.

METHODS

Human Umbilical cord was isolated and digested by collagenase type I,and then it was cultured in 1.5% geltain coated dish with 10% fetal bovine serum(FBS)，heparin sodium andβ-endothelial cell growth factor(β-ECGF) in human endothelial basal growth medium．HUVECs were identified by anti-human factor Ⅷ related antigen and CD31 immunohistochemical staining．

RESULTS

We could successfully culture HUVECs by using this method. HUVECs attached the dish in 24 hours and the confluence was seen in 5 days. HUVECs were generally positive for anti-human factor Ⅷ related antigen and CD31．

CONCLUSIONS

It is a fast and effective method to successfully culture purified HUVECs in which collagenase type I was used to digest HUVECs with glass tube connected to T-tube, human endothelial basal growth medium containing 10% FBS,heparin sodium and β-ECGF in 1.5% geltain coated dish.

Progestins diminish the estrogen-induced angiogenic potential related to basic fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) in uterine endometrial cancer cells. This led us to study the effect of various steroids on the expression of platelet-derived endothelial cell growth factor (PD-ECGF) as the other pertinent angiogenic factor in well-differentiated uterine endometrial cancer cell line Ishikawa. In Ishikawa cells, estradiol induced the expression of PD-ECGF and its mRNA. The estrogen-induced expression was increased approximately two-fold by progesterone and by its metabolite, 17alpha-hydroxyprogesterone, but not by medroxyprogesterone acetate (MPA). Therefore, progesterone and 17alpha-hydroxyprogesterone as endogenous steroids might induce PD-ECGF-related angiogenic potential in uterine endometrial cancer cells, but not MPA as a synthetic steroid. In conclusion, the failure of PD-ECGF induction by MPA might be the great merit of anti-angiogenic treatment with MPA for uterine endometrial cancers.

Thymidine phosphorylase (TP; EC 2.4.2.4) is involved regulation of intra- or extracellular thymidine concentration, angiogenesis, cancer chemotherapy, radiotherapy, as well as tumor imaging. Although the liver is main site of pyrimidine metabolism and contains high levels of TP, nonetheless, purification and characterization of human hepatic TP has not been accomplished. We here report the purification and characterization of native human hepatic TP. The enzyme was purified to apparent homogeneity by a procedure shorter and more efficient than previously reported methods. Human hepatic TP has an apparent Kthymidine of 285 ± 55 μM. Like the enzyme from other tissues, it is highly specific to 2'-deoxyribosides. However, in contrast to TP from other normal tissues, the hepatic enzyme is active in the phosphorolysis of 5'-deoxy-5-fluorouridine, and the riboside 5-fluorouridine. Furthermore, native hepatic TP exists in different aggregates of 50 kDa subunits, with unknown aggregation factor(s) while TP from extra tissues exists as a homodimer. Isoelectric point was determined as 4.3. A total of 65 residues in the N-terminal were sequenced. The sequence of these 65 amino acids in hepatic TP has 100% sequence and location homology to the deduced amino acid sequence of the platelet derived-endothelial cell growth factor (PD-ECGF) cDNA. However, and contrary to PD-ECGF, the N-terminal of hepatic TP is blocked. The block was neither N-formyl nor pyrrolidone carboxylic acid moieties. The differences in substrate specificities, existence in multimers, and weak interaction with hydroxyapatite resin strongly suggest that hepatic TP is distinct from the enzyme in normal extrahepatic tissues. These results may have important clinical implications when TP is involved in activation or deactivation of chemotherapeutic agents in different tissues.

Localization of platelet-derived endothelial cell growth factor (PD-ECGF) in the surgical specimens of 11 human glioblastomas and 12 meningiomas was immunohistochemically examined with a polyclonal anti-PD-ECGF rabbit IgG. PD-ECGF was mainly localized in macrophages distributing around blood vessels at the peripheries of tumor tissue, especially of glioblastoma. PD-ECGF-positive macrophages were frequently accumulated in the vascular-rich stroma of glioblastoma, where occasionally expressed proliferating cell nuclear antigen-positive endothelial cells. However, few macrophages expressing PD-ECGF were scatteringly seen in meningioma. These findings suggest that PD-ECGF plays an important role in the growth of glioblastoma by affecting the stromal angiogenesis.

The development of drug resistance and especially of multidrug resistance (MDR) is a serious problem during treatment of various malignant tumors. Overexpression of P-glycoprotein (P-gp) has been observed in various multidrug resistant cells. P-gp acts as an energy-dependent drug-efflux pump. We have shown that the expression of P-gp is closely related to clinical drug resistance in some type of leukemia. We have found agents that reverse MDR and elucidated the molecular basis for the reversal of MDR. Thymidine phosphorylase (dThdPase) is an enzyme involved in pyrimidine nucleoside metabolism, but little is known about its physiological functions. We purified dThdPase from human placenta, and isolated partial cDNA clones for dThdPase. Amino-acid sequences were deduced from nucleotide sequences of the longest clone (288 base pairs). This sequence was 100% identical to the sequence of platelet derived endothelial cell growth factor (PD-ECGF) (residues 149-244). dThdPase is one of the activating enzymes for fluorinated pyrimidines. The sensitivity of KB cells transfected with PD-ECGF cDNA to doxifluridine was considerably higher than that of non-transfected KB cells.

OBJECTIVE

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is an essential enzyme in converting 5'-deoxy-5-fluorouridine (5'-DFUR), and 5-fluorouracil (5-FU) to their active metabolites in vivo, and can be up-regulated by some cytokines such as interleukin-1, and interferon gamma (INFgamma). This study was to observe the regulative effect of INFgamma on expression of PD-ECGF/TP, and its relation with the anti-cancer effect of 5'-DFUR, and 5-FU on RT4 bladder cancer cells.

METHODS

PD-ECGF/TP mRNA, and protein expression were determined by reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot analysis, respectively. Cytotoxicity of 5'-DFUR, and 5-FU against RT4 cells was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymetho-xyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay.

RESULTS

Expression levels of PD-ECGF/TP mRNA and protein were elevated in RT4 cells after cultured with INFgamma. INFgamma reduced IC50s of 5'-DFUR [from (9.7+/-0.2) mmol/L to (3.7+/-0.9) mmol/L], and 5-FU [from (130.0+/-21.2) mmol/L to (49.3+/-18.4) mmol/L] in RT4 cells.

CONCLUSIONS

INFgamma enhances cytotoxicity of 5'-DFUR, and 5-FU against RT4 cells through induction of PD-ECGF/TP. INFgamma/5'-DFUR or INFgamma/5-FU combination treatment may lead to better chemotherapeutic results in human bladder cancer.

Delayed postoperative wound healing in previously radiated cancer patients is a common and debilitating occurrence. Prior studies have given evidence that endothelial cell growth factor (ECGF) can accelerate neovascularization in soft tissue. To explore its effects in irradiated tissue, an ECGF-heparin formulation (7200 micrograms/mL) contained in Gelfoam was applied to previously irradiated (N = 38) and nonirradiated skin flaps (N = 38) on rabbit ears. Both peripheral neovascularization and flap viability were quantitatively documented by polar planimetry and digital angiography in all flaps. The ECGF-heparin flaps had a greater than twofold increase in both vascularity and viability when compared to their controls among the irradiated and nonirradiated flaps (P < .01). Also, the additional viability and vascularization effects from ECGF-heparin did not appear statistically altered by previous radiation. These results support the promising angiogenic effect of ECGF-heparin in previously irradiated surgical wounds.