Different distributions of interstitial cells of Cajal and platelet-derived growth factor receptor-α positive cells in colonic smooth muscle cell/interstitial cell of Cajal/plateletderived growth factor receptor-α positive cell syncytium in mice

AIM To investigate the distribution and function of interstitialcells of Cajal(ICCs) and platelet-derived growth factor receptor-α positive(PDGFRα+) cells in the proximal and distal colon.METHODS The comparison of colonic transit in the proximal and distal ends was performed by colonic migrating motor complexes(CMMCs). The tension of the colonic smooth muscle was examined by smooth muscle spontaneous contractile experiments with both ends of the smooth muscle strip tied with a silk thread. Intracellular recordings were used to assess electrical field stimulation(EFS)-induced inhibitory junction potentials(IJP) on the colonic smooth muscle. Western blot analysis was used to examine the expression levels of ICCs and PDGFRα in the colonic smooth muscle.RESULTS Treatment with NG-nitro-L-arginine methyl ester hydrochloride(L-NAME) significantly increased the CMMC frequency and spontaneous contractions, especially in the proximal colon, while treatment with MRS2500 increased only distal CMMC activity and smooth muscle contractions. Both CMMCs and spontaneous contractions were markedly inhibited by NPPB, especially in the proximal colon. Accordingly, CyPPA sharply inhibited the distal contraction of both CMMCs and spontaneous contractions. Additionally, the amplitude of stimulationinduced nitric oxide(NO)/ICC-dependent slow IJPs(sIJPs) by intracellular recordings from the smooth muscles in the proximal colon was larger than that in the distal colon, while the amplitude of electric field stimulationinduced purinergic/PDGFRα-dependent fast IJPs(fIJPs) in the distal colon was larger than that in the proximal colon. Consistently, protein expression levels of c-Kit and anoctamin-1(ANO1) in the proximal colon were much higher, while protein expression levels of PDGFRα and small conductance calcium-activated potassium channel 3(SK3) in the distal colon were much higher.CONCLUSION The ICCs are mainly distributed in the proximal colon and there are more PDGFRα+ cells are in the distal colon, which generates a pressure gradient between the two ends of the colon to propel the feces to the anus.

Deficiency of platelet-derived growth factor receptor-α-positive cells in Hirschsprung's disease colon

AIM: To investigate whether the expression of platelet-derived growth factor receptor-α-positive (PDGFRα+)-cells is altered in Hirschsprung’s disease (HD).METHODS: HD tissue specimens (n = 10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 10). Immunolabelling of PDGFRα+-cells was visualized using confocal microscopy to assess the distribution of these cells, while Western blot analysis was undertaken to quantify PDGFRα protein expression.RESULTS: Confocal microscopy revealed PDGFRα+-cells within the mucosa, myenteric plexus and smooth muscle in normal controls, with a marked reduction in PDGFRα+-cells in the HD specimens. Western blotting revealed high levels of PDGFRα protein expression in normal controls, while there was a striking decrease in PDGFRα protein expression in the HD colon.CONCLUSION: These findings suggest that the altered distribution of PDGFRα+-cells in both the aganglionic and ganglionic HD bowel may contribute to the motility dysfunction in HD.

Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

High levels of serum platelet-derived growth factor-AA and human epidermal growth factor receptor-2 are predictors of colorectal cancer liver metastasis

AIM To develop predictive markers in blood for colorectal cancer liver metastasis.METHODS Twenty colorectal cancer patients were selected and divided into two groups. Group A consisted of 10 patients whose pathological TNM stage was ⅢC(T3-4N2M0), while another 10 patients with synchronous liver metastasis(TNM stage Ⅳ) were recruited for group B. During the surgical procedure, a 10-ml drainage vein(DV) blood sample was obtained from the DV of the tumor-bearing segment prior to the ligation of the DV. At the same time, a 10-ml peripheral vein(PV) blood sample was collected via peripheral venipuncture. The serum levels of 24 molecules that are potentially involved in the mechanism of liver metastasis in both DV blood and PV blood were analyzed by using high-throughput enzyme-linked immunosorbent assay technology.RESULTS Univariate analysis revealed that platelet-derivedgrowth factor AA(PDGFAA) in DV blood(d PDGFAA)(P = 0.001), PDGFAA in PV blood(p PDGFAA)(P = 0.007), and human epidermal growth factor receptor-2 in PV blood(p HER2)(P = 0.001), p MMP7(P = 0.028), pR ANTES(P = 0.013), and pE GF(P = 0.007) were significantly correlated with synchronous liver metastasis. Multivariate analysis identified d PDGFAA(HR = 1.001, P = 0.033) and p HER2(HR = 1.003, P = 0.019) as independent predictive factors for synchronous liver metastasis. Besides, high peripheral HER2 level may also be a risk factor for metachronous liver metastasis, although the difference did not reach statistical significance(P = 0.06). Significant correlations were found between paired DV and PV blood levels for PDGFAA(r = 0.794, P < 0.001), but not for HER2(r = 0.189, P = 0.424).CONCLUSION PDGFAA in tumor drainage and HER2 in PV blood may be useful predictive factors for synchronous liver metastasis of colorectal cancer.

Expression and functional characterization of platelet-derived growth factor receptor-like gene

AIM:To investigate the role of platelet-derived growth factor receptor-like gene(PDGFRL)in the anti-cancer therapy for colorectal cancers(CRC).METHODS:PDGFRL mRNA and protein levels were measured by reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry in CRC and colorectal normal tissues.PDGFRL prokaryotic expression vector was carried out in Escherichia coli(E.coli),and purified by immobilized metal affinity chromatography.The effect of PDGFRL protein on CRC HCT-116 cells was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide(MTT),clone counting,cell cycle,and wound healing assay.RESULTS:Both RT-PCR and immunohistochemistry showed that the expression of PDGFRL in colorectal normal tissues was higher than in cancer tissues.Recombinant pET22b-PDGFRL prokaryotic expression vector was successfully expressed in E.coli,and the target protein was expressed in the form of inclusion bodies.After purification and refolding,recombinant human PDGFRL(rhPDGFRL)could efficiently inhibit the proliferation and invasion of CRC HCT-116 cells detected by MTT,clone counting and wound healing assay.Moreover,rhPDGFRL arrested HCT-116 cell cycling at the G0/G1 phase.CONCLUSION:PDGFRL is a potential gene for application in the anti-cancer therapy for CRC.

Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer

The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.

Activation of JAK-STAT pathway is required for platelet-derived growth factor-induced proliferation of pancreatic stellate cells

AM: To clarify the role of Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway in platelet-derived growth factor (PDGF) induced proliferation in activated pancreatic stellate cells (PSCs). METHODS: PSCs were isolated from rat pancreas tissue, and used in their culture-activated, myofibroblast-like phenotype. STAT-specific binding activity was assessed by electrophoretic mobility shift assay. Activation of Src, JAK2, STAT1, STAT3, and ERK was determined by Western blotting using anti-phosphospecific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. RESULTS: PDGF-BB induced STAT-specific binding activity, and activation of Src, JAK2, STAT1, STAB, and ERK. Ethanol and acetaldehyde at clinically relevant concentrations decreased basal activation of JAK2 and STAT3. PDGF-induced activation of STAT1 and STAT3 was inhibited by a Src inhibitor PP1 and a JAK2 inhibitor AG490, whereas PDGF-induced activation of ERK was inhibited by PP1, and not by AG490. PDGF-induced proliferation was inhibited by PP1 and AG490 as well as by STAT3 antisense oligonucleotide. CONCLUSION: PDGF-BB activated JAK2-STAT pathway via Src-dependent mechanism. Activation of 3AK2-STAT3 pathway, in addition to ERK, may play a role in PDGF-induced proliferation of PSCs.

Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury

The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury.The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain,while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies.Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with plateletderived growth factor(80μg/kg)at the injury site.Our results showed that after platelet-derived growth factor administration,spinal cord injury,neuronal apoptosis,and blood-spinal cord barrier permeability were reduced,excessive astrocyte proliferation and the autophagyrelated apoptosis signaling pathway were inhibited,collagen synthesis was increased,and mouse locomotor function was improved.In vitro,human umbilical vein endothelial cells were established by exposure to 200μM H2O2.At 2 hours prior to injury,in vitro cell models were treated with 5 ng/mL platelet-derived growth factor.Our results showed that expression of blood-spinal cord barrier-related proteins,including Occludin,Claudin 5,andβ-catenin,was significantly decreased and autophagy was significantly reduced.Additionally,the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine,an autophagy inhibitor,for 3 successive days prior to spinal cord injury.Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy,improve the function of the blood-spinal cord barrier,and promote the recovery of locomotor function post-spinal cord injury.Approval for animal experiments was obtained from the Animal Ethics Committee,Wenzhou Medical University,China(approval No.wydw2018-0043)in July 2018.

Effect of recombinant human platelet-derived growth factor B on cat corneal endothelial cell viability mediated by adeno-associated virus

AIM: To transduce recombinant human platelet-derived growth factor B (PDGF-B) gene adeno-associated virus(AAV) to in vitro cultured cat corneal endothelial cell (CEC) and observe the effect of the expressed PDGF-BB protein on the viability of cat CEC. METHODS: Cat cornea endothelium was torn under microscope and rapidly cultivated in DMEM to form single layer CEC and the passage 2 endothelial cells were used in this study. The recombinant human PDGF-B gene AAV was constructed and transduced into cat CEC directly. Three groups were as following: blank control group, AAV control group and recombinant AAV group. At 24 hours, 48 hours, and 5 days after transduction, total RNA was extracted from the CEC by Trizol and the expression of PDGF-B gene was detected by fluorescence quantitative polymerase chain reaction. Viability of the transduced CEC was detected at 48 hours after transduction by MTT assay. Cell morphology was observed under inverted phase contrast microscope. RESULTS: With the torn endothelium culture technique, we rapidly got single layer cat CEC. At 24 hours, 48 hours and 5 days after transduction, fluorescence quantitative polymerase chain reaction showed there was no significant difference of the expressed PDGF-B gene mRNA between blank control group and AAV control group (P>0.05). In contrast, there were significant differences between two control groups and recombinant AAV group (P<0.05). MTT assay showed that in recombinant AAV group, the expressed PDGF-BB protein could promote the viability of cat CEC. Morphology observation showed at 48 hours after transduction, cells in CEC-AAV-PDGF-B group proliferated into bigger scales in regular triangle to hexagon shape with distinct boundary, while the number of cells was significantly less in the two control groups. CONCLUSION: The recombinant AAV-PDGF-B expresses biological active PDGF-BB protein in cat CEC, which promotes the viability and proliferation of cells.

Vascular endothelial growth factor/platelet-derived growth factor receptor pathway is involved in bone marrow mesenchymal stem cell differentiation and directional migration toward gliomas

BACKGROUND： Vascular endothelial growth factor （VEGF） induces bone marrow-derived mesenchymal stem cell （BMSC） differentiation into vascular endothelial-like cells and promotes BMSC migration toward gliomas. However, the molecular mechanisms by which VEGF induces BMSC differentiation and migration remain poorly understood. OBJECTIVE; To investigate the role of platelet-derived growth factor （PDGF） receptor （PDGFR） in BMSC differentiation and migration induced by VEGE DESIGN, TIME AND SETTING： A parallel, controlled, in vitro experiment was performed at the Molecular Neurobiology ＆ Neural Regeneration and Repairing Laboratory, Anhui Provincial Hospital of Anhui Medical University, China from June 2008 to March 2009. MATERIALS： U87 glioma cells were purchased from Shanghai Institutes for Biological Sciences; mouse anti-human PDGFR and VEGF receptor （VEGFR） monoclonal antibodies were purchased from Peprotech, USA. METHODS： Isolated BMSCs were precultured with neutralizing antibody for VEGFR-1, VEGFR-2, PDGFR-α, and PDGFR-β to block biological activity of related receptors, followed by induced differentiation with 50μg/L VEGF. BMSCs induced with 50μg/L VEGF alone served as the VEGF-induced group. The control group remained untreated. MAIN OUTCOME MEASURES： Cell surface markers were identified by flow cytometry; BMSC surface cytokine receptor expression was detected by reverse transcription-polymerase chain reaction; the Transwell model was used to observe cell migration. RESULTS： After blocking the PDGFR, VEGF did not induce BMSC cell surface marker CD-31 or von Willebrand factor （vWF） expression. However, inhibition with VEGF receptor blocking agents, VEGF induced BMSCs to express CD-31 and vWE Following inhibition of the PDGFR, the number of cells migrating through the polycarbonate membrane Transwell chamber was decreased, as well as the number of BMSCs migrating to glioma cells. However, through the use of VEGF receptor blocking agents, the number of migrating cells remained unchanged. VEGF preculture increased the number of BMSCs migrating to gliomas. CONCLUSION： VEGF interacts with PDGFRs on the BMSC surface to attract BMSC directional migration and induce BMSC differentiation. The VEGF/PDGFR pathway participates in BMSC directional migration to glioma. VEGF pretreatment increased efficiency of BMSC migration to glioma.

Effect of Electroacupuncture on Platelet-derived Growth Factor and the Ultrastructure of Mitochondria in Rats with Diabetic Gastroparesis

Objective To observe the effect of electroacupuncture(EA)at the pressure points Zu San Li(ST36),San Yin Jiao(SP6)and Liang Men(ST21)on platelet-derived growth factor(PDGF)and the ultrastructure of mitochondria in rats with diabetic gastroparesis(DGP).Methods Sixty Sprague Dawley(SD)rats were randomly separated into a normal control group(NC,n=10)and a modeling group(n=50).Rats in the modeling group received an injection of 2%streptozotocin(STZ)and a high-fat and highglucose diet for eight weeks to establish a DGP rat model.At the same time,blood glucose and a general symptom score were recorded every week.After modeling,30 successfully modeled rats were randomly separated into the following groups:the DGP group(n=10),the EA group(n=10)and the metoclopramide(MP)group(n=10).After three weeks of intervention,the gastrointestinal propulsive rate was measured by measuring the optical density(OD).The concentration of Ca2+was determined by fluorescence immunoassay,and levels of serum insulin(INS)and PDGF were determined by ELISA.The ultrastructure of mitochondria was observed with transmission electron microscopy.Results(1)After intervention,levels of blood glucose and the general symptom score were greatly decreased in the EA group compared to the DGP group(P<0.01).Compared with the DGP group,the gastric emptying rate and the intestinal propulsive rate of the EA group was significantly improved(P<0.01),and there was no statistically significant difference between the EA and the NC groups.(2)Compared with the NC group,the levels of INS in the DGP group markedly decreased(P<0.05),but there was no significant difference of INS levels between the EA and the MP roups.(3)Compared with the DGP group,theconcentration of Ca2+in the EA and the MP groups significantly increased(P<0.01,P<0.05,respectively).(4)Compared with the NC group,the average OD of PDGF in the DGP group was significantly higher(P<0.01).Compared with the DGP group,levels of PDGF in the EA group increased significantly(P<0.01).(5)There were abundant mitochondria with a clear structure and complete cristae in the NC group.However,in the DGP group,mitochondria were severely swollen,partly vacuolated,and cristae were either fractured,absent,or shortened.In the EA group,mitochondria were slightly swollen,with clear cristae.Conclusions Electroacupuncture at the points Zu San Li(ST36),San Yin Jiao(SP6)and Liang Men(ST21)may improve gastric motility in DGP by up-regulating the amount of PDGF and improving the ultrastructure of mitochondria.

KIT and platelet-derived growth factor receptor α wild-type gastrointestinal stromal tumor associated with neurofibromatosis type 1: Two case reports

BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of developing gastrointestinal tumors, including rare types such as GIST.CASE SUMMARY A 60-year-old male Chinese patient was diagnosed with NF-1 10 years ago and presented with upper abdominal discomfort and black stools. Endoscopic ultrasonography and an enhanced abdominal computed tomography scan revealed a mass located 4 cm from the muscular layer of the descending duodenum. A 59-year-old Chinese woman who was diagnosed with NF-1 25 years ago presented with sudden unconsciousness and black stools. Multiple masses in the duodenum were noted by echogastroscopy and an enhanced abdominal computed tomography scan. Both patients presented with cutaneous neurofibromas. The histologic examination of tumors from both patients revealed spindle cells and low mitotic activity. Immunohistochemically, the tumor cells showed strong positivity for KIT(CD117), DOG-1, CD34, and Dehydrogenase Complex Subunit B, and negativity for SMA, desmin, S-100, and β-catenin. None of the six tumors from two patients had KIT exon 9, 11, 13, or 17 or platelet-derived growth factor receptor α exon 12 or 18 mutation, which is a typical finding for sporadic GISTs. None of the six tumors from the two patients had a BRAFV600 E mutation. The patients were alive and well during the follow-up period(range:0.6-5 yr).CONCLUSION There have been only a few previous reports of GISTs associated with NF-1.Although GISTs associated with NF-1 have morphologic and immunohistochemical similarities with GISTs, the pathogenesis, incidence,genetic background, and prognosis are not completely known. A medical history of NF-1 in a patient who has gastrointestinal bleeding or anemia and an intraabdominal mass with nonspecific computed tomography features may help in diagnosing GIST by virtue of the well-known association of these two entities.Molecular genetic studies of cases indicated that GISTs in NF-1 patients have a different pathogenesis than sporadic GISTs.

Changes of Circulating Platelet-Derived Growth Factor and Granulocyte Colony-Stimulating Factor in Patients with Condyloma Acuminatum

Objective: To study the expression levels of platelet-derived growth factor (PDGF) and granulocyte colony-stimulatingfactor (G-CSF) in peripheral blood and their role in thepathogenesis of Condyloma acuminatum (CA). Methods: Sera were taken from 70 patients with Condylomaacuminatum and compared with 35 healthy controls. PDGFand G-CSF in serum were quantitated using a dual antibodysandwich enzyme-linked immunoabsorbent assay (ELISA). Results: Serum concentrations of PDGF and G-CSF weresignificantly increased in patients with Condylomaacuminatum (CA) compared to controls (P<0.001 and P<0.005respectively). Serum levels of PDGF and G-CSF correlatedwith clinical severity of CA, but no significant difference wasobserved between different duration of disease groups. Asignificant positive correlation was noticed between neutrophilcount and G-CSF levels (γ=0.38, P<0.001), and the neutrophilcount showed no significant correlation with PDGE Conclusion: The results indicated that increased expressionof PDGF an -CSF in peripheral blood might be involved in pathogenesis of CA.

Effect of Retinoic acid on Platelet-derived Growth Factorand Lung Development in Newborn Rats

Summary: The influence of platelet-derived growth factor (PDGF) on lung development in newborn rats and the effect of retinoic acid (RA) on PDGF in lung development were investigated. Newborn Sprague-Dawley (SD) rats were randomly assigned to two groups: control group and RA group. The rats in RA group was intraperitoneally injected with all trans-retinoic acid (500 μg/kg every day) for consecutive 3 days after birth, while those in the control group were not subjected to intervention. Immunohistochemical assay was performed to locate the expression of PDGF. mRNA levels of PDGF were measured by reverse transcription polymerase chain reaction (RT-PCR) at age of 1, 3, 5, 7, 10, 14, 21 days. The method of radial alveolar counts (RAC) was used to measure the amount of the alveoli of the lungs. It was found that with increasing days, levels of PDGF-A and PDGF-B changed to verying degrees. RA could elevate significantly the expression levels of PDGF-A mRNA and protein (P<0.01), but not affect the expression levels of PDGF-B mRNA and protein markedly (P>0.05). It is suggested that PDGF might play an important role in lung development. RA can stimulate lung development through increasing the expression levels of PDGF-A mRNA and protein.

Effects of interleukin-1α on platelet-derived growth factor release from bovine cerebral microvascular endothelial cells

The present study showed that, interleukin-1α (IL-1α) stimulateal cultured bovine cerebral microvascular endothelial cells (BCMEC) releasing growth factor which promoted bovine cerebral microvascular smooth muscle cells (BCMSMC) proliferation in a dose-dependent manner. The mitogenic activity in conditioned medium of BCMEC stimulated by IL-1α was neutralized significantly by the antibody to platelet-derived growth factor (PDGF). Imperatorin (Imp), iso-Imperatorin (iso Imp) and 6-(α,α-phenylacetylpiperazinyl)phenyl-5-methyl-4,5-dihydro-3 (2H)-pyridazinone (PMDP) did not affect the releasing of PDGF from IL-1α stimulated BCMEC, but inhibited the promotion of PDGF on the proliferation of BCMSMC. We concluded that the promotion of IL-1α on the proliferation of BCMSMC should be mediated by some growth factors, such as PDGF.

Expression of NG2 and platelet-derived growth factor receptor alpha in the developing neonatal rat brain

Platelet-derived growth factor receptor alpha （PDGFRct） is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphol- ogy of oligodendrocyte precursor cells labeled by NG2 or PDGFRa in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive （NG2＋） cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2~ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRct positive （PDGFRa＋） cells were coincident with NG2＋ cells. The co- localization of NG2 and PDGFRu in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRa were predominantly in the early postnatal stage of development. The numbers of NG2＋/PDGFRa＋ cells and PDGFRa＋ cells decreased, but the number of NG2＋ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRu, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRct are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.

Effects of IL-4 on cyclooxygenase-2 and platelet-derived growth factor in the lungs of COPD rats

Objective： To explore the role of interleukin 4（IL-4）, expressions of cyclooxygenase-2 （COX-2） and platelet-derived growth factor （PDGF） in the model of chronic obstructive pulmonary disease （COPD）, in the lungs of rats. Methods： Male Wistar rats were used to build up the model of COPD. Rats were randomly divided into the control group and model group, the IL-4 group and the dexamethasone group. The expressions of COX-2, PDGF-A and PDGF-B in the lung tissue were detected by western blotting and RT-PCR. Results： The expressions of COX-2, PDGF-A and PDGF-B in the model group were increased significantly. Those expressions in the IL-4 and dexamethasone group were notably decreased. Conclusion： IL-4 and dexamethasone could interfere in the establishment of COPD. The expressions of COX-2 and PDGF in the lung tissue of COPD were increased significantly and IL-4 and dexamethasone could decrease those expressions.

Human epidermal growth factor receptor-2 gene amplification in gastric cancer using tissue microarray technology

AIM:To assess human epidermal growth factor receptor-2 (HER2)-status in gastric cancer and matched lymph node metastases by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH).METHODS:120 cases of primary gastric carcinomas and 45 matched lymph node metastases from patients with full clinicopathological features were mounted onto multiple-punch and single-punch tissue microarrays,respectively,and examined for HER2 overexpression and gene amplification by IHC and CISH.RESULTS:Twenty-four tumors (20%) expressed HER2 immunohistochemically.An IHC score of ≥ 2+ was observed in 20 tumors (16.6%).HER2 amplification was detected by CISH in 19 tumors (15.8%) and in their matched lymph node metastases.A high concordancerate was found between HER2 positivity (as detected by IHC) and HER2 gene amplification (as detected by CISH),since 19 of the 20 IHC positive cases were amplified (95%).All amplified cases had 2+ or 3+ IHC results.Amplification was associated with intestinal phenotype (P < 0.05).No association with grading,staging or survival was found.CONCLUSION:In gastric cancer,HER2 amplification is the main mechanism for HER2 protein overexpression and is preserved in lymph node metastases.

Increased expressions of vascular endothelial growth factor(VEGF),VEGF-C and VEGF receptor-3 in prostate cancer tissue are associated with tumor progression

Aim： To investigate the differences in microvessel densities （MVD） and the expressions of vascular endothelial growth factor （VEGF）, VEGF-C and VEGF receptor-3 （VEGFR-3） between prostate cancer （PCa） tissues and adjacent benign tissues, and to explore the correlations among MVD, Jewett-Whitmore staging, Gleason scores and expressions of VEGF, VEGF-C and VEGFR-3 in the progression of PCa. Methods： An immunohistochemical approach was adopted to detect the expressions of CD34, VEGF, VEGF-C and VEGFR-3 in both cancer areas and peripheral benign areas of 71 primary prostatic adenocarcinoma specimens. A statistic analysis was then performed according to the experimental and clinic data. Results： Significantly upregulated expressions of VEGF, VEGF-C and VEGFR-3 were all found in malignant epithelium/cancer cells compared with adjacent benign epithelium （P 〈 0.01）. Patients in stage D had a significantly higher score than patients in stage A, B or C when comparing the expression of VEGF-C or VEGFR-3 in the tumor area （P 〈 0.01）. In addition, significant correlations were observed between Jewett-Whitmore staging and VEGF-C （rs = 0.738, P 〈 0.01）, clinical staging and VEGFR-3 （rs = 0.410, P 〈 0.01）, VEGF-C and Gleason scores （rs = 0.401, P 〈 0.01）, VEGFR-3 and Gleason scores （rs = 0.581, P 〈 0.001） and MVD and VEGF （rs = 0.492, P 〈 0.001）. Conclusion： Increased expressions of VEGF and VEGF-C were closely associ- ated with progression of PCa. The main contribution of increased VEGF expression for PCa progression was to upregulate MVD, which maintained the growth advantage of tumor tissue. However, the chief role of increased expressions of VEGF-C and VEGFR-3 was to enhance lymphangiogenesis and provide a main pathway for cancer cells to disseminate. （Asian J Androl 2006 Mar; 8： 169-175）

Basic Fibroblast Growth Factor and Fibroblast Growth Factor Receptor-1 in Human Meningiomas

The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features and angiogenesis were investigated by means of immunohistochemical technique. The expression of bFGF and FGFR-1 was detected by antibody of bFGF or FGFR-1. The tumors' angiogenesis was evaluated by microvascular density (MVD) and, which was observed by use of CD34-antibody immunohistochemically. The results showed that there were varied degrees of the expression of bFGF and FGFR-1 proteins in meningiomas. The expression was correlated with the tumors' histological characters and angiogenesis. It was concluded that bFGF and FGFR-1 might play important roles in meningiomas' angiogenesis and proliferation. The expression positive rate of bFGF and FGFR-1 may provide an indication of evaluating the histological and malignant degree of the tumor.