[Application of trifoliate flap design of radial forearm flap in reconstruction of defects after mouth floor cancer resection].

Objective: To evaluate the effect of trifoliate flap design of radial forearm flap in reconstruction of defects after mouth floor cancer resection. Methods: From June 2016 to December 2019, 12 patients with defect after resection of mouth floor cancer were treated with trifoliate flap design of radial forearm flap. All of these patients were T2 stage, included 9 well-differentiated squamous cell carcinoma (SCC) and 3 moderate differentiated SCC. The defect size ranged from 8.0 cm×6.0 cm to 5.0 cm×4.5 cm after resection of tumor and neck dissection. All defects were repaired with trifoliate flap design of radial forearm flap. The flap size ranged from 8.0 cm×2.0 cm to 4.0 cm×1.5 cm, the donor site was sutured directly on Z plasty. Results: All flaps completely survived well. Both the wound and the donor site were stage Ⅰ healing. With the average follow-up of 38.6 months, the swallowing and speech function were satisfactory. Conclusions: Trifoliate flap design of radial forearm flap can effectively repair the postoperative defect of mouth floor cancer, and the donor site can be directly sutured on Z plasty. This technique can avoid forearm scar caused by skin grafting and the formation of the second donor site.

Enhanced molybdenum(VI) removal using sulfide-modified nanoscale zerovalent iron: kinetics and influencing factors.

The overall goal of this study is to investigate the effect of sulfidated nanoscale zerovalent iron (S-nZVI) on the removal of hexavalent molybdate (MoO42-) under different aquatic chemistry conditions. Surface analysis suggests that Mo(VI) is removed mainly by adsorption and co-precipitation onto the surface of S-nZVI and a small amount of Mo(VI) can be reduced to Mo(V) species. The results of batch tests show that Mo(VI) removal by S-nZVI are well described with the pseudo-second-order adsorption model. The removal rate increases with a decrease in solution pH (4.0-9.0) and is significantly affected by the S/Fe ratio of S-nZVI, with the optimal S/Fe ratio being 0.5. The presence of anions WO42- or CrO42- can reduce the Mo(VI) removal, which is likely because they compete for adsorption sites on the solid surfaces. The divalent cations Ni2+, Cu2+ and Co2+ also inhibit the removal of Mo(VI) whereas Zn2+, Ca2+ and Mg2+ enhance it. After being aged for 35 d in water, S-nZVI still exhibits high reactivity towards Mo(VI) removal (57.39%). The study demonstrates that S-nZVI can be used as an environmentally friendly material for effectively removing Mo(VI) from contaminated water.

[Study on the differentiation of rat bone marrow mesenchymal stem cells into chondrocytes induced by TGF-beta 3].

Objective: To explore the methods for the differentiation of rat bone marrow mesenchymal stem cells (BMMSCs) into chondrocytes induced by transforming growth factor (TGF)-beta 3 in vitro, and search for a reliable seed cell for the regeneration and repair of articular cartilage in osteoarthritis. Methods: SD rat femoral and tibial BMMSCs were cultured by the whole bone marrow adherent method, and then the purity was identified by flow cytometry. P3 generation cells were induced and differentiated into chondrocytes by the induction of differentiation medium containing TGF-beta 3, and cell chondrogenic differentiation ability at different induction time points was detected. Results: The primary and passage cultured BMMSCs were spindle-shaped, and partly triangular. After passage, the proliferation rate of P3 generation cells was fast, like the growth of fish shoal or eddy. After chondrogenic induction, the cells were polygonal and triangular in the form of cluster growth, which was similar to chondrocyte morphology, and the cell proliferation was decreased. Immunofluorescence staining and Western blotting method showed that the cells had a large number of col Ⅱ fluorescent expression, and cells and extracellular matrix was stained blue by Alcian blue staining, with no significant difference at day 7 and day 14. After using Wnt signal blocker, col Ⅱ protein expression was significantly reduced, with statistically significant difference (P<0.05). Conclusion: TGF-beta 3 can rapidly induce the differentiation of BMMSCs into cartilage cells, which provides a good carrier for BMMSCs transplantation and the repair of articular cartilage, and thus to treat osteoarthritis.

Incorporation of log odds of positive lymph nodes into the AJCC TNM classification improves prediction of survival in oral cancer.

OBJECTIVES: To assess the prognostic performance of a new N classification that incorporates the log odds of positive lymph nodes (LODDS) into the routinely used pathological N classification for oral squamous cell carcinoma (OSCC) patients. DESIGN: Retrospective cohort study utilising LODDS into pN category was performed, and the AJCC TNM stage and T-New N-M stage were compared with respect to 5-year disease-specific survival (DSS) rates. The discriminability was evaluated from the linear trend chi-square test, Akaike information criterion (AIC) and Harrell's c-statistic. SETTING: Medical centrer in Taiwan. PARTICIPANTS: A total of 463 patients received primary surgery and neck dissection between 2004 and 2013 for OSCC. MAIN OUTCOME MEASURES: The discriminability for 5-year DSS rates. RESULTS: The median follow-up period was 54 months, the mean patient age was 54 ± 11 years and 428 patients (92.4%) were male. The patients with higher LODDS had worse 5-year DSS rates. Incorporation of LODDS into the prognostic model based on the seventh edition of the TNM classification significantly improved discriminative performance for 5-year DSS with a lower AIC (1883 versus 1897), and higher prediction accuracy (Harrell's c-statistic: 0.768 versus 0.764). CONCLUSIONS: By utilising a merger of the LODDS and pN classifications to create a new N classification has better discriminatory and predictive ability than pathological TNM staging and could help identify high-risk patients for intense adjuvant therapy.

miR-497 as a potential serum biomarker for the diagnosis and prognosis of osteosarcoma.

OBJECTIVE: The aim of this manuscript is to analyze the diagnostic and prognostic value of circulating miR-497 in the plasma of patients with osteosarcoma. PATIENTS AND METHODS: Serum miR-497 expression levels were measured by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Correlations between miR-497 expression and the clinicopathological features and prognosis of osteosarcoma patients were then evaluated. The receiver operating characteristic curve (ROC) and the area under the curve (AUC) were used to evaluate diagnostic accuracy. RESULTS: Our data showed that serum miR-497 expression was down-regulated in osteosarcoma patients compared with the matched healthy controls (p < 0.001). Then, low miR-497 expression was significantly associated with clinical stage (p = 0.001), distant metastasis (p = 0.001) and response to chemotherapy (p = 0.007). The receiver operating characteristic (ROC) curve analysis of the accuracy in distinguishing osteosarcoma patients from healthy controls yielded an area under the curve (AUC) value of 0.848 (95% confidence interval (CI), 0.773-0.923). Kaplan-Meier analysis results showed that patients with lower expression of miR-497 had shorter survival times (p < 0.001). Univariate and multivariate analyses revealed that the miR-497 expression level and various clinicopathological features were independent prognostic parameters. CONCLUSIONS: Our data showed that low serum miR-497 level was correlated with aggressive progression and poor prognosis of osteosarcoma. Serum miR-497 may be a potential biomarker for early detection and clinical evaluation in patients with osteosarcoma.

Outbreak of Serratia marcescens postoperative infection traced to barbers and razors.

BACKGROUND: Fourteen postoperative infections caused by Serratia marcescens were detected in patients on the neurosurgical wards and spinal surgery ward of a 2640-bed hospital between 26th December 2012 and 5th June 2013. AIM: To investigate the source of the outbreak, identify risk factors and implement infection control measures. METHODS: Cultures were collected from healthcare workers and potential environmental sources. S. marcescens isolates were characterized by antibiotic susceptibility testing and pulsed-field gel electrophoresis (PFGE). A retrospective case-control study was performed to identify the risk factors. FINDINGS: The outbreak involved 14 patients, five of whom required more than one surgical procedure. S. marcescens was isolated from cerebrospinal fluid, brain tissue, sputum and other secretions. S. marcescens was also cultured from samples taken from the hands of two barbers and their razors. Exposure to the two barbers [odds ratio (OR) 78.0, P < 0.0001] and wound drainage (OR 4.889, P = 0.028) were risk factors. Pre-operative shaving by the barbers was the only independent risk factor (OR 78.0, P < 0.0001). Isolates of S. marcescens from patients, barbers and razors were indistinguishable by PFGE and antibiotic susceptibility pattern. The outbreak ended after removal of the implicated barbers, extensive re-inforcement of infection control procedures and re-education. CONCLUSION: These results underscore the risk of postoperative infection associated with pre-operative wet shaving.

Fibroin protein/chitosan scaffolds and bone marrow mesenchymal stem cells culture in vitro.

A previous experiment demonstrated that fibroin protein and chitosan mixed in proper proportion presented good physical and chemical properties and biological characteristics, which can make up for their respective disadvantages. To observe the growth of bone marrow mesenchymal stem cells (BMSCs) on these fibroin protein/chitosan 3D scaffolds, induced rabbit BMSCs were seeded on fibroin protein/chitosan scaffolds. The cell adhesion rate was measured, and cell growth was observed under an inverted microscope and a scanning electron microscope. The cell adhesion rate increased with time. The inverted microscope observations showed that the cells on fibroin protein/chitosan scaffolds could not be seen clearly. As time passed, the number of cells around the stent increased and some cells stretched inside the scaffolds. Electron microscopy showed active cell growth and normal proliferation, and the granular and filamentous matrix substances could be seen around cells. The microfilaments of cell and scaffold materials were tightly connected. The cells not only grew on the surface of the adherent material, but also stretched inside of the materials. These results indicated that the fibroin protein/ chitosan mixed scaffolds have good biocompatibility.

The multidrug resistant modulator HZ08 reverses multidrug resistance via P-glycoprotein inhibition and apoptosis sensitization in human epidermoid carcinoma cell line KBV200.

Previous studies have demonstrated that the multidrug resistance modulator HZ08 has a strong multidrug resistance reversal effect in vitro and in vivo by inhibiting P-glycoprotein and multidrug resistance-associated protein 1 in K562/A02 and MCF-7/ADM cells, respectively. However, there are many other mechanisms responsible for resistance. In this study, MTT assay was used to examine the cytotoxicity and multidrug resistance reversal of HZ08 in KBV200 cells. It was also used to detect Rh123 and adriamycin accumulation in the presence of HZ08 to assess the effect on P-glycoprotein. Caspase-3 activity was analyzed under the incubation of HZ08 per se and in combination with vincristine. Results showed that HZ08 could increase the activity of caspase-3 with P-glycoprotein inhibition. Further studies revealed that HZ08 increased vincristine-induced apoptosis, characterized as an intrinsic apoptosis pathway with enhanced G2/M phase arrest, since HZ08 had an effect on the intrinsic apoptotic regulator Bcl-2 and Bax. Therefore, the outstanding reversal effect of HZ08 occurs not only through suppressing the P-glycoprotein function but also through activating the intrinsic apoptosis pathway.

Mc-hES, a novel plasmid carrying human endostatin gene, inhibits nasopharyngeal carcinoma growth.

Conventional plasmids for gene therapy produce low-level and short-term gene expression. Here, we first created minicircle carrying endostatin (mc-hES) for measurement of transfection efficiency. Compared with pcDNA-hES, MC-mediated endostatin gene transfer in vitro resulted in seven-fold greater endostatin expression levels in transfected cells and inhibited the growth of Human umbilical vein endothelial cells (HUVEC) more efficiently. HUVEC cell migration and tube-formation assays suggested that MC-mediated endostatin gene has significant anti-migration and anti-tube-formation capacity than that in pcDNA-hES. In vivo experiments showed that after transfection, mc-hES inhibited the growth of nasopharyngeal carcinoma xenografts. The tumor inhibition rates of mc-hES and pcDNA-hES were 60.8% and 26.9%, respectively (P<0.05). MC-mediated intratumoral endostatin expression in vivo was 2.2-17.9 times higher than pcDNA-hES in xenografted mice and lasted for 20 days. Our results suggest that minicircle DNA vectors might be a promising vector for biotherapy and should be further investigated.

Low expression of Mel-18 predicts poor prognosis in patients with breast cancer.

BACKGROUND: Our previous study suggested that melanoma nuclear protein 18 (Mel-18) acted as a tumor suppressor in human breast cancer. This study was designed to investigate the clinical and prognostic significance of Mel-18 in breast cancer patients. PATIENTS AND METHODS: Mel-18 was detected by immunohistochemistry in paraffin-embedded tissues from 287 breast cancer patients, of which 287 were from primary cancer sites, 63 from matched adjacent noncancerous sites, and 35 from metastatic lymph nodes. Differences in Mel-18 expression and clinical characteristics were compared by χ² test. Prognostic outcomes correlated with Mel-18 were examined using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: The decreased Mel-18 expression is incremental depending upon the magnitude of cancer progression (P < 0.001). Mel-18 was conversely correlated with the pathological classifications (P < 0.001 for T, N, and M classifications, respectively), clinical staging (P < 0.001), and progesterone receptor (P = 0.030). Furthermore, patients with higher level of Mel-18 showed prolonged overall survivals (P < 0.001). The diminished Mel-18 expression may be a risk factor for the patients' survival (P < 0.001). CONCLUSIONS: Lower Mel-18 expression is correlated with advanced clinicopathologic classifications and a poor overall survival in breast cancer patients. These findings suggest that Mel-18 may serve as a useful marker in prognostic evaluation for patients.

The pivotal role of c-Jun NH2-terminal kinase-mediated Beclin 1 expression during anticancer agents-induced autophagy in cancer cells.

The c-Jun NH2-terminal kinase (JNK) pathway represents one subgroup of MAP kinases that are activated primarily by cytokines and exposure to environmental stress. Autophagy is a protein-degradation system characterized by the formation of double-membrane vacuoles termed autophagosomes. Autophagy-related gene beclin 1 plays a key role in autophagosome formation. However, the relationships between activation of JNK pathway, autophagy induction and Beclin 1 expression remain elusive. In this study, we used human cancer cell lines CNE2 and Hep3B to investigate the role of JNK-mediated Beclin 1 expression in ceramide-induced autophagic cell death. Ceramide-treated cells exhibited the characteristics of autophagy (that is, acidic vesicular organelle formation and the LC3-II generation). JNK was activated in these two cell lines exposed to ceramide and the phosphorylation of c-Jun also increased. In the meantime, we found that ceramide upregulated Beclin 1 expression in cancer cells. The upregulation of Beclin 1 expression could be blocked by SP600125 (a specific inhibitor of JNK) or a small interfering RNA (siRNA) directed against JNK1/2 or c-Jun. Chromatin immunoprecipitation and luciferase reporter analysis revealed that c-Jun was involved in the regulation of beclin 1 transcription in response to ceramide treatment. In addition, inhibition of JNK activity by SP600125 could inhibit autophagy induction by ceramide. Furthermore, Beclin 1 knockdown by siRNA also inhibited ceramide-mediated autophagic cell death. JNK-mediated Beclin 1 expression was also observed in topotecan-induced autophagy. These data suggest that activation of JNK pathway can mediate Beclin 1 expression, which plays a key role in autophagic cell death in cancer cells.

PAC1 is a direct transcription target of E2F-1 in apoptotic signaling.

E2F-1 controls multiple cellular activities through transcriptional regulation of its target genes. As a mediator of cell death, E2F-1 can eliminate latent neoplastic cells through apoptosis. However, the mechanism by which E2F-1 mediates cancer cell killing is largely unknown. In this paper, we report that phosphatase of activated cells 1 (PAC1) phosphatase is a direct transcription target of E2F-1 in signaling apoptosis. We show that ectopic E2F-1 increases expression of PAC1 at both transcriptional and translational levels in breast cancer cells. E2F-1 physically interacts with the promoter of PAC1, binds to its consensus sequence in the promoter and transactivates the PAC1 promoter. E2F-1 suppresses extracellular signal-regulated kinase (ERK) phosphorylation through PAC1 and causes cancer cell death by apoptosis following treatment with a chemotherapeutic agent N-4-hydroxyphenylretinamide (4-HPR). Furthermore, ectopic PAC1 inhibits ERK phosphorylation and mediates cell killing. Moreover, endogenous E2F-1 upregulates PAC1 and suppresses ERK activity, leading to cell death in response to 4-HPR. These results reveal a crucial role of PAC1 in E2F-1-directed apoptosis. Our study demonstrates that E2F-1 mediates apoptosis through transcriptional regulation of PAC1 and subsequent suppression of the ERK signaling. Our findings establish a functional link between E2F-1 and mitogen-activated protein kinases. The E2F-1-PAC1 cascade in cancer cell killing may provide a molecular basis for cancer therapeutic intervention.

The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats.

Studies of spinal cord injury using contusion (impact) injury paradigms have shown that neuronal death is an acute event that is largely over within 24 h. However, much less is known about cell death following compression injury, despite compression being a key component of natural spinal injuries. We have therefore used neuronal nuclei (NeuN) immunostaining to examine the spatiotemporal pattern of neuronal loss after static compression injury in adult rats. 3D reconstruction was used to reveal the full effect of the injury. Neuronal loss at the injury epicentre, assessed by NeuN immunostaining, amounted to 44% at 1 day but increased to 73% at 3 days and 81% at 1 month. Neuronal loss was also seen 5 mm rostral and caudal to the epicentre, but was not significant until 3 days. NeuN loss was greatest in the ventral horns and in the intermediate grey matter, with the lateral dorsal horns relatively spared. Cystic cavities formed after injury, but were not evident until 4 weeks and were small in size. In contrast to the slow profile of neuronal loss, the compression injury also evoked a transient expression of activating transcription factor-3 (ATF3) and activated c-Jun in neurons. ATF3 expression peaked at 3 days and declined at 7 days. Our spatiotemporal analysis of compression injury shows that neuronal loss is much more protracted than in contusion injury, and highlights the potential for neuroprotective strategies. This study is also the first indication of ATF3 involvement in spinal cord injury.

Cotransplant of neural stem cells and NT-3 gene modified Schwann cells promote the recovery of transected spinal cord injury.

STUDY DESIGN: An animal model of transected spinal cord injury (SCI) was used to test the hypothesis that cografted neural stem cells (NSCs) and NT-3-SCs promote morphologic and functional recoveries of injured spinal cord. OBJECTIVE: To explore whether cotransplant of NSCs and NT-3-SCs could promote the injured spinal cord repair. SETTING: Zhongshan Medical College, Sun Yat-sen University, PR China. METHODS: Female Sprague-Dawley (SD) rats weighing on 200-220 g were used to prepare SCI models. The spinal cord was transected between T(9) and T(10), then NSCs, SCs+NSCs, LacZ-SCs+NSCs, or NT-3-SCs+NSCs were grafted into the transected site. RESULTS: (1) Part of NSCs could differentiate to neuron-like cells in the transected site and the percentage of differentiation was NT-3-SCs+NSCs group>SCs+NSCs group>NSCs group. (2) In the grafted groups, there were 5-HT, CGRP, and SP positive nerve fibres within the transected site. Some fluorogold (FG)-labeled cells were found in the spinal cord rostral to the transected site, the red nuclei and the inner pyramidal layer of sensorimotor cortex. (3) The cells grafted could enhance the injured neurons survival in inner pyramidal layer of sensorimotor cortex, red nuclei of midbrain, and Clark's nuclei of spinal cord's L1 segment, could decrease the latency and increase the amplitude of cortical somatosensory evoked potential (CSEP) and cortical motor evoked potential (CMEP), and could promote partly structural and functional recovery of the SCI rats. CONCLUSION: These results demonstrate that cografted NT-3-SCs and NSCs is a potential therapy for SCI. SPONSORSHIP: This research was supported by Chinese National Key Project for Basic Research (G1999054009), Chinese National Natural Science Foundation (30270700) and Social Developmental Foundation of Guangdong Province (2003C33808) to YS Zeng; Natural Science Foundation of Guangdong Province (04300468) and Medical Science Research Grant of Guangdong Province (A2004081) to JS Guo.

Senescence and telomere shortening induced by novel potent G-quadruplex interactive agents, quindoline derivatives, in human cancer cell lines.

Agents stabilizing G-quadruplexes have the potential to interfere with telomere replication by blocking the elongation step catalysed by telomerase or telomerase-independent mechanism and could therefore act as antitumor agents. In this study, we found that quindoline derivatives interacted preferentially with intramolecular G-quadruplex structures and were novel potent telomerase inhibitors. Treatment with quindoline derivatives reproducibly inhibited telomerase activity in human leukemia K562 cells and colon cancer SW620 cells. N'-(10H-Indolo [3,2-b] quinolin-11-yl)-N, N-dimethyl-propane-1,3-diamine (SYUIQ-5), (one of quindoline derivatives), when added to K562 and SW620 cell culture at nonacute cytotoxic concentrations, increased time of population doublings of K562 and SW620 cells, induced a marked cessation in cell growth and cellular senescence phenotype after 35 and 18 days, respectively. Growth cessation was accompanied by a shortening of telomere length, and induction of p16, p21 and p27 protein expression. However, another compound SYUIQ-7 with greater IC(50) for telomerase had no obvious cellular effect in nonacute cytotoxic concentrations. These results indicate that quindoline derivatives as novel potent G-quadruplex interactive agents induce senescence and telomere shortening in cancer cells and therefore are promising agents for cancer treatment.

Reversal of tumor multidrug resistance by 2-phenyl-3-(3',5'-dimorpholinomethyl-4'-hydroxy)-benzoyl-indole (HWL-12).

AIM: To explore the reversal of multidrug resistance (MDR) by indole derivative HWL-12. METHODS: Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-gp was examined by Fura 2-AM assay. Cellular accumulation of doxorubicin (Dox) was measured by fluorescence spectrophotometry. RESULTS: HWL-12 10 mumol.L-1 markedly increased Fura-2 accumulation and was 17.2-fold reversal of MDR in MCF-7/ADR cells. The cellular Dox accumulation in MDR cells was increased in the presence of HWL-12 on the MCF-7/ADR cells. No effect was observed for Dox accumulation in the presence of high Ca2+ (addition of CaCl2) or low Ca2+ (addition of egtazic acid). CONCLUSION: HWL-12 has a potent MDR reversal action which was associated with the increase of cellular Dox accumulation in MDR cells and not related with calcium ion concentration.

Expression of the Epstein-Barr virus DNA polymerase in Escherichia coli for use as antigen for the diagnosis of nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) encoded DNA polymerase (POL) was cloned and over-expressed in Escherichia coli. Western blot analysis confirmed the presence of antibody to this POL protein in sera from nasopharyngeal carcinoma (NPC) patients. By Western blot analysis, moderate to high concentration of IgG POL-specific antibodies were present in 43 of 48 NPC sera and only 4 of 48 healthy, seropositive controls. The POL-specific IgG antibodies appear as early as stage I of NPC, suggesting that the recombinant POL protein can be a useful diagnostic marker for early diagnosis of the disease. It was also found that human sera containing high titer of cytomegalovirus (CMV) antibodies or herpes simplex virus type 1 (HSV-1) antibodies did not cross-react with the recombinant EBV POL, despite the homology shared by DNA polymerase proteins of these viruses.

Analysis of T-lymphocyte subpopulations in inflammatory bowel diseases by three-color flow cytometry.

In order to better define changes in the relative proportion of peripheral blood T-lymphocyte subpopulations in patients with inflammatory diseases of the bowel, we performed simultaneous three-color fluorescence-activated cytometric (FACS) analysis using fluorophore-conjugated monoclonal antibodies with specificity for CD4, CD8, Leu 8, and CD45RA on 22 normal control subjects, 28 patients with Crohn's disease (CD), 15 patients with ulcerative colitis (UC), and 11 patients with intestinal inflammation secondary to etiologies other than inflammatory bowel disease (NIBD). This staining combination allowed enumeration of distinct T-cell subpopulations as follows: virgin CD4+, recall antigen helper T cells, nonspecific B-cell helper T cell, virgin CD8+, cytotoxic effector and suppressor effector and recall antigen cytotoxic T cells based on a synthesis of published functional analyses. No differences in the proportion of CD4+ or CD8+ cells or in the CD4+/CD8+ ratios were evident when UC and NIBD patients were compared to normal subjects. A significant reduction in the proportion of CD4+ cells and an increase in CD8+ cells was observed, however, in the CD group. When two-color analysis was performed, several significant differences in the proportions of circulating lymphocytes were seen. Specifically, these included significant increases in the number of CD4+, Leu 8- (P < 0.01) cells in all disease groups and an increase in CD4+, CD45RA+ cells in the NIBD group. Conversely, significant decreases in the proportions of CD8+, Leu 8+ (P < 0.01) cells were evident in the Crohn's disease group.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet derived growth factor (PDGF), androgens and inflammation: possible etiologic factors in the development of prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is characterized by varying degrees of epithelial and stromal hyperplasia in association with inflammation. Although androgens are known to be important for the growth and function of the prostate, their role in the development of BPH is unclear. The release of platelet-derived growth factor (PDGF) in response to inflammation suggests that PDGF may participate in the development of BPH. Cultured prostate cells derived from patients with BPH were examined for the presence of functional PDGF and androgen receptors. The cells expressed PDGF receptors and responded to PDGF stimulation by the activation of the PDGF signal transduction pathway and a dose-dependent stimulation of cell proliferation. Even though the cells expressed androgen receptors, dihydrotestosterone failed to elicit a mitogenic response. While the role of androgens in BPH remains unclear, these results suggest that inflammation and, specifically, PDGF may be important etiologic factors in the development of BPH.