[In vitro biological evaluation of PEGylated poly(glycerol sebacate)/ß-TCP-coating modified magnesium alloy].

PURPOSE: To prepare PEGS/ß-TCP modified magnesium alloy (PEGS/ß-TCP/MZG) membranes by forming a glycolated poly(sebacate)/ß-tricalcium phosphate (PEGS/ß-TCP) coating on the surface of magnesium-zinc-gadolinium alloy (MZG) membranes, and to evaluate the osteogenic induction activity and immunomodulatory properties of PEGS/ß-TCP/MZG using the material extract medium. METHODS: PEGS/ß-TCP coating was prepared on the surface of MZG by solvent method, and the PEGS/ß-TCP/MZG membrane was fabricated and compared with PEGS/ß-TCP and MZG to examine the morphology, composition, and hydrophilicity. The amount of magnesium ions released and the pH value of the materials were tested after 3 days of immersion. The cell viability and osteogenic differentiation of MC3T3 cells induced by extract medium were investigated by CCK-8 assay, ALP and mineralized nodule staining. The cell viability and polarization of RAW cells induced by extract medium were then investigated. The expression of macrophage-secreted cytokines was examined by PCR analysis. GraphPad Prism 9.0 software package was used for statistical analysis. RESULTS: PEGS/ß-TCP/MZG membranes with PEGS/ß-TCP coating tightly embedded with MZG were successfully fabricated, and the material had good hydrophilicity. The results of degradation experiments indicated that the PEGS/ß-TCP coating effectively slowed down the degradation rate of MZG, leading to a lower pH value and concentration of Mg2+ ion in the extract medium of PEGS/ß-TCP/MZG group. The results of in vitro cell experiments showed that PEGS/ß-TCP/MZG had no significant effect on the proliferation activity of both MC3T3-E1 and macrophages. PEGS/ß-TCP/MZG significantly enhanced the expression of ALP and mineralized nodule staining in MC3T3-E1. Although there was no significant difference in macrophage polarization pattern between PEGS/ß-TCP and PEGS/ß-TCP/MZG groups, PEGS/ß-TCP/MZG further reduced inflammation based on the immunomodulation of PEGS/ß-TCP coating related TNF-α expression and increased osteogenesis related TGF-ß expression. CONCLUSIONS: MZG membrane modified by PEGS/ß-TCP may provide a new material option for the development of bone tissue engineering.

[Ectopic opening of the ejaculatory duct into the urethra: A case report and literature review].

OBJECTIVE: To explore the diagnosis and treatment of ectopic seminal duct opening into the urethra. METHODS: We reviewed the literature and retrospectively analyzed the clinical data on a case of sex development abnormality. The patient was a 16-year-old gender female seeking medical improvement of female signs, admitted to hospital with "clitoris hypertrophy, no menstruation and chromosome karyotype 46XY", treated by bilateral orchiectomy, and simultaneously examined by seminal vesiculography and cystoscopy. RESULTS: Seminal vesiculography showed the ectopic opening of the right ejaculatory duct into the urethra accompanied by dysplasia of the seminal vesicle. Cystoscopy exhibited a fissrure-like opening in the right wall of the urethra but no verumontanum. Postoperative pathology revealed bilateral undeveloped testes and epididymides. CONCLUSION: Ectopic opening of the seminal duct into the urethra is extremely rare and often complicated by many malformations, for the diagnosis of which the most reliable options are seminal vesiculography and retrograde radiography through the ectopic orifice under the cystoscope. The treatment of the disease should follow the principles of timeliness, individualization and consideration of associated malformations.

[Ectopic seminal tract opening in enlarged prostatic utricle: A report of 22 cases].

OBJECTIVE: To explore the diagnosis, classification and treatment of ectopic seminal tract opening in enlarged prostatic utricle (EPU). METHODS: We retrospectively analyzed the clinical data on 22 cases of ectopic seminal tract opening in EPU confirmed by spermography, EPU open cannula angiography or intraoperative puncture of the vas deferens and treated by transurethral incision of EPU, cold-knife incision or electric incision of EPU, full drainage of the anteriorwal, and open or laparoscopic surgery from October 1985 to October 2017. RESULTS: Five of the patients were diagnosed with ectopic opening of the vas deferens and the other 17 with ectopic opening of the ejaculatory duct in EPU. During the 3－48 months of postoperative follow-up, symptoms disappeared in all the cases, semen quality was improved in those with infertility, and 2 of the infertile patients achieved pregnancy via ICSI. CONCLUSIONS: Ectopic seminal tract opening in EPU is rare clinically. Spermography is a reliable method for the diagnosis of the disease, and its treatment should be aimed at restoring the smooth flow of semen based on proper classification and typing of the disease.

A 30-year retrospective study of rare ectopic seminal tract opening cases.

Ectopic seminal tract opening is a rare congenital malformation. Until recently, there has been a lack of comprehensive reporting on the condition. The purpose of this retrospective study is to summarize the experience of diagnosis and treatment of this condition based on 28 clinical practice cases throughout the past 30 years. We conducted auxiliary examinations on such patients including routine tests, imaging examinations, and endoscopy. Among these 28 cases, there were ectopic opening of vas deferens into enlarged prostatic utricles (6 cases); ejaculatory ducts into enlarged prostatic utricles, Müllerian ducts cysts, and urethras (18 cases, 2 cases, and 1 case, respectively); and ectopic opening of the unilateral vas deferens and the contralateral ejaculatory duct into enlarged prostatic utricle (1 case). The size of the enlarged prostatic utricle, the type of ectopic seminal tract opening, and the opening's location effectively assisted in the selection of clinical treatment methods, including transurethral fenestration of the utricle, transurethral cold-knife incision, open operation, laparoscopic operation, and conservative treatment. Satisfactory effect was achieved during follow-up. In conclusion, a definite diagnosis and personalized treatment are especially important for patients with ectopic seminal tract opening.

FOXM1 contributes to docetaxel resistance in castration-resistant prostate cancer by inducing AMPK/mTOR-mediated autophagy.

Docetaxel-mediated chemotherapy is the first line therapy for metastatic castration-resistant prostate cancer (CRPC) patients, but its therapeutic benefit is limited by the development of resistance. Although Forkhead box protein M1 (FOXM1) has been implicated in prostate tumorigenesis and metastasis, its role in docetaxel resistance has not been studied. Here, we showed that FOXM1 expression was upregulated in the docetaxel resistant CRPC cell lines (PC3-DR and VCaP-DR) and knockdown of FOXM1 sensitized the cells to docetaxel both in vitro and in vivo. In addition, autophagy was found to be significantly enhanced in resistant cells. Moreover, FOXM1 overexpression cells showed increased autophagic flux and higher numbers of autophagosomes. Knockdown of ATG7, beclin-1 or cotreatment with chloroquine, partly restored sensitivity to docetaxel in the FOXM1-overexpressing cells. Mechanistically, FOXM1 targeted AMPK/mTOR to activate the autophagy pathway and altered docetaxel response in CRPC. These findings identify the role of FOXM1 as well as the mechanism underlying FOXM1 action in docetaxel sensitivity and may, therefore, aid in design of CRPC therapies.

[Diagnosis and treatment of ejaculatory duct cyst: A report of 2 cases and review of the literature].

OBJECTIVE: To investigate the diagnosis and treatment of ejaculatory duct cyst. METHODS: This study included 2 male patients present at the hospital for hemospermia and abnormal sensation in the perineal region in July and August 2014. Both underwent transrectal ultrasonography, routine semen examination, CT, MRI, cystoscopy, and vesiculography before transurethral fenestration of the cysts and pathological examination of the cyst wall specimens. Analyses were made on the clinical presentations, imaging features, pathological characteristics, differential diagnosis and treatment of ejaculatory duct cyst and relevant literature was reviewed. RESULTS: The cyst wall was mainly composed of smooth muscle, the inner wall lined with pseudostratified ciliated columnar epithelia, and with positive expressions of CD10 and Muc6 proteins on immunohistochemical staining, which indicated renal iatrogenic ejaculatory duct cyst. The patients were followed up for 18 and 20 months, respectively. All symptoms disappeared and no recurrence occurred after surgery. Routine semen examination for the two patients showed the semen volumes to be 3.5 and 3.1 ml, sperm concentrations 35 and 32 ×106/ml, grade a sperm 32.0 and 26.0%, grade b sperm 18.0 and 31.0%, and semen liquidation time 30 and 34 minutes, respectively. CONCLUSIONS: Pelvic cystic masses can be detected by transrectal ultrasonography, CT and MRI, but definite diagnosis relies on vesiculography, pathological examination and immunohistochemical staining. Transurethral fenestration is safe and effective for the treatment of ejaculation duct cyst.

Do Open Reduction and Internal Fixation With Articular Disc Anatomical Reduction and Rigid Anchorage Manifest a Promising Prospect in the Treatment of Intracapsular Fractures?

PURPOSE: In response to the increased attention to soft tissue reduction in the treatment of intracapsular condylar fractures (ICFs), a modified open reduction technique is proposed and its functional and radiographic outcomes were evaluated in this study. PATIENTS AND METHODS: This is a retrospective case series study of patients with all ICF types that were treated with open reduction and internal fixation (ORIF) with articular disc anatomic reduction and rigid anchorage. Inclusion and exclusion criteria were strictly applied. Preoperative and postoperative clinical examinations of malocclusion, maximum incisor opening (MIO), laterotrusion, and temporomandibular disorder symptoms were recorded and analyzed. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to assess articular position and condylar morphology and position. RESULTS: Thirty-four patients with ICFs (47 sides) were treated with the modified ORIF technique. At 6 months of follow-up, no malocclusion was found and the MIO considerably expanded to 3.56 ± 0.13 cm. Only 4 patients (12%) had temporomandibular joint discomfort with mouth opening. Interestingly, for unilateral type B ICFs, the laterotrusion distance to the ORIF sides was notably longer than to the non-ORIF sides. Postoperative CT and MRI showed that all fragments were properly reduced and the condyles were in the normal position. Postoperative anterior disc displacement occurred in 4 sides and condylar morphologic abnormalities (slight surface roughening and articular cartilage absorption) occurred in 3 sides (6.4%). CONCLUSIONS: This modified ORIF technique, which achieved good outcomes after treatment of all ICF types, shows promise for the treatment of ICFs.

[The volume of residual urine correlates with bladder outlet obstruction and detrusor contractility in patients with benign prostatic hyperplasia].

OBJECTIVE: To identify the correlation of the volume of residual urine (VRU) with the severity of bladder outlet obstruction (BOO) and detrusor contractility in patients with benign prostatic hyperplasia (BPH). METHODS: A total of 152 patients with clinically diagnosed BPH underwent ultrasonography for measurement of the prostate volume and RVU, free uroflowmetry, and urodynamic examination for the severity of BOO and detrusor contractility. Using the software SPSS20. 0, we analyzed the correlation between the ultrasonographic results and urodynamic parameters and compared the two sample means by the t-test. RESULTS: The prostate volume was correlated positively with BOO severity (r = 0.432, P < 0.01) and detrusor contractility (r = 0.343 , P < 0.01) while Qmax negatively with BOO severity (r = 0.327, P < 0.01) but not significantly with detrusor contractility (r = 0.123, P > 0.05). VRU showed a significantly negative correlation with detrusor contractility when > 150 ml (r = -0.490, P < 0.01), even more significantly when > 300 ml (r = -0.717, P < 0.01), but exhibited no significant correlation with it when ≤ 150 ml (r = 0.041, P > 0.05). CONCLUSION: VRU can somehow predict the detrusor function. For patients with VRU > 150 ml, especially for those with VRU > 300 ml, the detrusor function should be evaluated and urodynamic examination is recommended for exact assessment of BOO severity and detrusor contractility.

[Morphologic and histopathologic analysis of testicular appendages].

OBJECTIVE: To investigate the incidence of testicular appendages, observe their morphology, and analyze their histopathological origins. METHODS: We observed 67 testes in 54 patients (15 children and 39 adults) undergoing scrotal surgery, investigated the incidence of testicular appendages, and identified their histopathological origins. We used the Chi-square test to compare the findings from the children and adult patients, with P < 0.05 as statistically significant. RESULTS: The detection rates of the appendix testis, appendix epididymis, paradidymis, vas aberrans superior, and vas aberrans inferior were 80.6% (54/67), 23.9% (16/67), 1.5% (1/67), 3.0% (2/67), and 1.5% (1/67), respectively. The incidence of testicular appendages was higher in children than in adults (93.3% vs 80.8%), but with no statistically significant difference (Chi2 = 1.339, P > 0.05), and that of the appendix testis and epididymis with pedicles was significantly higher in the former than in the latter (82.4% vs 54.7%, chi2 = 4.149, P < 0.05). Pathological examination showed that the appendix testis originated from the paramesonephric duct, while the appendix epididymis, paradidymis, vas aberrans superior, and vas aberrans inferior from the mesonephric duct. CONCLUSION: Testicular appendages consist of five embryonic remnants, including appendix testis, appendix epididymis, paradidymis, vas aberrans superior, and vas aber- rans inferior. The appendix testis originates from the paramesonephric duct, and the other four from the mesonephric duct. The clinical implication of these testicular appendages is their tendency to torsion.

Computer-assisted orthognathic surgery combined with fibular osteomyocutaneous flap reconstruction to correct facial asymmetry and maxillary defects secondary to maxillectomy in childhood.

Maxillectomy in childhood not only causes composite primary defects but also secondary malformation of the middle and lower face. In the case presented, we introduced computer-assisted planning and simulation of orthognathic surgery combined with fibular osteomyocutaneous flap reconstruction to correct complex craniofacial deformities. Virtual orthognathic surgery and maxillary reconstruction surgery were undertaken preoperatively. LeFort I osteotomy, with bilateral sagittal split ramus osteotomy and lower border ostectomy, was performed to correct malocclusion and facial asymmetry. Maxillary reconstruction was accomplished using a fibular osteomyocutaneous flap. The patient recovered uneventfully with an adequate aesthetic appearance on 3D computed tomography. Our experience indicates that orthognathic surgery combined with fibular osteomyocutaneous flap reconstruction can used to correct complex facial asymmetry and maxillary defects secondary to maxillectomy. Computer-assisted simulation enables precise execution of the reconstruction. It shortens the free flap ischemia time and reduces the risks associated with microsurgery.

[Composition and morphology of stones in enlarged prostatic utricle].

OBJECTIVE: To investigate the composition and morphology of the stones in the enlarged prostatic utricle (EPU). METHODS: We took out 36 EPU stones from 11 patients by transurethral fenestration between 1992 and 2011, and analyzed the stones by scanning electron microscopy, x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIS). RESULTS: Under the scanning electron microscope, all the EPU stones were constituted of many intensive minicrystals and amorphous matrix. XRD and FTIS revealed that all were hydroxyapatite crystal. CONCLUSION: EPU stones belong to the category of prostatic pseudo-calculi, whose formation is ascribed not to the abnormal change of urine composition, but to the continuous secretion, absorption and concentration of EPU liquid and ablated epithelial cells from the EPU.

[Application of computer-assisted navigation in oral and maxillofacial surgery: retrospective analysis of 104 consecutive cases].

PURPOSE: To evaluate the application of computer-assisted navigation system (CANS) in Oral and Maxillofacial Surgery. METHODS: One hundred and four patients were included in this study, including 34 with zygomatic-orbital-maxillary fracture, 27 with unilateral TMJ ankylosis, 29 with fibrous dysplasia, 9 with mandibular angle hypertropia, 3 with cartilage and bone tumors and 2 with facial foreign bodies. CT scan was performed and the data was saved as Dicom (digital imaging and communications in medicine) format. With preoperative planning and 3-dimensional simulation, normal anatomic structures of the affected side were created by superimposing and mirroring the unaffected side. The osteotomy lines, amount and range of resection, the reduction position of bony segments and the reconstruction morphology was determined and displayed. All surgeries were performed under the guidance of navigation system. The accuracy of navigation was evaluated by comparing the postoperative CT three-dimensional model with preoperative surgical planning. RESULTS: Through registration, an accurate match between the intra-operative anatomy and the CT images was achieved. With the guidance of navigation, anatomic structures and the position of surgical instruments were shown real-time on the screen. No complications occurred in all patients and the systematic error was within 1 mm. Good coincidence with preoperative planning was achieved for osteotomy lines, the amount of resection and reduction of fractures. The mean error between virtual and real results was (1.46±0.24) mm. All patients healed uneventfully and facial symmetry was improved. CONCLUSIONS: With the ability of preoperative planning, surgical simulation and postoperative prediction, CANS shows its great value in improving the accuracy of oral and maxillofacial surgery, reducing trauma and restoring facial symmetry. It is regarded as a valuable and safe technique in this potentially complicated procedure.

Ectopic opening of cystic dilatation of the ejaculatory duct into enlarged prostatic utricle.

A 28-year-old man was referred to our department for the management of recurrent hemospermia during the past 5 years. Genital examination and hormonal levels were normal. Semen analysis showed no change in volume and pH; however, hemospermia and asthenozoospermia were observed. Ultrasonography and computed tomography scan revealed the presence of a cystic lesion with calcification in the terminal part of seminal vesicles adjoining the prostate gland. The following vasography and endoscopic retrograde urethrography demonstrated 2 communicating cystic dilatations arising from the verumontanum. The diagnosis of cystic dilatation of the ejaculatory duct opening into an enlarged prostatic utricle was reached. Transurethral unroofing of the cyst was separately performed with a successful outcome. The characteristic of the 2 cystic dilatations was confirmed by pathologic examination. To the best of our knowledge, this is the first case of ectopic cystic dilatation of the ejaculatory duct opening into an enlarged prostatic utricle.

[Prostatic middle lobe hyperplasia correlates with bladder outflow obstruction: analysis of 131 cases].

OBJECTIVE: To analyze the correlation between the size of prostatic middle lobe hyperplasia and the degree of bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH). METHODS: This study included 131 BPH patients who presented with dysuria between May 2008 and June 2010. The prostate volume and intravesical prostatic protrusion (IPP) were measured by transabdominal ultrasound, Qmax and detrusor pressure at Qmax (P(det@ Qmax)) detected by urodynamic examination, the obstruction degree and detrusor contractility judged using the LinPURR Figure, and the AG value calculated (AG = P(det@ Qmax) -2Qmax). The degrees of BOO were compared between different groups of IPP by variance analysis, and the prostate volume, IPP and AG values underwent Bivariate correlation analysis. RESULTS: IPP was highly positively correlated with BOO when it was > 10 mm (r = 0.821, P < 0.01), while PV and BOO had a lower correlation (r = 0.475, P < 0.01). There was also a high positive correlation between IPP and P(det@ Qmax) (r = 0.865, P < 0.01). CONCLUSION: A close correlation exists between prostatic middle lobe hyperplasia and BOO, and evaluating IPP by ultrasound is a reliable method to determine the degree of BOO.

[Therapeutic effects of FOLFOX6 versus TLF regimen as the first line chemotherapy for advanced gastric cancer].

OBJECTIVE: To compare the efficacy, time to disease progression (TTP), overall survival (OS) and toxicity of FOLFOX6 and TLF regimens for advanced gastric cancer. METHODS: The clinical data of 81 chemotherapy-naive patients with advanced gastric cancer were analyzed. Of the 81 patients, 41 were treated with FOLFOX6 regimen and 40 with TLF regimen. The patients in FOLFOX6 group received intravenous infusion of L-OHP(100 mg/m2) at day 1, bolus injection of 5-FU (400 mg/m2) at day 1, and continuous intravenous infusion of 5-FU (1200 mg/m2/d) for 22 h at days 1-2, each treatment cycle lasting 14 days. The patients in TCF group received TAX (90 mg/m2) at day 1, bolus injection of 5-FU (400 mg/m2) at days 1-2, and continuous intravenous infusion of 5-FU (400 mg/m2/d) for 22 h at days 1-2, and each treatment cycle also lasted 14 days. RESULTS: The objective response rates were 48.8% in FOLFOX6 group and 50.0% in TLF group (P=0.962). The median TTP in the two groups was 6.30 months and 6.50 months (P=0.958), with median survival time of 9.80 months and 10.70 months (P=0.578), respectively. The most frequent adverse events were nausea, vomiting and hematologic toxicities. The incidences of grade III-IV leucopenia and neutropenia were lower in FOLFOX6 group than in TLF group, but the difference was not statistically significant (12.2% vs 30.0%, P=0.112; 14.6% vs 32.5%, P=0.126). Three patients in FOLFOX6 group developed intestinal obstruction during the chemotherapy. CONCLUSION: Both FOLFOX6 and TLF regimens are effective in treating advanced gastric cancer and the toxicities can be tolerated.

[The comparison of the vasoactive effects of dopamine on isolated rabbit pulmonary and systemic arteries after incubation with lipopolysaccharide].

OBJECTIVE: To compare the vasoactive effects of dopamine (DOPA) of different concentrations on isolated rabbit pulmonary and systemic arteries after incubation with lipopolysaccharide (LPS). METHODS: Six white male rabbits were used. Thirty-six pulmonary arterial rings and 36 systemic arterial rings were prepared. The 36 pulmonary arterial rings were divided into six groups to determine the effect of different concentrations of DOPA (4x10(-5) , 8x10(-5), 16x10(-5) micromol/L) on the tension of the normal pulmonary artery (PN-DOPA4, PN-DOPA8, PN-DOPA16 groups, respectively), and the tension of the pulmonary artery rings after being incubated with LPS (PL-DOPA4, PL-DOPA8, PL-DOPA16 groups, respectively). The 36 systemic arterial rings were also divided into six groups as the pulmonary arterial rings, including normal groups (SN-DOPA4, SN-DOPA8 , SN-DOPA16) and LPS groups (SL-DOPA4, SL-DOPA8 , SL-DOPA16). RESULTS: (1) DOPA relaxed the arterial rings in PN-DOPA4 and SN-DOPA4 groups, while it produced contraction in PN-DOPA8, PN-DOPA16, SN-DOPA8 and SN-DOPA16 groups, and the contraction was more marked with the increase in concentration of DOPA. (2) After preincubation with LPS, the relaxation property of DOPA in PL-DOPA4 and SL-DOPA4 groups was observed to be reversed to contraction [(22.60+/-6.68)% vs. -(2.25+/-0.58)%, (3.80+/-0.52)% vs. -(3.65+/-0.75)%, P<0.05 and P<0.01]; the contraction response of DOPA in PL-DOPA8 group decreased compared with PN-DOPA8 group by (14.52+/-0.59)% (P<0.05), while increased by (25.90+/-1.75)% in SL-DOPA8 group compared with SN-DOPA8 group (P<0.05), and no response was observed in PL-DOPA16 and SL-DOPA16 groups. (3)After preincubation with LPS, changes in pulmonary arterial tension (PL/PN) in DOPA4 group were more obvious than those in systemic arterial tension (SL/SN, -10.90+/-5.06 vs. -1.00+/-0.24, P<0.05), while the SL/SN in DOPA8 group were more obvious (1.80+/-0.35 vs. 0.48+/-0.17, P<0.01). CONCLUSION: DOPA in low concentrations had the function of relaxation on the pulmonary arterial and systemic arterial rings. After the arterial rings are preincubated with LPS, the relaxation response of DOPA of low concentrations is changed to be vaso-contraction, and the changes in pulmonary arterial rings are most marked. DOPA of different concentrations all produce contraction effect on LPS-preincubated arterial rings.

[Expression of osteopontin and survivin in prostate cancer and the clinical significance].

OBJECTIVE: To determine the expression of osteopontin (OPN) and survivin in prostate cancer tissue, and study their correlation and roles in tumor invasion and metastasis. METHODS: The expressions of OPN and survivin in prostate cancer tissue, prostate hyperplasia tissue and normal prostate tissue were determined by RT-PCR and immunohistochemistry. RESULTS: The positive expression rates of OPN mRNA and protein in prostate cancer tissue [76.1% (35/46) and 69.6% (32/46)] were significantly correlated to survivin expression [67.4% (31/46) and 67.4% (31/46)] (P<0.05). The expressions of OPN and survivin were related to the tumor grade and clinical stages (P<0.05). OPN and survivin were not found in prostate hyperplasia and normal prostate tissues. CONCLUSION: OPN and survivin may play important roles in the progression of prostate cancer and can be potential markers for invasion and metastasis of prostate cancer. OPN and survivin might play synergetic roles in prostate carcinogenesis.

Delayed hepatocarcinogenesis through antiangiogenic intervention in the nuclear factor-kappa B activation pathway in rats.

BACKGROUND: The active form of nuclear factor-kappa B (NF-kappaB) is involved in the initiation, generation, and development of hepatocellular carcinoma (HCC), and is up-regulated in inflammation-associated malignancies. We investigated the dynamic expression of NF-kappaB and its influences on the occurrence of HCC through antiangiogenic (thalidomide) intervention in NF-kappaB activation. METHODS: Hepatoma models were induced with 2-fluorenylacetamide (2-FAA, 0.05%) in male Sprague-Dawley rats, and thalidomide (100 mg/kg body weight) was administered intragastrically to intervene in NF-kappaB activation. The pathological changes in the liver of sacrificed rats were assessed after hematoxylin and eosin staining. NF-kappaB mRNA was amplified by RT-nested PCR. The alterations of NF-kappaB and vascular endothelial growth factor (VEGF) expression were analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blotting. RESULTS: Rat hepatocytes showed denatured, precancerous, and cancerous stages in hepatocarcinogenesis, with an increasing tendency of hepatic NF-kappaB, NF-kappaB mRNA, and VEGF expression, and their values in the HCC group were higher than those in controls (P<0.001). In the thalidomide-treated group, the morphologic changes generated only punctiform denaturation and necrosis at the early or middle stages, and nodular hyperplasia or a little atypical hyperplasia at the final stages, with the expression of NF-kappaB (X2=9.93, P<0.001) and VEGF (X2=8.024, P<0.001) lower than that in the 2-FAA group. CONCLUSION: NF-kappaB is overexpressed in hepatocarcinogenesis and antiangiogenic treatment down-regulates the expression of NF-kappaB and VEGF, and delays the occurrence of HCC.

Characteristics of hepatic nuclear-transcription factor-kappa B expression and quantitative analysis in rat hepatocarcinogenesis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. We analyzed the expression of nuclear-transcription factor-kappa B (NF-kappaB) during hepatocarcinogenesis in order to evaluate its dynamic expression and its clinical value in the development and diagnosis of HCC. METHODS: Hepatoma models were induced by oral administration of 2-acetamidoflurene (2-FAA) to male Sprague-Dawley rats. Morphological changes were observed after hematoxylin and eosin staining. The cellular distribution of NF-kappaB expression during different stages of cancer development was investigated by immunohistochemistry, and the level of NF-kappaB expression in liver tissues was quantitatively analyzed by ELISA. The gene fragments of hepatic NF-kappaB were amplified by nested-polymerase chain reaction assay. RESULTS: Hepatocytes showed vacuole-like degeneration during the early stages, then had a hyperplastic nodal appearance during the middle stages, and finally progressed to tubercles of cancerous nests with high differentiation. The NF-kappaB-positive material was buff-colored, fine particles localized in the nucleus, and the incidence of NF-kappaB-positive cells was 81.8% in degeneration, 83.3% in precancerous lesions, and 100% in cancerous tissues. All of these values were higher than those in controls (P<0.01). Hepatic NF-kappaB expression and hepatic NF-kappaB-mRNA were also higher during the course of HCC development (P<0.01). CONCLUSION: The NF-kappaB signal transduction pathway is activated during the early stages of HCC development, and its abnormal expression may be associated with the occurrence of HCC.