Salvage neck surgery in recurrent nodal NPC: Do all patients require a comprehensive neck dissection in the modern MRI era?

OBJECTIVE: The standard treatment for regional failure in nasopharyngeal carcinoma (NPC) is the radical neck dissection (RND). Our study sought to determine if magnetic resonance imaging (MRI) may accurately predict nodal involvement to allow selected levels of neck dissection to be preserved. STUDY DESIGN AND SETTING: We analysed retrospectively all NPC patients in our centre undergoing neck dissections as salvage therapy for nodal recurrence. Nodal involvement based on the preoperative MRI was assessed and compared with postoperative histopathology. METHODS: This is a retrospective study conducted on patients in our centre with recurrent NPC from February 2002 to February 2017. Patients were identified from the database of the otolaryngology oncology division at our institution. Of these, 28 patients met all our inclusion and exclusion criteria. We calculated sensitivity and specificity as well as average number of nodes per patient. RESULTS: In our study, we calculated the false negative and false positive rates of preoperative MRI neck by levels. Overall sensitivity of MRI picking up disease by level was 76% and specificity was 86%. CONCLUSION: Based on our study, we will be missing a total of 10 (7.1%) diseased neck levels in eight (28.5%) patients. MRI alone, therefore, does not provide enough information to allow safe selective preservation of neck levels in surgical salvage of neck recurrences in NPC.

Knockdown of miR-125b-5p inhibits the proliferation and invasion of gastric carcinoma cells by targeting RYBP.

Gastric carcinoma, one of the most aggressive and lethal human malignancies, is associated with poor prognosis despite progress in therapeutic strategies. This study examined the potential function and mechanism of action of microRNA-125b-5p (miR-125b-5p) in the pathogenesis of gastric carcinoma. We recognized that miR-125b-5p was elevated in gastric carcinoma, and its decreased expression was associated with a better prognosis. Loss-of-function assays showed that miR-125b-5p suppression inhibited the proliferative and invasive abilities of gastric cancer cells. Furthermore, RING1 and YY1-binding protein (RYBP) was found to be target gene for miR-125b-5p action; miR-125b-5p negatively regulates RYBP expression. According to the results of rescue experiments, RYBP downregulation partially counteracted the miR-125b-5p silence-mediated inhibitory function in gastric cancer progression. Collectively, these data elucidated the molecular mechanisms of the miR-125b-5p/RYBP axis in gastric cancer invasion and growth.

Self-expanding metal stent insertion by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring in the management of acute colorectal obstruction: a 14-year experience.

BACKGROUND: Placement of a self-expanding metal stent (SEMS) in patients presenting with an acute colorectal obstruction (ACO) may obviate emergency surgery (ES), potentially effectively palliating incurable tumors, acting as a bridge to surgery (BTS) in patients with operable or potentially operable tumors and achieving effective decompression of other ACO. We present our experience with SEMS insertion by colorectal surgeons without fluoroscopic monitoring for ACO especially for acute malignant colorectal obstruction (AMCO) for nearly a 14-year period (2007-2020). AIM: To explore the safety and effectiveness of SEMS insertion in the management of ACO by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring. METHODS: We reviewed the medical records of patients retrospectively to identify all patients presenting to our unit with ACO especially with AMCO who had stenting carried out to achieve colonic decompression. All 434 procedures were performed by colorectal surgeons using a two-person approach colonoscopy without fluoroscopic monitoring. RESULTS: The overall technique success rate and clinic success rate by SEMS insertion were 428/434 (98.6%) and 412/434 (94.9%). The overall incidence of complications by SEMS insertion was 19/434 (4.4%). The complications included clinical perforation (6/434, 1.4%); stent migration (2/434, 0.5%), 1 of which re-stent; stent detachment (fell off) (3/434, 0.7%), none of them with re-stent; stool impaction (6/434, 1.4%), 1 of which re-stent; and abdominal or anal pain (2/434, 0.5%). There was no hemorrhage in any of the 434 patients. CONCLUSIONS: SEMS insertion is a relatively safe and effective technique for colonic decompression in dealing with ACO as either a BTS or as a palliative measure. It is also a solution to other causes of ACO such as recurrent tumor, benign diseases, or extra-luminal compression. Therefore, ES was largely avoided.

Quinone-amine polymers as metal-free and reductant-free catalysts for hydroxylation of benzene to phenol with molecular oxygen.

Quinone-amine polymers were employed as metal-free and reductant-free catalysts for the hydroxylation of benzene to phenol with molecular oxygen, yielding phenol as high as the transition metal catalyst.

[Diagnostic value of endobronchial ultrasonography with guide-sheath combined with virtual bronchoscopy navigation in peripheral lung cancer].

Objective: To explore the diagnostic value and safety of endobronchial ultrasonography with guide-sheath (EBUS-GS) combined with virtual bronchoscopy navigation (VBN) in peripheral lung cancer. Methods: Between Dec. 2015 to Dec. 2016, patients with pulmonary solitary nodule suspected of early lung cancer on computed tomography (CT) in Department of Respiratory, Tangdu Hospital, Fourth Military Medical University were enrolled for this study. The patients underwent EBUS-GS transbronchoscopic lung biopsy (TBLB) with or without VBN. The visibility rate, diagnostic yield, influencing factors, the operation time and complications were evaluated in the 2 groups. The data were compared using independent sample t test or chi-squared test. Results: A total of 134 patients were enrolled and completed this study. Among them 74 were males and 60 were females. There were 64 cases in the group of EBUS-GS with VBN (VBNA), and 70 in the group without VBN (NVBNA). The visibility rate and diagnosis rate of VBNA group were 87.5% (56/64) and 78.1% (50/64), respectively. The mean time of operation and confirming the target lesions were (25±5), (5.8±1.3) min, respectively. The visibility rate and diagnosis rate of NVBNA group were 81.4%(57/70) and 75.7%(53/70), respectively. The mean time of operation and confirming the target lesions were (27±6), (9.8±1.5)min .There was no significant difference in the visibility rate and diagnosis rate between the 2 groups (χ(2)=0.933, P=0.334; χ(2)=0.109, P=0.838). There was no significant difference in the mean operation time between the 2 groups(t=0.633, P=0.524). But the time of confirming the target lesions between the 2 groups was statistically different (t=17.41, P<0.01). EBUS-GS-TBLB was well tolerated. No severe complications such as pneumothorax or chest pain were observed. There were 3 patients in the VBNA group and 7 patients in the NVBNA group experiencing a small amount of biopsy site bleeding. The incidence of complications did not differ between the 2 groups(χ(2)=1.366, P=0.330). Conclusions: VBN could not improve the diagnostic yield of EBUS-GS. However, it could shorten the time needed to confirm the target lesions and did not increase the incidence of EBUS-GS complications, indicating that EBUS-GS with VBN was a safe and effective method.

Effect of high glucose, Porphyromonas gingivalis lipopolysaccharide and advanced glycation end-products on production of interleukin-6/-8 by gingival fibroblasts.

BACKGROUND AND OBJECTIVE: It is known that chronic periodontal infection can magnify the cytokine responses in patients with diabetes. Hyperglycemia increases the proinflammatory status, including the levels of advanced glycation end-products (AGEs), in patients with periodontitis. However, whether AGEs have additional effects on the production of those proinflammatory cytokines in diabetic patients with periodontitis is still unknown. To examine in vitro the effect of hyperglycemia and AGEs on the amounts of interleukin (IL)-6 and IL-8 produced in periodontally infected gingiva, human gingival fibroblasts (HGFs) were stimulated with glucose, AGE-modified bovine serum albumin (AGE-BSA) and Porphyromonas gingivalis LPS in the present study. MATERIAL AND METHODS: Primary culture of HGFs was incubated with various concentrations of AGE-BSA (0, 50, 100 and 200 µg/mL) and LPS (0, 10, 100 or 1000 ng/mL) at two different glucose concentrations - normal glucose (5 mm) and high glucose (25 mm). The amounts of IL-6 and IL-8 produced by HGFs were evaluated using ELISA. Expression of the AGE receptor on HGFs was determined by flow cytometry. RESULTS: High glucose stimulated a significant increase in the production of IL-6 and IL-8 by HGFs compared with normal glucose. This enhanced production of IL-6 and IL-8 could also be observed in the presence of LPS and/or AGE-BSA. When both LPS and AGE-BSA were present, especially at high concentrations (≥ 500 µg/mL of LPS and ≥ 25 µg/mL of AGE-BSA), a synergistic effect on IL-8 production was found in the high-glucose condition. CONCLUSIONS: A synergistic effect of the production of IL-8 could be induced in HGFs with the combination of high glucose, LPS and AGEs.

The effects of diallyl sulfide upon Porphyromonas gingivalis lipopolysaccharide stimulated proinflammatory cytokine expressions and nuclear factor-kappa B activation in human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: Diallyl sulfide (DAS), a flavor compound from garlic, has varied potential therapeutic activities. Periodontitis is a disease that develops because of host-mediated inflammation to periodontal pathogens. In this study, the effects of DAS on the common proinflammatory cytokines and nuclear factor-kappa B (NF-κB) in human gingival fibroblasts (HGFs) being stimulated with lipopolysaccharide from Porphyromonas gingivalis, a potent periodontal pathogen, were evaluated. MATERIAL AND METHODS: Cytotoxicities of DAS and lipopolysaccharide on HGFs were measured with MTS assay. The mRNA and protein expressions of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, from the HGFs treated with lipopolysaccharide with and without DAS were examined with reverse transcription-polymerase chain reaction and immunocytochemistry, respectively. In addition, the activation and nuclear translocation of NF-κB with and without DAS were compared. RESULTS: DAS and lipopolysaccharide treatments within 3 mm and 10 µg/mL, respectively, did not affect the survival rate of HGFs. Lipopolysaccharide (1 µg/mL) significantly increased the mRNA expressions of IL-1ß, IL-6 and TNF-α; however, DAS (1 mm) inhibited these expressions. The protein expressions of TNF-α, IL-1ß, as well as the NF-κB nuclear translocation were increased after lipopolysaccharide treatment, but decreased when there was a DAS pretreatment. CONCLUSION: DAS diminished P. gingivalis lipopolysaccharide-stimulated cytokine expression and NF-κB activation in HGFs; we therefore suggest DAS may be beneficial on periodontal inflammation.

Cyclosporine A up-regulates Sonic hedgehog in gingiva: role of the up-regulation on gingival cell proliferation.

BACKGROUND AND OBJECTIVE: Sonic hedgehog protein (SHH) is a mitogen that stimulates cell proliferation. Cyclosporine A enhances the proliferation of gingival cells; however, the relationships of SHH to cyclosporine A or to cyclosporine A-enhanced gingival cell proliferation have not been described. MATERIAL AND METHODS: Here, we investigated SHH expression in gingiva in vitro and in vivo after cyclosporine A treatment and tested the effect of SHH inhibition on cyclosporine A-enhanced gingival fibroblast proliferation in vitro. RESULTS: In human gingival fibroblasts, cyclosporine A treatment increased the expression of SHH transcripts and SHH protein, and stimulated cell proliferation; the addition of cyclopamine, an SHH signaling inhibitor, suppressed cyclosporine A-enhanced cell proliferation. Up-regulated expression of SHH and up-regulation of proliferating cell nuclear antigen transcripts and protein were observed in the edentulous gingiva of cyclosporine A-treated rats. CONCLUSION: Cyclosporine A up-regulates gingival SHH expression in vitro and in vivo, and the inhibition of the SHH pathway counteracts the stimulatory effect of cyclosporine A on gingival fibroblast proliferation. Therefore, we suggest that SHH mediates a novel molecular mechanism for cyclosporine A-induced gingival complications.

Suppression of lung cancer metastasis-related protein 1 (LCMR1) inhibits the growth of colorectal cancer cells.

Lung cancer metastasis-related protein 1 (LCMR1) is a critical subunit of the mediator complex, and plays an important role in the elaborate regulation of gene transcription. However, the functional role of LCMR1 in colorectal carcinoma (CRC) has not been clarified. In this study, LCMR1 expression in CRC specimens was quantified by using the quantitative reverse transcription polymerase chain reaction method. The effect of downregulation of LCMR1 by lentivirus-mediated small hairpin RNA (shRNA) on CRC cell proliferation and tumorigenesis was explored. There was a higher expression of LCMR1 in CRC tissue in comparison with adjacent normal colon tissue (P < 0.05). LCMR1 gene was effectively knocked down in human CRC RKO and DLD-1 cells that infected with lentivirus delivering shRNA against LCMR1, which resulted in inhibition of cell proliferation and augmentation of G0/G1 phase proportion. Moreover, the tumorigenicity of RKO cells was also dramatically inhibited after LCMR1 was knocked down. In conclusion, our results suggest that LCMR1 promotes CRC cell growth, and lentivirus-mediated silencing of LCMR1 may contribute to the gene therapy for CRC.

Up-regulation of retinoblastoma protein phosphorylation in gingiva after cyclosporine A treatment: an in vivo and in vitro study.

BACKGROUND AND OBJECTIVE: Cyclosporine A can induce gingival cell proliferation; however, the precise molecular regulation of the proliferation is uncertain. Therefore, this study was carried out to examine, in vivo and in vitro, the expression of genes and proteins associated with gingival cell proliferation after treatment with cyclosporine A. MATERIAL AND METHODS: Forty Sprague Dawley rats with right maxillary posterior edentulous gingivae were assigned to a cyclosporine A group (30 mg/kg daily of cyclosporine A, administered orally) or a control group (administered mineral oil only). The animals were killed 4 wk after treatment. The edentulous gingivae were dissected out and analyzed for the expression of proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (Rb1) mRNA and/or protein, and phosphorylated Rb1 (pRb1), by real-time RT-PCR or immunohistochemistry. In human gingival fibroblast (HGF) cultures, the expression of PCNA, CDK4, cyclin D1 and Rb1 proteins and Rb1 phosphorylation were determined by western blotting after cyclosporine A treatment (0-10(4) ng/mL). RESULTS: Proliferating cell nuclear antigen and cyclin D1 mRNAs (Pcna and Ccnd1, respectively) were expressed more strongly in the gingivae of cyclosporine A-treated animals than in the gingivae of the controls. Immunohistochemical analyses showed that a greater number of gingival cells stained positive for cyclin D1, CDK4 and pRb1 in the cyclosporine A group than in the control group. Increased expression of cyclin D1, CDK4 and PCNA proteins was observed in HGFs after cyclosporine A treatment. The phosphorylation of Rb1 was enhanced in HGFs after treatment with cyclosporine A at concentrations of 10(2)-10(3) ng/mL. CONCLUSION: The increases in cyclin D1, PCNA and CDK4, together with the enhanced phosphorylation of Rb1, suggest that cyclosporine A promotes cell-cycle progression through the G(1)/S transition in the gingiva.

Highly efficient multipotent differentiation of human periodontal ligament fibroblasts induced by combined BMP4 and hTERT gene transfer.

Because periodontal ligament (PDL) cells are reported to contain progenitor or stem cell populations, they are considered a beneficial cell source for clinical periodontal regeneration. Both bone morphogenetic protein 4 (BMP4) and human telomerase reverse transcriptase (hTERT) have essential roles in the modulation of stem cell properties. In this study we report for the first time that the combined ectopic expression of BMP4 and hTERT significantly enhanced the multipotent differentiation efficiency and capacity of human PDL fibroblasts (PFs), as shown by osteogenic, adipogenic and neurogenic differentiation in vitro, and cementum/PDL-like tissue regeneration in vivo. These findings may be attributed, at least in part, to the original upregulation of important stem cell markers, such as scleraxis, Stro-1 and CD146, and the extremely lowered threshold for BMP concentration to activate BMP signaling by enhanced basal phosphorylation levels of Smad 1/5/8. In addition, the significantly reduced expression levels of CD146 and CD90 with the presence of Noggin confirms the direct effect of BMP4 on the stem cell-like phenotype of genetically modified PF cells (BT-PFs). Furthermore, BT-PFs exhibited a high neural differentiation capacity (>75%). After transplantation into NOD/SCID mice, genetically modified-PFs generated cementum/PDL-like structures on the surface of the carrier. The multipotency of these modified cells potentially provides an attractive source of stem cells for therapeutic purposes and regenerative medicine.

The osteoinductive effect of chitosan-collagen composites around pure titanium implant surfaces in rats.

BACKGROUND AND OBJECTIVE: The enhancing effects of chitosan on activation of platelets and differentiation of osteoprogenitor cells have been demonstrated in vitro. The purpose of this study was to evaluate the in vivo osteoinductive effect of chitosan-collagen composites around pure titanium implant surfaces. MATERIAL AND METHODS: Chitosan-collagen composites containing chitosan of different molecular weights (450 and 750 kDa) were wrapped onto titanium implants and embedded into the subcutaneous area on the back of 15 Sprague-Dawley rats. The control consisted of implants wrapped with plain collagen type I membranes. Implants and surrounding tissues were retrieved 6 wks after surgery and identified by Alizarin red and Alcian blue whole mount staining. The newly formed structures in the test groups were further analyzed by Toluidine blue and Masson-Goldner trichrome staining, and immunohistochemical staining with osteopontin and alkaline phosphotase. The bone formation parameters of the new bone in the two test groups were measured and compared. RESULTS: New bone formed ectopically in both chitosan-collagen groups, whereas no bone induction occurred in the negative control group. These newly formed bone-like structures were further confirmed by immunohistochemical staining. Comparison of bone parameters of the newly induced bone revealed no statistically significant differences between the 450 and 750 kDa chitosan-collagen groups. CONCLUSION: Our results demonstrated that chitosan-collagen composites might induce in vivo new bone formation around pure titanium implant surfaces. Different molecular weights of chitosan did not show significantly different effects on the osteoinductive potential of the test materials.

Cyclosporine A enhances apoptosis in gingival keratinocytes of rats and in OECM1 cells via the mitochondrial pathway.

BACKGROUND AND OBJECTIVE: We reported previously that cyclosporine A induces a high level of expression of p21 in rat gingival keratinocytes and in OECM1 cells. In this study, the apoptosis of gingival keratinocytes after treatment with cyclosporine A was evaluated using the same models. MATERIAL AND METHODS: Forty Sprague-Dawley rats with right edentulous ridges were assigned into cyclosporine A (30 mg/kg) and control groups. Four weeks later, gingivae were screened for expression of apoptotic genes using microarray analyses and DNA fragmentation. The expression of bcl2-associated X protein (Bax), apoptosis-inducing factor (AIF) and Caspase 3 mRNAs, and the expression of Bax, AIF, Caspase 9 and Fas proteins, were analyzed using the reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. Apoptosis in OECM1 cells (keratinocytes of a gingival carcinoma cell line), after treatment with cyclosporine A, was evaluated by 4',6-diamidino-2-phenylindole (DAPI) staining and flow cytometry, whereas the expression of Bax, AIF, Caspase 3 and 8, Bcl-2 and Fas proteins were examined using western blotting. RESULTS: According to microarray analyses, the expression of certain apoptotic genes was altered in the gingiva of rats who received cyclosporine A, and increased number of DNA fragments were detected. Expression of mRNA or protein for Bax, AIF and Caspase 3 and 9 in the gingivae of rats increased after treatment with cyclosporine A. An increased number of apoptotic bodies and of OECM1 cells in the sub-G1 phase was observed after treatment with cyclosporine A. Increased expression of AIF, Bax and Caspase 3 protein, but not of bcl-2, Caspase 8 or Fas protein, was observed in cells after treatment with cyclosporine A. CONCLUSION: Based on the above findings, we suggest that cyclosporine A might enhance the apoptosis of gingival keratinocytes, mainly via the mitochondrial pathway.

Predictive factors of visual and anatomical outcome after intravitreal bevacizumab treatment of neovascular age-related macular degeneration: an optical coherence tomography study.

AIM: To evaluate the baseline visual and optical coherence tomography (OCT) factors on outcomes after intravitreal bevacizumab treatment of subfoveal neovascular age-related macular degeneration (AMD). METHODS: A retrospective analysis of 73 eyes treated with intravitreal bevacizumab for subfoveal neovascular AMD was performed. Change in best corrected Snellen visual acuity (BCVA) and central retinal thickness (CRT) on OCT were the primary outcomes. Automated and manual measurements were made for all OCT characteristics. RESULTS: Seventy-three (100%) and 58 (79.5%) eyes were followed for 3 and 6 months, respectively. The mean BCVA improved from 20/177 to 20/160 (p = 0.03) at 3 months and to 20/143 (p = 0.04) at 6 months. The mean CRT decreased 93 microm (p<0.0001) and 105 microm (p<0.0001) at 3 and 6 months, respectively. Baseline BCVA worse than 20/100 was associated with greater visual improvement (p< or =0.04). Eyes with baseline CRT greater than 400 microm experienced a greater mean CRT reduction (p<0.05). Treatment-naïve patients had a greater mean CRT reduction than those previously treated with any modality (p<0.05) CONCLUSIONS: Baseline BCVA and CRT positively influence mean visual and CRT improvement, respectively, after intravitreal bevacizumab in wet AMD. Any prior treatment predicted less CRT reduction.

Tetracycline release from tripolyphosphate-chitosan cross-linked sponge: a preliminary in vitro study.

BACKGROUND AND OBJECTIVE: The aim of this study was to design a tripolyphosphate-chitosan cross-linked tetracycline-containing (TPP-TC) sponge that slowly releases tetracycline, for future periodontal applications. MATERIAL AND METHODS: Chitosan sponge was made by freezing and drying 2.5% chitosan solution. Tripolyphosphate-chitosan cross-linked (TPP) sponge was made by immersing the chitosan sponge in tripolyphosphate solution and air drying it. Tetracycline-containing chitosan (TC) sponge was prepared by freezing and drying a mixture of chitosan and tetracycline. TPP-TC sponge was made by immersing the TC sponge in tripolyphosphate solution. The weight, thickness and diameter of the four chitosan sponges were recorded. Their surface microstructures were inspected using scanning electron microscopy. The amount of tetracycline released from the sponges was analyzed by spectrophotometry. Antimicrobial activities of the residual sponges were tested against Staphylococcus aureus and Escherichia coli. RESULTS: The topography of the scaffolds was intact after the addition of tetracycline. However, increased surface irregularities were noted. In sponges with tripolyphosphate, intensified surface folding was observed. The weight of the sponges increased after tripolyphosphate and tetracycline were added, but their thicknesses and diameters decreased after cross-linking. Tetracycline was detected in the solution containing TPP-TC sponges until day 11. On day 7, the tetracycline released from TC sponges was less than that released from TPP-TC sponges. Bacterial growth was inhibited by sponges containing tetracycline. The inhibitory effect of the TPP-TC sponges was detectable until day 11. CONCLUSION: Our data showed that TPP-TC sponge was suitable as a slow-release device for tetracycline and that it maintained antimicrobial effects against the bacteria tested for up to 11 d.

Expression of p21 and p53 in rat gingival and human oral epithelial cells after cyclosporine A treatment.

BACKGROUND AND OBJECTIVE: Expression of p21 and p53 were examined, at gene and protein levels, in edentulous gingival epithelial cells from rats and from a human oral epidermoid carcinoma cell line, OECM1, after cyclosporine A therapy. MATERIAL AND METHODS: In vivo: 20 partially edentulous SD rats were assigned into cyclosporine A feeding and control groups. After the rats were killed, p21 and p53 in gingiva were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. In vitro: after cyclosporine A treatment, p21 and p53 of OECM1 cells were evaluated by western blot and the luciferase assay. The distribution of OECM1 cells in each phase of the cell cycle was evaluated by flow cytometry. RESULTS: The mRNA expression of p21 was significantly higher in the cyclosporine A group than in the control group. A greater number of positive anti-p21-stained cells were observed in the gingival epithelium of the cyclosporine A group than in the control group. Significantly higher levels of p21 protein and activity were observed in OECM1 cells after cyclosporine A treatment than in cells without treatment. A relative increase of cells in G0/G1 phases, and a decrease of cells in G2/M phases, were observed in OECM1 cells after cyclosporine A treatment. CONCLUSION: In the present study, higher p21 mRNA and protein expressions were observed after cyclosporine A treatment. Thus, an up-regulation of p21 expression, via a p53-independent pathway, by cyclosporine A in gingival and oral epithelial cells was suggested.

Cyclosporin-A inhibits the expression of cyclooxygenase-2 in gingiva.

BACKGROUND AND OBJECTIVE: Various inflammatory mediators are involved in the development of cyclosporine A-induced gingival overgrowth. In this study, the gingival expression of cyclooxygenase-2 after cyclosporine A therapy was examined in vivo and in vitro. MATERIAL AND METHODS: After edentulous ridges on maxilla were established, 21 Sprague-Dawley rats received cyclosporine A daily for 4 wk, and a further 21 rats received solvent. After the rats were killed, the expression of cyclooxygenase-2 mRNA, interleukin-1beta mRNA, tumor necrosis factor-alpha mRNA, and interleukin-6 mRNA was examined in the edentulous gingiva. The expression of cyclooxygenase-2 protein and the production of prostaglandin E2 were also evaluated. RESULTS: In cultured human gingival fibroblasts and epithelial cells, the expression of cyclooxygenase-2 mRNA was measured after treatment with cyclosporine A. Significantly lower expression of cyclooxygenase-2 and interleukin-1beta mRNA, but higher interleukin-6 expression, were observed in gingiva from cyclosporine A-treated rats than in those from the control rats. Significantly less prostaglandin E2 production was observed in cyclosporine A-treated rats. Immunohistochemistry revealed that fewer gingival stromal cells were positively stained for cyclooxygenase-2 in cyclosporine A-treated rats. In cultured cells, significantly less cyclooxygenase-2 mRNA was detected after treatment with cyclosporine A. CONCLUSION: The expression of cyclooxygenase-2 was lower in the plaque nonretentive gingivae and the in vitro gingival cells upon treatment with cyclosporine A. Thus, we propose that cyclosporine A inhibits the expression of gingival cyclooxygenase-2.

Expression of fascin in oral and oropharyngeal squamous cell carcinomas has prognostic significance - a tissue microarray study of 129 cases.

AIMS: To elucidate the role of fascin in oral and oropharyngeal squamous cell carcinoma (OSCC) by correlation with clinical parameters. METHODS AND RESULTS: Paraffin sections using tissue microarrays of 129 patients with OSCC were investigated immunohistochemically. Fascin protein was overexpressed in OSCC cells compared with their non-neoplastic epithelial counterparts. For evaluating the intensity of fascin, 39 (30.2%) were classified as weakly immunoreactive, 76 (58.9%) as moderate reactive and 14 (10.9%) as intensely reactive. For evaluating the distribution of fascin, 64 (49.6%) were classified as < 55% and 65 (50.4%) were classified as >/= 55%. Fascin protein expression was correlated with size or extent of the tumour (P < 0.001), positive lymph node metastasis (P < 0.001), distant metastasis (P = 0.014) and clinical staging (P < 0.001). The immunoreactivity scores of fascin in OSCC were variable but showed significant correlation with histological grade, clinical TNM system and stage. CONCLUSION: Expression of fascin protein may play an important role in progression of OSCC. Overexpression of fascin contributes to a more aggressive clinical course and suggests the potential of fascin as a new molecular target for therapeutic intervention.

[Clinical, enteroscopic, and pathological characteristics of 796 cases of colorectal polyps].

OBJECTIVE: To study the age, clinical, enteroscopic and pathological characteristics of colorectal polyps and factors affected polyp-carcinoma. METHODS: We analyzed the clinical, enteroscopic and pathological characteristics of 7276 cases of colorectal polyps. RESULTS: The incidence of colorectal polyps was 10.94%, including 521 men and 275 women. The rate of colorectal polyp was 82.29% in 30-69 year olds. The adenomatous, inflammatory, hyperplastic and juvenile polyps were 43.84%, 42.09%, 11.06% and 1.51%, respectively. Polypoid lesions were located at cecum 3.29%, ascending 11.88%, transverse 4.89%, descending 11.58%, sigmoid 26.05%, and rectum 42.32%. Thirty-five cases (4.4%) were found to have polpous canceration. The canceration rates in villous, mixed and tubular adenomas were 29.73%, 11.11%, and 4.86%. The rate of canceration seemed to depend on its dimensions, being 1.3%, 7.4%, and 25.6% for the 0.6 - 1.0 cm, 1.1 - 1.9 cm, and > or = 2.0 cm in size, respectively. Conclusion The ages between 30-69 tend to suffer from colorectal polyps. The incidence in the male is higher than that in the female. Colorectal polyps are more likely to locate in left colon. The common pathological types were adenomatous and inflammatory polyps. There is a high canceration of polyps in the left colon, villous adenomas and > or = 2.0 cm polyps. The broader the pedicles and the larger the diameters of polyps are, the higher the canceration rate. All of the colon polyps should be excised and undergo the pathological examination. Enteroscopic polypectomy helps prevent colorectal polpous canceration.

Healing following tooth extraction in cyclosporine-fed rats.

Healing after tooth extraction was studied in rats treated with cyclosporine-A (CSA) for four weeks. Sixty male Sprague-Dawley rats were assigned to one of three groups of 20 rats each. The maxillary right molars were extracted from two groups; the third group served as a non-extraction control. The non-extraction group and one extraction group (vehicle control) received the solvent mineral oil daily, and the other extraction group received 15 mg/kg CSA in mineral oil. Five rats from each group were killed 5, 10, 14 and 28 days after extraction and samples analyzed histologically. On days 5 and 10, bone volume was significantly lower and marrow volume significantly higher in both extraction groups than in the non-extraction group. The fractional-formation surfaces were significantly lower in the extraction groups than in the non-extraction group on day 5 only. Osteoid volume was significantly higher in the extraction vehicle control group than in the other two groups on days 10 and 14; however, the osteoid volume was higher in the CSA group than in the other two groups on day 28. On days 14 and 28, bone volume was lower and marrow volume higher in the CSA group than in the extraction vehicle control and non-extraction groups. On day 28, bony surface areas were significantly greater in the CSA group than in the extraction vehicle control and non-extraction groups. Soft-tissue evaluation showed significantly greater epithelial areas, connective tissue areas and total tissue areas in the CSA group than in the extraction vehicle control group on day 28, but not on day 14. These data suggest that CSA may influence healing of both the gingival tissue and the alveolar bony sockets in the tooth-extraction wound. Further detailed study is needed to identify the mechanisms responsible.