Publications by authors named "Kentaro Imamura"

47 Publications

Characteristic endoscopic findings of gastric adenocarcinoma of fundic-gland mucosa type.

Gastric Cancer 2021 Jul 9. Epub 2021 Jul 9.

Department of Pathology, Fukuoka University Chikushi Hospital, Chikusino, Japan.

Background And Study Aims: Gastric adenocarcinoma of fundic-gland type (GA-FG) was first proposed as a new entity of gastric adenocarcinoma in 2010. Subsequently, gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM) was reported as a subtype of gastric adenocarcinoma. This study aimed to investigate the endoscopic findings of GA-FGM and to evaluate the differences between GA-FGM and GA-FG.

Patients And Methods: This was a single-center retrospective study. Participants were selected from patients with gastric cancer treated at Fukuoka University Chikushi Hospital, between September 2007 and May 2020. Patients histologically diagnosed with GA-FGM or GA-FG were enrolled, and endoscopic findings were analyzed in detail.

Results: A total of 12 GA-FGM lesions (12 patients) and 14 GA-FG lesions (13 patients) were analyzed. The two lesion types showed similar features: most lesions were of elevated type, located in the upper stomach, and developed in the stomach without Helicobacter pylori infection. On conventional endoscopy using the dye-spraying method, well-demarcated fine granular areas were observed in 7 GA-FGM lesions (58%) but not in any GA-FG lesions, with a significant difference between the two groups (P = 0.001). Magnifying endoscopy with narrow-band imaging (NBI) showed that 11 GA-FGM lesions (92%) met the diagnostic criteria for cancer according to the vessel plus surface classification system, whereas none of the GA-FG lesions met the same criteria (0%, 0/14) (P = 0.001).

Conclusion: Our results suggest that magnifying endoscopy with NBI is a potentially useful method for the diagnosis of GA-FGM.
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http://dx.doi.org/10.1007/s10120-021-01208-2DOI Listing
July 2021

Nature of a white opaque substance visualized by magnifying endoscopy in colorectal hyperplastic polyps.

Endosc Int Open 2021 Jul 17;9(7):E1077-E1083. Epub 2021 Jun 17.

Department of Pathology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.

 A white opaque substance (WOS) has been observed in the epithelia of gastric, duodenal, and colorectal epithelial adenomas and carcinomas, using magnifying endoscopy (ME). The WOS has been reported to be derived from a dense accumulation of minute lipid droplets in the epithelium. This study aimed to investigate whether the WOS in colorectal hyperplastic polyps was derived from lipid droplets accumulated in the epithelium, as observed in the case of gastric, duodenal, and colorectal epithelial neoplasms.  We analyzed 30 consecutive patients who were positive for the WOS, as visualized in colorectal hyperplastic polyps by ME with narrow-band imaging and 30 consecutive patients who were negative for the WOS. Biopsy specimens obtained from the polyps were immunostained with anti-adipophilin antibody to determine the correlation between the presence of the WOS and that of lipid droplets in the epithelium.  In all patients, the epithelial cells were histologically positive for adipophilin. However, the area of adipophilin-positive epithelial cells in the WOS-positive group was significantly larger than that in the WOS-negative group (  < 0.001). The density of the WOS was strongly and positively correlated with the area of adipophilin-positive cells.  This study reveals that the WOS visualized in the superficial layers of colorectal hyperplastic polyps is produced by a dense accumulation of minute lipid droplets in the epithelia of the polyps.
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http://dx.doi.org/10.1055/a-1452-9669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211482PMC
July 2021

Systemic administration of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-Ig abrogates alveolar bone resorption in induced periodontitis through inhibition of osteoclast differentiation and activation: An experimental investigation.

J Periodontal Res 2021 Jun 15. Epub 2021 Jun 15.

Department of Periodontology, Tokyo Dental College, Tokyo, Japan.

Background/objectives: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule expressed on T cells. CTLA-4 also binds to the surfaces of monocytes and macrophages, precursors of osteoclasts. Research on rheumatoid arthritis demonstrated that CTLA-4 suppresses inflammation and bone resorption. However, its effects on alveolar bone have yet to be understood. The purpose of this study was to investigate the role and potential mechanism of CTLA-4 in bone resorption in periodontitis.

Materials And Methods: In vivo, the effects of systemic administration of CTLA-4 immunoglobulin fusion protein (CTLA-4-Ig) on alveolar bone resorption were investigated using a periodontitis mouse model. A total of 20 C57BL/6J mice were randomly assigned to two groups according to the administration modes. Periodontitis was induced by placing a ligature around the left maxillary second molar. The contralateral tooth was left un-ligated. In the CTLA-4-Ig (+) group, CTLA-4-Ig was administered by intraperitoneal injection at 1 and 3 days after ligature placement. Animals in the CTLA-4-Ig (-) group were given only phosphate-buffered saline each time. At 5 days after ligature placement, bone resorption was assessed by micro-computed tomography and histological examination, and the prevalence of osteoclast-like cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining. In vitro, the effects of CTLA-4-Ig on osteoclasts were evaluated. Viability of RAW 264.7 cells treated with receptor activator of nuclear factor-κB ligand (RANKL) and CTLA-4-Ig was tested by WST-1 assay. Osteoclast-like cells were enumerated by TRAP staining, and osteoclast activity was evaluated by resorption pit assay. Gene expression levels of osteoclast differentiation markers (macrophage-colony stimulating factor receptor, carbonic anhydrase II, cathepsin K, and Trap) and protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, were assessed by quantitative real-time polymerase chain reaction. The effect of CTLA-4-Ig on the nuclear factor-κB (NF-κB) activation was assessed by enzyme-linked immunosorbent assay.

Results: In vivo, ligature-induced bone resorption and the numbers of osteoclast-like cells were significantly decreased by the administration of CTLA-4-Ig. In vitro, treatment with RANKL and CTLA-4-Ig had no significant effect on cell viability. CTLA-4-Ig significantly reduced the prevalence and activation of osteoclast-like cells and decreased the expressions of osteoclast differentiation markers, compared with the RANKL-treated control. CTLA-4-Ig significantly suppressed RANKL-induced phosphorylation of NF-κB p65 but increased PP2A expression.

Conclusion: These results suggest that CTLA-4-Ig abrogates bone resorption in induced periodontitis, possibly via inhibition of osteoclast differentiation and activation. The regulation of the NF-κB pathway and PP2A expression may be one mechanism by which CTLA-4-Ig suppresses osteoclast behavior.
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http://dx.doi.org/10.1111/jre.12909DOI Listing
June 2021

Healing of Experimental Periodontal Defects Following Treatment with Fibroblast Growth Factor-2 and Deproteinized Bovine Bone Mineral.

Biomolecules 2021 May 29;11(6). Epub 2021 May 29.

Department of Periodontology, Tokyo Dental College, Chiyoda-ku, Tokyo 1010061, Japan.

The aim of this study was to investigate the effects of fibroblast growth factor (FGF)-2 used in combination with deproteinized bovine bone mineral (DBBM) on the healing of experimental periodontal defects. Periodontal defects created in rats were treated by FGF-2, DBBM, FGF-2 + DBBM, or left unfilled. Microcomputed tomography, histological, and immunohistochemical examinations were used to evaluate healing. In vitro cell viability/proliferation on DBBM with/without FGF-2 was assessed by WST-1. Cell behavior was analyzed using scanning electron and confocal laser scanning microscopy. Osteogenic differentiation was evaluated by staining with alkaline phosphatase and alizarin red. Bone volume fraction was significantly greater in FGF-2 and FGF-2 + DBBM groups than in other groups at 2 and 4 weeks postoperatively. In histological assessment, newly formed bone in FGF-2 and FGF-2 + DBBM groups appeared to be greater than other groups. Significantly greater levels of proliferating cell nuclear antigen-, vascular endothelial growth factor-, and osterix-positive cells were observed in FGF-2 and FGF-2 + DBBM groups compared to Unfilled group. In vitro, addition of FGF-2 to DBBM promoted cell viability/proliferation, attachment/spreading, and osteogenic differentiation. The combination therapy using FGF-2 and DBBM was similarly effective as FGF-2 alone in the healing of experimental periodontal defects. In certain bone defect configurations, the combined use of FGF-2 and DBBM may enhance healing via promotion of cell proliferation, angiogenesis, and osteogenic differentiation.
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http://dx.doi.org/10.3390/biom11060805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226676PMC
May 2021

Usefulness of vessel plus surface classification system for the diagnosis of early gastric cancer after eradication.

Ann Gastroenterol 2021 26;34(3):354-360. Epub 2021 Feb 26.

Department of Pathology (Hiroshi Tanabe, Atsuko Ota, Seiji Haraoka, Akinori Iwashita), Fukuoka University Chikushi Hospital, Chikusino, Japan.

Background: It has been reported that it is sometimes difficult to make a diagnosis of gastric cancer detected after ) eradication. Therefore, we conducted a study to determine the usefulness of magnifying endoscopy using vessel plus surface classification system for making a diagnosis of early gastric cancer after eradication.

Method: Usefulness of the markers of the vessel plus surface classification system for diagnosing gastric cancer using magnifying endoscopy with narrow-band imaging was investigated for gastric cancer detected after eradication (-eradicated group) vs. -positive gastric cancer (-positive group).

Results: 85 lesions were included in this study. The -eradicated group comprised 27 lesions, whereas the -positive group comprised 58 lesions. As for magnified endoscopic findings based on the vessel plus surface classification system, the respective positivity rates in the -eradicated group vs. those in the -positive group were as follows: demarcation line, 100% (27/27) vs. 100% (58/58); irregular microvascular pattern, 100% (27/27) vs. 100% (58/58); and irregular microsurface pattern, 78% (21/27) vs. 95% (55/58). There was no significant difference in the positivity rates of the demarcation line and irregular microvascular pattern between the groups. The positivity rate of the irregular microsurface pattern was significantly lower in the -eradicated group than in the -positive group (P0.03).

Conclusion: We presume that the microvascular pattern is more useful than the microsurface pattern as a diagnostic marker in cases of gastric cancer detected after eradication.
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http://dx.doi.org/10.20524/aog.2021.0605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079864PMC
February 2021

Measurement of intragastric pressure: an objective method to ascertain whether gastric wall extension is sufficient for assessment of the non-extension sign.

Endosc Int Open 2021 Apr 17;9(4):E530-E536. Epub 2021 Mar 17.

Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikusino, Japan.

The optimal intragastric pressure (IP) for strong gastric wall extension is unclear. We aimed to develop an accurate method to measure IP using endoscopy and determine the pressure required for strong gastric wall extension. An in vitro experiment using an endoscope with a rubber attached at its tip was conducted. The process of inserting the pressure measurement probe into the forceps channel was skipped, and the tube of the pressure measurement device was directly connected to the forceps channel. In vivo, the pressure in 51 consecutive patients at the time of strong gastric wall extension was measured. Strong extension of the gastric wall was defined as when the folds in the greater curvature were flattened as a result of sufficient extension of the gastric wall by insufflated air during upper gastrointestinal endoscopy. The IP at that time was measured. In vitr , 20 mL of tap water was injected once into the forceps channel and then aspirated for 10 seconds. Pressure measurement after irrigation of the forceps channel as well as the measurement by inserting the probe procedure were accurately performed. In vivo, among the 51 included patients, the mean IP (range) was 14.7 mmHg (10-23). Strong extension of the gastric wall was obtained in 96.1 % of patients when the IP was 20 mmHg. We developed an accurate method to measure IP using upper gastrointestinal endoscopy. Strong extension of the gastric wall was obtained in almost all patients when the IP was 20 mmHg.
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http://dx.doi.org/10.1055/a-1352-2761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969131PMC
April 2021

Gastric metaplasia of the duodenal mucosa in Crohn's disease: novel histological and endoscopic findings.

Endosc Int Open 2021 Feb 25;9(2):E181-E189. Epub 2021 Jan 25.

Department of Pathology, Fukuoka, University Chikushi Hospital.

 Upper gastrointestinal endoscopy and biopsy are useful for differential diagnosis of Crohn's disease (CD) of the large intestine and ulcerative colitis (UC). We aimed to identify novel histopathological and endoscopic findings in the upper gastrointestinal tract in patients with CD who did not have infection.  Upper gastrointestinal endoscopy was performed on patients with CD and UC. Mucosal lesions detected were subsequently observed using magnifying endoscopy with narrow-band imaging (M-NBI), following which biopsy was performed. When no mucosal lesion was detected on conventional endoscopy, M-NBI and biopsy were performed on four sites: the gastric body, gastric antrum, duodenal bulb, and second portion of the duodenum.  The prevalences of gastric metaplasia (GM) were 48 % (24/50) and 16 % (8/50) in the CD and UC groups, showing a significant difference (  = 0.001). In 23 of 24 patients with histologically proven GM in the CD group, mucosal lesions were detected using conventional white-light imaging (C-WLI). In 22 of 24 patients with histologically proven GM in the CD group, disappearance of normal villous structure and the presence of curved marginal crypt epithelium were noted using magnifying endoscopic findings characteristic of GM (M-GM). A combination of C-WLI and M-NBI yielded a significantly increased specificity (  = 0.004) and accuracy (  = 0.039).  The prevalence of GM in the duodenal mucosa was significantly higher in patients with CD than in controls. The identified endoscopic findings may be useful as novel indicators for the histological diagnosis of GM in the duodenum.
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http://dx.doi.org/10.1055/a-1313-7239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834703PMC
February 2021

White Opaque Substance, a New Optical Marker on Magnifying Endoscopy: Usefulness in Diagnosing Colorectal Epithelial Neoplasms.

Clin Endosc 2021 Jan 13. Epub 2021 Jan 13.

Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.

Background/aims: A white substance that is opaque to endoscopic light is sometimes observed in the epithelium during narrowband imaging with magnifying endoscopy of gastric or colorectal epithelial neoplasms. This prospective observational study aimed to determine whether the morphology of the white opaque substance (WOS) allows differential diagnosis between colorectal adenoma and carcinoma.

Methods: A consecutive series of patients with colorectal adenomas or early carcinomas who underwent endoscopic resection or surgical excision were studied. The morphology of the WOS was determined based on endoscopic images before the histopathological diagnosis was performed. The primary outcome was the diagnostic performance of an irregular WOS as a marker of colorectal carcinoma.

Results: The study analyzed 125 lesions. A total of 33 lesions showed an irregular WOS, and 92 lesions showed a regular WOS. Among the 33 lesions found to show an irregular WOS, 30 were carcinomas. Among the 92 lesions showing a regular WOS, 79 were adenomas. With irregular WOS as a marker of carcinoma, the diagnostic accuracy was 87%, sensitivity was 91%, and specificity was 86%.

Conclusions: This study demonstrated the potential usefulness of the morphology of the WOS as a marker for the differential diagnosis between adenoma and carcinoma in cases of colorectal epithelial neoplasms.
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http://dx.doi.org/10.5946/ce.2020.205DOI Listing
January 2021

Histological subtype of gastric adenocarcinoma: two cases of mixed fundic and pyloric mucosa-type adenocarcinoma.

Ecancermedicalscience 2020 13;14:1143. Epub 2020 Nov 13.

Department of Gastroenterology, Fukuoka University Chikushi Hospital, 1-1-1 Zokumyoin Chikushino, Fukuoka 818-8052, Japan.

Adenocarcinomas with differentiation towards fundic or pyloric glands are rare histological subtypes. We herein describe two cases of new histological subtypes: mixed fundic and pyloric mucosa-type adenocarcinoma detected in uninfected patients. The first patient was a woman in her 40s. A glossy, reddish, nodular lesion with a flat elevated whitish area was detected at the gastric fundus. When the nodular lesion was visualised with magnifying narrow-band imaging (M-NBI), an absent microvascular pattern plus an irregular microsurface pattern with a demarcation line was observed. The second patient was a woman in her 60s. A glossy, reddish, elevated lesion was detected at the gastric body. M-NBI finding was a regular microvascular pattern plus a regular microsurface pattern with a demarcation line. Histological examination of the resected specimens from both cases showed a very well- to well-differentiated adenocarcinoma which has differentiation towards the mixed fundic and pyloric mucosa. The histological and serological findings of both cases indicated the absence of infection. The present two cases demonstrate further evidence of a new histological subtype of gastric adenocarcinoma: mixed fundic and pyloric mucosa-type adenocarcinoma, which has distinct characteristic endoscopic findings.
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http://dx.doi.org/10.3332/ecancer.2020.1143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738269PMC
November 2020

Histological Architecture of Gastric Epithelial Neoplasias That Showed Absent Microsurface Patterns, Visualized by Magnifying Endoscopy with Narrow-Band Imaging.

Clin Endosc 2021 Mar 24;54(2):222-228. Epub 2020 Nov 24.

Department of Pathology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.

Background/aims: The objective of this study was to elucidate the histological structure of the absent microsurface patterns (MSPs) that were visualized by magnifying endoscopy with narrow-band imaging (M-NBI).

Methods: The study included consecutive gastric epithelial neoplasias for which M-NBI findings and histological findings could be compared on a one-to-one basis. The lesions were classified as absent MSPs and present MSPs based on the findings obtained using M-NBI. Of the histopathological findings for each lesion that corresponded to M-NBI findings, crypt opening densities, crypt lengths, crypt opening diameters, intercrypt distances, and crypt angles were measured and compared.

Results: Thirty-six lesions were included in the analysis; of these, 17 lesions exhibited absent MSP and 19 lesions exhibited present MSP. Comparing the histological measurements for absent MSPs vs. present MSPs, median crypt opening density was 0.9 crypt openings/mm vs. 4.8 crypt openings/mm (p<0.001), respectively. The median crypt length, median crypt opening diameter, median intercrypt distance, and median crypt angle were 80.0 μm vs. 160 μm (p<0.001), 40.0 μm vs. 44.2 μm (p=0.09), 572.5 μm vs. 166.7 μm (p<0.001), and 21.6 degrees vs. 15.5 degrees (p<0.001), respectively.

Conclusion: Histological findings showed that lesions exhibiting absent MSPs had lower crypt opening density, shorter crypt length, greater intercrypt distance, and larger crypt angle.
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http://dx.doi.org/10.5946/ce.2020.090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039747PMC
March 2021

Surgical Treatment of Furcation Involvement Associated with Recurrence of Aggressive Periodontitis: A Case Report.

Bull Tokyo Dent Coll 2020 Dec 10;61(4):265-273. Epub 2020 Nov 10.

Department of Periodontology, Tokyo Dental College.

Here, we report a case of generalized chronic periodontitis with furcation involvement that was treated successfully by means of surgical intervention. The patient was a 43-year-old man requesting treatment for periodontal disease. An initial examination revealed 42% of sites with a probing depth of ≥4 mm and 42.9% of sites with bleeding on probing. The maxillary molars showed varying degrees of furcation involvement. Radiographic examination revealed bone resorption in the molar and mandibular anterior teeth regions. Microbiological examination of subgingival plaque revealed the presence of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Tannerella forsythia. The patient's oral health-related quality of life (OHRQL) was also assessed. Based on a clinical diagnosis of severe chronic periodontitis, initial periodontal therapy was performed. Plaque control, scaling and root planing, extraction, temporary fixed restoration, occlusal adjustment, and root canal treatment were implemented. Following reevaluation, open flap debridement was performed at selected sites. Root resection was performed on the distal root of #16. Prosthetic treatment was then initiated for recovery of oral function. After confirmation of appropriate occlusion and cleanability, the patient was placed on supportive periodontal therapy. Root resection improved cleanability. This clinical improvement has been adequately maintained over a 2-year period. The patient's OHRQL score showed a slight deterioration during the supportive periodontal therapy OK period, however. This indicates the need for further careful monitoring of periodontal conditions, as well as of how they are perceived by the patient themselves.
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http://dx.doi.org/10.2209/tdcpublication.2020-0020DOI Listing
December 2020

Root Coverage with Connective Tissue Graft in Patients with Thin Periodontal Biotype: A Case Series with 12-month Follow-up.

Bull Tokyo Dent Coll 2020 Dec 10;61(4):221-229. Epub 2020 Nov 10.

Department of Periodontology, Tokyo Dental College.

Preoperative gingival thickness is an important factor in the success of complete root coverage. Here, two cases are reported in which a biotype probe was used to assess the periodontal biotype before performance of a root coverage procedure. Clinical examinations were performed at baseline and at 3, 6, and 12 months postoperatively. The following clinical parameters were evaluated: probing depth, recession height, clinical attachment level, bleeding on probing, and width of keratinized gingiva. At baseline and at 12 months postoperatively, periodontal biotype was estimated using the biotype probe. The root coverage esthetic score was assessed to determine esthetic outcome at baseline and at 3, 6, and 12 months postoperatively. The periodontal biotypes in the mandibular central and lateral incisors were judged to be thin. These teeth presented with Miller Class II gingival recession after orthodontic therapy. Gingival recession was treated with a coronally advanced flap and autogenous connective tissue graft. In both cases, improvements in all clinical parameters and root coverage esthetic scores were evaluated at 3, 6, and 12 months postoperatively. The treated recession showed 100% root coverage. The periodontal biotype changed from one that was thin to one that was thick at the surgical sites. In both the present cases, objective preoperative assessment of the periodontal biotype allowed the appropriate surgical procedure to be selected.
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http://dx.doi.org/10.2209/tdcpublication.2020-0015DOI Listing
December 2020

Treatment of Chronic Periodontitis with Recombinant Human Fibroblast Growth Factor-2 and Deproteinized Bovine Bone Mineral in Wide Intrabony Defects:12-month Follow-up Case Series.

Bull Tokyo Dent Coll 2020 Dec 10;61(4):231-241. Epub 2020 Nov 10.

Department of Periodontology, Tokyo Dental College.

Clinical use of 0.3% recombinant human fibroblast growth factor (rhFGF)-2 for periodontal regeneration received formal approval in Japan in 2016. The combination of growth factor and bone graft material is used to enhance periodontal healing in regenerative therapy. The exact effects of combination therapy on periodontal healing remain unknown, however. Here, we report three cases of chronic periodontitis treated with the combination of rhFGF-2 and deproteinized bovine bone mineral (DBBM). Following initial periodontal therapy, periodontal regenerative therapy using rhFGF-2 in combination with DBBM was performed to treat wide intrabony defects. Periodontal parameters and radiographic bone fill were reevaluated at 3 months, 6 months, and 1 year postoperatively. Oral health-related quality of life (OHRQL) was assessed as a patient-reported measure of outcome. At 1 year postoperatively, probing pocket depth and clinical attachment level showed a significant improvement in comparison with at baseline. An improvement was also noted in radiographic evidence of bone fill and total OHRQL scores. Combination therapy yielded clinically favorable results in the present cases.
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http://dx.doi.org/10.2209/tdcpublication.2019-0050DOI Listing
December 2020

Diagnosis of early gastric cancer using image enhanced endoscopy: a systematic approach.

Transl Gastroenterol Hepatol 2020 5;5:50. Epub 2020 Oct 5.

Department of Pathology, Fukuoka University Chikushi Hospital, Chikushino City, Fukouka, Japan.

This paper provides an overview of the principles of a vessel plus surface (VS) classification system to explain the diagnostic system of early gastric cancer using image-enhanced magnifying endoscopy. Furthermore, this paper introduces the magnifying endoscopy simple diagnostic algorithm for gastric cancer (MEADA-G) developed according to the VS classification system, with a description of the procedures performed for diagnosis. In addition to the diagnostic system, white opaque substance (WOS), light blue crest (LBC), white globe appearance (WGA), and vessels within epithelial circle (VEC) patterns, which are representative findings that can be observed in the gastric mucosa by image-enhanced magnifying endoscopy, are also described. Image-enhanced magnifying endoscopy is particularly useful in the diagnosis of differentiated-type early gastric cancer. It is important to use the appropriate clinical strategies based on a comprehensive understanding of the usefulness and limitations of the diagnostic system described in this paper.
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http://dx.doi.org/10.21037/tgh.2019.12.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530321PMC
October 2020

Periodontal surgery using rhFGF-2 with deproteinized bovine bone mineral or rhFGF-2 alone: 2-year follow-up of a randomized controlled trial.

J Clin Periodontol 2021 01 12;48(1):91-99. Epub 2020 Nov 12.

Department of Periodontology, Tokyo Dental College, Tokyo, Japan.

Aim: To compare outcomes of rhFGF-2 + DBBM therapy with rhFGF-2 alone in the treatment of intrabony defects. This study provides 2-year follow-up results from the previous randomized controlled trial.

Materials And Methods: Defects were randomly allocated to receive rhFGF-2 + DBBM (test) or rhFGF-2 (control). Treated sites were re-evaluated at 2 years postoperatively, using original clinical and patient-centred measures.

Results: Thirty-eight sites were available for re-evaluation. At 2 years, both groups showed a significant improvement in clinical attachment level (CAL) from baseline. A gain in CAL of 3.4 ± 1.3 mm in the test group and 3.1 ± 1.5 mm in the control group was found. No significant inter-group difference was noted. Both groups showed a progressive increase in radiographic bone fill (RBF). The test treatment yielded greater RBF (56%) compared with the control group (41%). The control treatment performed better in contained defects in terms of CAL and RBF. There was no significant difference in patient-reported outcomes between groups.

Conclusions: At 2-year follow-up, the test and cotrol treatments were similarly effective in improving CAL, whereas the test treatment achieved a significantly greater RBF. In both treatments, favourable clinical, radiographic, and patient-reported outcomes can be sustained for at least 2 years.

Trial Registration: The University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) 000025257.
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http://dx.doi.org/10.1111/jcpe.13385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984167PMC
January 2021

Treatment with functionalized designer self-assembling peptide hydrogels promotes healing of experimental periodontal defects.

J Periodontal Res 2021 Jan 6;56(1):162-172. Epub 2020 Oct 6.

Department of Periodontology, Tokyo Dental College, Tokyo, Japan.

Background/objectives: It has been reported that self-assembling peptide (SAP) hydrogels with functionalized motifs enhance proliferation and migration of host cells. How these designer SAP hydrogels perform in the treatment of periodontal defects remains unknown. This study aimed to test the potential of local application of designer SAP hydrogels with two different functionalized motifs in the treatment of experimental periodontal defects.

Material And Methods: In vitro, viability/proliferation of rat periodontal ligament-derived cells (PDLCs) cultured on an SAP hydrogel RADA16 and RADA16 with functionalized motifs, PRG (integrin binding sequence) and PDS (laminin cell adhesion motif), was assessed. Cell morphology was analyzed by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). In vivo, standardized periodontal defects were made mesially in the maxillary first molars of Wistar rats. Defects received RADA16, PRG, PDS or left unfilled. At 2 or 4 weeks postoperatively, healing was assessed by microcomputed tomography, histological and immunohistochemical methods.

Results: Viability/proliferation of PDLCs was significantly greater on PRG than on RADA16 or PDS at 72 hours. rPDLCs in the PRG group showed enhanced elongations and cell protrusions. In vivo, at 4 weeks, bone volume fractions in the PRG and PDS groups were significantly greater than the RADA16 group. Histologically, bone formation was more clearly observed in the PRG and PDS groups compared with the RADA16 group. At 4 weeks, epithelial downgrowth in the hydrogel groups was significantly reduced compared to the Unfilled group. In Azan-Mallory staining, PDL-like bundles ran in oblique direction in the hydrogel groups. At 2 weeks, in the area near the root, proliferating cell nuclear antigen (PCNA)-positive cells were detected significantly more in the PRG group than other groups. At 4 weeks, in the middle part of the defect, a significantly greater level of vascular endothelial growth factor (VEGF)-positive cells and α-smooth muscle actin (SMA)-positive blood vessels were observed in the PRG group than in other groups.

Conclusion: The results indicate that local application of the functionalized designer SAP hydrogels, especially PRG, promotes periodontal healing by increasing cell proliferation and angiogenesis.
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http://dx.doi.org/10.1111/jre.12807DOI Listing
January 2021

Combined effects of systemic parathyroid hormone (1-34) and locally delivered neutral self-assembling peptide hydrogel in the treatment of periodontal defects: An experimental in vivo investigation.

J Clin Periodontol 2019 10;46(10):1030-1040

Department of Periodontology, Tokyo Dental College, Tokyo, Japan.

Aim: To evaluate in vivo combination therapy of systemic parathyroid hormone (PTH) and locally delivered neutral self-assembling peptide (SAP) hydrogel for periodontal treatment.

Materials And Methods: Viability/proliferation of rat periodontal ligament cells in a neutral SAP nanofibre hydrogel (SPG-178) was evaluated using WST-1 assay. Periodontal defects were created mesially to the maxillary first molars in 40 Wistar rats. Defects were filled with 1.5% SPG-178 or left unfilled. Animals received PTH (1-34) or saline injections every 2 days. Microcomputed tomography, histological, and immunohistochemical examinations were used to evaluate healing at 2 or 4 weeks postoperative.

Results: At 72 hr, cells in 1.5% SPG-178 showed increased viability/proliferation compared to cells in 0.8% SPG-178 or untreated controls. In vivo, systemic PTH resulted in significantly greater bone volume in the Unfilled group at 2 weeks (p = .01) and 4 weeks (p < .0001) than in the saline control. At 4 weeks, a significantly greater bone volume was observed in the PTH/SPG-178 (p = .0003) and PTH/Unfilled (p = .004) groups than in Saline/SPG-178 group. Histologically, greater bone formation was observed in PTH/SPG-178 at 4 weeks than in other groups. In the PTH/SPG-178 group, increased proportions of PCNA-, VEGF-, and Osterix-positive cells were observed in the treated sites.

Conclusions: These findings suggest that intermittent systemic PTH and locally delivered neutral SAP hydrogel enhance periodontal healing.
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http://dx.doi.org/10.1111/jcpe.13170DOI Listing
October 2019

Treatment of intrabony periodontal defects using rhFGF-2 in combination with deproteinized bovine bone mineral or rhFGF-2 alone: A 6-month randomized controlled trial.

J Clin Periodontol 2019 03;46(3):332-341

Department of Periodontology, Tokyo Dental College, Tokyo, Japan.

Aim: To evaluate the use of recombinant human fibroblast growth factor (rhFGF)-2 in combination with deproteinized bovine bone mineral (DBBM) compared with rhFGF-2 alone, in the treatment of intrabony periodontal defects.

Materials And Methods: Patients with periodontitis who had received initial periodontal therapy and had intrabony defects of ≥ 3 mm in depth were enrolled. Sites were randomly assigned to receive a commercial formulation of 0.3% rhFGF-2 + DBBM (test) or rhFGF-2 alone (control). Clinical parameters and a patient-reported outcome measure (PROM) were evaluated at baseline and at 3 and 6 months postoperatively.

Results: Twenty-two sites in each group were evaluated. A significant improvement in clinical attachment level (CAL) from baseline was observed in both groups at 6 months postoperatively. CAL gain was 3.16 ± 1.45 mm in the test group and 2.77 ± 1.15 mm in the control group, showing no significant difference between groups. Radiographic bone fill was significantly greater in the test group (47.2%) than in the control group (29.3%). No significant difference in PROM between groups was observed.

Conclusions: At 6 months, no significant difference in CAL gain or PROM between the two treatments was observed, although combination therapy yielded an enhanced radiographic outcome.
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http://dx.doi.org/10.1111/jcpe.13086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899590PMC
March 2019

Efficient siRNA delivery and gene silencing using a lipopolypeptide hybrid vector mediated by a caveolae-mediated and temperature-dependent endocytic pathway.

J Nanobiotechnology 2019 Jan 22;17(1):11. Epub 2019 Jan 22.

Department of Prosthodontics, New York University College of Dentistry, New York, NY, 10010, USA.

Background: We developed a non-viral vector, a combination of HIV-1 Tat peptide modified with histidine and cysteine (mTat) and polyethylenimine, jetPEI (PEI), displaying the high efficiency of plasmid DNA transfection with little toxicity. Since the highest efficiency of INTERFERin (INT), a cationic amphiphilic lipid-based reagent, for small interfering RNA (siRNA) transfection among six commercial reagents was shown, we hypothesized that combining mTat/PEI with INT would improve transfection efficiency of siRNA delivery. To elucidate the efficacy of the hybrid vector for siRNA silencing, β-actin expression was measured after siRNA β-actin was transfected with mTat/PEI/INT or other vectors in HSC-3 human oral squamous carcinoma cells.

Results: mTat/PEI/INT/siRNA produced significant improvement in transfection efficiency with little cytotoxicity compared to other vectors and achieved ≈ 100% knockdown of β-actin expression compared to non-treated cells. The electric charge of mTat/PEI/INT/siRNA was significantly higher than INT/siRNA. The particle size of mTat/PEI/INT/siRNA was significantly smaller than INT/siRNA. Filipin III and β-cyclodextrin, an inhibitor of caveolae-mediated endocytosis, significantly inhibited mTat/PEI/INT/siRNA transfection, while chlorpromazine, an inhibitor of clathrin-mediated endocytosis, did not inhibit mTat/PEI/INT/siRNA transfection. Furthermore, the transfection efficiency of mTat/PEI/INT at 4 °C was significantly lower than 37 °C.

Conclusions: These findings demonstrated the feasibility of using mTat/PEI/INT as a potentially attractive non-viral vector for siRNA delivery.
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http://dx.doi.org/10.1186/s12951-019-0444-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341701PMC
January 2019

Identification of a specific domain of Porphyromonas gingivalis Hgp44 responsible for adhesion to Treponema denticola.

Pathog Dis 2018 07;76(5)

Department of Microbiology, Tokyo Dental College, Tokyo 101-0061, Japan.

Interaction between two periodontal pathogens, Porphyromonas gingivalis and Treponema denticola, contributes to plaque biofilm formation. Porphyromonas gingivalis forms aggregates with T. denticola through its adhesion/hemagglutinin domain (Hgp44). In this study, we investigated the specific domain of P. gingivalis Hgp44 responsible for adhesion to T. denticola using expression vectors harboring P. gingivalis Hgp44 DNA sequences encoding amino acid residues 1-419. Six plasmids harboring fragments in this region were generated by PCR amplification and self-ligation, and recombinant proteins r-Hgp44 (residues 1-419), r-Hgp441 (residues 1-124), r-Hgp442 (1-199), r-Hgp443 (1-316), r-Hgp444 (199-419), r-Hgp445 (124-198) and r-Hgp446 (199-316) were produced, as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. r-Hgp44, r-Hgp443 and r-Hgp446 showed greater adhesion to T. denticola sonicates than the control, as determined by enzyme-linked immunosorbent assay. r-Hgp446 reduced the coaggregation of P. gingivalis and T. denticola. Scanning electron and confocal laser scanning microscopy analyses revealed that r-Hgp446 reduced dual-species biofilm formation. Our results indicate that residues 199-316 of P. gingivalis Hgp44 are mainly responsible for adhesion to T. denticola; inhibiting this domain could potentially disrupt periodontopathic biofilm formation and maturation.
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http://dx.doi.org/10.1093/femspd/fty047DOI Listing
July 2018

Released fibroblast growth factor18 from a collagen membrane induces osteoblastic activity involved with downregulation of miR-133a and miR-135a.

J Biomater Appl 2018 05 15;32(10):1382-1391. Epub 2018 Mar 15.

1 Department of Prosthodontics, 70241 New York University College of Dentistry , NY, USA.

We have developed a unique delivery system of growth factors using collagen membranes (CMs) to induce bone regeneration. We hypothesized that fibroblast growth factor18 (FGF-18), a pleiotropic protein that stimulates proliferation in several tissues, can be a good candidate to use our delivery system for bone regeneration. Cell viability, cell proliferation, alkaline phosphatase activity, mineralization, and marker gene expression of osteoblastic differentiation were evaluated after mouse preosteoblasts were cultured with a CM containing FGF-18, a CM containing platelet-derived growth factor, or a CM alone. Furthermore, expression of microRNA, especially miR-133a and miR-135a involving inhibition of osteogenic factors, was measured in preosteoblasts with CM/FGF-18 or CM alone. A sustained release of FGF-18 from the CM was observed over 21 days. CM/FGF-18 significantly promoted cell proliferation, alkaline phosphatase activity, and mineralization compared to CM alone. Gene expression of type I collagen, runt-related transcription factor 2, osteocalcin, Smad5, and osteopontin was significantly upregulated in CM/FGF-18 compared to CM alone, and similar to CM/platelet-derived growth factor. Additionally, CM/FGF-18 downregulated expression of miR-133a and miR-135a. These results suggested that released FGF-18 from a CM promotes osteoblastic activity involved with downregulation of miR-133a and miR-135a.
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http://dx.doi.org/10.1177/0885328218763318DOI Listing
May 2018

Delineation of the extent of early gastric cancer by magnifying narrow-band imaging and chromoendoscopy: a multicenter randomized controlled trial.

Endoscopy 2018 06 13;50(6):566-576. Epub 2018 Feb 13.

Department of Clinical Study Support Center, Wakayama Medical University, Wakayama, Japan.

Background: Accurate delineation of tumor margins is necessary for curative resection of early gastric cancer (EGC). The objective of this multicenter, randomized, controlled study was to compare the accuracy with which magnifying narrow-band imaging (M-NBI) and indigo carmine chromoendoscopy delineate EGC margins.

Methods: Patients with EGC ≥ 10 mm undergoing endoscopic or surgical resection were enrolled. The oral-side margins of the lesions were first evaluated with conventional white-light endoscopy in both groups and then delineated by either chromoendoscopy or M-NBI. Biopsies were taken from noncancerous and cancerous mucosa, each at 5 mm from the margin. Accurate delineation was judged to have been achieved when the histological findings in all biopsy samples were consistent with endoscopic diagnoses. The primary end point was the difference in rate of accurate delineation between the two techniques.

Results: Data on 343 patients were analyzed. The accurate delineation rate (95 % confidence interval) was 85.7 % (80.4 - 91.0) in the chromoendoscopy group (n = 168), and 88.0 % (83.2 - 92.8) in the M-NBI group (n = 175;  = 0.63). Lower third tumor location (odds ratio [OR] 2.9;  = 0.01), nonflat macroscopic type (OR 4.4;  < 0.01), and high diagnostic confidence (OR 3.6;  < 0.001) were associated with accurate delineation, whereas use of M-NBI was not (OR 1.2;  = 0.39). Even after adjustment for identified confounders, the difference in accurate delineation between the groups was not significant (OR 1.0;  = 0.82).

Conclusions: M-NBI does not offer superior delineation of EGC margins compared with chromoendoscopy; the two methods appear to be clinically equivalent.
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http://dx.doi.org/10.1055/s-0044-100790DOI Listing
June 2018

[Tracheobronchitis as an extraintestinal manifestation of Crohn's disease].

Nihon Shokakibyo Gakkai Zasshi 2017;114(12):2125-2133

Department of Respiratory Medicine, Tobata Kyoritsu Hospital.

A 27-year-old woman with Crohn's disease, who had sustained clinical remission for two years following treatment with mesalazine and nutrition therapy, was admitted to our hospital complaining of dry cough, mild dysphagia, and slight fever. A computed tomography of the chest demonstrated an increase in the thickness of the tracheal wall. Bronchoscopy showed a diffusely erythematous and edematous mucosa with whitish granular lesions in the trachea and main carina. Bronchial biopsy specimens showed epithelioid cell granuloma. We diagnosed tracheobronchitis as an extraintestinal manifestation of Crohn's disease. She was treated with 40mg/day prednisolone. Her symptoms improved immediately. However, dry cough recurred two months after prednisolone treatment, and further treatment with inhaled steroids was prescribed. Tracheobronchial involvement in Crohn's disease is rare, with only 13 cases having been reported. Tracheal involvement should be considered in Crohn's disease patients with respiratory symptoms.
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http://dx.doi.org/10.11405/nisshoshi.114.2125DOI Listing
June 2018

Clinical predictors of histologic type of gastric cancer.

Gastrointest Endosc 2018 Apr 6;87(4):1014-1022. Epub 2017 Nov 6.

Department of Endoscopy, Fukuoka University Chikushi Hospital, Chikushino, Japan.

Background And Aims: Gastric cancer is classified into differentiated and undifferentiated types according to the degree of glandular differentiation. Undifferentiated-type early gastric cancer (EGC) carries a higher risk of lymph-node metastasis than differentiated type, and therefore the indication criteria for endoscopic resection differ. This study aimed to clarify the ability of clinical predictors to distinguish between differentiated-type and undifferentiated-type EGCs.

Methods: This was a post hoc study of a multicenter prospective trial carried out in 5 Japanese hospitals, including 343 patients with cT1 EGC of ≥10 mm. According to the protocol, age, sex, and endoscopic findings of cancer (diameter, location, macroscopic type, and invasion depth) were evaluated, and the final diagnosis was confirmed from resected specimens. We evaluated the associations between these clinical factors and the histologic type of cancer and calculated the ability of the factors to diagnose differentiated-type EGC. The diagnostic ability of forceps biopsy was also calculated as a reference.

Results: Multivariate analysis identified older age (≥72 years), male sex, larger tumor size (>30 mm), elevated type, and shallower invasion depth (cT1a) as independent significant predictors for differentiated-type EGC, with elevated type showing the highest positive likelihood ratio. The sensitivity, specificity, accuracy, and positive and negative likelihood ratios of elevated type for differentiated-type EGC were 24%, 99%, 38%, 15.7, and 0.77, respectively, compared with 96%, 86%, 95%, 7.0, and 0.04 for forceps biopsy.

Conclusions: Endoscopic elevated type is a significant predictor for differentiated-type EGC and may exclude undifferentiated-type EGC without the need for forceps biopsy.
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http://dx.doi.org/10.1016/j.gie.2017.10.037DOI Listing
April 2018

Hydrogen generation by reaction of Si nanopowder with neutral water.

J Nanopart Res 2017 16;19(5):176. Epub 2017 May 16.

The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Osaka, Ibaraki 567-0047 Japan.

Si and its oxide are nonpoisonous materials, and thus, it can be taken for medical effects. We have developed a method of generation of hydrogen by use of reactions of Si nanopowder with water in the neutral pH region. Si nanopowder is fabricated by the simple bead milling method. Si nanopowder reacts with water to generate hydrogen even in cases where pH is set at the neutral region between 7.0 and 8.6. The hydrogen generation rate strongly depends on pH and in the case of pH 8.0, ∼55 ml/g hydrogen which corresponds to that contained in approximately 3 L saturated hydrogen-rich water is generated in 1 h. The reaction rate for hydrogen generation greatly increases with pH, indicating that the reacting species is hydroxide ions. The change of pH after the hydrogen generation reaction is negligibly low compared with that estimated assuming that hydroxide ions are consumed by the reaction. From these results, we conclude the following reaction mechanism: Si nanopowder reacts with hydroxide ions in the rate-determining reaction to form hydrogen molecules, SiO, and electrons in the conduction band. Then, generated electrons are accepted by water molecules, resulting in production of hydrogen molecules and hydroxide ions. The hydrogen generation rate strongly depends on the crystallite size of Si nanopowder, but not on the size of aggregates of Si nanopowder. The present study shows a possibility to use Si nanopowder for hydrogen generation in the body in order to eliminate hydroxyl radicals which cause various diseases.
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http://dx.doi.org/10.1007/s11051-017-3873-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434163PMC
May 2017

Extending magnifying NBI diagnosis of intestinal metaplasia in the stomach: the white opaque substance marker.

Endoscopy 2017 Jun 10;49(6):529-535. Epub 2017 Apr 10.

Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan.

 Intestinal metaplasia (IM) of the stomach is associated with an increased risk of differentiated gastric cancer. While it is important to diagnose IM endoscopically, it can be difficult to observe by white-light endoscopy. In magnifying endoscopy with narrow-band imaging (M-NBI) of the stomach, a light-blue crest (LBC) is widely known to be a useful marker in the endoscopic diagnosis of IM. However, IM that exhibits only white opaque substance (WOS) without an LBC can also occur. The aim of this study was to elucidate whether the presence of WOS on M-NBI of the stomach could serve as a marker of IM in the same way that an LBC does.  The subjects were 40 consecutive patients who underwent M-NBI between July and December 2014. The primary endpoint in this study was to evaluate the diagnostic performance of M-NBI for histologically observed IM in WOS- and LBC-positive mucosa.  The sensitivity and specificity of WOS for histologically diagnosed IM were 50.0 % (95 % confidence interval [CI] 40.0 % - 50.0 %) and 100.0 % (95 %CI 85.0 % - 100.0 %), respectively. Meanwhile, the sensitivity and specificity of LBC were 62.5 % (95 %CI 51.1 % - 65.9 %) and 93.8 % (95 %CI 76.7 % - 98.9 %), respectively. The sensitivity and specificity of WOS and/or LBC (WOS positive and LBC positive, WOS positive and LBC negative, or WOS negative and LBC positive) for histologically diagnosed IM were 87.5 % (95 %CI 76.9 % - 90.9 %) and 93.8 % (95 %CI 77.9 % - 98.9 %), respectively.  LBC and WOS are both useful markers for endoscopic diagnosis of IM. Combining both markers improves the sensitivity.Clinical trial number: UMINCTR000014453.
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http://dx.doi.org/10.1055/s-0043-103409DOI Listing
June 2017

Ex vivo nonviral gene delivery of μ-opioid receptor to attenuate cancer-induced pain.

Pain 2017 02;158(2):240-251

Oral and Maxillofacial Surgery, New York University College of Dentistry, New York, NY, USA.

Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 (∼45-fold) relative to HGF-1 (human gingival fibroblasts) cells. We used the nonviral vector to transfect cancer with OPRM1, the μ-opioid receptor gene, as a novel method for treating cancer-induced pain. After HSC-3 cells were transfected with OPRM1, a cancer mouse model was created by inoculating the transfected HSC-3 cells into the hind paw or tongue of athymic mice to determine the analgesic potential of OPRM1 transfection. Mice with HSC-3 tumors expressing OPRM1 demonstrated significant antinociception compared with control mice. The effect was reversible with local naloxone administration. We quantified β-endorphin secretion from HSC-3 cells and showed that HSC-3 cells transfected with OPRM1 secreted significantly more β-endorphin than control HSC-3 cells. These findings indicate that nonviral delivery of the OPRM1 gene targeted to the cancer microenvironment has an analgesic effect in a preclinical cancer model, and nonviral gene delivery is a potential treatment for cancer pain.
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http://dx.doi.org/10.1097/j.pain.0000000000000750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584564PMC
February 2017

The potential of stromal cell-derived factor-1 delivery using a collagen membrane for bone regeneration.

J Biomater Appl 2017 02 5;31(7):1049-1061. Epub 2017 Jan 5.

4 Department of Prosthodontics, New York University College of Dentistry, New York, NY, USA.

Stromal cell-derived factor-1 (SDF-1) is a cytokine that is important in stem and progenitor cell recruitment in tissue repair after injury. Regenerative procedures using collagen membranes (CMs) are presently well established in periodontal and implant dentistry. The objective of this study is to test the subsequent effects of the released SDF-1 from a CM on bone regeneration compared to platelet-derived growth factor (PDGF) in vitro and in vivo. For in vitro studies, cell proliferation, alkaline phosphatase activity, and osteoblastic differentiation marker genes were assessed after MC3T3-E1 mouse preosteoblasts were cultured with CMs containing factors. In vivo effects were investigated by placement of CMs containing SDF-1 or PDGF using a rat mandibular bone defect model. At 4 weeks after the surgery, the new bone formation was measured using micro-computed tomography (µCT) and histological analysis. The results of in vitro studies revealed that CM delivery of SDF-1 significantly induced cell proliferation, ALP activity, and gene expression of all osteogenic markers compared to the CM alone or control, similar to PDGF. Quantitative and qualitative µCT analysis for volume of new bone formation and the percentage of new bone area showed that SDF-1-treated groups significantly increased and accelerated bone regeneration compared to control and CM alone. The enhancement of bone formation in SDF-1-treated animals was dose-dependent and with levels similar to those measured with PDGF. These results suggest that a CM with SDF-1 may be a great candidate for growth factor delivery that could be a substitute for PDGF in clinical procedures where bone regeneration is necessary.
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http://dx.doi.org/10.1177/0885328216686727DOI Listing
February 2017

Periodontal Surgery Involving Modified Widman Flap Procedure and Connective Tissue Graft for Generalized Aggressive Periodontitis: A Case Report.

Bull Tokyo Dent Coll 2016 ;57(4):259-268

Department of Periodontology, Tokyo Dental College.

We report a case of generalized aggressive periodontitis (AgP) requiring periodontal treatment including flap surgery and ridge augmentation. The patient was a 39-year-old woman who presented with the chief complaint of pus discharge from tooth #36. No other obvious signs of gingival inflammation were observed. Periodontal examination revealed multiple sites with a probing depth of ≥10 mm. Radiography showed pro-nounced bone defects in the maxillary incisors and molar region. Real-time PCR was used to detect Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythia in subgingival plaque; all 3 pathogens were found. Based on a clinical diagnosis of generalized AgP, periodontal therapy was initiated, which resulted in an improvement in clinical and microbiological parameters. A modified Widman flap procedure was then performed on sites with residual periodontal pockets. Next, a connective tissue graft was performed for ridge augmentation at #22, which had shown evidence of ridge resorption. Postoperative reevaluation revealed a reduction in probing depth and an improvement in marginal bone levels. Oral function was then restored using a fixed bridge prosthesis and maintenance therapy initiated. The periodontal condition has remained stable over a 2.5-year period. In the present case of AgP, surgical intervention reduced periodontal pockets and periodontal pathogens and improved the architecture of both the hard and soft tissues, allowing subsequent care of the periodontium to be performed efficiently by the patient.
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http://dx.doi.org/10.2209/tdcpublication.2016-1700DOI Listing
January 2018
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