Seiji Asoda

xCT inhibition depletes CD44v-expressing tumor cells that are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma

The targeting of antioxidant systems that allow stem-like cancer cells to avoid the adverse consequences of oxidative stress might be expected to improve the efficacy of cancer treatment. Here, we show that head and neck squamous cell carcinoma (HNSCC) cells that express variant isoforms of CD44 (CD44v) rely on the activity of the cystine transporter subunit xCT for control of their redox status. xCT inhibition selectively induces apoptosis in CD44v-expressing tumor cells without affecting CD44v-negative differentiated cells in the same tumor. In contrast to CD44v-expressing undifferentiated cells, CD44v-negative differentiated cells manifest EGF receptor (EGFR) activation and rely on EGFR activity for their survival. Combined treatment with inhibitors of xCT-dependent cystine transport and of EGFR resulted in a synergistic reduction of EGFR-expressing HNSCC tumor growth. Thus, xCT-targeted therapy may deplete CD44v-expressing undifferentiated HNSCC cells and concurrently sensitize the remaining differentiating cells to available treatments including EGFR-targeted therapy.

Mechanical attachment of soft fibrous tissues to implants by using mesh structures.

OBJECTIVES Increase of soft tissue attachment is a major concern for improving the design of novel dental implants. This study evaluated the use of mesh structures placed on the implant surface for the anchorage of fibrous tissues. MATERIAL AND METHODS Specimens were prepared by covering their surfaces with a nylon mesh. The following mesh spacings were used: 30, 46, 100, 200, and 500 microm. The specimens were retrieved along with the surrounding subcutaneous tissues at 4 weeks after their implantation into the dorsal subcutaneous tissues of rats. A tensile test was performed by using a material testing machine, and the load required to tear the tissue from the mesh was measured. Histological sections stained with hematoxylin-eosin or Azan were prepared and examined by performing light microscopy. The amount of fibrous tissue contributing to the mechanical attachment of the fibers to the mesh was qualitatively evaluated by performing image analysis. RESULTS The attachment strength was the greatest in the 200-microm mesh-spacing group and considerably greater than that in the 30-microm mesh-spacing group. In addition, the effective width of the anchoring fibrous tissues was the greatest in the 200-microm mesh-spacing group. As compared with the other groups, the 200- and 500-microm mesh-spacing groups exhibited a considerably greater width of the anchoring fibrous tissues. CONCLUSIONS The efficiency of mesh structures for the attachment of soft tissues to implants was demonstrated. A mesh spacing of approximately 200 microm was observed to be favorable for the anchorage of fibrous tissues.

Mechanical attachment of soft tissue to dental and maxillofacial implants with mesh structures: An experiment in percutaneous model†

Soft tissue attachment is a major concern for the improved design of dental and maxillofacial implants. This study evaluated the efficacy of mesh structures for soft tissue attachment in a rat percutaneous model. Four kinds of implant specimens were prepared - TI implants made of titanium cylinders, HA implants of hydroxyapatite-coated titanium, TI-Mesh implants with a titanium mesh covering a groove machined around a titanium cylinder, and similar HA-Mesh implants with a hydroxyapatite-coated mesh. These specimens were implanted percutaneously into the skin tissue of rats. The detachments of the implants were examined during the experimental period of 4 weeks. Survived implants were subjected to mechanical tests for the attachment strength and histological examinations. TI and HA implants demonstrated 0% of survival rates, while TI-Mesh and HA-Mesh showed significantly higher rates of 93.3% and 100% respectively. The attachment strengths were 159 ± 47 kPa in the TI-Mesh and 135 ± 16 kPa in the HA-Mesh. Histological observations revealed that collagen fibers originating from surrounding subcutaneous tissues were anchored to the mesh structures of the TI- and HA-Mesh implants. The results demonstrated the efficacy of the mesh structures for the attachment of soft connective tissues to implants.

Collagen fiber anchoring platforms for percutaneous devices

In this study, we investigated the use of perforated sheet platforms to improve the attachment of percutaneous devices to surrounding tissues. The model platform was created by a poly(methyl methacrylate) (PMMA) sheet with a matrix of 200-&mgr;m diameter perforations covering the groove (width, 3 mm; depth, 0.5 mm) prepared on the PMMA cylinder (diameter, 10 mm; length, 6 mm). Velour cuffs from peritoneal dialysis catheters were used as controls. Specimens were implanted percutaneously in rats, harvested with the surrounding tissues at 4 weeks after surgery, and subjected to mechanical tests and histological observations. The attachment strength of the experimental specimens to tissue was 138.4 ± 123.6 kPa (n = 5, mean ± SD); although it was greater than the 67.23 ± 45.78 kPa (n = 5) of the controls, no statistical significance was found. Histological observations of the experimental specimens revealed the collagen fibers originating from the surrounding tissues, passing through the perforations of the sheet, merging into the collagen fibers running behind the sheet, and thus anchoring the tissues to the device. In contrast, such anchoring of collagen fibers was not evident in the controls. These results suggest that the proposed perforated sheet structures are effective for soft tissue attachment.

The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report

Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.

Desmoid-type fibromatosis of the head and neck in children: a case report and review of the literature.

BackgroundDesmoid-type fibromatosis is defined as an intermediate tumor that rarely occurs in the head and neck of children. There is no doubt as to the value of complete surgical excision for desmoid-type fibromatosis. However, in pediatric patients, surgeons may often be concerned about making a wide excision because of the potential for functional morbidity. Some studies have reported a lack of correlation between margin status and recurrence. Therefore, we discussed our findings with a focus on the state of surgical margins.Case presentationWe report an unusual case of a 9-month-old Japanese girl who prior to presenting at our hospital underwent debulking surgery twice with chemotherapy for desmoid-type fibromatosis of the tongue at another hospital. We performed a partial glossectomy and simultaneous reconstruction with local flap and achieved microscopic complete resection. We also reviewed available literature of pediatric desmoid-type fibromatosis in the head and neck.ConclusionsWe described successful treatment for the refractory case of pediatric desmoid-type fibromatosis. The review results showed that some microscopic incomplete resections of tumors in pediatric patients with desmoid-type fibromatosis tended to be acceptable with surgical treatment.

Treatment of severe generalized chronic periodontitis in a patient with Behçet’s disease: A case report

Behçet’s disease is a systemic disorder of unknown etiology. It involves multiple organ systems and is characterized by recurring episodes of oral ulcers as well as ocular, genital, and skin lesions. Oral ulcers can affect tooth brushing and impair proper oral hygiene. As a result, a dental biofilm accumulates, and the condition of the teeth and periodontal tissue deteriorates. The aim of this case report is to highlight the efficacy of periodontal treatment for patients with Behçet’s disease. A 51-year-old man with Behçet’s disease presented with generalized severe periodontitis. After basic treatment of the periodontal tissues, periodontal surgery was performed at several sites with bony defects. However, the patient developed severe stomatitis in the oral mucosa and gingiva after periodontal surgery. Administration of the antimicrobial agent cefdinir had little effect on recovery; however, subsequent administration of sitafloxacin resulted in significant improvement of the stomatitis. This case demonstrates that periodontal therapy is very useful for alleviating the oral signs and symptoms of Behçet’s disease. Systemic antibiotic treatment with sitafloxacin (but not cefdinir) and mechanical debridement were effective in preventing the recurrence of aphthous ulcer outbreaks after periodontal surgery.

Recurrent Spindle Cell Carcinoma Shows Features of Mesenchymal Stem Cells

This study investigated a case of spindle cell carcinoma (SpCC) in tongue pathological lesions. The patient experienced a local recurrence and distant metastasis after surgical intervention. Although standard chemotherapy was administered, a granulomatous mass continued to develop. This aggressive growth led to survival of the tumor. Secondary debulking surgery was performed to improve the patient’s quality of life at the request of the patient. Using a tissue sample derived from the secondary debulking surgery, we performed an analysis of the tumor’s cell surface antigens, differentiation potential, metastatic ability, and inhibition potential by anticancer reagents. In vitro analysis revealed that the cell population grown under adherent culture conditions expressed the mesenchymal stem cell (MSC) markers CD73, CD90, and CD105. The cell line established from this SpCC contained colony-forming unit fibroblasts (CFU-Fs) and exhibited multipotent differentiation into several mesenchymal lineages, including bone, cartilage, and fat. The SpCC cells also displayed vigorous mobilization. These characteristics suggested that they had the differentiation potential of mesenchymal cells, especially MSCs, rather than that of epithelial cells. The surgical specimen analyzed in this study resisted the molecular target reagent cetuximab, which is an epidermal growth factor receptor inhibitor. This clinical insight revealed that chemotherapy-resistant SpCC cells have different characteristics compared to most other cancer cells, which are sensitive to cetuximab. Our cell death assay revealed that SpCC cell death was induced by the anticancer drug imatinib, which is known to inhibit protein tyrosine kinase activity of ABL, platelet-derived growth factor receptor α (PDGFRα), and KIT. Here, we report recurrent SpCC with characteristics of MSCs and potential for treatment with imatinib.

A study of clinical initial symptoms for recurrent oral cancers-A relationship between recurrence and pain

口腔癌治療後の再発症例の初期症状について, 特に疼痛を中心とした自覚的初期症状と再発の関連について検討した。対象は1976年1月から2000年12月までに当科にて根治目的に治療した口腔癌のうち, 局所再発または頸部再発した50例とした。臨床的, または病理組織学的に再発と診断した時期より以前に発現した症状を初期症状とし, その初期症状を自覚症状と他覚症状に分けて, 症状の種類と発現時期を検討した。特に自覚症状については, 口腔癌患者のうち再発・転移ともに認めなかった50症例を対照群として, 発現率を比較した。そして, 最後に自覚症状の治療法別, および進展度による出現率の違いを検討した。結果は, 口腔癌再発症例50例のうち35例, 70%に何らかの自覚症状が発現し, そのうち32例が疼痛で, その発現時期は, 平均で再発診断日の44日前で, 他覚的症状の25日前と比較して, 有意に早期に発現していた。対照群50例と比較した場合, 再発症例は自覚症状の出現率は70%で, 対照群の14%と比較し有意に高頻度に自覚症状が発現し, その自覚症状の出現の有無は, 一次治療の方法や進展度とは関連が小さい結果となった。疼痛を中心とした自覚症状が, 治療法や進展度とは関係なく, 再発の早期発見に有効であり, 患者の訴えの要性を今更ながら再確認する結果となった。