To date, therapeutic method for in vivo gene delivery has not been established on bone engineering though its potential usefulness has been suggested. For clinical applications, an effective condition should be developed to transfer the genes in vivo without any transfection reagents or virus vectors. In this study, to facilitate the clinical setting of this strategy, particularly aimed at atrophic bone repair, we simply investigated whether manufactured gene-activated matrix (GAM) with atelocollagen containing a certain amount of plasmid (p) DNA encoding osteogenic proteins could augment the cranial bone in rat. GAMs were manufactured by mixing 0.02, 0.1, or 1 mg of AcGFP plasmid vectors harboring cDNA of BMP4 (pBMP4) or Runx2 (pRunx2) with 2% bovine atelocollagen and β-tricalcium phosphate granules. Before manufacturing GAMs, to determine the biological activity of generated pDNAs, we confirmed GFP expression and increased level of alkaline phosphatase activities in MC3T3-E1 cells transfected with pBMP4 or pRunx2 during culture. Then, GAMs were lyophilized and transplanted to onlay placement on the cranium. At 2 weeks of transplantation, GFP-expressing cells could be detectable in only GAMs containing 1 mg of AcGFP plasmid vectors. Then, at 4 weeks, significant bone formation was recognized in GAMs containing 1 mg of pDNAs encoding BMP4 or Runx2 but not in 0.02 or 0.1 mg of GAMs. These newly formed bone tissues surrounded by osteocalcin-stained area were augmented markedly until 8 weeks after transplantation. In contrast, minimal bone formation was observed in GAMs without harboring cDNA of osteogenic proteins. Meanwhile, when GAMs were transplanted to the cranial bone defect, bone formation was detectable in specimens containing 1 mg of pBMP4 or pRunx2 at 8 weeks as well. Thus, atelocollagen-based GAM reliably could form the engineered bone even for the vertical augmentation when containing a certain amount of plasmid vectors encoding osteogenic proteins. This study supports facilitating the clinical application of GAM for bone engineering.
Basaloid squamous cell carcinoma (BSCC) is a rare variation of squamous cell carcinoma which was first described by Wain in 1986. According to the WHO classification, BSCC shows high malignancy and poor prognosis. Alcohol consumption and smoking are thought to be associated with the onset of this tumor. We report a case of BSCC at the floor of the mouth in a 62-year-old man. Physical examination demonstrated a 25×20 mm mass at the left floor of the mouth. Histological examination revealed that the tumor consisted of solid nests of basaloid cells, comedo-like necrosis within tumor islands, cellular pleomorphism and nuclear mitotic activity, and epithelial dysplasia adjacent to the tumor. A pathological diagnosis of BSCC was made. The patient underwent wide resection of the oral floor tumor with marginal left mandibulectomy and functional neck dissection of the left side. Two years later, the patient remains in good health and free of disease.
Background: Although taxanes have become a key chemotherapeutic drug in breast cancer treatment. Taxanes inhibit the growth of cancer cells by disrupting the functioning of their microtubules; however, the microtubules of nerve cells are also affected by this process, which can cause neurological disorders. The Kampo medicine Goshajinkigan (GJG) is a traditional Japanese medicine that is used for the treatment of several neurological symptoms including pain and numbness, GJG is comprised of 10 herbs, each of which contains numerous active ingredients. Recently, GJG has been reported to prevent anticancer drug-induced peripheral neuropathy in colorectal cancer. We performed the present prospective randomized study to confirm the effects of GJG and mecobalamin (B12) against docetaxel (DOC)-associated peripheral neurotoxicity in breast cancer patients. Patients and method: Between May 2007 and April 2011, 60 breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 μg/day B12. The patients were treated with TC (75mg/m2 docetaxel and 600 mg/m2 cyclophosphamide) every 3 weeks for 4 cycles, docetaxel alone (100mg/m2) every 3 weeks for 4 cycles, and XT (900mg/m2 capecitabine administered orally twice a day on days 1–14 plus 60 mg/m2 docetaxel) every 3 weeks for 6 cycles. Peripheral neuropathy was evaluated during every course according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver.3.0, and a visual analogue scale (VAS). Results: The median age of the GJG group was 58 years old (35 to 70 years old), the B12 group was 55 years old (33 to 69 years old), and they were all females. For the regimens, in the GJG group, TC, DOC only, and XT were administered in 19 cases, 13 cases and 1 case, respectively. In the B12 group, they were 15 cases, 11 cases and 12 cases, respectively. The cumulative dose of DOC was 338.5 mg/m2 in the GJG group, and 340 mg/m2 in the B12 group. Peripheral neuropathy occurred significantly less frequently in the GJG group (39.3%) than the B12 group (88.9%) (p < 0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases. In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case. The mean VAS scores for numbness after chemotherapy were 2.7 in the GJG group and 4.9 in the B12 group (p < 0.01). The incidence of grade 2/3 peripheral neuropathy was lower in the GJG group than the B12 group. Peripheral neuropathy was significantly controlled in the GJG group. Conclusion: The present study is the first prospective control study to prove the efficacy of GJG against docetaxel-induced peripheral neuropathy in breast cancer patients. Our findings suggest that DOC-associated peripheral neurotoxicity can be suppressed by the administration of GJG. It will be necessary to confirm the usefulness of GJG in larger prospective studies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-11.
We herein report a case of squamous cell carcinoma (SCC) arising in a pectoralis major musculocutaneous (PMMC) flap used for reconstruction after the resection of tongue cancer. A 54-year-old woman underwent resection of tongue SCC, right modified radical neck dissection, and reconstruction with a forearm flap in 2010. Soon after the surgery, another reconstruction was performed with a PMMC flap owing to necrosis of the forearm flap. She was making steady progress, but SCC was found in the center of PMMC flap, and the lesion was resected 5 years after the first surgery. There has been no finding of recurrence for over 1 year. There are some hypotheses on the causes of tumorigenesis in reconstructive flaps, such as chronic stimuli, mucosalization of the skin of the flap, and human papillomavirus (HPV) infection. Our patient showed persistent contact of the flap with the teeth due to immobilization of the flap, and immunohistochemical expression of p16, which is induced by HPV infection in dysplastic epithelium and SCC. Therefore, we considered that multiple factors were involved in the carcinogenesis in the PMMC flap. It is important to remove the stimulus and perform long-term follow up owing to the risk that SCC might develop in the reconstructive flap. : squamous cell carcinoma (扁平上皮癌) ,oral cavity cancer (口腔癌) ,reconstructive flap (再建皮弁) 1) 長崎大学医歯薬総合研究科展開医療科学講座顎口腔再生 外科学分野 (主任:朝比奈 泉教授) 2) 公益社団法人昭和会今給黎総合病院・昭和会クリニック 歯科・歯科口腔外科 (主任:吉田雅司部長) 3) 長崎大学医歯薬総合研究科生命科学講座口腔病理学分野 (主任:藤田修一准教授) 1)
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