Targeted drug delivery system for oral cancer therapy using sonoporation.

Ultrasound-mediated destruction of microbubbles has been proposed as an innovative non-invasive drug delivery system for cancer therapy. We developed a specific drug delivery system for squamous cell carcinoma that uses sonoporation with the anti-epidermal growth factor receptor (EGFR) antibody. Administration of a low dose of bleomycin (BLM) by sonoporation with the anti-EGFR antibody produced a marked growth inhibition of Ca9-22 cells in vitro. In addition, scanning electron microscopic analysis revealed apparent surface deformation of Ca9-22 cells treated with sonoporation in the presence of the antibody. Interestingly, the population of apoptotic cells was remarkably increased when a low dose of BLM was delivered using sonoporation with the Fab fragment of the anti-EGFR antibody. These findings indicate that sonoporation with the Fab fragment makes it possible to administer drugs into cells more efficiently and specifically, suggesting a novel application for chemotherapy and gene therapy treatments for oral squamous cell carcinoma.

Relationship between cortical bone formation on mandibular condyles and alternation of the magnetic resonance signals characteristic of growth.

INTRODUCTION: The purpose of this study was to elucidate the significance of double contour-like structures (DCLS) relative to the maturity of mandibular condyles and the possible constituents of DCLS. We evaluated the relationship between the alternation of DCLS and the ossification on the top of mandibular condyles. METHODS: In 36 subjects, aged 9 to14 years at the first examination, magnetic resonance imaging characteristics of the mandibular condyles were obtained from fast spin echo intermediate-weighted images and T2-weighted images; 2 or 3 years later, magnetic resonance images were again obtained from 23 of the same 36 subjects. RESULTS: A significant relationship was found between the absence of DCLS and the continuity of void-signal lines on the tops of the mandibular condyles. DCLS disappeared, and the void-signal lines on the tops of the mandibular condyles became continuous as the children grew. The top of DCLS was seen as a hypersignal on T2-weighted images. CONCLUSIONS: Alternations of DCLS might be a useful criterion for evaluating the maturity of mandibular condyles in children. Possible constituents of DCLS might be hypervascular loose fibrous tissue and a proliferation of cartilage accompanied by active ossification on the tops of the mandibular condyles.

Utility of diffusion-weighted images using fast asymmetric spin-echo sequences for detection of abscess formation in the head and neck region.

OBJECTIVE: The objective of this study was to evaluate the utility of new diffusion-weighted magnetic resonance images (DWI) using fast asymmetric spin-echo (FASE) sequences for the detection of abscess formation in patients with phlegmon in the oral and maxillofacial regions. METHODS: We compared diffusion-weighted images using FASE sequences with those using the gradient-echo type of echo-planar images (EPI) in 10 control volunteers and 10 patients with phlegmon in the oral and maxillofacial regions. RESULTS: Many kinds of tissues in the oral and maxillofacial regions were relatively well visualized in all subjects on FASE-DWI, but not well on EPI-DWI. Apparent diffusion coefficients calculated from FASE sequences in abscess areas of patients with phlegmon were significantly lower than those in abscess-free areas; however, apparent diffusion coefficients calculated from EPI were not significantly different due to prominent distortion in small sample size study. CONCLUSIONS: We could accurately recognize the presence of abscess formation within inflammatory tissue in 5 patients with phlegmon using FASE-DWI. As an additional magnetic resonance examination, FASE-DWI might be useful in the detection of abscess formation in the oral and maxillofacial regions.

Three-dimensional identification of hemangiomas and feeding arteries in the head and neck region using combined phase-contrast MR angiography and fast asymmetric spin-echo sequences.

OBJECTIVE: To evaluate a proposed technique for the 3-dimensional (3D) detection of hemangiomas, including vascular malformation and their feeding arteries, in the head and neck. The new technique combines phase-contrast magnetic resonance angiography (PCMRA) without contrast medium and 3D fast asymmetric spin-echo (FASE) sequences. METHODS: The technique was applied to 3 patients having hemangiomas in the head and neck region. In 1 patient the image obtained with the proposed technique was compared to that obtained by standard contrast angiography. RESULTS: In all 3 patients, the 3D presence of the hemangiomas and the feeding arteries were well defined in images created by the proposed technique. Additionally, the characterization of the hemangioma's 3D structure and distribution of the feeding arteries coincided with those observed using contrast angiography in the case for which contrast angiography was also performed. CONCLUSIONS: Preliminary experience shows that the proposed technique combining 3D-FASE and 3D-PCMRA is useful to visualize both the 3D structure of hemangiomas and to identify the 3D distribution of the feeding arteries without using contrast medium.

Delivery of cytolethal distending toxin B induces cell cycle arrest and apoptosis in gingival squamous cell carcinoma in vitro.

The cytolethal distending toxin (Cdt) from Actinobacillus actinomycetemcomitans consists of three proteins, CdtA, CdtB, and CdtC, which are responsible for cell cycle arrest and apoptosis. In the present study, local delivery systems of recombinant CdtB and CdtB-expressing plasmid were established using Ca9-22, human gingival squamous cell carcinoma cell line. When CdtB was delivered to Ca9-22 cells using a BioPORTER, a 32-kDa protein was detected by Western blotting, and G2 cell cycle arrest and apoptosis occurred. In addition, the CdtB delivered upregulated the expression of phosphorylated p53 and the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) in Ca9-22 cells, suggesting that these intracellular molecules might contribute to the induction of G2 cell cycle arrest and apoptosis. When the CdtB-expressing plasmid was transfected into Ca9-22 cells by lipofection or electroporation, CdtB (32 kDa) was clearly detected. Further, TdT-mediated dUTP nick end labeling positive cells were observed after transfection of the CdtB-expressing plasmid. These findings indicated that delivery of the CdtB protein and transfection of the cdtB gene induced cell cycle arrest and apoptosis in Ca9-22 cells in vitro, and we conclude that it may be possible to induce apoptosis in human gingival squamous cell carcinoma by electroporation of the cdtB gene.

Alternation of the magnetic resonance signals characteristic of mandibular condyles during growth.

OBJECTIVE: In a previous study, we named the magnetic resonance imaging (MRI) signal that is characteristic of mandibular condyles in growing children the "double contour-like structure" (DCLS). In the current study, we evaluated the alternating appearance and disappearance of the DCLS in children as they grow to elucidate the significance of the DCLS. STUDY DESIGN: In 11 subjects who were 9-14 years old at the time of the first examination, MRI characteristics of mandibular condyles were sought from fast spin-echo intermediate-weighted images; 2 or 3 years later, repeat MRI were obtained from the same subjects. RESULTS: At the second examination, 10 of the 16 DCLSs detected at the first examination had disappeared. A significant relationship was found between the alternation of the DCLS and the bone marrow conversion from red to yellow in mandibular condyles. Alternation of the DCLS tended to coincide with eruption of the permanent maxillary second molars. The DCLS was also shown to appear as a hypersignal on T2-weighted images. CONCLUSIONS: Double contour-like structure signals in mandibular condyles appeared and disappeared as children grew, and these signal alternations may be useful as a criterion for the staging of mandibular condyle development in children. Possible constituents of the DCLS may be hypervascular loose fibrous tissue and a proliferation of cartilage.