Yasuo Okada

Relationships of cervical lymph node metastasis to histopathological malignancy grade, tumor angiogenesis, and lymphatic invasion in tongue cancer

Cervical lymph node (CLN) metastasis from oral cancer correlates with poor prognosis. Therefore, accurate assessment of CLN status is crucial in treatment planning. However, there are few reports focusing on CLN metastasis from tongue cancer. Further, the growth and progress of the tumor are known to be profoundly related to histological malignancy, tumor angiogenesis, and lymphangiogenesis. Thus, this study aimed to identify predictive factors for CLN metastasis in tongue squamous cell carcinoma (SCC). Initial biopsy specimens obtained from 30 patients with tongue SCC were examined to evaluate histological malignancy according to Anneroth’s classification. In addition, blood vessel density, lymph vessel density, and lymphatic invasion in the tumor were evaluated immunohistochemically using CD31, CD34, D2-40, and AE1/AE3, and then the relationships of CLN metastasis to these parameters were investigated. Histological malignancy grade, blood vessel density, and lymphatic invasion were significantly related to CLN metastasis (P < 0.05), but there was no relationship between lymph vessel density and CLN metastasis. However, double immunostaining showed that lymphatic invasion by tumor cells was significantly related to CLN metastasis. The results indicate that Anneroth’s histological malignancy grade of 16 or more, tumor blood vessel density of more than 37, and the presence of lymphatic invasion by tumor cells can be predictive factors for CLN metastases in tongue SCC.

Experimental study of antiangiogenic gene therapy targeting VEGF in oral cancer

It is well known that tumor angiogenesis plays an important role in local growth and metastasis of oral cancer; therefore, inhibiting angiogenesis is considered to be effective for treating oral cancer. This study aimed to investigate the effectiveness of systemically available antiangiogenic gene therapy targeting vascular endothelial growth factor (VEGF), which is one of the most important angiogenesis accelerators. We administered a soluble form of VEGF receptor-expressing gene incorporated into adenovirus (AdVEGF-ExR) intraperitoneally to nude mice to which oral cancer cell lines (SAS, HSC-3, and Ca9-22) had been transplanted subcutaneously in vivo to inhibit angiogenesis and tumor proliferation. Then, we measured tumor volumes over time, and tumors were enucleated and examined histopathologically and immunohistologically at 28 days after AdVEGF-ExR administration. Compared to the controls to which we administered AdLacZ or saline, significant antiproliferative effects were observed (P < 0.05) in the AdVEGF-ExR administration group, and extensive tumor necrosis was found histopathologically. Immunohistochemical analysis with CD34 (NU-4A1) revealed tumor angiogenesis was suppressed significantly (P < 0.05), and that with ssDNA revealed apoptosis induction was significantly high (P < 0.05) in the AdVEGF-ExR group. However, analysis with Ki-67 (MIB-1) revealed tumor proliferative capacity was not significantly different between the groups. Consequently, we consider that AdVEGF-ExR administration achieved tumor growth suppression by inhibiting angiogenesis and inducing apoptosis, but not by inhibiting the proliferative capacity of tumor cells. Neither topical administration of a soluble form of VEGF receptor (sVEGFR) to the tumor nor a megadose was needed to achieve this inhibition effect. These results suggest gene therapy via sVEGFR would be an effective oral cancer therapy and benefit future clinical applications.

Study of MYB-NFIB chimeric gene expression, tumor angiogenesis, and proliferation in adenoid cystic carcinoma of salivary gland

Adenoid cystic carcinoma (ACC) is one of the common malignant tumors in salivary glands, and the clinical prognosis is poor with frequent distant metastasis which may lead to death. Expression of the MYB-NFIB chimeric gene in ACC has been reported recently. MYB is an oncogene with transcription regulating functions, and NFIB encodes nuclear transcription factor although detailed functions are unknown. This study investigated whether MYB-NFIB chimeric gene expression affects tumor angiogenesis and proliferation in salivary gland ACC. In 26 salivary gland ACC cases, MYB-NFIB chimeric gene expression was analyzed by RT-PCR and direct sequencing. Immunohistochemical studies for CD31, vascular endothelial growth factor (VEGF) and Ki-67 were performed. Tumor angiogenesis was evaluated by blood vessel (CD31-positive) density and tumor proliferation by Ki-67 labeling index, and the relationship with MYB-NFIB chimeric gene expression was analyzed. MYB-NFIB chimeric gene expression was detected in nine of 26 ACC cases. Blood vessel density was significantly higher in chimeric gene-expressing cases compared to non-expressing cases. VEGF score tended to be higher in chimeric gene-expressing cases than in non-expressing cases, while Ki-67 labeling index was not significantly different. The number of chimeric gene-expressing cases increased with age, peaking in the sixties age group and declining thereafter, while the number of non-expressing cases increased with age continuously. In ACC, blood vessel density was significantly higher in MYB-NFIB chimeric gene-expressing cases compared to non-expressing cases, which may be due to higher VEGF production capability. MYB-NFIB chimeric gene expression may also be related to the onset age of ACC.

HER2-Targeted Multifunctional Silica Nanoparticles Specifically Enhance the Radiosensitivity of HER2-Overexpressing Breast Cancer Cells

We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage to normal cells. Hyperbranched polyamidoamine (PAMAM) was grafted onto the surface of amorphous silica nanoparticles to functionalize them. The PAMAM-coated silica nanoparticles (PCSNs) were then conjugated with fluorescent dyes. Anti-HER2 antibodies were covalently attached to the labeled PCSNs. The HER2-overexpressing SK-BR3 breast cancer cell line was incubated in medium containing the PCSN probes. After incubation; the cells were exposed to X-ray radiation. Cells were counted in all samples using cell proliferation assays; and apoptotic cells were detected. The cell survival results showed that the combination of the targeted PCSN probes and radiation reduced the survival rate of SK-BR3 cells to a greater extent than when either PCSN probes, PCSNs or radiation were applied individually. The results also showed an increase in apoptosis in the SK-BR3 cells that internalized the PCSN probes and were then irradiated. Based on these data, PCSN probes act as specific radiosensitizing agents for HER2-overexpressing cells.

Extraosseous plasmacytoma of the Maxilla: CT and MRI findings

Abstract Plasmacytomas are a localized proliferation of plasma cells in the bone marrow and are less frequently seen in extraosseous organs or tissues. Extraosseous plasmacytoma is a rare malignant neoplasm and constitutes 3–5% of all plasma cell neoplasms. In this article, we describe a case of a patient with extraosseous plasmacytoma of the maxilla and the related computed tomography (CT) and magnetic resonance imaging (MRI) findings.

Metastasis of colon adenocarcinoma to the mandible: A case report

Abstract Metastatic tumors to the oral cavity are uncommon. In this article, we report a case of metastatic adenocarcinoma of the colon to the mandible with imaging features. A 73-year-old man with a history of colon cancer and liver metastasis was referred to our hospital with a chief complaint of swelling and pain in the right mandible. Panoramic radiograph revealed a radiolucency with ill-defined margin. Computed tomography showed an osteolytic lesion with cortical bone destruction. Magnetic resonance imaging showed a round-shaped homogeneous intensity mass expanding from the mandible. Histopathological diagnosis revealed metastatic adenocarcinoma of the colon.

Glandular odontogenic cyst: a report of four cases

Abstract A glandular odontogenic cyst is a developmental cyst that is a clinically rare and histopathologically unusual type of odontogenic cyst. In this article, we describe four cases of glandular odontogenic cyst. Glandular odontogenic cyst was defined as a well-defined unilocular lesion on panoramic radiographs and multidetector computed tomography. Furthermore, the connection of the cyst to the periodontal tissue was one of the common features of the four cases. The results of the present study indicate the clinical and imaging features of glandular odontogenic cyst.

Diagnostic value of computed tomography, magnetic resonance imaging, and scintigraphy in diagnosing actinomycosis of the mandible

Mandibular actinomycosis is an uncommon disease caused by Actinomyces israelii. Actinomycosis infection typically manifests as a chronic disease resulting in multiple abscesses, firm soft tissue mass, and presence of sulfur granules in exudates or tissues. A few reports have provided imaging findings of actinomycosis in the head and neck, but computed tomography (CT), magnetic resonance imaging (MRI), and scintigraphy of mandibular actinomycosis have not been fully described. Here, we report a case of mandibular actinomycosis with CT, MRI, and scintigraphy. The purpose of this article is to characterize the CT, MRI, and scintigraphy findings in cases of actinomycosis. Contrast-enhanced CT of the masticator space showed heterogeneous enhancement and a nonenhancing portion, suggestive of necrotic foci. Bone tissue algorithm CT showed an osteolytic lesion in the ramus of the left mandible only. On post-contrast T1-weighted images, the masticator space showed heterogeneous enhancement and nonenhancing portion, suggestive of necrotic foci. Bone scintigraphy revealed monostatic involvement of the mandible with a homogeneous intense uptake pattern. Gallium scintigraphy revealed significantly increased uptake in the left side of the face. These findings can be helpful for differentiating actinomycosis from other tumors of the mandible.

Central giant cell lesion of the mandible in a 2-year old girl

Central giant cell lesions are rare, benign, osteolytic, pseudocystic, solitary, localized lesions that are common in the skeletal structure, but less so in the maxillofacial region. Furthermore, to perform panoramic radiography and cone-beam computed tomography, it is necessary to prepare patients properly and to position their heads carefully. However, this can be difficult in pediatric patients, who may be anxious. In this report, we describe the case of a central giant cell lesion of the mandible in a 2-year-old girl that was evaluated with multidetector computed tomography.