Shinsuke Ohta

Alterations of p16 and p14ARF genes and their 9p21 locus in oral squamous cell carcinoma.

The p16 gene encodes a 16-kDa cyclin kinase inhibitor, and the p14ARF gene a 14-kDa protein, which acts as a cell cycle regulator or tumor suppressor in human cancer cells. Both genes are mapped on chromosome 9p21. Previous studies have suggested that the p16 gene has important roles in head and neck squamous cell carcinoma. To clarify carcinogenesis in oral squamous cell carcinoma (OSCC), we examined 44 primary OSCCs for alterations of p16 and p14ARF mRNA expression, the methylation status of the p16 gene promoter, the loss of heterozygosity (LOH) at the 9p21 locus, and p16 and p14ARF gene mutations. Alterations of p16 and p14ARF mRNA expression were seen in 27 (61.4%) of 44 and 10 (22.7%) of 44 of OSCC samples, respectively. Methylation of the p16 gene promoter region was detected in 28 (63.6%) of 44 samples, and LOH at 9p21 locus was found in 30 (68.2%) of 44. p16 and p14ARF gene mutations were observed in 4 (9.0%) of 44 and 2 (4.5%) of 44 samples, respectively. Suspected homozygous deletion (HD) was seen in 9 (20.5%) of 44. All cases except one (97.7%) showed alterations in p16, p14ARF, and their locus. These data indicate that the status of p16 and p14ARF genes in OSCC is frequently influenced by methylation, gene mutation, and allelic deletions. Furthermore, these genes and their 9p21 locus have various roles in the pathogenesis of OSCC.

55 kDa nuclear matrix protein (nmt55) mRNA is expressed in human prostate cancer tissue and is associated with the androgen receptor

Most prostate cancer grows in a hormone‐dependent manner. Most patients, however, show hormone‐independent growth after several years of hormone therapy. The mechanism of hormone‐refractory prostate cancer remains unknown. It is important, therefore, to identify gene(s) related to prostate cancer that are up‐ or downregulated. We studied differences in gene expression in pairs of prostate cancer and normal prostate tissue utilizing the differential display method. Expression of the identified gene was examined by RT‐PCR and real time quantitative PCR (TaqMan‐PCR) using 26 pairs of human prostate cancer and normal tissues. We identified a specific upregulated gene encoding a 55 kDa nuclear matrix protein (nmt55) in human prostate cancer. nmt55 gene expression in human prostate cancer tissue was higher (20/26 cases) than that in normal prostate tissue. Moreover, the relationship between nmt55 and androgen receptor (AR) expression showed a positive correlation. In another experiment, transcriptional activity of the prostate specific antigen (PSA) promoter was upregulated by nmt55 in 293 cells. nmt55 showed high expression in prostate cancer compared to normal tissue and its expression showed a positive correlation with AR expression. The PSA promoter was activated by nmt55 expression. These results suggest the possibility that nmt55 expression is related to hormone‐dependency or ‐independence associated with the AR.

In vivo antitumor effects of electrochemotherapy in a tongue cancer model

PURPOSE This study investigated the in vivo antitumor effects of electrochemotherapy (ECT) using electroporation and bleomycin in a hamster tongue cancer model to assess its clinical applicability. MATERIALS AND METHODS Twenty animals with chemically induced tongue cancer were divided into four experimental groups designated B-E-, B-E+, B+E-, and B+E+. The B+E+ and B+E- groups received an intraperitoneal injection of 100 microg bleomycin. Fifteen minutes after the injection, the B+E+ animals received electric pulses. The B-E+ group received only electric pulses. The B-E- group received neither bleomycin nor electric pulses. Each group received the same treatment twice. The antitumor effects were assessed based on tumor volume reduction and histologic findings. RESULTS The B+E+ group showed remarkable tumor volume reduction, decreasing an average to 8.8% of its original volume 14 days after the treatment. Complete loss of the protruding tumor was observed in two of the five animals. Histologically, the tumors of the B+E+ group consisted of severely degenerated tumor cells and desquamative keratinizing cells. No living cancer cells were detected in three animals. The B+E-, B-E+, and B-E- groups showed progressive tumor growth, exceeding 200% of initial tumor volume during the experimental period. CONCLUSION The current study showed remarkable antitumor effects of ECT with bleomycin in the hamster tongue cancer model. ECT with bleomycin may be clinically applicable to the treatment of oral cancer.

Antitumour effect of electrochemotherapy with bleomycin on human prostate cancer xenograft

To investigate the antitumour effect of electroporation (EP), a drug delivery system that has been shown to be effective synergistically with antitumour drugs, with bleomycin on the growth of prostate cancer xenografts in nude mice.

Rapid tumor necrosis induced by electrochemotherapy with intratumoral injection of bleomycin in a hamster tongue cancer model

This study evaluated the effects of electrochemotherapy (ECT) with intratumoral injection of bleomycin (BLM) on the chemically induced tongue cancer model in the hamster. Intratumoral injection of BLM followed by high-voltage electrical treatment induced rapid necrosis of the tumor within 48 hours and subsequent rapid tumor volume reduction. Three weeks after the ECT with BLM, 3 of the 6 animals showed no palpable tumor, while no antitumor effects were observed in the control groups. Because of the remarkable antitumor effect with no major observed side effects, we concluded that ECT combined with intratumoral injection of BLM has the potential to enhance treatment results for tongue cancer.

Mandibular Ewing sarcoma with chromosomal translocation t(21;22)(q22;q12).

Ewing sarcoma (ES) is a primary bone malignant neoplasm and is the second most common primary malignancy of the bone found in childhood and adolescence after osteosarcoma. ES has an annual frequency in the population younger than 20 years of approximately 2.9 per million. ES occurs most frequently in the long bones of the extremities and pelvis and very rarely in the jaw. Recently, it was revealed that chromosomal translocation t(11;22)(q24;q12), which fuses the EWS gene on chromosome 22 and the FLI-1 gene on chromosome 11, occurs in most cases of ES. We report here a rare case of mandibular ES in a 10-year-old child with chromosomal translocation t(21;22)(q22;q12) in which the EWS gene is fused with the ERG gene on chromosome 21.

A Case of Bilateral Submandibular Gland Stones in a Child

Sialolith commonly occurs unilaterally in the submandibular gland of adults, while submandibular gland stones occur rarely in children. Here we report a case of bilateral submandibular gland stones in a child. A 7-year-old boy had swelling of the left submandibular gland. The patient was referred to our department for endoscopic removal to avoid submandibular gland removal after bilateral hilar stones of the submandibular gland had been diagnosed in another hospital. Because the left stone, 1.7×1.7×1.1mm in size, was located at the orifice of the papilla at the first visit, the stone was removed under local anesthesia. But, the right stone, 3.0×1.6×1.5mm in size, was located at the hilar, and the patient was followed up. Eight months after the initial visit, the patient had swelling of the right submandibular gland. Because the right stone was located at the orifice of the papilla, the right stone was removed under local anesthesia. There was no recurrence after the removal of submandibular gland stones.