New radiological findings and radiculomegaly in oculofaciocardiodental syndrome with a novel BCOR mutation: A case report.

RATIONALE: Oculofaciocardiodental syndrome (OFCD) patients who show radiculomegaly are very rare. We treated a new OFCD patient orthodontically, and performed longitudinal observation for 30 years. New findings, termed calcified-dental-papillae (CDPs) beneath open-apices (OAs) of developing radiculomegalies, pulp-stone-like-calcifications (PSLCs) and the process of radiculomegaly development were observed. A novel mutation of BCL-6 interacting corepressor (BCOR) was identified. Cone-beam-computed-tomography (CBCT) images of the radiculomegalies clarified their morphology. PATIENT CONCERNS: A female patient and her parents were referred to orthodontic clinic for alignment of the teeth. DIAGNOSIS: A CDP that harbored bulbous-round-calcified-tissue in the dental papilla beneath the OA of a developing radiculomegaly was found radiographically. PSLCs were observed in the dental pulp. Genetic analysis revealed a novel mutation c.265G>A on Exon 4 and diagnosed as OFCD. CBCT images confirmed round-calcified-tissue and PSLC and that the length of an affected canine was 38.0 mm and calculated as +14.8SD. These novel findings were not observed in lateral incisors and molars. INTERVENTIONS: Observation was performed for 29 years and 3 months including orthodontic treatment for 2 years and 9 months. OUTCOME: Longitudinal follow-up for 26 years and 7 months after the treatment revealed that the development of radiculomegaly every few months or years, CDPs beneath OAs and PSLCs were observed. CDPs, PSLCs, and OAs were associated with radiculomegaly. The patient and the affected teeth including aligned teeth showed no particular change after the completion of the radiculomegaly. CBCT images showed bulbous-calcified-tissue and PSLCs in the mature dental pulp associated with radiculomegaly. LESSONS: The radiographical findings of CDP, OA and PSLC help early diagnose of OFCD and have importance for initiating orthodontic treatment until radiculomegaly completion.

The effectiveness of palliative resection for advanced esophageal carcinoma: analysis of 24 consecutive cases.

PURPOSE: In some patients who already have advanced esophageal cancer at the time of presentation, symptoms like the inability to eat, and complications such as bronchoesophageal fistula are so debilitating that palliative resection may be beneficial. However, resection of the esophagus is associated with significant risk, and whether this operation should be performed for palliation remains controversial. Because few reports have been published on this subject, we retrospectively analyzed 24 patients with esophageal cancer who underwent palliative resection. METHODS: Esophageal resection was performed with palliative intent in 12 patients and with curative intent in another 12 who were left with residual cancer. RESULTS: There was no operative death. All of the ten patients who had been unable to eat preoperatively were able to eat after the operation, and four patients with a life-threatening bronchoesophageal fistula were free of symptoms after the operation. Two patients died in hospital during the postoperative chemotherapy but the other 22 were discharged. The mean survival period was 264 days. CONCLUSIONS: With improved postoperative care, the risk of palliative esophageal resection is no longer considered unacceptable.

Tooth-type specific expression of dHAND/Hand2: possible involvement in murine lower incisor morphogenesis.

dHAND/Hand2 is a basic helix-loop-helix transcription factor required for the development of the heart, pharyngeal arches, and vasculature and is expressed during embryogenesis. However, there are no reports on the involvement of the dHAND gene in tooth development. In the present study, the expression of dHAND was examined in developing tooth germs of mice. The dHAND gene was expressed in the mesenchyme of the presumptive incisor region of the lower jaw at an early stage and in the mesenchyme of the lower incisor tooth germ at a later stage. However, the dHAND gene was not expressed in the upper incisor region or the upper and lower molar regions during jaw development. Treatment of tooth germ explants of lower incisors with antisense oligodeoxinucleotide (ODN) against dHAND prevented the differentiation of tooth germ cells, including ameloblasts and odontoblasts, the formation of dentin and enamel, and the proliferation of tooth germ cells and increased the apoptosis of tooth germ cells, suggesting that dHAND is essential for these cells during development. On the other hand, the treatment of tooth germ explants of upper incisor and upper or lower molars did not induce severe effects on their development. Treatment of the explants with basic fibroblast growth factor in association with antisense ODN partially rescued them from the effects of antisense ODN. The present results suggest that the dHAND gene plays important roles in type-specific development of lower incisors, and that basic fibroblast growth factor is involved downstream of the dHAND pathway in tooth germ cells.

Telomerase activity in esophageal squamous cell carcinoma: down-regulation by chemotherapeutic agent.

BACKGROUND AND OBJECTIVES: Telomerase has been suggested as being necessary for continued cell growth and progression of cancer. Esophageal cancer and matched normal esophageal tissue from 54 patients were analyzed for telomerase activity, human telomerase reverse transcriptase (hTERT) mRNA expression, and their correlation with clinicopathological factors. METHODS: Telomeric repeat amplification protocol was used for detection of telomerase activity and real time quantitative RT-PCR was used for hTERT mRNA. An esophageal carcinoma cell line was used to study the effect of chemotherapeutic agent on telomerase. RESULTS: Telomerase activity was detectable in 79.6% of the tumor and 59.3% of the normal esophageal tissue. The level of telomerase activity in the tumor was significantly higher than that in the normal tissue. A significantly higher telomerase activity was observed in tumors with extensive blood vessel invasion. A significantly lower telomerase activity was observed in tumors that showed good response to preoperative chemotherapy than those with poor response. TE-9 cells exposed to 5-FU showed a diminished telomerase activity preceded by a time-dependent decrease in the mRNA expression of hTERT. CONCLUSIONS: Telomerase activity was high in esophageal cancer tissue and showed positive correlation with blood vessel invasion. Chemotherapeutic agents may down-regulate telomerase activity.

Role of matrix metalloproteinase-9 in in vitro invasion of esophageal carcinoma cells.

BACKGROUND AND OBJECTIVES: Although some investigators recently suggested that MMP-9 may play a critical role in invasion and metastasis, along with MMP-2, in esophageal carcinoma, there has been no direct evidence that MMPs play a critical role in the actual invasion of esophageal carcinoma cells. Here, we investigated the role of MMPs in the in vitro invasion of esophageal carcinoma cell lines (TE-series). METHODS: Our methods included in vitro invasion assay, gelatin zymography, and enzyme-linked immunosorbent assay (ELISA). RESULTS: Four cell lines (but not TE-5) secreted MMP-2 and MMP-9 in the culture medium. Using a quantitative in vitro invasion assay, we found a significant (P = 0.002) correlation between the extent of in vitro invasion and the amount of MMP-9, but not of MMP-2, secreted into the conditioned medium in the four cell lines. In these cell lines, R-94138, a specific MMP-9 inhibitor, inhibited in vitro invasion in a dose-dependent manner. Although TE-5 did not secrete MMP-2 or MMP-9, the cells showed a strong in vitro invasion. CONCLUSIONS: Our data suggest that most of the esophageal carcinoma cell lines use MMP-9 for in vitro invasion, but others may use proteinase(s) other than MMP-9.

Expression and role of Lhx8 in murine tooth development.

We examined the expression and possible functions of Lhx8, a member of the LIM-homeobox gene family, during tooth morphogenesis of the mouse. Lhx8 was expressed in the dental mesenchyme between the bud and early bell stage of the molar tooth germ. Tooth germ explants from embryonic day 12.5 mice treated for 5 to 7 days with antisense-oligodeoxynucleotides (AS-ODN) against Lhx8 showed a marked decrease in the number of mesenchymal cells. The explants treated with AS-ODN for 11 to 14 days were filled with a large number of undifferentiated epithelial cells and a limited number of undifferentiated mesenchymal cells, but did not contain a tooth germ. Treatment of explants with AS-ODN for 7 days suppressed the proliferation of dental mesenchymal cells and induced apoptosis; the latter was confirmed by histochemical and ultrastructural examinations. Moreover, the expression of Lhx6, Msx1, Msx2, Bmp4 and Gsc, which are also known to be involved in tooth morphogenesis, were suppressed after the application of AS-ODN against Lhx8 for 7 days. The present results suggest that Lhx8 plays an important role in the survival of mesenchymal cells of the tooth germ during development.

Expression of PTTG (pituitary tumor transforming gene) in esophageal cancer.

BACKGROUND: Recently, a vertebrate securin [pituitary tumor transforming gene (PTTG) in humans] has been identified that inhibits sister chromatid separation and is involved in malignant transformation and tumorigenesis. Abundance of this protein would disrupt cell division, generate chromosomal instability and thereby increase cell susceptibility to acquisition of further mutations during subsequent division. Esophageal cancer is a disease with poor prognosis with early local invasion and lymph node metastasis. It is important to identify factors that influence the aggressiveness of esophageal cancer. METHODS: Expression of PTTG messenger ribonucleic acid (mRNA) was evaluated by real-time reverse transcription polymerase chain reaction in 48 esophageal cancer specimens and matched normal esophageal mucosa. The data were analyzed with reference to clinicopathological factors. RESULTS: Tumor tissue expressed a significantly higher level of PTTG1 mRNA than the corresponding normal tissue (P < 0.0001). PTTG1 mRNA expression was significantly higher in tumors with higher pathological stage (IV vs 0-III, P = 0.0442) or more extensive lymph node metastasis (pathological N factor; N4 vs N0-3, P = 0.003). The median survival for patients with high PTTG1 expression (8.5 months) was less than that for patients with low PTTG1 expression (14.0 months, P = 0.039). PTTG1 expression was one of the significant predictors of survival on univariate analysis (hazard ratio 2.225; 95% confidence interval 1.007-4.915). CONCLUSIONS: Detection of high PTTG1 expression in surgically excised esophagus tumor tissues might help to identify patients with aggressive disease who require adjuvant therapy and provide prognostic information.

Decreased peroxisome proliferator-activated receptor gamma gene expression is correlated with poor prognosis in patients with esophageal cancer.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR gamma) induces apoptosis by ligand stimulation in various tumor cell lines. In esophageal cancer cell lines, PPAR gamma activation also has suppressed the proliferation. METHODS: In 55 primary esophageal squamous cell carcinomas (ESCCs) we examined the correlation between the expression of PPAR gamma mRNA with prognosis of esophageal cancer patients. The expression of PPAR gamma mRNA was quantified by real-time reverse transcription polymerase chain reaction using LightCycler. Immunohistochemistry was used to study the expression of PPAR gamma protein. RESULTS: The expression of PPAR gamma mRNA was significantly decreased in esophageal cancer cells compared with normal esophageal mucosa (P = 0.0084). Among the clinical factors, PPAR gamma mRNA expression was lower in the tumors with extensive lymph node metastasis (n4) than those with less extensive lymph node metastasis (n0-3) (P = 0.0059). Patients with low PPAR gamma mRNA expression had significantly shorter postoperative survival time than those with high PPAR gamma mRNA expression (P = 0.0191). In immunohistochemistry, PPAR gamma protein was expressed in the nuclei of cells in some cases and expressed in the nuclei and cytoplasm in others. The expression of PPAR gamma protein is decreased in esophageal cancer tissue compared with normal esophageal squamous epithelium. However, we could not deduce the apparent relation for the expression between PPAR gamma mRNA and PPAR gamma proteins in immunohistochemistry (P = 0.284). CONCLUSIONS: In esophageal cancer tissues, the expression of PPAR gamma was decreased compared with normal esophageal epithelium. The mRNA expression level of PPAR gamma may be a marker of prognosis after operation in esophageal cancer patients.