[Long-term results of chemoradiation therapy for the patients with locally advanced (T4) esophageal cancer].

The prognosis of patients with advanced esophageal cancer is still poor. Recently, concurrent chemoradiation therapy for esophageal cancer is being utilized with increasing frequency. In this study, we reported concurrent chemoradiation for patients with T4 esophageal cancer. From July 2000, we treated 21 consecutive patients with radiation and concurrent chemotherapy using intermittent low-dose FP chemoradiation (40 Gy radiation, 2 Gy/day, for 4 weeks 280/m(2) 5-FU intermittent 24 continuous, CDDP 8 mg/m(2)/intermittent). All patients who underwent the treatment with concurrent CRT completed the planned chemoradiation. Out of 21 patients, 2 (9.5%) showed a complete response and 9 patients (42.8%) showed a partial response. The 5-year survival rate of the T4 patients with CRT was almost the same as for those who underwent surgery alone. Concurrent chemoradiation therapy for T4 esophageal cancer patients is feasible and seems to be a standard treatment for T4 esophageal cancer patients. The results indicated that CRT is an effective therapy for advanced esophageal cancer.

[A case of recurrent gastric cancer effectively treated by combination chemotherapy of weekly paclitaxel and 5'- DFUR after showing resistance to weekly paclitaxel].

The patient was a 35-year-old woman with lung, bone and lymphnode metastases of gastric cancer after a total gastrectomy two years earlier. For the first-line treatment, we performed TS-1+CDDP therapy but it showed no effect. Then, weekly paclitaxel was administered as second-line, but again without effect. Therefore, combination chemotherapy of weekly paclitaxel and 5'-DFUR was performed as third-line therapy. 5'-DFUR was given orally at a dose of 600 mg/day for consecutive daily administration, and paclitaxel was administered at a dose of 70 mg/m(2) on day 1, 8 and 15. This regimen was repeated every 4 weeks. No serious adverse reaction was observed. The condition of the patient had improved after 1 course, making it possible to conduct treatment on an ambulatory basis in the 2 courses and subsequent cycles. After 3 courses, the size of the lung metastasis was remarkably decreased. This case suggests that combination chemotherapy of weekly paclitaxel and 5'-DFUR might be a promising regimen for recurrent gastric cancer even for patients who show no effect with only paclitaxel administration.

[Two case reports on intra-tumor injection therapy of dendritic cells].

DC (dendritic cells) vaccine therapy against cancer has attracted attention in recent years. However, the existence of the immunosuppressive state in cancer individuals leads to anergy and failure in cytotoxic T cell (CTL) induction and DC migration to the target organ. It has been reported that injected intra-tumor DC is expected to work phagocytosis of the tumor as a localized effect, the consequent CTL induction in the tumor and the regional lymphnodes, resulting in a systemic effect. Two cases reported in this article were performed with intra-tumor DC injection therapy by means of EUS (endoscopic ultrasonography) which indicated interesting immunoreaction.

ING2 regulates the onset of replicative senescence by induction of p300-dependent p53 acetylation.

ING2 is a candidate tumor suppressor gene that can activate p53 by enhancing its acetylation. Here, we demonstrate that ING2 is also involved in p53-mediated replicative senescence. ING2 protein expression increased in late-passage human primary cells, and it colocalizes with serine 15-phosphorylated p53. ING2 and p53 also complexed with the histone acetyltransferase p300. ING2 enhanced the interaction between p53 and p300 and acted as a cofactor for p300-mediated p53 acetylation. The level of ING2 expression directly modulated the onset of replicative senescence. While overexpression of ING2 induced senescence in young fibroblasts in a p53-dependent manner, expression of ING2 small interfering RNA delayed the onset of senescence. Hence, ING2 can act as a cofactor of p300 for p53 acetylation and thereby plays a positive regulatory role during p53-mediated replicative senescence.

[Verification of guideline for gastric cancer treatment based on a questionnaire].

We reported the results of a questionnaire survey of doctors and patients in relation to the guideline for gastric cancer treatment which was first published 3 years ago. The purpose of this questionnaire was to know whether the degree of recognition and availability of this guideline is satisfactory or not. The results were as follows. 1) The recognition and availability of the guideline among doctors proved satisfactory. 2) For patients who underwent gastrectomy, this guideline is still unfamiliar. Reconsideration of the guideline contents is needed in accord with the medical level from time to time. Moreover, patients must be more and more educated regarding the guideline.

p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity.

We identified and characterized two new ING family genes, p29ING4 and p28ING5,coding for two proteins of 249 and 240 amino acids, respectively. Both p29ING4 and p28ING5 proteins have a plant homeodomain finger motif also found in other ING proteins, and which is common in proteins involved in chromatin remodeling. p29ING4 or p28ING5 overexpression resulted in a diminished colony-forming efficiency, a decreased cell population in S phase, and the induction of apoptosis in a p53-dependent manner. Both p29ING4 and p28ING5 activate the p21/waf1 promoter, and induce p21/WAF1 expression. p29ING4 and p28ING5 enhance p53 acetylation at Lys-382 residues, and physically interact with p300, a member of histone acetyl transferase complexes, and p53 in vivo. These results indicate that p29ING4 and p28ING5 may be significant modulators of p53 function.

New attempt of preoperative differential diagnosis of thyroid neoplasms by telomerase activity measurement.

Telomerase activity (TA) has been shown highly expressed in various solid malignant neoplasms, but only rarely in benign tumor or normal tissues. Most reports examined TA by the qualitative method, telomeric repeat amplification protocol (TRAP) assay. We examined TA in tissues of thyroid neoplasm by quantitative method to establish whether TA was a useful marker for preoperative differential diagnosis of thyroid tumors. TA was measured by the quantitative method, TRAP assay, fluorescence based TRAP method in 32 frozen tissues of thyroid tumors (17 malignant, 15 benign). Cut-off values in TA were 0 unit and 9 units from mean +/- 2SD of TA in benign thyroid tumors. Mean (SD) TA levels in benign thyroid tumors and thyroid carcinomas were 2.06 (3.58) units and 30.5 (38.2), respectively. Mean TA of carcinomas was significantly higher than that of benign disease in thyroid tumors (p=0.0092). The sensitivity of the malignancy was 64.7% (cut-off <0) (p=0.162), 52.9% (cut-off <9) (p=0.0048). TA in thyroid carcinoma was significantly correlated with UICC stage (p=0.029), and slightly correlated with tumor size, pN and M. Positive rate of TA in microfollicular adenoma was slightly higher than that in macrofollicular adenoma. Conclusively, quantitative TA might be a useful marker for differential diagnosis between benign and malignant thyroid tumors.