S100A16 up-regulates Oct4 and Nanog expression in cancer stem-like cells of Yumoto human cervical carcinoma cells.

Cancer stem-like cells (CSCs), which possess the ability to self-renewal and are multipotent, are regarded as the cause of tumor formation, recurrence, metastasis and drug resistance. It is necessary to understand the properties of CSCs in order to treat them effectively. It has been previously reported that S100 family proteins, which carry calcium-binding EF-hand motifs and are associated with tumorigenic processes, serve crucial roles in maintaining cancer stem-like properties. S100A16 is upregulated in various types of cancer, including bladder, lung and pancreatic. However, the roles of S100A16 in cancer cells, particularly CSCs, are not clear. The present study investigated the roles of S100A16 in CSCs using the sphere formation assay of Yumoto cells, which are a human cervical carcinoma cell line. The mRNA expression levels were evaluated by reverse transcription-polymerase chain reaction and the protein expression levels were detected by western blot analysis. Following the sphere formation of Yumoto cells, the mRNA and protein expression level of Oct4, Nanog and S100A16 were increased compared with the control cells. Following transfection with S100A16 small interfering RNA (siRNA), the mRNA and protein expression of Oct4 and Nanog were decreased and the spheroid size was significantly decreased in the sphere formation of Yumoto cells compared with control siRNA treated cells. There was no change in the p53 mRNA expression level, whereas the p53 protein expression level, which was decreased by the sphere formation, was recovered by S100A16 knockdown. In addition, the protein expression levels of Oct4 and Nanog, which were increased in the sphere formation, were decreased by the proteasome inhibitor lactacystin. No differences were observed in the S100A16 protein expression between the presence or absence of lactacystin. These results suggest that S100A16 serves an important role in the CSCs of human cervical carcinoma and is a positive regulator of Oct4 and Nanog.

[Two cases of recurrent GIST successfully treated with imatinib mesylate at 100mg/day].

Case 1: Recurrent tumors from gastric GIST in the liver and the abdominal wall showed partial response with 200mg/day imatinib and maintained partial response at 100mg/day. Case 2: Metastatic liver tumors from the jejunal GIST showed partial response with 200mg/day imatinib. The tumors have been enlarged for interruption of imatinib administration, however, re- treatment with imatinib resulted in partial response again and kept partial response at 100mg/day of imatinib. The two cases seldom encountered adverse events at 100mg/day of imatinib. There are some cases successfully treated with low-dose imatinib mesylate for recurrent GIST.

[A case of recurrent breast cancer with lung metastasis resection showing four disease-free years under trastuzumab treatment].

We report a case of recurrent breast cancer with solitary lung metastasis that has shown no recurrence with treatment by trastuzumab alone after partial resection of the right lung upper lobe. A 56-year-old woman, who presented with left breast cancer, underwent quadrantectomy and axillar lymph node dissection in March 2004. Pathological findings were as follows: invasive ductal carcinoma, 3. 7 cm in size, histological grade 3, positive invasion of lymphatic and blood vessels, negative nodal status, negative ER/PgR status, and overexpression of HER2/ neu. She had received adjuvant radiotherapy followed by cyclophosphamide, methotrexate and fluorouracil combination chemotherapy; however, a lung nodule developed 14 months after first operation, which had grown gradually. Partial resection of the lung with thoracoscope assistance revealed metastatic lung cancer from breast cancer. Trastuzumab treatment for 6 months after second operation has maintained no recurrence for 4 years.

Safety, efficacy and pharmacokinetics of S-1 in a hemodialysis patient with advanced gastric cancer.

PURPOSE: The safety and efficacy of S-1 in hemodialysis patients have not been established. We evaluated the safety and efficacy and pharmacokinetics of S-1 in a hemodialysis patient with advanced gastric cancer. PATIENT: A 66-year-old Japanese man with chronic renal failure, who had undergone hemodialysis three times a week for 3 years. Based on the diagnosis of stage IV gastric cancer, S-1 therapy was started. S-1 was administered 11 times at a daily dose of 23.5 mg/m(2) (40 mg/body)after hemodialysis, followed by a rest. One course was a period of 28 days. Blood samples were obtained after the first administration of S-1 and before beginning the fourth course. The concentration of 5-FU was determined by high-performance liquid chromatography. RESULTS: Area under the concentration-time curve (AUC)of 5-FU was 2647.2 ng h/mL after administration of S-1 of 23.5 mg/m(2) (40 mg/body). During the S-1 treatment,serious adverse events such as neutropenia were not observed; however, decreases in hemoglobin level were observed (grade 3). The treatment was well tolerated. After the second course of chemotherapy, the primary lesion showed a partial response and lymph node metastases and liver metastases showed stable disease. CONCLUSIONS: Our results suggest that S-1 is an important treatment option for patients with hemodialysis with advanced gastric cancer.