To maintain the homeostasis of stem cells and prevent their ability to initiate tumorigenesis, it is important to identify and modify factors that prevent or accelerate stem cell senescence. We used microarrays to attempt to identify such factors in human amniotic fluid (HAF)-derived stem cells.

To identify gene expression changes over a time course, we compared gene expression profiles of HAF-derived stem cells in different passages (1^st, 2^nd, 4^th, 6^th, 8^th, and 10^th) using a Sentrix Human illumina microarray.

Of the 25,804 genes in the microarray chip, 1,970 showed an over 2-fold change relative to the control (the 1^st passage)-either upregulated or downregulated. Quantitative real-time PCR validated the microarray data for selected genes: markedly increased genes were CXCL12, cadherin 6 (CDH6), and folate receptor 3 (FOLR3). Downregulated genes included cyclin D2, keratin 8, insulin-like growth factor 2 (IGF2), natriuretic peptide precursor B (NPPB) and cellular retinoic acid binding protein 2 (CRABP2). The expression pattern of the selected genes was consistent with the microarray data except for CXCL12 and IGF2. Interestingly, the expression of NPPB was dramatically downregulated along the time course; it was almost completely shut-down by the 10^th passage. In contrast, FOLR3 mRNA expression was dramatically increased.

Taken together, although a function for NPPB and FOLR3 in stem cell senescence has not been reported, our results strongly suggest that NPPB and/or FOLR3 play a significant role in the regulation of stem cell senescence.

Palliative chemotherapy for patients with recurrent or metastatic gastric cancer has been shown to have a survival benefit. Docetaxel monotherapy has achieved appreciable results for treating gastric cancer. We investigated the clinical efficacy and feasibility of a docetaxel and cisplatin combination regimen for patients suffering with recurrent or metastatic gastric cancer.

Patients with histologically proven, bidimensionally measurable lesions of recurrent or metastatic gastric cancer, and they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and no prior palliative chemotherapy were eligible for this study. The combination chemotherapy regimen consisted of docetaxel 75 mg/m² plus cisplatin 75 mg/m² on day 1, and this was repeated every 3 weeks until disease progression.

32 patients were enrolled from 2002 to 2005. The objective response rate was 31.3% (95% confidence interval (CI): 14.2~48.2%) with no CR. The disease control rate was 59.4%. At a median follow up of 38.9 months, the median overall survival was 7.4 months (95% CI: 6.3~8.5). The median time to progression was 4.7 months (95% CI: 3.1~6.3). During a total of 106 cycles, grade 3 or 4 hematological toxicities were observed as follows: neutropenia (39 of 106 cycles) and anemia (3 of 106 cycles). The grade 3 or 4 non-hematological toxicities included anorexia (18.9%) and nausea/vomiting (21.7%).

Docetaxel and cisplatin combination chemotherapy showed promising anti-tumor activity and this was well tolerated as a first-line treatment for patients with recurrent or metastatic gastric cancer. Further large, randomized phase III studies are warranted.

We prospectively conducted a non-randomized phase II trial to evaluate the efficacy and safety of combination irinotecan, leucovorin (LV) and 5-fluorouracil (FU) as a first-line regimen for treating patients with previously untreated advanced colorectal cancer (CRC).

Twenty-six previously untreated patients with advanced, recurrent or metastatic CRC were enrolled in this study. The patients received either irinotecan 180 mg/m² on day 1 with LV bolus of 200 mg/m² and FU bolus of 400 mg/m², and this was followed by FU continuous infusion of 600 mg/m² on day 1 and day 2 (the FOLFIRI regimen), or they were treated with LV bolus of 400 mg/m² and FU bolus of 400 mg/m² followed by FU continuous infusion of 2,400 mg/m² for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression.

The objective response rate was 23.1% (6/26) respectively, for both treatments. The median time to progression was 5.3 months (range: 0.4~19.9), and the overall survival was 11.2 months (range: 0.5~52.3). The prognostic factor for longer survival was the Eastern Cooperative Oncology Group (ECOG) performance status (PS). The non-hematological toxicities were similar for both treatment groups, with more frequent grade ≥3 neutropenia being noted for the simplified FOLFIRI regimen.

The biweekly irinotecan based regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and the ECOG PS was the independent prognostic factor.