Previously, we found that sperm-associated antigen 5 (SPAG5) was upregulated in pelvic lymph node metastasis–positive cervical cancer. The aim of this study is to examine the role of SPAG5 in the proliferation and tumorigenicity of cervical cancer and its clinical significance in tumor progression. In our study, SPAG5 expression in cervical cancer patients was detected using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry; cervical cancer cell function with downregulated SPAG5 in vitro was explored using tetrazolium assay, flow cytometry, and colony formation and Transwell assays. SPAG5 was upregulated in tumor tissue compared with paired adjacent noncancerous tissues; SPAG5 upregulation in tumor tissues indicated poor disease-free survival, which was also an independent prognostic indicator for cervical cancer patients. In vitro study demonstrated that SPAG5 downregulation inhibited cell proliferation and growth significantly by G2/M arrest and induction of apoptosis, and hindered cell migration and invasion. Under SPAG5 downregulation, the sensitivity of cervical cancer cells differed according to taxol dose, which correlated with mammalian target of rapamycin (mTOR) signaling pathway activity. In general, SPAG5 upregulation relates to poor prognosis in cervical cancer patients, and SPAG5 is a regulator of mTOR activity during taxol treatment in cervical cancer.

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18018 Background: Erlotinib significantly improved survival versus placebo and was well tolerated in patients (pts) with previously treated advanced NSCLC in the phase III BR.21 study (Shepherd et al. N Engl J Med 2005;353;123–32). TRUST, an open-label, multicenter study was initiated to provide erlotinib access to pts with advanced NSCLC. Here we report data for E/SE Asian pts. Methods: Eligible pts had failed 1–2 prior standard chemotherapy (CT) regimens, or were unsuitable for CT. Erlotinib 150 mg/day p.o. was given until disease progression/unacceptable toxicity. NCI CTC v3.0 was used to grade toxicities. Results: At data cut-off of 20/11/06, 885 pts were included in the analysis: n= Taiwan 297, mainland China 248, Hong Kong 160, South Korea 146, Thailand 30, Indonesia 2, Malaysia 2. Median age was 61yrs (range 22–95). Pt characteristics (%): male/female 55/45, ECOG PS 0/1/2/3 15/67/14/4, stage IIIb/IV 20/79, adenocarcinoma/other 68/32, erlotinib as 1st/2nd/3rd/other line therapy 11/55/33/<1, never/ever smoker 52/47 (no data <1). 83% pts experienced rash, of which 9% was grade (gr)3/4. Safety data forms were available for 598 pts; 54% had at least one adverse event (AE).104 pts (17%) had a treatment (tx)-related unexpected adverse event (AE) but no single AE occurred in >3% pts and only 3% were ≥gr3. Serious tx-related AEs were experienced by 19 pts (3%); 17 were gr3/4, most commonly gastrointestinal (n=6). One pt had suspected tx-related interstitial lung disease (gr2); the patient continued tx. 18 pts (3%) withdrew due to a tx-related event; 11 were gr3/4, most commonly gastrointestinal (n=4) and respiratory (idiopathic pulmonary fibrosis n=1, pneumonitis n=2). 76 pts (13%) required dose reduction due to a tx-related event (13%), mainly due to rash (n=57). 83% pts received erlotinib for >4 weeks. Efficacy will be presented. Conclusions: The results reported here for E/SE Asian pts in the TRUST study confirm in a community setting the good tolerability observed with erlotinib in clinical trials. Importantly, erlotinib was generally well tolerated and so could be administered at full tx dose to most pts. [Table: see text]

7666 Background: Bone sialoprotein (BSP) and osteopontin (OPN) have been demonstrated predictive of bone metastases in breast and prostate carcinoma, consistent with the proposed role of BSP as a stimulator of bone mineralization and OPN in differentiation and activation of osteoclasts. Bone metastasis (BM) is often developed in non-small-cell lung cancer (NSCLC), but no predictive biomarker was identified for high risk of metastatic bone dissemination. Methods: 180 completely resected NSCLC patients were included in this study. 38 patients subsequently developed BM. Paraffin embedded primary tumor tissue of patients were supplied to produce a tissue microarray, and immunohistochemistry method was used for evaluation the expression of BSP and OPN. Different expressions of these two biomarkers among BM group and non-BM group were estimated by χ2 test. Bone metastasis-free survival was analyzed by Kaplan-Meier method. The prognostic impact of clinicopathologic parameters and biomarker expression was evaluated by Cox propotional hazards model. Results: BSP expression was associated with BM (P=0.027), while OPN expression could not reach statistical significance (P=0.495). Univariate analysis demonstrated that expression of BSP (P=0.036), N stage (P=0.000) and clinical stage (P=0.001) were associated with time interval to BM. Multivariate analyses showed BSP expression (RR=1.779, P=0.012) and clinical stage (RR=1.620, P=0.005) were independent prognostic factors for BM. Conclusions: BSP protein expression in the primary resected NSCLC is strongly associated with BM and could be used to identify high-risk patients. Correlation of OPN protein expression and bone metastasis need further investigation. No significant financial relationships to disclose.