Syntaphilin Is a Novel Biphasic Biomarker of Aggressive Prostate Cancer and a Metastasis Predictor.

Easily accessible biomarkers that may inform on the metastatic potential of localized prostate cancer are urgently needed. Herein, we show that syntaphilin (SNPH), a molecule originally identified as a negative regulator of mitochondrial dynamics in neurons, is abundantly expressed in prostate cancer. SNPH distribution in prostate cancer is spatially biphasic, with high expression at the invasive front, correlating with increased proliferative rates, as determined by Ki-67 labeling, and reduced levels in the central tumor bulk, which are further decreased in patients with distant metastases. Higher levels of SNPH are observed with increasing Gleason grade. Prostate tumors predominantly express a novel, extraneuronal isoform of SNPH that accumulates in mitochondria and maintains oxidative metabolism and tumor cell proliferation. These data suggest that SNPH is a novel marker of high Gleason grade prostate cancer, differentially expressed at the invasive front compared with the central tumor bulk, and is potentially down-regulated in metastatic disease. This biphasic pattern of expression may reflect a dual function of SNPH in controlling the balance between cell proliferation and invasion in tumors.

Capecitabine monotherapy as salvage treatment after failure of chemotherapy containing oxaliplatin and irinotecan in patients with metastatic colorectal cancer.

AIM: There has been limited data on capecitabine monotherapy in metastatic colorectal cancer (CRC) patients who were previously treated with both oxaliplatin/5-fluorouracil(FU)/leucovorin (FOLFOX) and irinotecan/5-FU/leucovorin (FOLFIRI). METHODS: We analyzed 20 patients between August 2002 and March 2008 with metastatic CRC who had been treated with capecitabine monotherapy after the failure of FOLFOX and FOLFIRI. RESULTS: Overall, one partial response was observed (overall response rate, 5%) and stable disease was observed in 11 patients (55.0%). The disease control rate was 60.0%. The median progression-free survival (PFS) was 2.3 months (95% CI 1.9-2.7) and the median overall survival (OS) was 5.3 months (95% CI 4.6-6.0). Patients without ascites had longer PFS than those with ascites (P=0.02). Patients with more than three metastatic sites had poorer OS than those with less than two (P=0.01). Grade 3 or 4 non-hematological toxicities included hand-foot syndrome in one patient. There were no grade 3 or 4 hematological toxicities or treatment-related deaths. CONCLUSION: The capecitabine monotherapy had a moderate disease control rate and a tolerable toxicity profile as third-line or fourth-line treatment for metastatic CRC patients who were refractory to standard chemotherapy with no further treatment options.

Three-dimensional immobilization of beta-galactosidase on a silicon surface.

Many alternative strategies to immobilize and stabilize enzymes have been investigated in recent years for applications in biosensors. The entrapment of enzymes within silica-based nanospheres formed through silicification reactions provides high loading capacities for enzyme immobilization, resulting in high volumetric activity and enhanced mechanical stability. Here we report a strategy for chemically associating silica nanospheres containing entrapped enzyme to a silicon support. beta-galactosidase from E. coli was used as a model enzyme due to its versatility as a biosensor for lactose. The immobilization strategy resulted in a three-dimensional network of silica attached directly at the silicon surface, providing a significant increase in surface area and a corresponding 3.5-fold increase in enzyme loading compared to enzyme attached directly at the surface. The maximum activity recovered for a silicon square sample of 0.5 x 0.5 cm was 0.045 IU using the direct attachment of the enzyme through glutaraldehyde and 0.16 IU when using silica nanospheres. The immobilized beta-galactosidase prepared by silica deposition was stable and retained more than 80% of its initial activity after 10 days at 24 degrees C. The ability to generate three-dimensional structures with enhanced loading capacity for biosensing molecules offers the potential to substantially amplify biosensor sensitivity.

A Phase II study of paclitaxel by 24-hour infusion and ifosfamide in anthracycline-resistant metastatic breast carcinoma.

BACKGROUND: A Phase II study was performed to investigate the efficacy and tolerability of paclitaxel and ifosfamide chemotherapy for the treatment of anthracycline-resistant metastatic breast carcinoma (MBC). METHODS: Recurrent or progressed MBC within 12 months after anthracycline-based chemotherapy was defined as anthracycline-resistant. A 24-hour infusion of paclitaxel (175 mg/m(2)) on Day 1 and subsequent infusions of ifosfamide (1.8 g/m(2)/day) with mesna (360 mg/m(2)/day) on Days 2- 4, were performed every 3 weeks. Twenty-one patients were eligible for toxicity analysis. Response rate and survival duration were evaluated in 21 patients. Frontline chemotherapy was the FAC (5-fluorouracil, doxorubicin, cyclophosphamide) regimen in all patients. RESULTS: Objective response was found in 9 patients (42.9%), including complete response in 3 (13.4%). Median response duration and median survival duration were 10 months (range, 2-24+) and 19+ months (range, 2-32+), respectively. Sixteen (76%) experienced Grade 3/4 leukopenia controllable with granulocyte macrophage colony-stimulating factor. Other significant toxicities were peripheral neuropathy (n = 3), mucositis (n = 2), and liver dysfunction (n = 1). However, there was no chemotherapy-related death. CONCLUSIONS: Paclitaxel by 24-hour infusion combined with ifosfamide is efficacious in the treatment of anthracycline-resistant MBC with tolerable toxicity. Further trials verifying the result of the authors' study are warranted.