Comparing Concurrent Chemoradiotherapy to Chemotherapy Alone for Locally Advanced Unresectable Pancreatic Cancer / 대한방사선종양학회지

PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable pancreatic cancer. However, the introduction of gemcitabine and the recognition of a benefit in patients with advanced disease stimulated the design of trials that compare chemotherapy alone to concurrent chemoradiation. Therefore, we evaluated role of CCRT for locally advanced unresectable pancreatic cancer. MATERIALS AND METHODS: We carried out a retrospective analysis of treatment results for patients with locally advanced unresectable pancreatic cancer between January 2000 and January 2008. The radiation was delivered to the primary tumor and regional lymph nodes with a 1~2 cm margin at a total dose of 36.0~59.4 Gy (median: 54 Gy). The chemotherapeutic agent delivered with the radiation was 5-FU (500 mg/m2). The patients who underwent chemotherapy alone received gemcitabine (1,000 mg/m2) alone or gemcitabine with 5-FU. The follow-up period ranged from 2 to 38 months. The survival and prognostic factors were analyzed using Kaplan-Meier method and log-rank test, respectively. RESULTS: Thirty-four patients received concurrent chemoradiotherapy, whereas 21 patients received chemotherapy alone. The median survival time was 12 months for CCRT patients, compared to 11 months for chemotherapy alone patients (p=0.453). The median progression-free survival was 8 months for CCRT patients, compared to 5 months for chemotherapy alone patients (p=0.242). The overall response included 9 partial responses for CCRT and 1 partial response for chemotherapy alone. In total, 26% of patients from the CCRT group experienced grade 3~4 bowel toxicity. In contract, no grade 3~4 bowel toxicity was observed in the chemotherapy alone group. The significant prognostic factors of overall survival were lymph node status, high CA19-9, and tumor location. CONCLUSION: The response rate and progression-free survival were more favorable in the CCRT group, when compared with the chemotherapy alone group. Therefore, radiation therapy seems to be an effective tool for local tumor control.

Survival Analysis of Patients with Brain Metastsis by Weighting According to the Primary Tumor Oncotype / 대한방사선종양학회지

PURPOSE: This study was performed to retrospectively analyze patient survival by weighting according to the primary tumor oncotype in 160 patients with brain metastasis and who underwent whole brain radiotherapy. MATERIALS AND METHODS: A total of 160 metastatic brain cancer patients who were treated with whole brain radiotherapy of 30 Gy between 2002 and 2008 were retrospectively analyzed. The primary tumor oncotype of 20 patients was breast cancer, and that of 103 patients was lung cancer. Except for 18 patients with leptomeningeal seeding, a total of 142 patients were analyzed according to the prognostic factors and the Recursive Partitioning Analysis (RPA) class. Weighted Partitioning Analysis (WPA), with the weighting being done according to the primary tumor oncotype, was performed and the results were correlated with survival and then compared with the RPA Class. RESULTS: The median survival of the patients in RPA Class I (8 patients) was 20.0 months, that for Class II (76 patients) was 10.0 months and that for Class III (58 patients) was 3.0 months (p<0.003). The median survival of patients in WPA Class I (3 patients) was 36 months, that for the patients in Class II (9 patients) was 23.7 months, that for the patients in Class III (70 patients) was 10.9 months and that for the patients in Class IV (60 patients) was 8.6 months (p<0.001). The WPA Class might have more accuracy in assessing survival, and it may be superior to the RPA Class for assessing survival. CONCLUSION: A new prognostic index, the WPA Class, has more prognostic value than the RPA Class for the treatment of patients with metastatic brain cancer. This WPA Class may be useful to guide the appropriate treatment of metastatic brain lesions.

Rat Organic Anion Transporter 3 Co-localized with Caveolin-2 in Rat Kidney / 대한신장학회잡지

BACKGROUND: The recently identified organic anion transporter 3 (rOAT3) was mainly expressed in kidney, liver and brain tissue, and it contributes the movement of endogenous or exogenous substances across the cell membrane. Although the properties of rOAT3 are gradually accumulated, the regulatory mechanism of rOAT3 remains to be elucidated. Caveolin (Cav) also plays a role as a membrane transporter and as a modulating protein for some functional proteins. Therefore, we investigated the protein-protein interaction between rOAT3 and Cav-2 in rat kidney. METHODS: The expressions of rOAT3 and Cav-2 (mRNA and protein) were observed using RT-PCR and Western blot analysis. The localization of rOAT3 and Cav-2 was determined in the caveolae-rich membrane fraction isolated by sucrose gradient ultra-centrifugation. For the direct binding between the rOAT3 and Cav-2 proteins, the immuno-precipitation method and confocal microscopy were employed. In order to perform functional analysis, a Xenopus oocytes expression system with the antisense oligodeoxynucleotides (ODN) technique was used. RESULTS: The expressions of rOAT3 and Cav-2 (mRNA and protein) were detected in the kidney. The caveolae-rich membranous fractions from the kidney contained both rOAT3 and Cav-2 in the same fractions. The immuno-precipitation experiments showed the formation of a complex between the rOAT3 and Cav-2 in the kidney. The confocal microscopic results using primary cultured renal proximal epithelial cells also supported the co-localization of rOAT3 and Cav-2 at the plasma membrane. The uptake function of rOAT3, as tested for by using a Xenopus oocytes expression system was slightly inhibited (with statistical significance) by the Xenopus Cav-2 antisense ODN. CONCLUSION: rOAT3 co-localizes with caveolin-2 in the caveolae, and caveolin-2 plays an important role in regulating the function of rOAT3.