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BackgroundMicroRNA expression is altered in cancer cells, and microRNAs could serve as diagnostic/prognostic biomarker for cancer patients. Our study was designed to analyze circulating serum microRNAs in patients with renal cell carcinoma (RCC).Methodology/Principal FindingsWe first explored microRNA expression profiles in tissue and serum using TaqMan Low Density Arrays in each six malignant and benign samples: Although 109 microRNAs were circulating at higher levels in cancer patients' serum, we identified only 36 microRNAs with up-regulation in RCC tissue and serum of RCC patients. Seven candidate microRNAs were selected for verification based on the finding of up-regulation in serum and tissue of RCC patients: miR-7-1*, miR-93, miR-106b*, miR-210, miR-320b, miR-1233 and miR-1290 levels in serum of healthy controls (n = 30) and RCC (n = 33) patients were determined using quantitative real-time PCR (TaqMan MicroRNA Assays). miR-1233 was increased in RCC patients, and thus validated in a multicentre cohort of 84 RCC patients and 93 healthy controls using quantitative real-time PCR (sensitivity 77.4%, specificity 37.6%, AUC 0.588). We also studied 13 samples of patients with angiomyolipoma or oncocytoma, whose serum miR-1233 levels were similar to RCC patients. Circulating microRNAs were not correlated with clinical-pathological parameters.Conclusions/SignificanceMicroRNA levels are distinctly increased in cancer patients, although only a small subset of circulating microRNAs has a tumor-specific origin. We identify circulating miR-1233 as a potential biomarker for RCC patients. Larger-scaled studies are warranted to fully explore the role of circulating microRNAs in RCC.

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BACKGROUNDLiposomal encapsulation of doxorubicin has been shown to reduce nonspecific delivery of this agent to normal tissue and to increase specific delivery to malignant cells. On the basis of doxorubicin's demonstrated clinical efficacy against hormone‐refractory prostate carcinoma (HRPCA), the authors conducted a prospective, randomized Phase II clinical trial to evaluate the feasibility, toxicity, and therapeutic efficacy associated with the pegylated form of this agent.METHODSForty‐eight patients with symptomatic HRPCA were randomized to receive pegylated liposomal doxorubicin at either 25 mg/m2 every 2 weeks for 12 cycles (Group A) or 50 mg/m2 every 4 weeks for 6 cycles (Group B). Thirty‐eight of these 48 patients (79%) presented with severe pain (corresponding to a pain score of 7.5 on a visual analog scale [VAS] ranging from 0 to 10) due to osseous metastases. Therapeutic efficacy was assessed by serial evaluation of serum prostate‐specific antigen (PSA) concentrations and by serial measurement of pain levels (using a VAS ranging from 0 to 10). Toxicity data were obtained using the National Cancer Institute of Canada/Cancer and Leukemia Group B criteria and the 30‐item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.RESULTSThe median patient age was 68.9 years (range, 58–79 years), and the mean follow‐up duration was 42 months. The mean pretreatment PSA level was 660.4 ng/mL (mean, 8–6340 ng/mL); an objective decrease in PSA levels (i.e., a decrease of > 50%) was observed in 8 of 31 patients (25.8%) in Group B, whereas no other patient in either group experienced such a decrease. The mean time to disease progression was 6.5 months, and the mean survival duration was 13.4 months. Patients in Group B had a significantly higher rate of response with respect to pain (52.6% vs. 28.6%; P = 0.04), and the mean 1‐year survival rate also was significantly higher in Group B (42% vs. 15%; P = 0.02). Severe side effects were observed, with 24 patients (50%) experiencing World Health Organization Grade 3/4 toxicity. Toxicity types differed significantly between Group A and Group B; palmar‐plantar erythrodysesthesia developed in 60% of patients in the former group (P < 0.0005), whereas tachycardia was more common in the latter group (39% of patients; P < 0.0005). No dose‐limiting cardiotoxicities or hematotoxicities were documented.CONCLUSIONSPegylated liposomal doxorubicin yielded a noteworthy objective palliative response rate and a mean survival of 13 months for patients with symptomatic HRPCA. The dosage tested in the current study should be used in future Phase II and Phase III trials of pegylated liposomal doxorubicin–containing combination regimens for patients with HRPCA. Cancer 2004. © 2004 American Cancer Society.

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COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).