Experimental validation of specificity of the squamous cell carcinoma antigen-immunoglobulin M (SCCA-IgM) assay in patients with cirrhosis.

BACKGROUND: Squamous cell carcinoma antigen-immunoglobulin M (SCCA-IgM) is a useful biomarker for the risk of development of hepatocellular carcinoma (HCC) in patients with cirrhosis due to its progressive increase associated to HCC evolution. In patients with cirrhosis, other assays have been affected by interfering reactivities of IgM. In this study, the analytical specificity of the SCCA-IgM assay was assessed by evaluating SCCA-IgM measurement dependence on different capture phases, and by measuring the recovery of SCCA-IgM reactivity following serum fractionation. METHODS: Serum samples from 82 patients with cirrhosis were analyzed. SCCA-IgM was measured using the reference test (Hepa-IC, Xeptagen, Italy) that is based on rabbit oligoclonal anti-squamous cell carcinoma antigen (SCCA) and a dedicated ELISA with a mouse monoclonal anti-SCCA as the capture antibody. RESULTS: SCCA-IgM concentrations measured with the reference assay (median value=87 AU/mL) were higher than those measured with the mouse monoclonal test (median value=78 AU/mL). However, the differences in the SCCA-IgM distribution were not statistically significant (p>0.05). When SCCA-IgM concentrations measured with both tests were compared, a linear correlation was found (r=0.77, p<0.05). Fractionation of the most reactive sera by gel-filtration chromatography showed that total recovery of SCCA-IgM reactivity was seen only in the fractions corresponding to components with a molecular weight higher than IgM and SCCA (>2000 kDa) with both tests. CONCLUSIONS: The equivalence of both SCCA-IgM assays and the absence of reactivity not related to immune complexes support the analytical specificity of SCCA-IgM measurements. The results validate the assessment of SCCA-IgM for prognostic purposes in patients with cirrhosis.

Urinary reference ranges and exposure profile for lithium among an Italian paediatric population.

The aims of the present study were to establish reference values useful in monitoring Lithium (Li) treatment and to trace environmental Li exposure profiles in paediatric age. A cross-sectional study was conducted on a group of healthy Italian children aged 5-11. Data on possible predictors were assessed through a questionnaire, and Li levels in morning and evening urinary samples were determined by ICP-MS technique. The reference intervals for the evening and morning samples were respectively 3.8-51.9µgL-1 or 5.6-60.6µgg-1 creatinine and 4.8-71.7µgL-1 or 4.8-73.2µgg-1 creatinine. Urinary Li levels showed a significantly inverse correlation with age and a positive correlation with urinary creatinine in both the evening and morning samples. No other studied variables influenced Li urinary excretion. These results, obtained using a readily available matrix as urine, can be useful for both environmental research and Li treatment monitoring.

Development of a website and biobank database for the Nanosized Cancer Polymarker Biochip Project: a Multicenter Italian Experience.

The Nanosized Cancer Polymarker Biochip Project (RBLA03S4SP) funded by an Italian MIUR-FIRB grant (Italian Ministry of University and Research - Investment Funds for Basic Research) has led to the creation of a free-access dynamic website, available at the web address https://serviziweb.ulss12.ve.it/firbabo, and of a centralized database with password-restricted access. The project network is composed of 9 research units (RUs) and has been active since 2005. The aim of the FIRB project was the design, production and validation of optoelectronic and chemoelectronic biosensors for the simultaneous detection of a novel class of cancer biomarkers associated with immunoglobulins of the M class (IgM) for early diagnosis of cancer. Biomarker immune complexes (BM-ICs) were assessed on samples of clinical cases and matched controls for breast, colorectal, liver, ovarian and prostate malignancies. This article describes in detail the architecture of the project website, the central database application, and the biobank developed for the FIRB Nanosized Cancer Polymarker Biochip Project. The article also illustrates many unique aspects that should be considered when developing a database within a multidisciplinary scenario. The main deliverables of the project were numerous, including the development of an online database which archived 1400 case report forms (700 cases and 700 matched controls) and more than 2700 experimental results relative to the BM-ICs assayed. The database also allowed for the traceability and retrieval of 21,000 aliquots archived in the centralized bank and stored as backup in the RUs, and for the development of a centralized biological bank in the coordinating unit with 6300 aliquots of serum. The constitution of the website and biobank database enabled optimal coordination of the RUs involved, highlighting the importance of sharing samples and scientific data in a multicenter setting for the achievement of the project goals.

The combination of the selective cyclooxygenase-2 inhibitor celecoxib with weekly paclitaxel is a safe and active second-line therapy for non-small cell lung cancer: a phase II study with biological correlates.

PURPOSE: The selection of effective schedules of treatment for metastatic non-small cell lung cancer still remains a challenge for the oncologist. The present multicentric phase II study was designed in order to investigate the activity and safety of the combination of weekly paclitaxel and celecoxib as second-line treatment for non-small cell lung cancer. As a secondary endpoint, the possible correlation of biomarkers with objective response was investigated in a subset of patients. PATIENTS AND METHODS: Patients with platinum-refractory non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0-2 entered the present phase II study. Paclitaxel was administered at the dose of 80 mg/m(2) i.v. weekly for 6 weeks, followed by a 2-week rest, and celecoxib, 400 mg p.o. b.i.d. administered continuously. A cycle consisted of 8 weeks of treatment. Determination of circulating vascular endothelial growth factor and interleukin 6 was performed at baseline and every two cycles. RESULTS: Fifty-eight patients were enrolled: median age, 60 years (range, 30-77 years); male/female ratio = 44/14; performance status, 0, 31 patients; 1, 25 patients; and 2, two patients. Predominant histotype was adenocarcinoma (34 cases), and most patients had at least two sites of disease. According to the intent-to-treat analysis, 14/58 objective responses (24.1%) and 24/58 (41.3%) stabilizations of disease were observed, with a median duration of 4 months (range, 2-22+ months) and 5 months (range, 1-13 months), respectively. Median time to progression and median overall survival were 5 and 11 months, respectively. One-year survival was 42.5%. The main toxicity was neuropathy (4% of grade 3). Preliminary results suggest that decrease in serum vascular endothelial growth factor level is significantly associated with clinical response. DISCUSSION: Combination of celecoxib and weekly paclitaxel is safe and active new regimen in pretreated non-small cell lung cancer. Toxicity appears not to be worsened by the addition of celecoxib. According to preliminary results, serum vascular endothelial growth factor level seems to be predictive of response, suggesting that it should be further investigated as a surrogate marker of response.