Increased serological cancer-associated biomarker levels at large bowel endoscopy and risk of subsequent primary cancer (†).

Background: Frequently, subjects offered colonoscopy due to symptoms of colorectal neoplasia are diagnosed with diverticula. The symptoms may, however, also be related to extra-colonic neoplasia. The present retrospective study evaluated a possible association between increased levels of predefined biomarkers in subjects diagnosed with diverticula and risk of developing a primary malignant disease.

Blood-based Biomarkers at Large Bowel Endoscopy and Prediction of Future Malignancies.

Soluble cancer-related protein biomarker levels may be increased in subjects without findings at large bowel endoscopy performed due to symptoms associated with colorectal cancer. The present study focused on a possible association between increased biomarker levels in such subjects and subsequent development of malignant diseases. In a major study of 4,990 subjects undergoing large bowel endoscopy, 691 were without pathology and comorbidity.

Plasma biomarker signature associated with improved survival in advanced non-small cell lung cancer patients on linifanib.

Objectives: Linifanib, a potent and selective inhibitor of the tyrosine kinase activity of vascular endothelial growth factor and platelet-derived growth factor receptors, has clinical activity in advanced non-small cell lung cancer (NSCLC) both as monotherapy in the relapsed setting or with carboplatin and paclitaxel in the first-line setting. Though benefit was observed in unselected patient populations, identification of predictive biomarkers is critical for further development of this novel agent.

Materials And Methods: Data from 4 randomized studies in relapsed NSCLC with linifanib (n=116) or other treatments (n=125) were examined in an exploratory analysis to identify a biomarker profile predictive of favorable survival.

Plasma TIMP-1 and CEA as Markers for Detection of Primary Colorectal Cancer: A Prospective Validation Study Including Symptomatic and Non-symptomatic Individuals.

Background/aim: The combination of plasma tissue inhibitor of metalloproteinases-1 (1) and CEA has been shown to have utility in early detection of colorectal cancer (2). A prospective study was performed to validate previous findings.

Patients And Methods: Individuals undergoing large bowel endoscopy were prospectively included (N=1965).

Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma.

Background: The efficacy and safety of linifanib (ABT-869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases, were assessed in this phase 2, single-arm, open-label, multicenter trial.

Methods: Eligible patients had unresectable or metastatic hepatocellular carcinoma and had received ≤ 1 prior systemic therapy. Patients received oral linifanib at a fasting dose of 0.

Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer.

Purpose: Bcl-2 is a critical regulator of apoptosis that is overexpressed in the majority of small cell lung cancers (SCLC). Nativoclax (ABT-263) is a potent and selective inhibitor of Bcl-2 and Bcl-x(L). The primary objectives of this phase IIa study included safety at the recommended phase II dose and preliminary, exploratory efficacy assessment in patients with recurrent and progressive SCLC after at least one prior therapy.

Improvement and multicenter evaluation of the analytical performance of an automated chemiluminescent immunoassay for alpha fetoprotein.

Background: A new ARCHITECT® alpha fetoprotein (AFP) assay was developed to improve the linearity at the upper end of the calibration curve and to enhance other performance characteristics. In addition, this reformulation eliminated the possibility of falsely depressed samples at high AFP concentrations. The purpose of this study was to evaluate its analytical performance at multiple sites.

Phase I/II study of pemetrexed with or without ABT-751 in advanced or metastatic non-small-cell lung cancer.

Purpose: ABT-751 is an antimitotic and vascular disrupting agent with potent preclinical anticancer activity. We conducted a phase I and randomized double-blind phase II study of pemetrexed with ABT-751 or placebo in patients with recurrent advanced or metastatic non-small-cell lung cancer (NSCLC).

Methods: One hundred seventy-one patients received intravenous pemetrexed 500 mg/m(2) day 1 and oral ABT-751 or placebo days 1 to 14 of 21-day cycles.

A comparative evaluation of Golgi protein-73, fucosylated hemopexin, α-fetoprotein, and PIVKA-II in the serum of patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Background: Golgi protein-73 (GP73) and fucosylated proteins have been proposed as potential serum markers for liver disease and/or hepatocellular carcinoma (HCC). The purpose of this study was to compare the sensitivity and specificity of serum GP73 and fucosylated hemopexin (Fuc-HPX) with α-fetoprotein (AFP) and with protein induced by the absence of vitamin K or antagonist-II (PIVKA-II) for diagnosing chronic hepatitis, cirrhosis, and HCC.

Methods: The concentration of GP73 in human sera was determined using an enzyme-linked immunosorbent assay employing mouse monoclonal and rabbit polyclonal GP73 antibodies.

Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals.

Objective: The combination of plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) and carcinoembryonic antigen (CEA) may be valuable biomarkers for early detection of colorectal cancer (CRC). A prospective, population based study was performed to validate this hypothesis.

Material And Methods: Individuals (n = 4509) referred for large bowel endoscopy due to symptoms of CRC were prospectively included.

Development and analytical performance evaluation of an automated chemiluminescent immunoassay for pro-gastrin releasing peptide (ProGRP).

Background: Pro-gastrin releasing peptide (ProGRP) concentrations in blood play an important role in the diagnosis and treatment of patients with small cell lung cancer (SCLC). The automated quantitative ARCHITECT ProGRP assay was developed to aid in the differential diagnosis and in the management of SCLC. The purpose of this study was to evaluate the analytical performance of this chemiluminescent microparticle immunoassay at multiple sites.

National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers.

Background: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed.

Methods: Published reports relevant to use of tumor markers for 5 cancer sites--testicular, prostate, colorectal, breast, and ovarian--were critically reviewed.

Results: For testicular cancer, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are recommended for diagnosis/case finding, staging, prognosis determination, recurrence detection, and therapy monitoring.

Emerging biomarkers for the diagnosis and prognosis of prostate cancer.

Background: Early detection of prostate cancer (CaP), the most prevalent cancer and the second-leading cause of death in men, has proved difficult, and current detection methods are inadequate. Prostate-specific antigen (PSA) testing is a significant advance for early diagnosis of patients with CaP.

Content: PSA is produced almost exclusively in the prostate, and abnormalities of this organ are frequently associated with increased serum concentrations.

Stability of pro-gastrin-releasing peptide in serum versus plasma.

Background/aims: Although serum assays for pro-gastrin-releasing peptide (ProGRP) assays have been commercially available in Japan for several years, the stability of ProGRP in serum and plasma has not been well documented. We investigated the stability of ProGRP in serum and plasma with fresh and stored (frozen) specimens, as well as the cause of the observed instability in serum.

Methods/results: ProGRP concentrations in fresh serum were decreased by 6-28% after room temperature storage for 2 h and by 8-32% after 2-8 degrees C storage for 24 h.

Biology and potential clinical implications of tissue inhibitor of metalloproteinases-1 in colorectal cancer treatment.

Colorectal cancer (CRC) is the second leading cause of cancer-related death in the industrialized world. About half of "curatively" resected patients develop recurrent disease within the next 3-5 years despite the lack of clinical, histological and biochemical evidence of remaining overt disease after resection of the primary tumour. Availability of validated biological markers for early detection, selection for adjuvant therapy, prediction of treatment efficacy and monitoring of treatment efficacy would most probably increase survival.

Dependence of TIMP-1 plasma levels on preanalytical specimen handling.

Background: Tissue inhibitor of metalloproteinases-1 (TIMP-1) in blood might be a helpful biomarker in various diseases. However, various authors report that TIMP-1 is dependent on preanalytical procedures. Our study was performed to determine how storage conditions and time to centrifugation influence TIMP-1.

Evaluation of an improved tissue inhibitor of metalloproteinase 1 dual monoclonal sandwich immunoassay.

Background: It has previously been shown that increased levels of plasma tissue inhibitor of metalloproteinase 1 (TIMP-1) is associated with shorter survival for patients with colorectal cancer (CRC). Furthermore, plasma TIMP-1 levels have been found to be elevated in patients with early-stage CRC.

Objective: It was the aim of this study to develop a new dual monoclonal antibody (mAb) sandwich immunoassay for TIMP-1 in order to achieve better resolution of non-cancer and cancer plasma specimens.

Establishment and characterization of 7 new monoclonal antibodies to tissue inhibitor of metalloproteinases-1.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) plays a pivotal role in tissue remodeling processes, such as inflammation, wound healing and cancer invasion. Experimental results have pointed to a role in angiogenesis, cell proliferation, apoptosis and in malignant transformation. In clinical investigations high tumor tissue or plasma levels of TIMP-1 have been shown to have a strong and independent association with shorter survival time for breast and colorectal cancer patients, respectively.