Urinary protein biomarkers in the early detection of lung cancer.

The early detection of lung cancer has the potential to greatly impact disease burden through the timely identification and treatment of affected individuals at a manageable stage of development. The insufficient specificity demonstrated by currently used screening and diagnostic techniques has led to intense investigation into biomarkers as diagnostic tools. Urine may represent a noninvasive alternative matrix for diagnostic biomarker development.

Circulating mediators of inflammation and immune activation in AIDS-related non-hodgkin lymphoma.

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation.

Prediagnostic serum biomarkers as early detection tools for pancreatic cancer in a large prospective cohort study.

Background: The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools.

Methods: Sixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).

Results: The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective.

An extensive targeted proteomic analysis of disease-related protein biomarkers in urine from healthy donors.

The analysis of protein biomarkers in urine is expected to lead to advances in a variety of clinical settings. Several characteristics of urine including a low-protein matrix, ease of testing and a demonstrated proteomic stability offer distinct advantages over current widely used biofluids, serum and plasma. Improvements in our understanding of the urine proteome and in methods used in its evaluation will facilitate the clinical development of urinary protein biomarkers.

Biomarker testing for ovarian cancer: clinical utility of multiplex assays.

The improved detection of ovarian cancer at the earliest stages of development would confer a significant benefit in the therapeutic efficacy and overall survival associated with this devastating disease. The inadequate performance of currently used imaging modalities and the CA 125 biomarker test have precluded the establishment of screening programs and hindered the development of diagnostic tests for ovarian cancer. Two recently completed large clinical trials of ovarian cancer screening have reported findings of mixed impact, further clouding the issue.

Circulating prolactin levels and risk of epithelial ovarian cancer.

Purpose: Indirect evidence from experimental and epidemiological studies suggests that prolactin may be involved in ovarian cancer development. However, the relationship between circulating prolactin levels and risk of ovarian cancer is unknown.

Methods: We conducted a nested case-control study of 230 cases and 432 individually matched controls within three prospective cohorts to evaluate whether pre-diagnostic circulating prolactin is associated with subsequent risk of ovarian cancer.

Multianalyte assay systems in the differential diagnosis of ovarian cancer.

Introduction: The efficient triage of women diagnosed with a pelvic mass presents a current area of unmet need. Unnecessary surgical intervention performed on patients at a decreased risk of malignancy represents a significant source of preventable morbidity, anxiety and cost. Likewise, delayed or overlooked referral of patients harboring malignant tumors is strongly associated with diminished outcomes.

Serum biomarker profiles as diagnostic tools in lung cancer.

Background: Computed tomography (CT) scanning has emerged as an effective means of early detection for lung cancer. Despite marked improvement over earlier methodologies, the low level of specificity demonstrated by CT scanning has limited its clinical implementation as a screening tool. A minimally-invasive biomarker-based test that could further characterize CT-positive patients based on risk of malignancy would greatly enhance its clinical efficacy.

Protein biomarkers of ovarian cancer: the forest and the trees.

The goal of effective population-based screening for ovarian cancer remains elusive despite intense efforts aimed at improving upon biomarker and imaging modalities. While dozens of potential serum biomarkers for ovarian cancer have been identified in recent years, none have yet overcome the limitations that have hindered the clinical use of CA-125. Avenues of opportunity in biomarker development are emerging as investigators are beginning to appreciate the significance of remote, as well as local or regional, sources of biomarkers in the construction of diagnostic panels, as well as the importance of evaluating biomarkers in prediagnostic settings.

Factors associated with inflammation markers, a cross-sectional analysis.

Epidemiological studies have reported associations between circulating inflammation markers and risk of chronic diseases. It is of interest to examine whether risk factors for these diseases are associated with inflammation. We conducted a cross-sectional analysis to evaluate whether reproductive and lifestyle factors and circulating vitamin D were associated with inflammation markers, including C-reactive protein, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα), and cytokine modulators (IL-1RA, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1/R2), among 616 healthy women.

-The advancement of biomarker-based diagnostic tools for ovarian, breast, and pancreatic cancer through the use of urine as an analytical biofluid.

Despite considerable advancements, the development of effective cancer screening tools based on serum biomarker measurements has thus far failed to achieve a meaningful clinical impact. The incremental progress observed over the course of serum biomarker development suggests that further refinements based on novel approaches may yet result in a breakthrough. The use of urine as an analytical biofluid for biomarker development may represent such an approach.

Circulating inflammation markers and risk of epithelial ovarian cancer.

Background: Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer. The purpose of this study was to assess the association between circulating levels of inflammation mediators and subsequent risk of ovarian cancer.

Methods: We conducted a case-control study of 230 cases and 432 individually matched controls nested within three prospective cohorts to evaluate the association of prediagnostic circulating levels of inflammation-related biomarkers (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα, IL-1Ra, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1, and sTNF-R2) measured using Luminex xMap technology with risk of ovarian cancer.

Serum biomarker panels for the detection of pancreatic cancer.

Purpose: Serum-biomarker based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations.

Experimental Design: Eighty-three circulating proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n = 333), benign pancreatic conditions (n = 144), and healthy control individuals (n = 227). Samples from each group were split randomly into training and blinded validation sets prior to analysis.

Temporal reliability of cytokines and growth factors in EDTA plasma.

Background: Cytokines are involved in the development of chronic diseases, including cancer. It is important to evaluate the temporal reproducibility of cytokines in plasma prior to conducting epidemiologic studies utilizing these markers.

Findings: We assessed the temporal reliability of CRP, 22 cytokines and their soluble receptors (IL-1α, IL-1β, IL-1RA, IL-2, sIL-2R, IL-4, IL-5, IL-6, sIL-6R, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, TNFα, sTNF-R1, sTNF-R2, IFNα, IFNγ) and eight growth factors (GM-CSF, EGF, bFGF, G-CSF, HGF, VEGF, EGFR, ErbB2) in repeated EDTA plasma samples collected an average of two years apart from 18 healthy women (age range: 42-62) enrolled in a prospective cohort study.

Development of a multimarker assay for early detection of ovarian cancer.

Purpose: Early detection of ovarian cancer has great promise to improve clinical outcome.

Patients And Methods: Ninety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, colorectal, and lung cancers, using multiplex xMAP bead-based immunoassays. A Metropolis algorithm with Monte Carlo simulation (MMC) was used for analysis of the data.

Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass.

Objectives: The diagnosis of an adnexal mass is a prevalent issue among women in the United States, although current methods of identifying those at high risk of malignancy remain insufficient. Ineffective triage of women with malignant masses is associated with delayed or inappropriate treatment and a negative effect on disease outcome.

Methods: We performed an evaluation of 65 ovarian cancer-related biomarkers in the circulation of women diagnosed with an adnexal mass.

Targeting CCL11 in the treatment of ovarian cancer.

Importance Of The Field: The chemokine network, comprised of mediators of inflammation, has been implicated in the development of a number of human cancers. The eosinophil chemoattractant CCL11 was recently shown to play a role in the development of ovarian cancer. Here we review findings regarding CCL11 and discuss its use as a target in the treatment of ovarian cancer.

Screening for ovarian cancer: old tools, new lessons.

The early detection of ovarian cancer represents a clinical objective with an enormous potential for a meaningful improvement in our ability to treat and cure afflicted patients. The magnitude of this potential is matched by the challenges associated with attaining it. In addition to the well noted aspects of ovarian cancer which have thus far precluded the development a effective screening strategies, recent work regarding the differential pathogenesis and origins of the various histological subtypes of epithelial ovarian cancer have further revealed the challenges ahead.

Biological significance of prolactin in gynecologic cancers.

There is increasing evidence that prolactin (PRL), a hormone/cytokine, plays a role in breast, prostate, and colorectal cancers via local production or accumulation. Elevated levels of serum PRL in ovarian and endometrial cancers have been reported, indicating a potential role for PRL in endometrial and ovarian carcinogenesis. In this study, we show that serum PRL levels are significantly elevated in women with a strong family history of ovarian cancer.

Role of eotaxin-1 signaling in ovarian cancer.

Purpose: Tumor cell growth and migration can be directly regulated by chemokines. In the present study, the association of CCL11 with ovarian cancer has been investigated.

Experimental Design And Results: Circulating levels of CCL11 in sera of patients with ovarian cancer were significantly lower than those in healthy women or women with breast, lung, liver, pancreatic, or colon cancer.

Aberrant tumor-associated antigen autoantibody profiles in healthy controls detected by multiplex bead-based immunoassay.

There is an increasing amount of emphasis being placed on serological biomarkers as tools for early detection of various cancers. In addition to the tumor-related circulating antigens under current investigation, autoantibodies to tumor-associated antigens are emerging as alternative candidates due to their potential high sensitivity and specificity. Already a number of specific autoantibodies have been identified and several groups have reported on the ability of panels of autoantibodies to discriminate malignant from non-malignant conditions.

Autoantibodies for cancer detection: still cause for excitement?

The identification of circulating biomarkers of early stage malignancy is a critical component of ongoing efforts aimed at reducing the overall public and personal impact of human cancer through early detection. The human immune system is capable of identifying and reporting the presence of tumor-derived factors appearing during the initial events of tumorigenesis with a sensitivity and specificity far beyond currently developed biochemical assays. Tapping into the process of immune surveillance through the identification and evaluation of autoantibodies against tumor-associated antigens (TAAs) represents a promising avenue of biomarker development.

A serum based analysis of ovarian epithelial tumorigenesis.

Objectives: Ovarian epithelial carcinoma can be subdivided into separate histological subtypes including clear cell, endometrioid, mucinous, and serous. These carcinoma subtypes may represent distinctive pathways of tumorigenesis and disease development. This distinction could potentially be reflected in the levels of tumor produced factors that enter into the circulation and serve as biomarkers of malignant growth.

Chemotherapeutic drugs and human tumor cells cytokine network.

The ability of human tumor cell lines to produce various cytokines, chemokines, angiogenic and growth factors was investigated using Luminex multiplex technology. Media conditioned by tumor cells protected tumor cells from drug-induced apoptosis and stimulated tumor cell proliferation. Antibodies neutralizing IL-6, CXCL8, CCL2 and CCL5 blocked this stimulation.