Acute kidney injury and multivessel percutaneous coronary interventions in chronic renal disease: the AMICI study.

Background: Patients with chronic kidney disease (CKD) often have multivessel coronary artery disease and the risk of acute kidney injury (AKI) after percutaneous coronary interventions (PCI) is high. The aim of this study was to evaluate the risk of AKI in patients with CKD who underwent single vessel PCI versus multivessel PCI.

Methods: We retrospectively screened all PCI performed from January 2011 to December 2017 and we included all the procedures performed in patients with a baseline glomerular filtration rate <60 mL/min/1.

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.

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.

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.

Oxidants and not alkylating agents induce rapid mtDNA loss and mitochondrial dysfunction.

Mitochondrial DNA (mtDNA) is essential for proper mitochondrial function and encodes 22 tRNAs, 2 rRNAs and 13 polypeptides that make up subunits of complex I, III, IV, in the electron transport chain and complex V, the ATP synthase. Although mitochondrial dysfunction has been implicated in processes such as premature aging, neurodegeneration, and cancer, it has not been shown whether persistent mtDNA damage causes a loss of oxidative phosphorylation. We addressed this question by treating mouse embryonic fibroblasts with either hydrogen peroxide (H(2)O(2)) or the alkylating agent methyl methanesulfonate (MMS) and measuring several endpoints, including mtDNA damage and repair rates using QPCR, levels of mitochondrial- and nuclear-encoded proteins using antibody analysis, and a pharmacologic profile of mitochondria using the Seahorse Extracellular Flux Analyzer.

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.

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.

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.

A framework for evaluating biomarkers for early detection: validation of biomarker panels for ovarian cancer.

A panel of biomarkers may improve predictive performance over individual markers. Although many biomarker panels have been described for ovarian cancer, few studies used prediagnostic samples to assess the potential of the panels for early detection. We conducted a multisite systematic evaluation of biomarker panels using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial.

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.

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.

Elimination of human lung cancer stem cells through targeting of the stem cell factor-c-kit autocrine signaling loop.

Cancer stem cells (CSC) are thought to be responsible for tumor initiation and tumor regeneration after chemotherapy. Previously, we showed that chemotherapy of non-small cell lung cancer (NSCLC) cells lines can select for outgrowth of highly tumorigenic and metastatic CSCs. The high malignancy of lung CSCs was associated with an efficient cytokine network.

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.

Multiplex analysis of cytokines as biomarkers that differentiate benign and malignant thyroid diseases.

Thyroid cancer incidence is increasing, and its diagnosis can be challenging. Fine needle biopsy, the principal clinical tool to make a tissue diagnosis, leads to inconclusive diagnoses in up to 30% of the cases, leading to surgery. Advances in proteomics are improving abilities to diagnose malignant conditions using small samples of tissue or body fluids.

Reproducibility of serum cytokines and growth factors.

Background: In most studies, circulating biomarkers are usually assessed from a single sample, assuming that this single measurement represents the long-term biomarker status of the individual. Such an assumption is rarely tested although it may not be valid for all biomarkers. The objective of this study was to investigate the temporal reproducibility of a panel of cytokines and growth factors.

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.

Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties.

Background: Cancer stem cells (CSCs) are thought to be responsible for tumor regeneration after chemotherapy, although direct confirmation of this remains forthcoming. We therefore investigated whether drug treatment could enrich and maintain CSCs and whether the high tumorogenic and metastatic abilities of CSCs were based on their marked ability to produce growth and angiogenic factors and express their cognate receptors to stimulate tumor cell proliferation and stroma formation.

Methodology/findings: Treatment of lung tumor cells with doxorubicin, cisplatin, or etoposide resulted in the selection of drug surviving cells (DSCs).

Multiple effects of TRAIL in human carcinoma cells: induction of apoptosis, senescence, proliferation, and cytokine production.

TRAIL is a death ligand that induces apoptosis in malignant but not normal cells. Recently the ability of TRAIL to induce proliferation in apoptosis-resistant normal and malignant cells was reported. In this study, we analyzed TRAIL effects in apoptosis sensitive MCF7, OVCAR3 and H460 human tumor cell lines.

Reliability of tumor markers, chemokines, and metastasis-related molecules in serum.

There is a growing interest in the role that cancer biomarkers, metastasis-related molecules, and chemokines may play in the development and progression of various cancers. However, few studies have addressed the reliability of such biomarkers in healthy individuals over time. The objective of this study was to investigate the temporal reliability of multiple proteins in serum samples from healthy women who donated blood over successive years.

Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin.

Objective: Endometrial carcinoma is the most common gynecologic cancer. Although the prognosis for endometrial cancer is generally good, cancers identified at late stages are associated with high levels of morbidity and mortality. Therefore, prevention and early detection may further reduce the burden of this challenging disease.

Multiplex analysis of serum cytokines in melanoma patients treated with interferon-alpha2b.

Purpose: Interferon (IFN)-alpha2b is the only Food and Drug Administration-approved treatment for operable high-risk melanoma that has been shown to significantly and durably prolong relapse-free survival (RFS) of patients with stage IIB-III melanoma. Development of reliable serum assays may contribute to the development of methods for earlier detection of melanoma and the selection of patients who may be most susceptible to current available interventions with IFNalpha.

Experimental Design: A powerful high-throughput xMAP multiplex immunobead assay technology (Luminex Corp.

Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling.

Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease that has been linked to altered immune, inflammatory, and angiogenesis responses. A better understanding of these aberrant responses might improve early detection and prognosis of SCCHN and provide novel therapeutic targets. Previous studies examined the role of multiplexed serum biomarkers in small cohorts or SCCHN sera.

Multianalyte profiling of serum cytokines for detection of pancreatic cancer.

Early detection of pancreatic cancer might improve clinical outcome. Significant alterations in the levels of individual serum cytokines have been reported in pancreatic cancer. We hypothesized that a multicytokine panel could serve as biomarkers for pancreatic cancer.