The Role of Ion Channels and Chemokines in Cancer Growth and Metastasis: A Proposed Mode of Action Using Peptides in Cancer Therapy.

Metastasis (Met) largely contributes to the major cause of cancer deaths throughout the world, rather than the growth of the tumor mass itself. The present report brings together several of the pertinent contributors to cancer growth and metastatic processes from an activity standpoint. Such biological activities include the following: (1) cell adherence and detachment; (2) cell-to-cell contact; (3) contact inhibition; (4) the cell interfacing with the extracellular matrix (ECM); (5) tumor cell-to-stroma communication networks; (6) chemotaxis; and (7) cell membrane potential.

Alpha-fetoprotein is an autoantigen in hepatocellular carcinoma and juvenile Batten disease.

Failure of immune tolerance leads to production of autoantibodies to self-antigens. The repertoire of autoantibodies detected in cancer patients can indicate the presence of autoimmune disease. Alpha-fetoprotein (AFP) autoantibodies have been found in patients with hepatocellular carcinoma (HCC) and in juvenile Batten disease (BD), a neurodegenerative condition involving autoimmunity.

Breast cancer and amyloid bodies: is there a role for amyloidosis in cancer-cell dormancy?

Breast cancer and Alzheimer's disease (AD) are major causes of death in older women. Interestingly, breast cancer occurs less frequently in AD patients than in the general population. Amyloidosis, the aggregation of amyloid proteins to form amyloid bodies, plays a central role in the pathogenesis of AD and other human neuropathies by forming intracellular fibrillary proteins.

The alpha-fetoprotein (AFP) third domain: a search for AFP interaction sites of cell cycle proteins.

The carboxy-terminal third domain of alpha-fetoprotein (AFP-3D) is known to harbor binding and/or interaction sites for hydrophobic ligands, receptors, and binding proteins. Such reports have established that AFP-3D consists of amino acid (AA) sequence stretches on the AFP polypeptide that engages in protein-to-protein interactions with various ligands and receptors. Using a computer software program specifically designed for such interactions, the present report identified AA sequence fragments on AFP-3D that could potentially interact with a variety of cell cycle proteins.

Does alpha-fetoprotein contribute to the mortality and morbidity of human hepatocellular carcinoma? A commentary.

The fifth most common cancer worldwide is hepatocellular carcinoma (HCC), while being the third leading cause of global cancer-related deaths. Although HCC incidence is less frequent in North America, it is a common malignancy in Asia and Africa associated with a high rate of mortality and morbidity due to ineffective therapies against cancer growth, invasion, and metastasis. It is well established that serum alpha-fetoprotein (AFP) is the "gold standard" biomarker for liver cancer; however, less known are the biological activities of AFP regarding carcinogenesis, growth, proliferation, and metastasis.

Alpha-fetoprotein and Fanconi Anemia: Relevance to DNA Repair and Breast Cancer Susceptibility.

Elevations of serum alpha-fetoprotein (sAFP) have been reported in fetal and infant states of anemia. Fanconi anemia (FA) belongs to a family of genetic instability disorders which lack the capability to repair DNA breaks. The lesion occurs at a checkpoint regulatory step of the G2 to mitotic transition, allowing FA cells to override cell-cycle arrest.

Review of the Third Domain Receptor Binding Fragment of Alphafetoprotein (AFP): Plausible Binding of AFP to Lysophospholipid Receptor Targets.

Alpha-fetoprotein (AFP) is a 69 kD fetal- and tumor-associated single-chain glycoprotein belonging to the albuminoid gene family. AFP functions as a carrier/transport molecule as well as a growth regulator and has been utilized as a clinical biomarker for both fetal defects and cancer growth. Lysophospholipids (LPLs) are plasma membrane-derived bioactive lipid signaling mediators composed of a small molecular weight single acyl carbon chain (palmitic, oleic acid) attached to a polar headgroup; they range in molecular mass from 250-750 daltons.

Route of antigen delivery impacts the immunostimulatory activity of dendritic cell-based vaccines for hepatocellular carcinoma.

Background: Dendritic cells (DC) are uniquely equipped to capture, process, and present antigens from their environment. The context in which an antigen is acquired by DC helps to dictate the subsequent immune response. Cancer vaccination promotes antitumor immunity by directing an immune response to antigens expressed by tumors.

Nonsecreted cytoplasmic alpha-fetoprotein: a newly discovered role in intracellular signaling and regulation. An update and commentary.

The concept of a non-secreted cytoplasmic-bound form of alpha-fetoprotein is not a new notion in AFP biological activities. Cytoplasmic AFP (CyAFP) is a long known but forgotten protein in search of a function other than a histochemical biomarker. In this report, CyAFP is presented as an "old" protein with a newly described intracellular function.

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets.

Recent studies have demonstrated that the carboxyterminal third domain of alpha-fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the last decade have established that AFP-CD contains a large fragment of amino acids that interact with several different receptor types. Using computer software specifically designed to identify protein-to-protein interaction at amino acid sequence docking sites, the computer searches identified several types of scavenger-associated receptors and their amino acid sequence locations on the AFP-CD polypeptide chain.

Cancer during pregnancy: what is the role of maternal serum and placental biomarkers? A review and commentary.

Cancer during pregnancy, referred to as gestational cancer (GC), is infrequent but can occur in 1.0% of pregnant women. Hepatocellular carcinoma (HCC) is often lethal and is the fifth most common cancer worldwide, while breast adenocarcinoma (breast cancer) is the most common cancer seen during pregnancy.

Engineering α-fetoprotein-based gene vaccines to prevent and treat hepatocellular carcinoma: review and future prospects.

Activation of a patient's immune system offers an attractive approach to prevent and treat hepatocellular carcinoma (HCC). However, the antitumor efficacy of current HCC vaccines was weak owing to insufficient immune activation of targeting self/tumor antigens. We recently found that epitope-optimized α-fetoprotein effectively activated CD8 T cells and generated potent antitumor effects in the carcinogen-induced autochthonous HCC mouse model.

The adenocarcinoma cell surface mucin receptor for alpha-fetoprotein: is the same receptor present on circulating monocytes and macrophages? A commentary.

The mucin family of proteins is largely expressed on sedentary epithelial cells lining the gastrointestinal, pulmonary, and reproductive tracts and their associated organs and malignant tumors. It is less well-known that mucins are also expressed on circulatory cells of the immune and inflammatory systems, such as monocytes, macrophages, leukemic, and lymphoma cells. The epithelial mucins function in (a) protection and lubrication of mucosal linings, (b) cell adhesion and cell-to-cell contact, (c) cell migration and metastasis, and (d) signal transduction.

Newborn screening for autism: in search of candidate biomarkers.

Background: Autism spectrum disorder (ASD) represents a wide range of neurodevelopmental disorders characterized by impairments in social interaction, language, communication and range of interests. Autism is usually diagnosed in children 3-5 years of age using behavioral characteristics; thus, diagnosis shortly after birth would be beneficial for early initiation of treatment.

Aim: This retrospective study sought to identify newborns at risk for ASD utilizing bloodspot specimens in an immunoassay.

Review of the adenocarcinoma cell surface receptor for human alpha-fetoprotein; proposed identification of a widespread mucin as the tumor cell receptor.

The identification of a tumor cell receptor for alpha-fetoprotein (AFP) has long been sought in the field of medicine. The uptake and endocytosis of AFP by rat tumor cells in 1983 sparked a series of confirmatory reports which were extended to include multiple tumor types in rats, mice, and humans. The following year, French investigators characterized the binding properties of the AFP receptor but they did not purify and characterize the receptor.

Alpha fetoprotein is more than a hepatocellular cancer biomarker: from spontaneous immune response in cancer patients to the development of an AFP-based cancer vaccine.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with a poor prognosis and limited therapeutic options. Due to its overexpression in the majority of HCCs, alpha-fetoprotein (AFP) represents one of the most useful markers for hepatocarcinomas and for monitoring patients' response to therapy. Although it was earlier reported that AFP has immunosuppressive properties, it has been recently demonstrated that AFP induces spontaneous T and B cells responses in HCC patients.

Mechanism of Cancer Growth Suppression of Alpha-Fetoprotein Derived Growth Inhibitory Peptides (GIP): Comparison of GIP-34 versus GIP-8 (AFPep). Updates and Prospects.

The Alpha-fetoprotein (AFP) derived Growth Inhibitory Peptide (GIP) is a 34-amino acid segment of the full-length human AFP molecule that inhibits tumor growth and metastasis. The GIP-34 and its carboxy-terminal 8-mer segment, termed GIP-8, were found to be effective as anti-cancer therapeutic peptides against nine different human cancer types. Following the uptake of GIP-34 and GIP-8 into the cell cytoplasm, each follows slightly different signal transduction cascades en route to inhibitory pathways of tumor cell growth and proliferation.

Review of the putative cell-surface receptors for alpha-fetoprotein: identification of a candidate receptor protein family.

The identification of a receptor for alpha-fetoprotein (AFP) has long been sought in the field of medicine. The uptake and endocytosis of AFP by rat tumor cells in 1984 sparked a series of confirmatory reports and the original studies were then extended to include multiple tumor types in rats, mice, and humans. The following year, French investigators partially characterized the binding properties of the AFP receptor, but they were not able to purify the receptor.

Targeted delivery of anti-cancer growth inhibitory peptides derived from human alpha-fetoprotein: review of an International Multi-Center Collaborative Study.

The alpha-fetoprotein derived growth inhibitory peptide (GIP) is a 34-amino acid peptide composed of three biologically active subfragments. GIP-34 and its three constituent segments have been synthesized, purified, and studied for biological activity. The GIP-34 and GIP-8 have been characterized as anticancer therapeutic peptides.

Can prenatal screening for fetal alcohol spectrum disorder be justified? A commentary.

Fetal alcohol spectrum disorder (FASD) is the leading cause of non-genetic mental retardation in the USA, possibly exceeding even Down syndrome, which is currently approaching 1 in 500 live births. Alcohol consumption during pregnancy results in brain, craniofacial and heart defects, neurotoxicity, and immune dysfunction. The preferred action taken to prevent alcohol consumption during pregnancy is abstinence.

Alpha-fetoprotein (AFP)-derived peptides as epitopes for hepatoma immunotherapy: a commentary.

The various immunological roles of human alpha-fetoprotein (HAFP), and its correlation with hepatomas, that is, hepatocellular carcinomas (HCCs), are not often addressed together in biomedical reports considering that HAFP is an established biomarker for hepatomas. Studies reporting measurement of HAFP serum levels in hepatoma patients in basic/clinical research settings has greatly increased over the years. Recent reports have now expanded our base knowledge in the mounting of an immune response against AFP, a self antigen, during hepatoma tumorigenesis.

Physiology of alpha-fetoprotein as a biomarker for perinatal distress: relevance to adverse pregnancy outcome.

The many physiologic roles of human alpha-fetoprotein (HAFP) and its correlation with perinatal distress/pregnancy outcome are rarely addressed together in the biomedical literature, even though HAFP has long been used as a biomarker for fetal birth defects. Although the well being of the fetus can be monitored by the measurement of gestational age-dependent HAFP in biologic fluid levels (serum, amniotic fluid, urine, and vaginal fluids) throughout pregnancy, the majority of clinical reports reflect largely second trimester and (less likely) first trimester testing due to regulatory clinical restrictions. However, reports of third-trimester and pregnancy term measurement of HAFP levels performed in clinical research and/or investigational settings have gradually increased over the years and have expanded our base knowledge of AFP-associated pregnancy disorders during these stages.

The alpha-fetoprotein-derived growth inhibitory peptide 8-mer fragment: review of a novel anticancer agent.

This review describes the antigrowth and anticancer activities of the alpha-fetoprotein (AFP)-derived growth inhibitory peptide (GIP) 8-mer fragment. The 8-amino acid peptide (GIP-8) comprises the carboxy-terminal portion of a 34-amino acid peptide (GIP-34) previously identified as an occult epitopic segment of the full-length human AFP molecule. The GIP-8 segment has been chemically synthesized, purified, characterized, and bioassayed.