muramidase and Neoplasms

Protein-based nanocarriers have gained considerable attention as colloidal carrier systems for the delivery of anticancer drugs. Protein nanocarriers possess various advantages including their low cytotoxicity, abundant renewable sources, high drug-binding capacity, and significant uptake into the targeted tumor cells. Moreover, the unique protein structure offers the possibility of site-specific drug conjugation and tumor targeting using various ligands modifying the surface of protein nanocarriers. In this chapter, we highlight the most important applications of protein nanoparticles (NPs) for the delivery of anticancer drugs. We examine the various techniques that have been utilized for the preparation of anticancer drug-loaded protein NPs. Finally, the current chapter also reviews the major outcomes of the in vitro and in vivo investigations of surface-modified tumor-targeted protein NPs.

Topics: Albumins; Antineoplastic Agents; Drug Delivery Systems; Elastin; Gelatin; Gliadin; Humans; Hydrophobic and Hydrophilic Interactions; Milk Proteins; Molecular Targeted Therapy; Muramidase; Nanoparticles; Neoplasms; Static Electricity; Zein

Recent developments of mass spectrometry (MS) allow us to identify, estimate, and characterize proteins and protein complexes. At the same time, structural biology helps to determine the protein structure and its structure-function relationship. Together, they aid to understand the protein structure, property, function, protein-complex assembly, protein-protein interaction and dynamics. The present chapter is organized with illustrative results to demonstrate how experimental mass spectrometry can be combined with computational structural biology for detailed studies of protein's structures. We have used tumor differentiation factor protein/peptide as ligand and Hsp70/Hsp90 as receptor protein as examples to study ligand-protein interaction. To investigate possible protein conformation we will describe two proteins, lysozyme and myoglobin.

Topics: Animals; Computational Biology; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Humans; Mass Spectrometry; Muramidase; Myoglobin; Neoplasm Proteins; Neoplasms; Structure-Activity Relationship

Human α-lactalbumin made lethal to tumor cells (HAMLET) and equine lysozyme with oleic acid (ELOA) are complexes consisting of protein and fatty acid that exhibit cytotoxic activities, drastically differing from the activity of their respective proteinaceous compounds. Since the discovery of HAMLET in the 1990s, a wealth of information has been accumulated, illuminating the structural, functional and therapeutic properties of protein complexes with oleic acid, which is summarized in this review. In vitro, both HAMLET and ELOA are produced by using ion-exchange columns preconditioned with oleic acid. However, the complex of human α-lactalbumin with oleic acid with the antitumor activity of HAMLET was found to be naturally present in the acidic fraction of human milk, where it was discovered by serendipity. Structural studies have shown that α-lactalbumin in HAMLET and lysozyme in ELOA are partially unfolded, 'molten-globule'-like, thereby rendering the complexes dynamic and in conformational exchange. HAMLET exists in the monomeric form, whereas ELOA mostly exists as oligomers and the fatty acid stoichiometry varies, with HAMLET holding an average of approximately five oleic acid molecules, whereas ELOA contains a considerably larger number (11- 48). Potent tumoricidal activity is found in both HAMLET and ELOA, and HAMLET has also shown strong potential as an antitumor drug in different in vivo animal models and clinical studies. The gain of new, beneficial function upon partial protein unfolding and fatty acid binding is a remarkable phenomenon, and may reflect a significant generic route of functional diversification of proteins via varying their conformational states and associated ligands.

Topics: Animals; Apoptosis; Autophagy; Chromatin; Cytoplasmic Vesicles; Fatty Acids; Humans; Lactalbumin; Models, Molecular; Muramidase; Neoplasms; Oleic Acids; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Protein Binding; Protein Conformation; Protein Folding

The therapeutic effectiveness of lysozyme (large scale manufactured hen egg-white lysozyme) is actually based on its ability to control the growth of susceptible bacteria and to modulate host immunity against infections and depressions of immune responses. If the former is based on the first evidence of the biological activity of this enzyme, the second is a relatively recent acquisition of extreme importance for the possibilities offered in terms of the regulation of the functioning of the host's immune system. Antibotic activity and immune stimulating effects are also used together, as in the case of the treatment of gastrointestinal infections, including those originated by therapeutical treatments. Based on these biological properties, in addition to the wide range of therapeutic activities for which lysozyme was exploited in the past, at present the most promising data concern the prevention of bacterial cariogenesis and treatment of cancer patients to improve the effectiveness of anticancer drugs or to allow the host to recover from the immune suppression caused by anticancer treatments. However, lysozyme does not yet hold a clear place as an immune modulating agent, in spite of the fact that it has been shown to stimulate immunity with no difference between experimental animals and human beings. The hope is therefore that doctors will understand its potential and that they will take advantage of the existence of this simple and useful molecule.

Topics: Adjuvants, Immunologic; Animals; Anti-Bacterial Agents; Digestive System; Humans; Immunocompromised Host; Infections; Muramidase; Neoplasms

Serum enzyme measurements are not useful in screening for cancer or in primary diagnosis. Just as is the case for other tumor markers, they have an important role in confirming diagnosis and establishing the stage of disease. They also are useful in predicting prognosis and then in following the course of the disease.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amylases; Biomarkers, Tumor; Creatine Kinase; DNA Nucleotidylexotransferase; Hexosyltransferases; Humans; Isoenzymes; L-Lactate Dehydrogenase; Muramidase; Neoplasms; Phosphopyruvate Hydratase

Topics: Cell Membrane; Humans; Hydrogen-Ion Concentration; Hyperthermia, Induced; Kinetics; Microclimate; Muramidase; Neoplasms; Nucleic Acids; Oxygen; Oxygen Consumption; Temperature; Time Factors

Topics: Cell Division; Cell Movement; Chemotaxis; Cytotoxicity Tests, Immunologic; Humans; Lymphoma; Macrophages; Muramidase; Neoplasms; Phagocytes; Phagocytosis

Topics: Adenoma; alpha 1-Antitrypsin; alpha-Fetoproteins; Animals; Antigens; Carcinoembryonic Antigen; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Immunoglobulins; Lymphoma; Muramidase; Neoplasms; Pituitary Hormones; Pituitary Neoplasms

Topics: Animals; Epitopes; Genes, MHC Class II; Immunosuppression Therapy; Major Histocompatibility Complex; Mice; Molecular Weight; Muramidase; Myoglobin; Neoplasms; Peptides; T-Lymphocytes

Topics: Antineoplastic Agents; Bone Neoplasms; Breast Neoplasms; Drug Tolerance; Gastrointestinal Neoplasms; Granulocytes; Hematopoiesis; Hodgkin Disease; Humans; Leukemia; Lymphoma; Muramidase; Neoplasm Metastasis; Neoplasms

The participation of the monocyte-macrophages cells in the host immune defence mechanisms against cancer has been recognized since a few years. Testing this component of host homeostasis appears as an additional tool necessary for evaluation of immune deficiency in cancer patient. We review here the most current tests used in the frame of such an evaluation, and also the most interesting results.

Topics: Chemotaxis, Leukocyte; Humans; Macrophages; Monocytes; Muramidase; Neoplasms; Phagocytosis; Skin Window Technique

Topics: Aging; Animals; Antibodies; Bacteria; Cardiolipins; Chemical Phenomena; Chemistry; Chromatography; Diet; Enzymes; Escherichia coli; Fatty Acids; Humans; Insulin; Intracellular Membranes; Membranes, Artificial; Mitochondria; Muramidase; Neoplasms; Osmolar Concentration; Solvents; Subcellular Fractions

Topics: Clinical Enzyme Tests; Enzymes; Fructose-Bisphosphate Aldolase; gamma-Glutamyltransferase; Humans; L-Lactate Dehydrogenase; Leukemia; Muramidase; Neoplasms; Oxygen Consumption; Phosphoric Monoester Hydrolases

Topics: Adult; Animals; Bence Jones Protein; Blood Urea Nitrogen; Calcium; Carcinoma; Electrolytes; Fanconi Syndrome; Humans; Kidney; Kidney Diseases; Leukemia; Lymphoma; Multiple Myeloma; Muramidase; Neoplasms; Nephrotic Syndrome; Phosphorus; Potassium; Proteinuria; Sodium

A summary is presented of those organ specific enzyme assays traditionally used in evaluation of the patient with cancer. In addition, the use of certain serum enzymes such as gamma-glutamyl transpeptidase, phosphohexose isomerase or 5'-nucleotidase as aids in following the course of the disease, particularly in patients with metastatic spread to the liver is outlined. Also considered is the utility of enzyme analysis in biopsy tissue, biologic fluids, and washings of body cavities. Newer enzymes are considered which might, in the future, be developed as diagnostic tools or as probes for the understanding of the etiology of cancer.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amylases; Aryl Hydrocarbon Hydroxylases; Bone Neoplasms; Clinical Enzyme Tests; gamma-Glutamyltransferase; Humans; Isoenzymes; Isomerases; Leucyl Aminopeptidase; Lipase; Liver Neoplasms; Lung Neoplasms; Male; Muramidase; Neoplasms; Nucleotidases; Oxidoreductases; Pancreatic Neoplasms; Prostatic Neoplasms; Sulfatases

Topics: Acid Phosphatase; alpha-Fetoproteins; Antigens, Neoplasm; Blood Proteins; Breast Neoplasms; Calcitonin; Carcinoembryonic Antigen; Chorionic Gonadotropin; Clinical Enzyme Tests; Female; Humans; Isoenzymes; Male; Milk Proteins; Molecular Weight; Muramidase; Neoplasm Metastasis; Neoplasms; Nucleosides; Phosphoric Diester Hydrolases; Polyamines; Procollagen-Proline Dioxygenase; Sialyltransferases

Topics: Animals; Binding Sites; Breast Neoplasms; Cell Aggregation; Cell Movement; Cell Transformation, Neoplastic; Female; Humans; Iatrogenic Disease; Immunity; Immunoglobulin G; Immunosuppression Therapy; Lectins; Lymphocyte Activation; Macrophages; Mammary Neoplasms, Experimental; Muramidase; Neoplasms; Protein Binding; Rats; T-Lymphocytes; Thymus Gland

Topics: Acridines; Alkylating Agents; Base Sequence; Coliphages; DNA Replication; DNA Viruses; DNA, Viral; Escherichia coli; Genetic Code; Hemoglobins, Abnormal; Heterocyclic Compounds; Humans; Models, Chemical; Muramidase; Mutagens; Mutation; Neoplasms; Saccharomyces; Salmonella typhimurium; Transcription, Genetic

Topics: Acid Phosphatase; Alkaline Phosphatase; Amylases; Animals; Asparaginase; Body Fluids; Clinical Enzyme Tests; Enzyme Induction; Enzyme Therapy; Escherichia coli; Female; gamma-Glutamyltransferase; Glucuronidase; Humans; Isoenzymes; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Muramidase; Neoplasm Metastasis; Neoplasms; Nucleotidases

Topics: Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Drug Synergism; Hyperbaric Oxygenation; Muramidase; Neoplasms; Thyroid Hormones; Thyrotropin

Topics: Acid Phosphatase; Alkaline Phosphatase; Fructose-Bisphosphate Aldolase; Glucose-6-Phosphate Isomerase; Humans; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Leukemia; Liver Neoplasms; Mass Screening; Muramidase; Neoplasm Metastasis; Neoplasms; Nucleotidases; Phosphoglucomutase

Topics: Animals; Bacteria; Citric Acid Cycle; DNA; DNA Replication; Electron Transport; Endoplasmic Reticulum; Ions; Ligases; Membranes; Mitochondria; Mitochondrial Swelling; Muramidase; Neoplasms; Neuraminic Acids; Protein Biosynthesis; Ribosomes; RNA; RNA, Transfer; Viruses

The aim of this work was to study the evolution of neutrophil functions in non-neutropenic cancer patients. Thirty non-neutropenic patients, median age 35 years (range 19-52), with solid tumors (n = 21) or lymphomas (n = 9) entered a phase I study of five days of s.c. (n = 24) or i.v. bolus (n = 6) lenograstim, recombinant human glycosylated granulocyte colony-stimulating factor (rHuG-CSF Chugai-Rhône-Poulenc), with dose escalation from 1 to 40 micrograms/kg/day. Neutrophil functions were studied before lenograstim (D1) and 24 h after the last dose (D6). Granulocyte count rose in a significant way, and enzyme release, phagocytosis and bacterial killing were stimulated. All patients had improvement of at least one neutrophil function. Directed migration was depressed, although it was still in the normal range. These findings confirm that lenograstim is a potent activator of neutrophil functions in non-neutropenic cancer patients and may be useful as an adjunct to conventional antimicrobial therapy.

Topics: Adult; Cell Adhesion; Chemotaxis, Leukocyte; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Hodgkin Disease; Humans; In Vitro Techniques; Lenograstim; Leukocyte Count; Leukocyte Elastase; Lymphoma; Lymphoma, Non-Hodgkin; Male; Middle Aged; Muramidase; N-Formylmethionine Leucyl-Phenylalanine; Neoplasms; Neutrophils; Pancreatic Elastase; Phagocytosis; Recombinant Proteins

Karyomegalic interstitial nephropathy (KIN) has been reported as an incidental finding in patients with childhood cancer treated with ifosfamide. It is defined by the presence of tubular epithelial cells (TECs) with enlarged, irregular, and hyperchromatic nuclei. Cellular senescence has been proposed to be involved in kidney fibrosis in hereditary KIN patients. We report that KIN could be diagnosed 7-32 months after childhood cancer diagnosis in 6/6 consecutive patients biopsied for progressive chronic kidney disease (CKD) of unknown cause between 2018 and 2021. The morphometry of nuclear size distribution and markers for DNA damage (γH2AX), cell-cycle arrest (p21+, Ki67-), and nuclear lamina decay (loss of lamin B1), identified karyomegaly and senescence features in TECs. Polyploidy was assessed by chromosome fluorescence in situ hybridization (FISH). In all six patients the number of p21-positive TECs far exceeded the typically small numbers of truly karyomegalic cells, and p21-positive TECs contained less lysozyme, testifying to defective resorption, which explains the consistently observed low-molecular-weight (LMW) proteinuria. In addition, polyploidy of TEC was observed to correlate with loss of lysozyme staining. Importantly, in the five patients with the largest nuclei, the percentage of p21-positive TECs tightly correlated with estimated glomerular filtration rate loss between biopsy and last follow-up (R

Topics: Biopsy; Cellular Senescence; Child; Humans; Ifosfamide; In Situ Hybridization, Fluorescence; Kidney; Muramidase; Neoplasms; Nephritis, Interstitial; Polyploidy; Proteinuria; Renal Insufficiency, Chronic

To better understand the effects of PEGylation and biotinylation on the delivery efficiency of proteins, the cationic protein lysozyme (LZ) and anionic protein bovine serum albumin (BSA) were chemically conjugated with poly(ethylene glycol) (PEG) and biotin-PEG to primary amine groups of proteins using N-hydroxysuccinimide reactions. Four types of protein conjugates were successfully prepared: PEGylated LZ (PEG-LZ), PEGylated BSA (PEG-BSA), biotin-PEG-conjugated LZ (Bio-PEG-LZ), and biotin-PEG-conjugated BSA (Bio-PEG-BSA). PEG-LZ and Bio-PEG-LZ exhibited a lower intracellular uptake than that of LZ in A549 human lung cancer cells (in a two-dimensional culture). However, Bio-PEG-BSA showed significantly improved intracellular delivery as compared to that of PEG-BSA and BSA, probably because of favorable interactions with cells via biotin receptors. For A549/fibroblast coculture spheroids, PEG-LZ and PEG-BSA exhibited significantly decreased tissue penetration as compared with that of unmodified proteins. However, Bio-PEG-BSA showed tissue penetration comparable to that of unmodified BSA. In addition, citraconlyated LZ (Cit-LZ) showed reduced spheroid penetration as compared to that of LZ, probably owing to a decrease in protein charge. Taken together, chemical conjugation of targeting ligands-PEG to anionic proteins could be a promising strategy to improve intracellular delivery and in vivo activity, whereas modifications of cationic proteins should be more delicately designed.

Topics: Amines; Anions; Biotin; Biotinylation; Humans; Ligands; Muramidase; Neoplasms; Polyethylene Glycols; Serum Albumin, Bovine

The translation of nanocarrier-based theranostics into cancer treatment is limited by their poor cellular uptake, low drug-loading capacity, uncontrolled drug release, and insufficient imaging ability.. In this study, novel hybrid nanogels were fabricated as theranostic nanocarriers by modifying chitosan (CTS)/tripolyphosphate (TPP) nanoparticles (NPs) with polyacrylic acid (PAA) and further conjugating cysteine-functionalized gold nanoparticles (AuNPs).. The resultant nanogels, referred to as CTS/TPP/PAA@AuNPs (CTPA), exhibited excellent colloidal stability and a high encapsulation rate of 87% for the cationic drug doxorubicin (DOX). In the tumour microenvironment, the acidic pH and overexpression of lysozyme triggered CTPA@DOX to degrade and emit smaller nanoblocks (30-40 nm), which sequentially released the drug in a tumour-responsive manner. Cellular uptake experiments demonstrated that CTPA facilitates the entry of DOX into the cytoplasm. Furthermore, as visualised through AuNP-mediated computed tomography (CT) imaging, CTPA@DOX enabled favourable accumulation in the tumour. Our in vitro and in vivo data demonstrated that CTPA enabled advanced tumour cell-targeting delivery of DOX, which showed greater anti-tumour activity and biosafety than free DOX.. The natural polymer CTS was developed for degradable nanogels, which can precisely track drugs with high antitumour activity. Additionally, the surface adjustment strategy can be assembled to achieve cationic drug loading and high drug-loading capacity, controlled drug release, and sufficient imaging ability. Therefore, multifunctional CTPA enables efficient drug delivery and CT imaging, which is expected to provide a valuable strategy for designing advanced theranostic systems.

Topics: Chitosan; Cysteine; Doxorubicin; Drug Carriers; Gold; Humans; Hydrogen-Ion Concentration; Metal Nanoparticles; Muramidase; Nanogels; Nanoparticles; Neoplasms; Polymers; Precision Medicine; Theranostic Nanomedicine; Tomography, X-Ray Computed

Communicated by Ramaswamy H. Sarma.

Topics: Antineoplastic Agents; Biophysical Phenomena; Circular Dichroism; Flavanones; Humans; Muramidase; Neoplasms; Protein Binding; Spectrometry, Fluorescence

The assembly of protein-inorganic nanoparticles is an important yet challenging approach that is utilized to develop functional materials in numerous areas, such as bio-catalysis, drug delivery, and biosensing. In this study, we report on a facile, photo-inducible self-assembly method to generate protein-inorganic hybrid nanoplatforms. More specifically, photo-treated disulfide bond rich proteins of lysozyme (LYS) were able to be used as host materials in order to encapsulate nanoparticles (i.e., as-synthesized hydrophobic NIR quantum dots (QDs)) and anti-cancer small molecule drugs (i.e., paclitaxel (PTX)), constructing functional theranostic protein-inorganic hybrid nanoparticles. The modification of the functional polymer of cRGD-PEG contributes to the active tumour targeting characteristic of this protein-inorganic nanocarrier. This novel PTX loaded protein-inorganic hybrid nanoplatform showed high tumour homing accumulation as well as effective tumour inhibition. We believe that this general approach represents a new direction for the development of a photo-induced assembly of protein-inorganic nanoparticles towards versatile applications in both materials science and biomedical fields.

Topics: Animals; Cell Line, Tumor; Cell Survival; Drug Carriers; Humans; Male; Mice; Mice, Inbred BALB C; Microscopy, Atomic Force; Muramidase; Nanoparticles; Neoplasms; Oligopeptides; Paclitaxel; Polyethylene Glycols; Quantum Dots; Theranostic Nanomedicine; Tissue Distribution; Transplantation, Heterologous; Ultraviolet Rays

In this report, using NMR and molecular modeling, we have studied the structure of lysozyme-S100A6 complex and the influence of tranilast [N-(3, 4-dimethoxycinnamoyl) anthranilic acid], an antiallergic drug which binds to lysozyme, on lysozyme-S100A6 and S100A6-RAGE complex formation and, finally, on cell proliferation. We have found that tranilast may block the S100A6-lysozyme interaction and enhance binding of S100A6 to RAGE. Using WST1 assay, we have found that lysozyme, most probably by blocking the interaction between S100A6 and RAGE, inhibits cell proliferation while tranilast may reverse this effect by binding to lysozyme. In conclusion, studies presented in this work, describing the protein-protein/-drug interactions, are of great importance for designing new therapies to treat diseases associated with cell proliferation such as cancers.

Topics: Cell Cycle Proteins; Cell Proliferation; HCT116 Cells; Humans; Molecular Docking Simulation; Muramidase; Neoplasm Proteins; Neoplasms; ortho-Aminobenzoates; Protein Binding; Protein Domains; Receptor for Advanced Glycation End Products; S100 Calcium Binding Protein A6

ABIN1, an important immune regulator, has been shown to be involved in various cellular functions, such as immunity, development, tissue homeostasis, and tumor progression. It inhibits TNF- and TLR-induced NF-κB signaling activation and the consequent gene expression. Despite its functional significance, the mechanism of ABIN1 in the regulation of various cellular functions remains unclear. In this study, we identified HDAC1, a key regulator of eukaryotic gene expression and many important cellular events, including cell proliferation, differentiation, cancer and immunity, as an interacting partner of ABIN1. The results showed that ABIN1 acted as a modulator to down-regulate HDAC1 ubiquitination via three different linkages, thereby stabilizing HDAC1 by inhibiting its lysosomal and proteasomal degradation. Interestingly, the inhibitory function of ABIN1 required direct binding with HDAC1. Moreover, the level of p53, which was a tumor suppressor and a well-studied substrate of HDAC1, was under the regulation of ABIN1 via the modulation of HDAC1 levels, suggesting that ABIN1 was physiologically significant in tumor progression. This study has revealed a new function of ABIN1 in mediating HDAC1 modification and stability.

Topics: A549 Cells; Carcinoma, Hepatocellular; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Gene Knockout Techniques; HeLa Cells; Hep G2 Cells; Histone Deacetylase 1; Humans; K562 Cells; Liver Neoplasms; Lung Neoplasms; Muramidase; Neoplasms; Proteasome Endopeptidase Complex; Protein Stability; Tumor Suppressor Protein p53; Ubiquitination

Amalgamation of delivery and tracking of therapeutically relevant moieties on a single platform is made possible by the application of metal nanoclusters, an innovative class of luminescent nanomaterials. Metal nanoclusters, possessing molecule-like attributes, display extraordinary size and shape tunable properties befitting theranostic applications. Herein, we report successful assembly of therapeutically significant phosphatase protein PTEN and fluorescent lysozyme-stabilized silver nanoclusters to accomplish delivery and tracking of the protein. Down-regulation of PTEN perturbs the cellular networking leading to copious pathological conditions. The integration of purified recombinant PTEN with silver nanoclusters was evaluated by fluorescence spectroscopy study. A key feature of this study is the use of polyethylene glycol coating that allows fabrication of the assembly into spherical nanocomposites as characterized by transmission electron microscope along with retention of both optical functionality of the cluster and biological activity of the protein. Prior to cellular application, the functional integrity of PTEN in the composite was determined in vitro, by enzymatic assay employing para-nitrophenylphosphate as substrate. Cellular internalization of the cargo was studied by confocal microscopy and flow cytometry analysis. The efficacy of the payload on modulation of cellular signaling was assessed on cell lines that expressed PTEN differentially. PTEN null U-87 MG and PTEN expressing MCF7 cell lines displayed successful alteration of AKT and FAK signaling proteins culminating in cell cycle arrest and reduced wound healing capacity. A dose dependent reduction in cell proliferation of MCF7 cells was achieved. For U-87 MG, treatment with the payload resulted in chemosensitization toward anti-cancer drug erlotinib. Thus, PEG coated GST-PTEN loaded silver nanoclusters serves as a comprehensive system encompassing cellular imaging and protein delivery with potential biomedical implications.

Topics: Antineoplastic Agents; Cell Proliferation; Disease Transmission, Infectious; Erlotinib Hydrochloride; Flow Cytometry; Humans; MCF-7 Cells; Microscopy, Confocal; Models, Biological; Muramidase; Neoplasms; PTEN Phosphohydrolase; Silver; Spectrometry, Fluorescence; Theranostic Nanomedicine

Background. The purpose of this study is to understand the oral mucosal immune status of cancer patients and to make clear whether antibacterial proteins such as salivary secretory immunoglobulin (SIgA) and lysozyme in saliva were influenced by patients' health status and certain medical treatment therapy. Materials and Methods. This study included 221 patients with malignant tumor receiving antineoplastic treatment and 171 age- and gender-matched healthy controls. Results. The results showed that patients suffering malignant tumor had lower level of SIgA and higher level of lysozyme than healthy subjects (P < 0.05). The SIgA level was significantly different among different cancer tumors, while the lysozyme level showed significant difference only between patients with digestive tract malignant tumor and hematopoietic system tumor. Pretreatment before transplantation for hematopoietic system tumor patients significantly affected the lysozyme level other than SIgA. SIgA level was affected by many factors such as age, therapy factors, and oral hygiene. Conclusion. Malignant tumor and the antineoplaston may weaken the patients' oral mucosal immunity, influence levels of some salivary proteins, and decrease the level of SIgA, resulting in aggregation of oral bacteria and failure of clearing them from the oral cavity.

Topics: Adult; Case-Control Studies; Female; Humans; Immunoglobulin A, Secretory; Male; Middle Aged; Muramidase; Neoplasms; Saliva

Boron clusters represent a vast family of boron-rich compounds with extraordinary properties that provide the opportunity of exploitation in different areas of chemistry and biology. In addition, boron clusters are clinically used in boron neutron capture therapy (BNCT) of tumors. In this paper, a novel, in solid state (solvent free), thermal method for protein modification with boron clusters has been proposed.. The method is based on a cyclic ether ring opening in oxonium adduct of cyclic ether and a boron cluster with nucleophilic centers of the protein. Lysozyme was used as the model protein, and the physicochemical and biological properties of the obtained conjugates were characterized.. The main residues of modification were identified as arginine-128 and threonine-51. No significant changes in the secondary or tertiary structures of the protein after tethering of the boron cluster were found using mass spectrometry and circular dichroism measurements. However, some changes in the intermolecular interactions and hydrodynamic and catalytic properties were observed.. To the best of our knowledge, we have described the first example of an application of cyclic ether ring opening in the oxonium adducts of a boron cluster for protein modification. In addition, a distinctive feature of the proposed approach is performing the reaction in solid state and at elevated temperature.. The proposed methodology provides a new route to protein modification with boron clusters and extends the range of innovative molecules available for biological and medical testing.

Topics: Boron; Boron Compounds; Boron Neutron Capture Therapy; Catalysis; Muramidase; Neoplasms

Iminoboronates have been utilized to successfully install azide and alkyne bioorthogonal functions on proteins, which may then be further reacted with their bioorthogonal counterparts. These constructs were also used to add polyethylene glycol (PEG) to insulin, a modification which has been shown to be reversible in the presence of fructose. Finally, iminoboronates were used to assemble a folic acid/paclitaxel small-molecule/drug conjugate in situ with an IC50  value of 20.7 nM against NCI-H460 cancer cells and negligible cytotoxicity against the CRL-1502 noncancer cells.

Topics: Alkynes; Animals; Antineoplastic Agents, Phytogenic; Azides; Boronic Acids; Cell Line; Cell Line, Tumor; Folic Acid; Humans; Imines; Insulin; Lysine; Models, Molecular; Muramidase; Neoplasms; Paclitaxel; Polyethylene Glycols; Proteins

Advanced materials that have controllable pH-responsive properties when submerged in the lysosome have a great potential in intracellular drug delivery. We developed novel poly(L-amino acid) nanogels that were prepared by a facile cross-linking of poly[L-aspartic acid-g-(3-diethylaminopropyl)]-b-poly(ethylene glycol)-maleimide [poly(L-Asp-g-DEAP)-b-PEG-Mal] and poly(L-aspartic acid-g-ethyl thiol)-b-PEG [poly(L-Asp-SH)-b-PEG] in an oil/water emulsion condition. Interestingly, these nanogels (~125 nm in diameter) modulated volume expansion (~375 nm in diameter) in a lysosomal pH (~pH 5.0) due to an extensive proton absorption of DEAP at a low pH, which mediated lysosome swelling and the subsequent lysosome destabilization. In the in vitro tumor cell cytotoxicity test, they encouraged tumor cell death, probably owing to the leakage of lysosomal enzymes. Furthermore, encapsulating antitumor drug (e.g., doxorubicin, DOX) into these nanogels enhanced tumor cell cytotoxicity. We conclude that this nanogel system will have great potential for tumor therapy.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Doxycycline; Drug Carriers; Drug Delivery Systems; Female; Gels; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Confocal; Microscopy, Fluorescence; Muramidase; Nanostructures; Neoplasm Transplantation; Neoplasms; Ovarian Neoplasms; Peptides

The antibody-mediated targeted delivery of cytokines, growth factors and immunomodulators offers great potential for the therapy of cancer and other serious conditions. Interferon-alpha has long been used in the clinic for the treatment of patients with certain malignancies or with viral disease. Promising anticancer activity has recently been reported for two fusion proteins consisting of immunoglobulins bearing the interferon-alpha polypeptide at the C-terminal end of the molecule. Here we describe the design, production and characterization of a novel immunocytokine, in which murine interferon-alpha2 was sequentially fused with the tumor-targeting antibody fragment scFv(F8), specific to the alternatively-spliced EDA domain of fibronectin. The resulting fusion protein (F8-IFNa) could be produced to homogeneity and was shown to retain both antigen binding activity and interferon-alpha activity. Biodistribution studies in tumor-bearing mice with radioiodinated protein preparations confirmed the ability of F8-IFNa to selectively localize at the tumor site. However, using two different murine models of cancer (F9 teratocarcinomas and Cloudman S91 melanomas in immunocompetent mice), we could not detect a striking superiority for the therapeutic performance of F8-IFNa as compared to KSF-IFNa, a fusion protein of irrelevant specificity in the mouse which was used as negative control. In the paper, we present hypotheses why the antibody-based pharmacodelivery of interferon-alpha fails to eradicate tumors, in contrast to the situation observed by our group for other immunocytokines, which benefit from a selective localization at the tumor site.

Topics: Animal Structures; Animals; Antineoplastic Agents; Blood Vessels; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Fibronectins; Humans; Immunoconjugates; Interferon-alpha; Leukocytes, Mononuclear; Melanoma; Mice; Mice, 129 Strain; Muramidase; Neoplasms; Neovascularization, Pathologic; Recombinant Fusion Proteins; Single-Chain Antibodies; Teratocarcinoma; Tissue Distribution; Treatment Outcome

Developing new technologies applicable to the sensitive detection of cancer in its early stages has always been attractive in diagnosis. A stable gold nanoparticle layer (GNPL)-modified high-binding ELISA plate was obtained via chemical plating and was proven to be more efficient in binding proteins while maintaining their activity. GNPL-based ELISA for the representative biomarker carcinoembryonic antigen (CEA) demonstrated that GNPL markedly amplified the ELISA signal and significantly improved the limit of detection (LOD). Antithrombin detection further confirms the effectiveness and universality of this GNPL-based platform. The entire assay procedure is simple and low in cost and does not require special facilities. All these virtues indicate that this GNPL platform holds great promise in clinical applications for the early diagnosis of cancer.

Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Enzyme-Linked Immunosorbent Assay; Fibrinogen; Gold; Humans; Metal Nanoparticles; Muramidase; Neoplasms; Serum Albumin

Recent studies suggest that lysozyme, rich in hen egg, has an antitumor function. In the present study, we investigated the antitumor and antiangiogenesis effects of a newly isolated marine lysozyme both in vitro and in vivo. First, we showed that this marine-derived lysozyme specifically inhibits the proliferation of endothelial cells (ECV304) in a dose-dependent manner with no cytotoxicity (IC(50) = 3.64 microM). Second, we showed that this marine lysozyme directly suppresses neovascularization in chicken embryos using chorioallantoic membrane assay. Third, we demonstrated that this marine lysozyme markedly inhibits tumor growth in mice bearing either sarcoma 180 or hepatoma 22. Unexpectedly, hen egg lysozyme has no effects on the proliferation of endothelial cells in vitro or neovascularization in chicken embryos or tumor growth in nude mice at the same dosage range. Taken together, our studies clearly show that the newly identified marine lysozyme is a potent antitumor molecule, which may inhibit tumor growth and inhibit angiogenesis. We believe that this marine lysozyme may have a therapeutic value in antitumor drug development.

Topics: Angiogenesis Inhibitors; Animals; Antibiotics, Antineoplastic; Bacillus; Cell Line, Tumor; Cell Proliferation; Chick Embryo; Chorioallantoic Membrane; Dose-Response Relationship, Drug; Endothelial Cells; Female; Mice; Muramidase; Neoplasms; Neovascularization, Physiologic; Seawater; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Paclitaxel (Taxol)-containing chitin and chitin-Pluronic F-108 microparticles were formulated as biodegradable systems for localized administration in solid tumors. The microparticles were characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and swelling studies in phosphate-buffered saline (PBS, pH 7.4). Lysozyme-induced degradation and in vitro release of paclitaxel was examined in PBS at 37 degrees C. The percent change in tumor volume was used to assess efficacy of the Formulations after local administration in murine Lewis lung carcinoma model. FT-IR confirmed higher degree of acetylation in chitin microparticles from the starting chitosan sample and the SEM showed that the chitin-Pluronic F-108 microparticles were significantly more porous than chitin microparticles. Due to higher porosity, chitin-Pluronic microparticles were able to imbibe higher swelling medium and degraded much faster in the presence of lysozyme than chitin microparticles. After 48 h. 51% of incorporated paclitaxel was released from chitin-Pluronic microparticles as compared to 28% from chitin microparticles. In vivo studies in Lewis lung carcinoma-bearing mice showed that the tumor volumes after 6 days using paclitaxel-loaded chitin and chitin-Pluronic F-108 microparticles was 458 and 307 mm3, respectively. In contrast, the tumor volume was 997 mm3 for the untreated control. The results of this study show that chitin and chitin-Pluronic F-108 microparticles are biodegradable drug delivery systems that can be useful for localized delivery of paclitaxel in solid tumors.

Topics: Acetylglucosamine; Animals; Antineoplastic Agents, Phytogenic; Biocompatible Materials; Biodegradation, Environmental; Chitin; Drug Delivery Systems; Female; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Microspheres; Muramidase; Neoplasms; Neoplasms, Experimental; Paclitaxel; Poloxamer; Rats; Spectroscopy, Fourier Transform Infrared; Surface-Active Agents; Temperature; Time Factors; Tumor Cells, Cultured

The mouse tag7 gene was cloned and characterized in our previous works. This work is devoted to identifying and cloning its homologs. The human homolog of the tag7 gene was cloned. Data of analysis of the primary structure of the human tag7 and results from the study of the production of the corresponding protein in human organs and tissues indicate that this gene plays a major role in the mammalian immune system. The mouse and human tagL gene carrying an extended region of structural homology with the tag7 gene was detected by computer analysis and was subsequently cloned. Sequence analysis suggested the possible membrane localization of the gene, whereas the specific expression pointed to the role of this gene in the immune system. Both genes, tag7 and tagL, were localized in the human chromosome 19.

Topics: Amino Acid Sequence; Animals; Bacteriophage T7; Base Sequence; Blotting, Northern; Blotting, Southern; Cloning, Molecular; Cytokines; Humans; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Molecular Sequence Data; Muramidase; N-Acetylmuramoyl-L-alanine Amidase; Neoplasms; Organ Specificity; Proteins; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Tumor Cells, Cultured

Expression of tissue- and development-specific genes is coordinately regulated during maturation of hematopoietic precursor cells toward functional, end-stage peripheral blood (PB) cells. To study the expression and methylation of several myeloid-specific genes during in vitro differentiation of normal hematopoietic progenitor cells, we used a model of CD34+ selected PB progenitor cells (PBPCs). PBPCs from six patients with solid tumors were recruited by standard-dose chemotherapy and subsequent administration of recombinant granulocyte colony-stimulating factor (G-CSF). PBPCs were collected and CD34+ cells selected by immunoadsorption columns using a biotinylated anti-CD34 monoclonal antibody. Enriched cells contained between 78% and 90% (median, 84%) CD34+ cells as determined by fluorescence-activated cell sorting analysis. Cell preparations were cultured in the presence of interleukin-1 beta (IL-1 beta), IL-3, IL-6 and stem cell factor and with or without G-CSF for various time intervals up to 20 days. Genes for CD34 surface antigen, lysozyme (LZM) and myeloperoxidase (MPO) were examined by RNA and DNA analyses. A rapid and early downregulation of CD34 transcripts was observed, with concomitant, time-dependent upregulation of expression of both the LZM and MPO genes. These effects were enhanced in the presence of G-CSF. Analysis of the DNA methylation status at key sites within these genes showed a pattern of differentiation- and expression-associated demethylation of the LZM gene, which was also enhanced by G-CSF, and constitutive and unaltered demethylation at key regions of the CD34 and MPO genes. In conclusion, the genes for CD34, LZM, and MPO are regulated during in vitro culture of very immature PBPCs in the presence of stem cell factor, IL-1, IL-3, IL-6; their effects are enhanced by G-CSF.

Topics: Antigens, CD34; Biomarkers; Cell Differentiation; Cells, Cultured; DNA; DNA (Cytosine-5-)-Methyltransferases; Gene Expression Regulation, Developmental; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Interleukins; Methylation; Muramidase; Neoplasms; Peroxidase; Recombinant Proteins; Stem Cell Factor

To date, the diagnosis of mast cell disease (MCD) relied on routine plus histochemical stains. Its differential diagnosis, however, includes a variety of other hematopoietic and particularly B-cell lymphoid neoplasms that are best identified in paraffin sections using immunostains. To determine the paraffin-section immunoreactivity of MCD, 20 specimens from 14 patients with MCD and 1 bone marrow sample (from a patient with probable MCD) that showed equivocal metachromasia, were stained with antitryptase, CD68 (KP-1), CD20 (L26), antilysozyme, and antimyeloperoxidase antibodies. Ten hairy cell leukemias (HCLs), six lymphomas of parafollicular and/or monocytoid B-cell (MBCLs) and low-grade mucosa-associated lymphoid tissue (MALT) types, six granulocytic sarcomas, and five acute myeloid leukemias with monocytic differentiation (M4 and M5 types) were also stained. Tryptase positivity was identified in all of the MCD cases. The staining was moderate to strong in 20 of the 21 specimens, including the probable MCD case. No other neoplasms tested were tryptase positive. CD68 showed similar to even stronger staining in all of the specimens of MCD, HCL, granulocytic sarcoma, and acute myeloid leukemia (M4 and M5 types) tested and in five of the six MBCL and/or MALT-type lymphomas. Weak-to-moderate lysozyme staining seemed to be present in at least 7 of the MCD specimens, whereas there was a lack of staining for myeloperoxidase in 12 specimens, and 7 specimens were nonevaluable (1 case was not tested). Myeloperoxidase was identified in all of the granulocytic sarcomas and acute myeloid leukemias (M4 and M5 types) but not in any HCLs, MBCLs, or low-grade lymphomas of MALT type. CD20 was negative in all of the MCD and myelomonocytic neoplasms but positive in all of the HCLs, MBCLs, and low-grade B-cell lymphomas of MALT type. MCD, therefore, has a characteristic tryptase-positive, CD68-positive, and CD20-negative phenotype in paraffin sections. This distinguishes MCD from the hematopoietic and/or lymphoid disorders that it most closely resembles.

Topics: Antibodies, Monoclonal; Antigens, CD; Antigens, CD20; Antigens, Differentiation, Myelomonocytic; Bone Marrow; Chymases; Humans; Immunoenzyme Techniques; Leukemia; Liver; Lymph Nodes; Lymphoma; Mast Cells; Mastocytosis; Microtomy; Muramidase; Neoplasms; Paraffin Embedding; Peroxidase; Serine Endopeptidases; Skin; Tryptases

Lysozyme, a bacteriolytic protein discovered by Fleming in 1922 and found to be phylogenetically ancient and almost ubiquitous among living organisms, is probably the most studied enzyme in biology and medicine. Evidence of its involvement in resistance to bacterial infection is compelling but remains indirect. Muramyl peptides (fragments of bacterial cell wall peptidoglycan) exert many effects on the immune system and the CNS, and appear to contribute to non-specific resistance to infection, fever, fatigue, and the pathogenesis of bacterial infection. Synthetic muramyl peptide analogues are currently used as adjuvants in vaccine trials in humans. Several pathological conditions are associated with changes in lysozyme concentrations, and egg-white lysozyme treatment has been tried on a small scale. With the cloning of the human lysozyme gene in yeast cells the enzyme can now be produced on a large scale, which will enable its therapeutic applications to be evaluated.

Topics: Bacterial Infections; History, 20th Century; Humans; Muramidase; Neoplasms

Topics: Humans; Inflammation; Muramidase; Neoplasms; Neutrophils

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Immunohistochemistry; Macrophages; Muramidase; Neoplasms

Topics: Biological Assay; Humans; Leukocyte Count; Muramidase; Neoplasms; Nephelometry and Turbidimetry; Neutrophils; Reference Values

Topics: Clinical Enzyme Tests; Diagnosis, Differential; Humans; Muramidase; Neoplasms; Pleural Effusion; Predictive Value of Tests; Tuberculosis, Pleural

Topics: Adult; Aged; Clinical Enzyme Tests; Diagnosis, Differential; Female; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Muramidase; Neoplasms; Pleural Effusion; Tuberculosis, Pleural

Serum lysozyme activity (SLA) was measured in a turbidimetric assay with a microcentrifugal analyzer. In a control group of 53 healthy dogs of both sexes and ranging in age from 4 to 10 years, SLA had a mean value of 1.2 mg/l with a range (+/- 2 SD) of 0.6 - 1.8 mg/l. In 80 dogs with a variety of neoplastic diseases the histopathological diagnosis was compared with the SLA value. SLA value was increased in 83% of the cases with malignant tumors and in 29% of the cases with benign tumors. Proper clinical examination is essential in differentiating between neoplastic disease and some interfering diseases, e.g. chronic dermatitis, pyometra and chronic nephritis. Measuring of SLA in dogs may be helpful in screening those animals with suspected malignancies.

Topics: Adenoma; Animals; Carcinoma; Dog Diseases; Dogs; Female; Immunodiffusion; Male; Mammary Glands, Animal; Melanoma; Muramidase; Neoplasms; Nephelometry and Turbidimetry; Reference Values; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms

Topics: Adult; Aged; Ascitic Fluid; Female; Heart Failure; Humans; Lung Diseases; Male; Middle Aged; Muramidase; Neoplasms; Pleural Effusion

Serum lysozyme activity was measured in samples from 65 children with acute lymphatic and myelogenous leukemia, solid tumors and malignant lymphoma in comparison with 45 healthy children. All children with acute lymphatic leukemia (ALL) had significantly reduced levels of lysozyme before starting therapy compared with a control group (p less than 0,01). Children with ALL in complete remission had lysozyme levels comparable to normal children, while children with ALL in relapse showed pathological low levels again. Children with acute myelogenous leukemia (AML), solid tumors and malignant lymphomas had higher lysozyme concentration before therapy than healthy children. Determination of lysozyme activity in children with acute leukemia and malignant tumors is of value for diagnosis and to control the effect of therapy.

Topics: Child; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Muramidase; Neoplasms

Topics: Female; Humans; Muramidase; Neoplasms; Neutrophils

Using the peroxidase antiperoxidase (PAP) method, lysozyme (LZM) was shown to exist in normal, reactive and neoplastic cells belonging to the mononuclear phagocyte system (MPS), but was not detected in histiocytosis X cells. Immunostaining for cytoplasmic LZM by the PAP method is useful for identification of mononuclear phagocytes and for diagnosis of the diseases in which these cells participate.

Topics: Granulomatosis with Polyangiitis; Histiocytes; Hodgkin Disease; Humans; Immunoenzyme Techniques; Inflammation; Leukemia, Myeloid; Lymphadenitis; Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Mononuclear Phagocyte System; Muramidase; Neoplasms

Lysozyme and alpha 1-antichymotrypsin are useful in differentiation of histiocytic tumours. Both enzymes, however, also can be expressed in epithelial tissues. In contrast to lysozyme, alpha 1-antichymotrypsin is more often found to be positive in non-histiocytic neoplasias. In general, the activity of parent tissue is retained in tumour cells. In malignant melanoma and in single cases of other epithelial tumours an activity of alpha 1-antichymotrypsin was found which could not be demonstrated in normal parent tissue and which may find its explanation in a dedifferentiation of tumour cells.

Topics: alpha 1-Antichymotrypsin; Chymotrypsin; Epithelium; Histiocytes; Humans; Muramidase; Neoplasms

In a control group of fifty-three clinically healthy dogs of either sex and ranging in age from four to ten years, the serum lysozyme activity (SLA) showed a mean value of 1.2 mg/l with a range (+/- 2 SD) of 0.6-1.8 mg/l. SLA was measured in a turbidimetric assay using a microcentrifugal analyser. In dogs with a variety of neoplastic diseases, the histopathological diagnosis was compared with the SLA-level. In a large number of cases, the increased SLA-levels corresponded with malignancy in neoplastic disease. Measuring the SLA-level in dogs may be helpful in the diagnosis of malignancies. Proper clinical examination is essential in differentiating between some interfering diseases.

Topics: Animals; Dog Diseases; Dogs; Female; Muramidase; Neoplasms; Nephelometry and Turbidimetry

General immunobiologic studies in cancer patients have stressed measurements of lymphocyte function and have commonly ignored the monocyte-macrophage system. A preliminary study of peripheral blood monocyte-macrophage function was undertaken in a group of 90 cancer patients (18 breast, 32 colon, 13 head and neck, 9 lung, and 18 melanoma) and 70 controls. Studies included enumeration of extractible monocytes (EM), quantitation of differentiation into macrophages (macrophage precursor test: MP), evaluation of antibody-dependent cellular cytotoxicity (ADCC), and spontaneous cellular cytotoxicity (SCC) as measured with human erythrocytes, and measurements of monocyte and serum lysozyme activity. Breast cancer patients had normal profiles. Colon cancer patients showed the most profound abnormalities with decreased EM and MP and increased ADCC and SCC. Patients with Stage I and Stage II melanoma had normal profiles, whereas those with advanced melanoma had significantly decreased MP. This defect was restored in two patients by BCG immunotherapy. Head and neck cancer and benign breast disease patients had decreased EM, whereas patients with lung cancer had increased EM. Monocyte lysozyme production was unchanged in the cancer patients compared to controls. Serum lysozyme levels, however, were significantly increased in patients with cancers of the colon, head and neck, and lung. Although patients with localized breast cancer and melanoma had normal levels, these were increased in both patient groups with advanced disease. It would appear that the source of the increased serum lysozyme is probably not the peripheral blood monocytes, but could have originated in the intra-tumoral or tissue-bound macrophages which were not examined. Selected assays of peripheral blood monocyte function were deranged in certain types of cancer patients but were fully normal in others, and did not show consistent correlations with tumor type or stage. Tissue-bound or intra-tumoral macrophages might provide a more fruitful area for study in these disease categories.

Topics: Adult; Antibody-Dependent Cell Cytotoxicity; Cytotoxicity, Immunologic; Humans; Leukocyte Count; Middle Aged; Monocytes; Muramidase; Neoplasms

Topics: Animals; Ascitic Fluid; Female; Lymphocytes; Macrophages; Male; Mice; Mice, Inbred BALB C; Muramidase; Neoplasms; Peroxidases; Phosphodiesterase I; Phosphoric Diester Hydrolases; Phytohemagglutinins; Rats; Rats, Inbred Lew

The following enzyme activities were measured in cell lysates and supernatants from mouse peritoneal macrophages incubated with products of cultured tumour and other cells: acid phosphatase, beta-D-glucuronidase, N-acetyl-D-glucosaminidase, muramidase (lysozyme), lactic dehydrogenase (supernatant only) and plasminogen activator (supernatant only). There were no noteworthy changes in enzyme activities. Hydrogen peroxide production by appropriately stimulated mouse and/or guinea-pig peritoneal exudate macrophages was variably inhibited by supernatants from some tumour cells and some normal cells. Changes in these biochemical activities of macrophages do not appear to be closely related to the anti-inflammatory activity of tumour cell products.

Topics: Animals; Cell Line; Cells, Cultured; Female; Hydrogen Peroxide; Hydrolases; L-Lactate Dehydrogenase; Macrophage Activation; Macrophages; Male; Mice; Muramidase; Neoplasms; Plasminogen Activators

Forty-five human malignant tumours and three benign lesions were stained histochemically for non-specific esterase (NSE) and acid phosphatase (AP), and immunohistochemically for lysozyme. Most of the tumours contained small numbers of lysozyme positive macrophages (LPM), but colonic tumours showed moderate numbers of LPM around the edge of the lesions. Gastric and secondary duodenal tumours (n = 3) contained moderate numbers of intralesional LPM in addition. Most squamous and all mesenchymal tumours contained no lysozyme positive macrophages. The usefulness of the three staining methods was assessed and it was concluded that lysozyme was specific but detected only part of the macrophage population. Neutrophil polymorphs were also stained but could be recognised by nuclear morphology. AP and NSE detected more cells but stained tumour cells as well as macrophages, making these methods of limited use in tumours showing invasion of the stroma by single cells or small groups of cells.

Topics: Acid Phosphatase; Breast Neoplasms; Cell Count; Esterases; Female; Gastrointestinal Neoplasms; Humans; Immunoenzyme Techniques; Macrophages; Male; Muramidase; Neoplasms

The lysozyme (muramidase) activity was measured in the sera of 84 dogs with neoplastic disease. Neoplasms included 32 lymphomas, 13 primary bone neoplasms, 5 melanomas, 5 thyroid neoplasms, 9 soft tissue sarcomas, 5 mast cell sarcomas, and 15 carcinomas. The sera from 21 healthy dogs served as control. Dogs with neoplastic disease had significantly (P less than 0.005) higher serum lysozyme activity than did the healthy controls. For lymphosarcoma, dogs with clinical signs of systemic disease had significantly higher serum lysozyme activity than did dogs without clinical signs. For bone neoplasms, dogs with metastatic disease had higher serum lysozyme activity than did dogs without metastasis. Increased lysozyme activity may be a useful marker of macrophage-mediated host responses to neoplasms in dogs.

Topics: Animals; Bone Neoplasms; Dog Diseases; Dogs; Lymphoma; Mast-Cell Sarcoma; Muramidase; Neoplasms; Sarcoma; Thyroid Neoplasms

The effects of active nonspecific immunotherapy were studied in 42 patients receiving daily iv Corynebacterium parvum at 2 mg/m2 in 14-day courses and in 14 patients receiving iv methanol extraction residue of BCG (MER) at 0.5 mg/m2 weekly. The host defense evaluations included measurement of the number of adherent macrophage precursors per milliliter of blood (monocyte adherence), serum lysozyme, and antibody-dependent cell-mediated cytotoxicity (ADCC) of peripheral blood mononuclear cells to chicken red blood cells (CRBC) or human red blood cells (HRBC). During a single course of C. parvum, monocyte adherence did not rise significantly, whereas ADCC of peripheral blood mononuclear cells to CRBC and HRBC rose significantly (15.7-49.9% and 34.8-53.5% lysis of target cells, respectively). However, after a mean of 4.5 months on therapy, monocyte adherence increased an average of 7.5-fold. During weekly MER therapy, monocyte adherence, serum lysozyme, and ADCC of peripheral blood mononuclear cells to CRBC rose significantly within 4-7 days after the first dose (3.8-8.7 adherent cells/ml blood x 10(4), 7.6-10.8 microgram, and 34.4-41.4% target cell lysis, respectively). The host defense parameter, which was subnormal in the cancer patients (monocyte adherence), was boosted into the normal range in all the deficient patients by iv MER. The host defense parameters, which were normal or slightly elevated in the patients before therapy (serum lysozyme and ADCC of peripheral blood mononuclear cells to CRBC and HRBC), were hyperactivated above the upper limit of the normal range in 71.4, 71.4, and 50% of the patients, respectively, by iv MER. These methods can quantitatively reflect activation of monocytes and killer cells by C. parvum and MER and may be useful for evaluation and quantitation of both active nonspecific and immunorestorative immunotherapy in general.

Topics: Adult; Antibody-Dependent Cell Cytotoxicity; Bacterial Vaccines; BCG Vaccine; Humans; Immune Adherence Reaction; Injections, Intravenous; Lymphocytes; Monocytes; Muramidase; Neoplasms; Propionibacterium acnes

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Kenya; Leprosy; Male; Middle Aged; Muramidase; Neoplasms

Serum lysozyme has been demonstrated to be an indicator for macrophage activity in the tumor-bearing host. Therefore, we investigated lysozyme levels in the sera of 336 untreated tumor patients (121 malignant melanoma, 61 lung cancers, 70 cervical cancers, 49 breast cancers and 35 benign breast tumors, and 36 healthy controls). Patients with malignant melanoma and lung cancer had significantly higher lysozyme levels than the healthy controls. Within the clinical stages in melanoma, there was a decrease of lysozyme in stages II and III in comparison to stage I, but still above that of the control values. Patients with benign breast tumors had normal levels, whereas in breast cancer patients of stages I and II there was a significant reduction in the lysozyme levels. In stages III and IV no differences to the control group could be detected. In patients with cervical cancer (FIGO II and III) serum lysozyme levels were found to be within the normal range. From this study it can not be concluded that serum lysozyme reflects the immunological reactivity of the tumor bearer. Nevertheless, the reduced levels in stages I and II of breast cancer might point to an immunological defect.

Topics: Breast Neoplasms; Female; Humans; Lung Neoplasms; Melanoma; Muramidase; Neoplasms; Uterine Cervical Neoplasms

Topics: Antibody Specificity; Autoantibodies; Cell Nucleus; Complement C3; Complement C4; Female; Humans; Immunity; Muramidase; Neoplasms; Organ Specificity; Radiotherapy; Rheumatoid Factor; Time Factors

The present studies were performed in order to evaluate monocyte function in patients with solid neoplasms before and after administration of C. parvum. The results demonstrate that monocytes from cancer patients display increased numbers of C3 and Fc receptor sites after administration of C. parvum. It is concluded that characterization of monocyte receptor activity may be helpful in monitoring the effects of immunotherapy in the immune system.

Topics: Chemotaxis, Leukocyte; Complement C3; Female; Humans; Immunoglobulin Fc Fragments; Immunotherapy; In Vitro Techniques; Male; Monocytes; Muramidase; Neoplasms; Propionibacterium acnes

Topics: Antineoplastic Agents; Bone Marrow; Bone Neoplasms; Breast Neoplasms; Drug Therapy, Combination; Granulocytes; Humans; Leukocyte Count; Muramidase; Neoplasm Metastasis; Neoplasms; Neutrophils

A reliable immunoperoxidase schedule for the cellular demonstration of tumour and normal cell products which can be completed in well under two hours is described. The preparations are as clear and readable as those stained by routine histological techniques and should form a valuable adjunct in research and diagnostic studies.

Topics: alpha 1-Antitrypsin; Calcitonin; Carcinoembryonic Antigen; Hepatitis B Antigens; Hormones; Humans; Immunoenzyme Techniques; Immunoglobulins; Muramidase; Neoplasms

Urinary and serum proteins were studied in 55 patients with extrarenal epithelial carcinoma, using an automated immunopreciptin reaction. The 24 h excretion and renal clearance of 6 high molecular weight proteins: albumin, transferrin, haptoglobin, IgG, IgA, and IgM were significantly increased compared with a control group, implying a glomerular injury. The 24 h excretion of 4 low molecular weight proteins: free lambda and kappa light chains of immunoglobulin, lysozyme, and beta2-microglobulin was significantly increased in patients with disseminated carcinoma compared with patients with localized carcinoma. The serum concentrations of albumin and transferrin were significantly decreased and the serum concentration of haptoglobin significantly increased in patients with disseminated carcinoma compared with patients with localized tumours.

Topics: Adult; Aged; Albuminuria; beta 2-Microglobulin; Blood Proteins; Female; Haptoglobins; Humans; Immunoglobulins; Male; Middle Aged; Muramidase; Neoplasms; Proteinuria; Transferrin

Intracytoplasmic lysozyme (muramidase) may be readily identified in paraffin sections of tissues fixed in formalin or Zenker's acetic acid and in smears of peripheral blood or bone marrow using an immunoperoxidase technique. Sites of intracellular lysozyme in normal human tissues and in various specimens from patients with myeloproliferative and lymphoproliferative disorders, hairy cell leukemia, granulomatous diseases, toxoplasmic lymphadenitis, and other pathologic processes were defined by this method. Intracellular lysozyme was demonstrated in mature and immature neutrophilic and eosinophilic myeloid cells, in monocytic cells, and in some types of histiocytes and had a limited distribution in normal tissues. The neoplastic cells of hairy cell leukemia were devoid of intracytoplasmic lysozyme. Identification of intracellular lysozyme, as determined by the immunoperoxidase technique, was compared with various cytochemical methods, particularly chloroacetate esterase and alpha-naphthyl butyrate esterase studies, for detection and characterization of myeloid cells, monocytes, and histiocytes.

Topics: Eosinophils; Esterases; Granuloma; Histiocytes; Humans; Immunoenzyme Techniques; Leukemia, Hairy Cell; Lymphadenitis; Monocytes; Muramidase; Myeloproliferative Disorders; Neoplasms; Neutrophils; Tissue Distribution; Toxoplasmosis

Topics: Acid Phosphatase; Clinical Enzyme Tests; Humans; L-Lactate Dehydrogenase; Leukemia; Liver Neoplasms; Muramidase; Neoplasms

Infusion of cycloheximide i.v., an antibiotic known to inhibit synthesis of protein, at a rate of 0.2 mg/kg/hr, reliably caused lysis of fever in 15 chronically febrile patients with Hodgkin's disease who did not have detectable bacterial, fungal, or viral infection. Antipyretic effects were also seen in some patients with reticulum cell sarcoma, lymphosarcoma, acute leukemia, histiocytic medullary reticulosis, plasma cell myeloma, carcinoma of the lung, and carcinoma of the cervix. The drug failed to produce defervescence in four patients with normal granulocyte reserves, who were febrile due to bacterial infection. When infused at a rate of 0.2 mg/kg/hr, the drug apparently caused an acute alteration of protein metabolism in man in that plasma amino acid nitrogen rose acutely while plasma levels of muramidase and ribonuclease fell during the period of the infusion. The data suggest that continuing synthesis of protein may be involved in nonbacterial fever of neoplastic disease. Mammalian granulocytes and monocytes are known to elaborate a pyrogenic protein following appropriate stimulation; it is suggested that in some types of neoplastic disease, particularly Hodgkin's disease, tumor cells may produce and release a pyrogenic protein and that drug-induced inhibition of its synthesis is responsible for the observed lysis of fever.

Topics: Bacterial Infections; Cycloheximide; Female; Fever; Hodgkin Disease; Humans; Leukemia; Lung Neoplasms; Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Muramidase; Neoplasm Proteins; Neoplasms; Nitrogen; Ribonucleases; Uterine Cervical Neoplasms

Topics: Humans; Interferon Inducers; Interferons; Leukocytes; Muramidase; Neoplasm Transplantation; Neoplasms

Topics: Animals; Cross Reactions; Guinea Pigs; Mice; Models, Immunological; Muramidase; Neoplasms; Protein Denaturation

Topics: Arthritis, Rheumatoid; Electrophoresis; Humans; Kidney Diseases; Kidney Function Tests; Kidney Glomerulus; Kidney Tubules; Leukemia; Lupus Erythematosus, Systemic; Multiple Myeloma; Muramidase; Neoplasms; Proteinuria

Topics: Humans; Injections, Intravenous; Leukemia, Myeloid; Lung Neoplasms; Mitomycins; Mononuclear Phagocyte System; Muramidase; Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Stomach Ulcer

Topics: Candida; Candidiasis; Hodgkin Disease; Humans; In Vitro Techniques; Leukemia; Leukocytes; Lymphoma; Multiple Myeloma; Muramidase; Neoplasms; Neutrophils; Peroxidases; Phagocytosis; Polycythemia Vera

Topics: Complement System Proteins; Humans; Immunity; Muramidase; Neoplasms; Time Factors

Topics: Antitubercular Agents; Bacteria; Bacteriological Techniques; Blood Cells; Culture Media; Dimethyl Sulfoxide; Ethambutol; Hodgkin Disease; Humans; In Vitro Techniques; Leukemia; Lymphoma; Muramidase; Neoplasms; Staining and Labeling

Topics: Drug Synergism; Humans; Muramidase; Neoplasms; Otorhinolaryngologic Diseases; Papain; Radiotherapy

Topics: Adult; Aged; Female; Humans; Leukopenia; Male; Middle Aged; Muramidase; Neoplasms; Radiation Effects; Radiation Injuries; Radiation-Protective Agents; Radioisotope Teletherapy

Topics: Cyclophosphamide; Female; Fluorouracil; Humans; Leukocytes; Male; Muramidase; Neoplasms; Triaziquone

Topics: Bone Neoplasms; Dermatologic Agents; Humans; Leukocytes; Muramidase; Neoplasms; Radiation-Protective Agents

Topics: Antineoplastic Agents; Antiviral Agents; Humans; Iatrogenic Disease; Leukocyte Disorders; Leukopenia; Muramidase; Neoplasms; Radiation-Protective Agents; Toxicology

Topics: Ascorbic Acid; Cyclophosphamide; Leadership; Leukocyte Disorders; Leukopenia; Muramidase; Neoplasms; Propionates; Radiation-Protective Agents; Testosterone; Toxicology

Topics: Acetobacter; Adenoviridae; Animals; Antineoplastic Agents; Biological Products; Carcinoma, Ehrlich Tumor; Fish Oils; Interferons; Muramidase; Neoplasms; Neoplasms, Experimental; Peptides; Pharmacology; Pigments, Biological; Polysaccharides; Polysaccharides, Bacterial; Prodigiosin; Rabbits; Research; Sarcoma 180; Tissue Culture Techniques; Tumor Virus Infections

Topics: Analgesia; Antineoplastic Agents; Female; Gamma Rays; Genital Neoplasms, Female; Humans; Muramidase; Neoplasms; Pain Management; Radioisotope Teletherapy; Radium

Topics: C-Reactive Protein; Complement System Proteins; Female; Genital Neoplasms, Female; Humans; Immunity, Innate; Muramidase; Neoplasms; Properdin

Topics: Humans; Muramidase; Neoplasms; Pain; Toxicology

Topics: Animals; Muramidase; Neoplasms; Rats; Sarcoma; Sarcoma, Experimental

Topics: Humans; Kidney; Muramidase; Neoplasms

Topics: Animals; Anti-Infective Agents, Local; Antiviral Agents; Dermatologic Agents; Muramidase; Neoplasms; Neoplasms, Experimental; Rats

Topics: Analgesia; Analgesics; Humans; Muramidase; Neoplasms; Pain Management

Topics: Animals; Antiviral Agents; Electrons; Microscopy; Microscopy, Electron; Muramidase; Neoplasms; Pharmacology; Poultry; Research; Tissue Culture Techniques

Topics: Animals; Kidney; Muramidase; Neomycin; Neoplasms; Spleen

Topics: Antiviral Agents; Bone and Bones; Dermatologic Agents; Muramidase; Neoplasms

Topics: Dermatologic Agents; Muramidase; Neoplasms; Pain; Virus Diseases

Topics: Antiviral Agents; Humans; Muramidase; Neoplasms; Pain

Topics: Animals; Ascites; Glycolipids; Humans; Lipids; Muramidase; Neoplasms; Phospholipids; Sarcoma; Sarcoma, Yoshida

Topics: Interleukin-2; Muramidase; Neoplasms; Phospholipids; Serum Albumin; Serum Albumin, Human

Topics: Anti-Infective Agents, Local; Dermatologic Agents; Muramidase; Neoplasms; Pain

Topics: Antineoplastic Agents; Antiviral Agents; Genitalia; Genitalia, Female; Gynecology; Muramidase; Neoplasms

Topics: Adult; Anti-Infective Agents, Local; Carcinoma; Hematologic Diseases; Humans; Lymphatic Diseases; Muramidase; Neoplasms

Topics: Humans; Lung; Muramidase; Neoplasms; Tuberculoma; Tuberculosis; Tuberculosis, Pulmonary