acid-phosphatase and Fibrosarcoma

The use of activable cell-penetrating peptides (ACPPs) as molecular imaging probes is a promising new approach for the visualization of enzymes. The cell-penetrating function of a polycationic cell-penetrating peptide (CPP) is efficiently blocked by intramolecular electrostatic interactions with a polyanionic peptide. Proteolysis of a proteinase-sensitive substrate present between the CPP and polyanionic peptide affords dissociation of both domains and enables the activated CPP to enter cells. This ACPP strategy could also be used to modify antitumor agents for tumor-targeting therapy. Here, we aimed to develop a conjugate of ACPP with antitumor drug doxorubicin (DOX) sensitive to matrix metalloproteinase-2 and -9 (MMP-2/9) for tumor-targeting therapy purposes. The ACPP-DOX conjugate was successfully synthesized. Enzymatic cleavage of ACPP-DOX conjugate by matrix metalloproteinase (MMP)-2/9 indicated that the activation of ACPP-DOX occurred in an enzyme concentration-dependent manner. Flow cytometry and laser confocal microscope studies revealed that the cellular uptake of ACPP-DOX was enhanced after enzymatic-triggered activation and was higher in HT-1080 cells (overexpressed MMPs) than in MCF-7 cells (under-expressed MMPs). The antiproliferative assay showed that ACPP had little toxicity and that ACPP-DOX effectively inhibited HT-1080 cell proliferation. These experiments revealed that the ACPP-DOX conjugate could be triggered by MMP-2/9, which enabled the activated CPP-DOX to enter cells. ACPP-DOX conjugate may be a potential prodrug delivery system used to carry antitumor drugs for MMP-related tumor therapy.

Topics: Acid Phosphatase; Antineoplastic Agents; Biological Transport, Active; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Drug Delivery Systems; Female; Fibrosarcoma; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Nanomedicine; Protein Tyrosine Phosphatases

The effects of single and multiple fractionated whole body hyperthermia (WBH) 41.5 degrees C on benzo(a) pyrene induced fibrosarcoma of mice were evaluated in terms of tumour response and systemic alterations of the host. While single exposure of WBH(S) 2 hrs, caused moderate inhibition of tumours and increase in the median survival time, multiple fractionated exposures [WBH(M)] caused significant enhancement of tumours with decrease in mean survival time. Tumoricidal effects associated with increased acid phosphatase and beta-glucuronidase activity were observed in both the regimes of WBH. In WBH(M) the development of thermotolerance was indicated by decreased activity of these enzymes in subsequent treatments. Elevation of plasma corticosterone and significant lymphocytopenia occurred in both the regimes. The alterations were transient in WBH(S) but persisted for more than two weeks in WBH(M), indicating that tumour enhancement is possibly influenced by corticosterone-mediated immunosuppression. In the WBH(M), the tumoricidal effects were counteracted and surpassed by the growth stimulatory physiological alterations of the host. Therefore the mode of application of WBH and the systemic responses of the host are critical factors that should be considered in designing therapeutic regimes with WBH.

Topics: Acid Phosphatase; Animals; Benzo(a)pyrene; Corticosterone; Female; Fibrosarcoma; Glucuronidase; Hyperthermia, Induced; Leukocyte Count; Lymphocytes; Mice; Mice, Inbred A; Time Factors

Topics: Acid Phosphatase; Carcinoma, Basal Cell; Clinical Enzyme Tests; Diagnosis, Differential; Fibrosarcoma; Histiocytoma, Benign Fibrous; Humans; Liposarcoma; Rhabdomyosarcoma; Soft Tissue Neoplasms; Tartrates

The reactivity of lysosomal enzymes in 17 fibrohistiocytic tumors were examined histochemically to evaluate the histiocytic nature of the tumors. The lysosomal enzymes examined were acid phosphatase (Ac-P), non-specific esterase (NS-E), beta-glucuronidase (beta-GL), and N-acetyl-beta-glucosaminidase (N-GA). The tumors examined were eight malignant fibrous histiocytomas (MFH) (i.e., five common types, two myxoid types, and one inflammatory type), one atypical fibroxanthoma of the skin (AFX), one dermatofibrosarcoma protuberans (DFSP), two giant cell tumors of the tendon sheath (GCT), and five dermatofibromas (DF). Seven of 8 MFH showed strong reactivity for all enzymes examined. Positive reactions were seen as evenly distributed granules in the cytoplasm of fibroblastic, histiocytic and giant cells in all types of the tumors. Almost all AFX, GCT, and DF showed moderate to strong reactivity. These findings suggest that these tumors were composed of cells with the enzymatic character of histiocytes. However, DFSP contained no cells giving a positive reaction, and thus its histiocytic nature could not demonstrated.

Topics: Acetylglucosaminidase; Acid Phosphatase; Adult; Aged; Carboxylesterase; Carboxylic Ester Hydrolases; Female; Fibroma; Fibrosarcoma; Glucuronidase; Histiocytoma, Benign Fibrous; Histocytochemistry; Humans; Lysosomes; Male; Middle Aged; Skin Neoplasms; Xanthomatosis

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Bone Neoplasms; Child; Chondroma; Chondrosarcoma; Diagnosis, Differential; Female; Fibrosarcoma; Giant Cell Tumors; Histiocytoma, Benign Fibrous; Humans; Lymphoma; Male; Middle Aged; Osteosarcoma

Supernatants from in vivo asbestos-activated macrophages failed to show any cytostatic activity against a syngeneic fibrosarcoma cell line in vitro. UICC chrysotile-induced peritoneal exudate cells also failed to demonstrate any growth inhibitory effect on the same cells in Winn assays of tumor growth. Mixing UICC crocidolite with inoculated tumor cells resulted in a dose-dependent inhibition of tumor growth; this could, however, be explained by a direct cytostatic effect on the tumor cells of high doses of crocidolite, which was observed in vitro.

Topics: 5'-Nucleotidase; Acid Phosphatase; Animals; Asbestos; Asbestos, Crocidolite; Asbestos, Serpentine; Cell Division; Cell Membrane; Fibrosarcoma; Lysosomes; Macrophages; Mice; Mice, Inbred CBA; Nucleotidases; Time Factors

We have separated subpopulations of macrophages from an immunogenic fibrosarcoma by the technique of unit gravity velocity sedimentation. The activation state of these subpopulations was determined by measurement of the Fc receptor avidity of adherent cells, and by their 5' nucleotidase and acid phosphatase activity. The subpopulations were compared to resident peritoneal macrophages and the peritoneal macrophage subpopulations elicited by injection of proteose peptone or C. parvum. The results show that two macrophage subpopulations exist within the tumour. The smaller, peroxidase-positive population, with a sedimentation velocity of 1-5 mm/h, is similar to proteose peptone stimulated macrophages with respect to Fc receptor expression, while the other, rapidly sedimenting population (5-9 mm/h) is partially activated. However, neither population achieved the level of activation demonstrated by rapidly sedimenting, C. parvum-activated macrophages. Analysis of the enzyme activity of rapidly adherent macrophages indicated that tumour, proteose peptone or C. parvum macrophages were all activated when compared to resident peritoneal macrophages. No significant differences were found with respect to the elevated levels of acid phosphatase in the three activated macrophage populations, but the 5' nucleotidase activity of C, parvum-elicited macrophages was significantly lower than either the proteose peptone or tumour macrophages. This again demonstrated that the tumour macrophages were less activated than C. parvum macrophages. These data show that tumour-infiltrating macrophages are a heterogeneous population composed of at least two subpopulations existing in different activation states and that within the tumour microenvironment they are not capable of differentiating to the higher activation state, demonstrated by C. parvum macrophages.

Topics: Acid Phosphatase; Animals; Cell Separation; Fibrosarcoma; Macrophages; Mice; Neoplasms, Experimental; Nucleotidases; Propionibacterium acnes; Receptors, Fc

Topics: Acid Phosphatase; Aged; Basement Membrane; Central Nervous System Diseases; Desmosomes; Esterases; Female; Fibrosarcoma; Humans; Male; Meningeal Neoplasms; Microscopy, Electron; Middle Aged; Neoplasms, Radiation-Induced

The transplantable fibrosarcoma of the Rat gives birth to different modifications in the splenic structures, and a strong perturbation is found within the enzymatic activities. The macrophages have an altered acid phosphatase activity. This is in marked contrast to the increase in number of the alkaline phosphatase polymorphonuclear cells, which are originated from myeloid areas in the red pulp. Lymphoïd-reticular cells, possessing one 5'nucleotidase activity, seem to be responsible, possibly, by forming numerous clonal systems during the development of this fibrosarcoma. The role of this separate system is discussed.

Topics: 5'-Nucleotidase; Acid Phosphatase; Alkaline Phosphatase; Animals; Female; Fibrosarcoma; Histocytochemistry; Macrophages; Mononuclear Phagocyte System; Neutrophils; Nucleotidases; Sarcoma, Experimental; Spleen

Topics: Acid Phosphatase; Alkaline Phosphatase; Connective Tissue; Connective Tissue Cells; DNA; Enzymes; Esterases; Fibroma; Fibrosarcoma; Granulation Tissue; Histiocytoma, Benign Fibrous; Histocytochemistry; Humans; Leprosy; Leucyl Aminopeptidase; Lymphoma, Large B-Cell, Diffuse; Mycosis Fungoides; Skin; Skin Diseases; Skin Neoplasms; Tuberculosis, Cutaneous

Topics: Acid Phosphatase; Adolescent; Adult; Bone Neoplasms; Child; Child, Preschool; Female; Fibrosarcoma; Fibrous Dysplasia of Bone; Giant Cell Tumors; Humans; Infant; Isoenzymes; Male; Middle Aged; Osteosarcoma; Sarcoma, Ewing; Soft Tissue Neoplasms

Tumours induced in mice, either CBA normal and chimaerical, or C3H, by (90)Sr or (226)Ra or plutonium have been examined histochemically with (1) diazotate fast red violet LB salt in naphthol AS-MX phosphate buffer at pH 8·6 and 5·2, (2) 1: 9 dimethyl methylene blue (Taylor).It is concluded:(a) The diagnosis of osteosarcoma is facilitated with Taylor's Blue which stains osteoid metachromatically. Cells of osteosarcoma, like normal osteoblasts, contain alkaline phosphatase but this may be lost by mutation either in the original tumour or subsequently on passage of the tumour serially to compatible hosts.(b) Osteosarcomata may contain giant-cells of two forms, bizarre tumour cells and osteoclasts; the latter contain acid phosphatase. Osteosarcomata which retain their osteoid on serial passage have few cells containing acid phosphatases.(c) Primitive mesenchymal cell tumours of angiomatous form may occur, if the bone marrow is irradiated, e.g. by (90)Sr-(90)Y and Pu. These tumours lack osteoid and cells interpretable as osteoblasts or osteoclasts (though they destroy bone).(d) Tumours classifiable as fibrosarcomata occur rarely, and may be truly of fibroblastic origin or be mutated osteosarcomata.(e) Lymphomata also occur when the marrow is irradiated ((90)Sr-(90)Y and Pu). They may be generalized, when their cells may contain alkaline phosphatase or lack it. They may be localized to abdominal viscera, the reticulo-sarcomatous form, in which case the cells lack alkaline phosphatase.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Clinical Enzyme Tests; Color; Coloring Agents; Fibrosarcoma; Hemorrhage; Histocytochemistry; Lymphoma; Mesenchymoma; Mice; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphoric Monoester Hydrolases; Plutonium; Radiation Dosage; Radioisotopes; Radium; Staining and Labeling; Strontium Radioisotopes; Succinate Dehydrogenase; Yttrium Isotopes

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Bone Neoplasms; Child; Child, Preschool; Esterases; Female; Femoral Neoplasms; Fibroma; Fibrosarcoma; Fibrous Dysplasia of Bone; Glucuronidase; Humans; Humerus; Hydrolases; Infant, Newborn; Leucyl Aminopeptidase; Male; Mandibular Neoplasms; Middle Aged; Osteosarcoma; Tibia

Topics: Acid Phosphatase; Animals; Brain Neoplasms; Culture Techniques; Fibrosarcoma; Glucosephosphate Dehydrogenase; Glucosephosphates; Histocytochemistry; Histological Techniques; L-Lactate Dehydrogenase; Methylcholanthrene; Mice; Oxidoreductases; Sarcoma, Experimental; Staining and Labeling; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adenosine Triphosphatases; Animals; Animals, Newborn; Benz(a)Anthracenes; Carcinogens; Fibrosarcoma; Guinea Pigs; Histocytochemistry; Lactones; Leucyl Aminopeptidase; Methylcholanthrene; Neoplasm Transplantation; Quinolines; Skin Neoplasms

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Esterases; Female; Fibrosarcoma; Male; Rats; Spleen; Thymus Gland

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Cell Transformation, Neoplastic; Culture Techniques; Electrophoresis, Disc; Fibrosarcoma; Histocytochemistry; Humans; Kidney; Liver; Male; Mice; Molybdenum; Muscles; Myocardium; Neoplasms, Experimental; Plants; Prostate; Prostatic Neoplasms; Sarcoma 180; Skin Neoplasms; Tartrates

Topics: Acid Phosphatase; Adenocarcinoma; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Classification; DNA, Neoplasm; Female; Fibrosarcoma; Genetics; Liver Neoplasms; Mammary Neoplasms, Experimental; Methylcholanthrene; Mice; Neoplasms, Experimental; Ribonucleases; RNA, Neoplasm; Sarcoma, Experimental; Uterine Cervical Neoplasms

Topics: Acid Phosphatase; Animals; Culture Techniques; DNA, Neoplasm; Fibrosarcoma; Mice; Motion Pictures; Neoplasms, Experimental; Phagocytosis

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Bone Neoplasms; Carboxylesterase; Child; Chondroblastoma; Chondroma; Chondrosarcoma; Coloring Agents; Esterases; Fibroma; Fibrosarcoma; Fibrous Dysplasia of Bone; Geriatrics; Giant Cell Tumors; Glucuronidase; Histocytochemistry; Histological Techniques; Humans; Osteosarcoma; Pathology; Phosphoric Monoester Hydrolases; Sarcoma, Synovial; Staining and Labeling

Topics: Acid Phosphatase; Adenocarcinoma; Benz(a)Anthracenes; Carcinogens; Carcinoma, Squamous Cell; Esterases; Fibrosarcoma; Galactosidases; Histocytochemistry; Neoplasms, Experimental; Pathology; Rats; Research; Salivary Gland Neoplasms; Submandibular Gland; Submandibular Gland Neoplasms; Succinate Dehydrogenase; Toxicology

Topics: Acid Phosphatase; Aminopeptidases; Benzopyrenes; Cytoplasm; Esterases; Fibroblasts; Fibrosarcoma; Galactosidases; Histocytochemistry; Neoplasms; Neoplasms, Experimental; Pathology; Rats; Research; Salivary Gland Neoplasms; Submandibular Gland

Topics: Acid Phosphatase; Alkaline Phosphatase; Aminopeptidases; Animals; Benz(a)Anthracenes; Benzopyrenes; Esterases; Fibrosarcoma; Glucuronidase; Methylcholanthrene; Neoplasms, Experimental

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Breast Neoplasms; Fibrosarcoma; Humans; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Ribonucleases

Topics: Acid Phosphatase; Adenocarcinoma; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; DNA; DNA, Neoplasm; Fibrosarcoma; Metabolism; Mice; Neoplasms; Neoplasms, Experimental; Oxidoreductases; Research; Ribonucleases; RNA; RNA, Neoplasm; Xanthines