concanavalin-a and Bone-Neoplasms

A novel multifunctional nanodevice based in doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) as nanoplatforms for the assembly of different building blocks has been developed for bone cancer treatment. These building blocks consists of: i) a polyacrylic acid (PAA) capping layer grafted to MSNs via an acid-cleavable acetal linker, to minimize premature cargo release and provide the nanosystem of pH-responsive drug delivery ability; and ii) a targeting ligand, the plant lectin concanavalin A (ConA), able to selectively recognize, bind and internalize owing to certain cell-surface glycans, such as sialic acids (SA), overexpressed in given tumor cells. This multifunctional nanosystem exhibits a noticeable higher internalization degree into human osteosarcoma cells (HOS), overexpressing SA, compared to healthy preosteoblast cells (MC3T3-E1). Moreover, the results indicate that small DOX loading (2.5 µg mL. The development of highly selective and efficient tumor-targeted smart drug delivery nanodevices remains a great challenge in nanomedicine. This work reports the design and optimization of a multifunctional nanosystem based on mesoporous silica nanoparticles (MSNs) featuring selectivity towards human osteosarcoma cells and pH-responsive antitumor drug delivery capability. The novelty and originality of this manuscript relies on proving that the synergistic assembly of different building blocks into a unique nanoplatform increases antitumor effectiveness and decreases toxicity towards healthy cells, which constitutes a new paradigm in targeted bone cancer therapy.

Topics: 3T3 Cells; Animals; Antibiotics, Antineoplastic; Bone Neoplasms; Cell Line, Tumor; Concanavalin A; Doxorubicin; Drug Carriers; Drug Delivery Systems; Humans; Hydrogen-Ion Concentration; Lectins; Mice; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Nanoparticles; Polysaccharides; Porosity; Sialic Acids; Silicon Dioxide; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction

Cell mediated immune responses as measured by lymphocyte proliferation induced by the mitogens phytohemagglutinin and concanavalin A and antigen extracts of donor derived bone were studied within 2 years after wide resection of bone tumors in 18 patients receiving fresh frozen massive osteoarticular allografts. No uniform changes were seen in mitogen induced responses in 18 patients. However, five of nine patients tested with antigen extracts of donor derived bone showed elevated immune responses, one moderate and four weak. The incorporation of the allograft (evaluated by repeated radiographs; specific isotope techniques; clinical outcome assessed by the functional rating scores of Mankin-Waber and the Musculoskeletal Tumor Society; and histologic biopsy findings on new bone formation) did not differ in these patients from those in patients without any response to donor derived tissue. During a long term followup (mean, 11 years; range, 2-20 years), degenerative joint and sclerotic density bone changes developed after 2 to 4 years without correlation to immune responses. Histologic specimens showed no signs of immunologic reaction, and no clinical rejection episodes were recorded. A slightly variable immune response to allograft bone seems to occur, but its clinical significance for outcome of the grafts remains to be determined. The low immune responses might reflect a low antigen release rate through an indirect pathway or immunologic tolerance to antigens or proteins shed from massive allografts that are nonliving scaffold implants during the creeping substitution process, corresponding to the low immune response and the slow histologic repair.

Topics: Adolescent; Adult; Bone Neoplasms; Bone Transplantation; Concanavalin A; Female; Humans; Joint Diseases; Lymphocytes; Male; Phytohemagglutinins; Treatment Outcome

Clear cell chondrosarcoma, a subtype and separate entity from the conventional chondrosarcoma, is characterized by its special histologic features, site of predilection, slow growth and better prognosis. Three cases are presented with elucidation of clinicopathologic correlation and detection by ABC immunohistochemical method using several antibodies. The observation of positive reaction to S-100 protein, vimentin, anti-alpha-chymotrypsin and Lysozyme by the tumor cells of clear cell chondrosarcoma, similar to chondrosarcoma and chondroblastoma, proves that this tumor has its origin from the cartilaginous tissue. It was found for the first time that the clear cell chondrosarcoma was positive for wheat germ agglutinin and concanavalin A. The authors believe that clear cell chondrosarcoma may result from the anaplastic change of chondroblastoma cells into another subtype of that tumor. The osteoblastlike multinucleated giant cells, retaining the antigens of phagocytes, are not considered to be neoplastic.

Topics: Adult; Bone Neoplasms; Chondrosarcoma; Concanavalin A; Female; Femoral Neoplasms; Histocytochemistry; Humans; Immunohistochemistry; Male; Tibia; Wheat Germ Agglutinins

The responses to Concanavalin A (Con A) of peripheral blood mononuclear cells were studied in 22 patients with malignant bone and soft tissue sarcoma. The decreases of response were shown in many cases depending on their clinical stages. The responses were increased by removal of the adherent cells from mononuclear cells by passing through a Sephadex G-10 column in 7 of 13 cases tested. The enhancement of responses to Con A was also found when indomethacin, a inhibitor of prostaglandin biosynthesis, was added to mononuclear cell suspensions. However, no additional increase of the responses was found when indomethacin was supplemented to the adherent cell-depleted mononuclear cell suspensions. Since it has been previously shown that prostaglandin was primarily produced from macrophages, the author concluded that the suppressor cells affecting on the lymphocyte transformation probably belong to monocyte-macrophage series and their suppressive effect may be mediated by prostaglandin. In the normal control, the responses of mononuclear cells to Con A stimulation were rather reduced by removal of the adherent cells, suggesting that these suppressor cells were contained only in mononuclear cells of the tumor-bearing hosts.

Topics: Bone Neoplasms; Cell Adhesion; Concanavalin A; Humans; Indomethacin; Monocytes; Sarcoma; Soft Tissue Neoplasms; T-Lymphocytes, Regulatory