bromochloroacetic-acid and Osteolysis

After an epoch in which was pretended to explain the etiopathogenetic phenomena observed in Cholesteatoma through enzymatic studies, nowadays other investigations focus the topic in the possible presence of immunobiologic alterations at cellular level, so the research work is directed to the occurrence, distribution and activity of several growth factors and leukins. In this paper the AA. made a perusal of the new acquisitions and devote themselves to two important aspects of the cholesteatoma: the biologic behaviour of the squamous cell epithelia with an uncontrolled growth and to the immunobiologic mechanisms responsible for the bone resorption.

Topics: Bone Resorption; Cholesteatoma; Ear, Middle; Epithelial Cells; HLA-DR Antigens; Humans; Keratinocytes; Keratins; Osteolysis; Transforming Growth Factor alpha

A rare case of mucinous adenocarcinoma with neuroendocrine differentiation of the mandibular ramus is presented. The patient, an 80-year-old man, was referred to our hospital with chief complaint of swelling and pain in the left buccal mucosa. CT and MRI examination showed an osteolytic tumor mass occupying the upper region of the left mandibular ramus. Macroscopically, the excised tumor was a relatively well-defined, solid mass with diffuse bone resorption, measuring 3 cm x 3.2 cm x 3 cm. Microscopical examination showed that the tumor forming glandular structures with abundant mucous production and high cellular atypia. Immunohistochemical studies demonstrated the positive reactivities for pan-keratin, cytokeratin 7, vimentin,alpha-amylase, alpha-smooth muscle actin, neuron-specific enolase, glial fibrillary acid protein, calcitonin, and somatostatin in tumor cells. These findings suggested that the tumor was originated from heterotopic or misplaced salivary gland in the mandible.

Topics: Actins; Adenocarcinoma, Mucinous; Aged; Aged, 80 and over; alpha-Amylases; Calcitonin; Glial Fibrillary Acidic Protein; Humans; Keratin-7; Keratins; Male; Mandibular Neoplasms; Neurosecretory Systems; Osteolysis; Phosphopyruvate Hydratase; Somatostatin; Vimentin

We have developed a series of novel mammary epithelial cell lines from tumors arising in strain 129 mice, with the ultimate goal of evaluating the role of host factors in the development of bone metastases. Mammary tumors were induced in mice with subcutaneously implanted medroxyprogesterone acetate (MPA) pellets followed by administration of DMBA by oral gavage. Mammary tumor development was efficient in the 129 strain and was independent of osteopontin (OPN) expression. Epithelial cell lines were isolated from these tumors; surprisingly, these cells did not form tumors upon inoculation into the mammary fat pad of syngeneic mice, even when MPA was present. One OPN-deficient cell line was selected for further study; full transformation of these cells required expression of both polyoma middle T and activated ras. These doubly transfected cells, 1029 GP+Er3, grew in soft agar, and formed hormone-independent tumors efficiently in the mammary fat pad that spontaneously metastasized to several soft tissue sites but not to the bone. Derivatives of these cells were isolated from tumors arising in the fat pad and from a lung metastasis (r3T and r3L, respectively): these cells formed tumors more rapidly in the fat pad than the parental GP+Er3 cells. Upon left ventricle injection, the r3T and r3L cells formed osteolytic bone metastases in 129 mice, with few metastases seen in other organs. These tumors filled the marrow cavity, and caused extensive destruction of both cortical and trabecular bone. Intriguingly, in an alternative syngeneic host, (129xC57B1/6) F1, osteolytic bone metastases were not seen on x-ray; instead extensive liver metastasis was present in these mice, indicating that genetic factors in these two strains regulate tumor cell homing and distribution during metastasis. These cell lines provide an important new tool in the study of bone metastasis, particularly in elucidating the role of host factors in the development of these lesions, as the 129 mouse strain is frequently used for genetic manipulations in the mouse.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antigens, Polyomavirus Transforming; Antineoplastic Agents, Hormonal; Bone Neoplasms; Carcinogens; Cell Transformation, Neoplastic; Epithelial Cells; Female; Genes, ras; Heart Ventricles; Humans; Keratins; Liver Neoplasms, Experimental; Male; Mammary Neoplasms, Experimental; Medroxyprogesterone Acetate; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Neoplastic Cells, Circulating; Osteolysis; Osteopontin; Retroviridae; Sialoglycoproteins; Transfection; Tumor Cells, Cultured

This study assessed effects of the bisphosphonate zoledronic acid (ZLNA) on osteoclastogenesis. To assess the effect of ZLNA on osteoclast formation in vitro, we cultured mouse bone marrow cells under conditions that promote osteoclastogenesis. Administered at concentrations from 10(-6) to 10(-9) mol/L, ZLNA led to a dose-dependent inhibition of osteoclastogenesis. Combined TUNEL staining and histochemical staining for tartrate-resistant acid phosphatase showed that ZLNA induced apoptosis in osteoclasts and monocytic precursor cells. To study the effects of ZLNA in vivo, we placed keratin particles onto the surface of the parietal bone of mice to induce localized inflammatory bone resorption. Three experimental groups received daily subcutaneous injections of ZLNA (1, 3, or 10 microg/kg body weight) from 4 days before surgery until 5 days after keratin implantation. The ZLNA significantly reduced osteoclast recruitment in a dose-dependent manner, but did not affect the degree of inflammation or the mineral apposition rate.

Topics: Animals; Bone Marrow Cells; Bone Resorption; Cell Division; Cells, Cultured; Diphosphonates; Dose-Response Relationship, Drug; Imidazoles; Injections, Subcutaneous; Keratins; Male; Mice; Mice, Inbred C57BL; Minerals; Osteitis; Osteoclasts; Osteolysis; Parietal Bone; Periosteum; Prostheses and Implants; Skull; Zoledronic Acid

Sarcomatous transformation in chordoma is a very rare condition and has been emphasized as a distinct entity because of its more aggressive clinical course. Here we describe a case of dedifferentiated chordoma arising from the skull base region of an 11-year-old boy, with tumor recurrence within one year. This tumor showed features of pleomorphic cell sarcoma with areas more typical of chordoma. Most of tumor cells expressed cytokeratin, epithelial membrane antigen, vimentin and S-100 protein, thus confirming the diagnosis of dedifferentiated chordoma.

Topics: Biomarkers, Tumor; Cell Differentiation; Cervical Atlas; Child; Chordoma; Combined Modality Therapy; Cranial Irradiation; Disease Progression; Fatal Outcome; Humans; Keratins; Male; Mucin-1; Neoplasm Proteins; Neoplasm Recurrence, Local; Osteolysis; Prognosis; S100 Proteins; Sarcoma; Skull Base Neoplasms; Spinal Neoplasms; Torticollis; Vimentin

We implanted keratin and poly(methyl methacrylate) (PMMA) particles to the surface of mouse calvariae to produce a quantitative, localized, inflammatory bone remodeling similar to that seen in cholesteatoma. Both types of particles resulted in increased osteoclast density compared with controls. Osteoclasts infiltrated from marrow and vascular spaces and were active at the periphery of these spaces leading to significant bone remodeling, as demonstrated by the incorporation of bone-labelling fluorophores. Osteoclasts were rarely found on the surface of the calvariae, and mineral apposition rate at the ventral surface was not altered in keratin-implanted animals compared with nonoperated controls. While not useful for the study of the root cause of cholesteatoma, this model will allow the study ofpathologic bone remodeling related to cholesteatoma in a genetically defined animal.

Topics: Animals; Bone and Bones; Bone Diseases; Bone Remodeling; Calcification, Physiologic; Cholesteatoma; Disease Models, Animal; Inflammation; Keratins; Mice; Mice, Inbred C57BL; Osteoclasts; Osteolysis; Peptide Fragments; Skull

Histological, immunohistochemical and electron microscopical studies revealed one feline and four canine calcifying epithelial odontogenic tumours in 115 oral tumours over a 10-year period. The tumours consisted of islands and sheets of odontogenic epithelium of varying size within a stroma of fibrous connective tissues. The tumour cells were pleomorphic with variable amounts of eosinophilic cytoplasm and large hyperchromatic, polymorphic nuclei with prominent nucleoli. Clusters of keratinized tumour cells ("shadow cells") were frequently seen within the islands and sheets. The multiple spherules of homogeneous eosinophilic material stained positively with Congo red and Dylon stains and produced an apple green birefringence under polarization microscopy, indicative of amyloid. Mineralized foci were scattered throughout the tumour masses and in the homogeneous spherules. Immunohistochemically, the tumour cells reacted with anti-human keratin antibody, but not with anti-human vimentin or anti-chicken desmin antibodies. The homogeneous spherules did not react with anti-human keratin, anti-human vimentin, anti-chicken desmin, anti-amyloid A, anti-laminin or anti-human collagen (type I, III, IV) antibodies. Ultrastructurally, the cytoplasm of tumour cells was abundant and contained a large number of electron-dense bundles of tonofilaments. The homogeneous spherules consisted of fine filaments measuring about 10-12 nm in diameter.

Topics: Amyloid; Animals; Calcinosis; Cat Diseases; Cats; Dog Diseases; Dogs; Female; Keratins; Male; Mandibular Neoplasms; Maxillary Neoplasms; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Odontogenic Tumors; Osteolysis; Retrospective Studies

Topics: Adult; Aged; Dentigerous Cyst; Female; Follow-Up Studies; Humans; Jaw Diseases; Keratins; Male; Middle Aged; Odontogenic Cysts; Osteolysis; Radicular Cyst; Radiography; Recurrence; Retrospective Studies