Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human osteosarcoma cell line, MG63, responds both to GM-CSF and to G-CSF in vitro. To assess the significance of these observations to tumor growth in vivo, MG63 cells were engineered by retroviral infection to produce human GM-CSF or G-CSF. These retrovirally infected cells become autostimulatory as measured by increased [3H]-thymidine incorporation (3- to 7-fold) and anchorage-independent colony formation (7- to 10-fold) as compared with uninfected MG63 cells or cells infected with control (neor) retrovirus. The increased proliferation induced by exogenous GM-CSF or G-CSF on uninfected MG63 cells in both assays could be completely inhibited by anti-GM-CSF or anti-G-CSF antibodies, while the same antibodies only partially abrogated proliferation by the growth-factor-producing cells. None of 34 nude or SCID mice developed tumors when injected s.c. with uninfected or neor-virus-infected cells. In contrast, all 30 mice injected with GM-CSF- or G-CSF-producing MG63 cells developed tumors which were G418-resistant and factor-producing. Tumor cell DNA showed a polyclonal retroviral integration pattern indistinguishable from that in the DNA of cells injected into mice. Tumors that formed following injection of a mixture of G418-resistant, GM-CSF-producing cells and cells infected with virus containing only the hygror gene contained hygromycin-resistant cells in the same proportion as was present in the original cell mixture. These data indicate that GM-CSF and G-CSF can support the growth of an osteosarcoma cell line both in vitro and in vivo whether the factor is supplied by autocrine production or from exogenous sources.
 ...
PMID:The effect of GM-CSF and G-CSF on the growth of human osteosarcoma cells in vitro and in vivo. 750 89

Canine tumors resected at surgery or autopsy were subcutaneously xenotransplanted into SCID mice. Thirty of the seventy-three tumors (41.1%) grew primarily in SCID mice. The primary take rate of mammary tumors and skin and subcutaneous tumors was 55.9% (19/34) and 28.6% (8/28), respectively. One thyroid carcinoma, one oral leiomyosarcoma and one osteosarcoma also underwent successful primary growth. Thirteen of the forty-one benign tumors (31.7%) and 17 of the thirty-two malignant ones (53.1%) were successfully transplantable. The histological features of the primary xenografts and their original tumors were similar to each other in all the cases. Three xenografts of the four malignant tumors with metastasis in the canine patients were shown to grow also in SCID mice and two mammary tumor xenografts out of the three metastasized to the lungs of SCID mice as well. All the 30 primary tumor xenografts grown in the first recipient were successfully transplantable to the second generation of the SCID mice. Xenotransplantation using SCID mice appears to be a valuable tool for investigating the biological characteristics of canine neoplasmas.
 ...
PMID:Xenotransplantation of canine tumors into severe combined immunodeficient (SCID) mice. 769 97

An antagonistic monoclonal antibody, designated EM164, has been developed which binds specifically to the human insulin-like growth factor I receptor (IGF-IR) and inhibits the proliferation and survival functions of the receptor in cancer cells. EM164 was initially selected by a rapid cell-based screen of hybridoma supernatants to identify antibodies that bind to IGF-IR but not to the homologous insulin receptor and that show maximal inhibition of IGF-I-stimulated autophosphorylation of IGF-IR. EM164 binds tightly to IGF-IR with a dissociation constant K(d) of 0.1 nM, inhibits binding of IGF-I and antagonizes its effects on cells completely, and has no agonistic activity on its own. EM164 inhibits IGF-I-, IGF-II-, and serum-stimulated proliferation and survival of diverse human cancer cell lines in vitro, including breast, lung, colon, cervical, ovarian, pancreatic, melanoma, prostate, neuroblastoma, rhabdomyosarcoma, and osteosarcoma cancer lines. It also suppresses the autocrine or paracrine proliferation of several cancer cell lines. EM164 was the most potent antagonistic anti-IGF-IR antibody tested when compared with several commercially available antibodies. The in vitro inhibitory effect could be extended to in vivo tumor models, where EM164 caused regression of established BxPC-3 human pancreatic tumor xenografts in SCID mice. The antitumor effect of treatment with EM164 could be enhanced by combining it with the cytotoxic agent gemcitabine. These data support the development of EM164 as a candidate therapeutic agent that targets IGF-IR function in cancer cells.
 ...
PMID:An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. 1294 37

Nodular masses and granulomas of the esophagus are among the most frequent lesions caused by Spirocerca lupi, a nematode parasite of dogs, and neoplastic transformation of these granulomas to osteosarcoma or fibrosarcoma has been described. In this study, we developed a xenograft murine model of S. lupi-associated sarcoma. Samples of esophageal fibrosarcoma and osteosarcomas were excised from three dogs diagnosed with spirocercosis. These sarcomas were inoculated into three groups of 6-week-old NOD/SCID mice to create three tumor lines of S. lupi-associated sarcomas. Mice in all groups developed tumors after inoculation, and the cell lines could be further propagated as second-generation xenografts. We successfully established xenograft murine models of three different lines of S. lupi-associated sarcoma that offer readily available sources of these tumors for further experiments. This resource will facilitate studies on the malignant transformation of the granulomas, establishment of efficient chemotherapy and radiotherapy regimens, and identification of diagnostic molecular markers.
 ...
PMID:Murine xenograft model of Spirocerca lupi-associated sarcoma. 1642 46

A cell line, MCO-Y4, was established from a mammary gland osteosarcoma of a 16-year-old female mongrel dog. Histopathologically the tumor was composed of osteoblastic cells with an osteoid meshwork and chondroid matrix. The mean doubling time of the cells at the 93rd passage was 32.39+/-4.66 hr. Immunohistochemically, the osteoblastic and chondroblastic cells were positive for bone morphogenetic protein (BMP)-2/4 and BMP receptor (BMPR) II. The cultured cells were spindle in shape during the growth and the confluent phases. No tumor matrix was detected in the culture dish by alcian blue staining or von-Kossa silver impregnation. MCO-Y4 cells on the chamber slides showed intense immunoreactivity for BMP-2/4 and BMPR II. Noggin, an antagonist for BMP-2/4, showed the growth inhibition on MCO-Y4 cells. In addition, fibronectin might be potential for stimulating growth of MCO-Y4 cells. When transplanted into severe combined immunodeficiency mice, the cells formed tumors consisting of solid proliferation of osteoblastic and fibroblastic cells with woven-bone trabeculae. These tumor cells were intensely positive for BMP-2/4 and BMPR II. Our results suggested that the cell line might be useful for studying the role of BMPs in canine osteosarcoma and the mechanism of ossification.
 ...
PMID:Establishment and characterization of a cell line, MCO-Y4, derived from canine mammary gland osteosarcoma. 1708 82

Primary tumors developing in immunocompetent hosts escape immunosurveillance by acquiring immune evasive properties. This raises the prospect that metastases derived from such tumors will also evade immunity. To investigate whether immune surveillance plays a role in preventing metastases, we studied a murine model which mimics the clinical progression of osteosarcoma: primary tumor growth in the lower extremity, amputation, minimal residual disease followed by the development of overt metastases. K7M2 implants readily escaped immune surveillance since normal BALB/c mice, T cell deficient SCID and T/NK cell deficient SCID-bg mice showed no difference in the rate of growth of primary osteosarcomas. However, both SCID and SCID-bg mice had higher rates of metastases than immunocompetent mice. Similarly, immune reconstitution following transfer of naive T cells to SCID or SCID-bg mice did not impact primary tumor growth, but significantly diminished metastatic recurrence. T cells in osteosarcoma bearing mice produced IFNgamma in response to tumor and IFNgamma production by immune reconstituting T cells was required to prevent metastases. These results demonstrate an important role for T cell based immune surveillance in preventing metastases, even when metastases develop from tumors that adeptly evade immunosurveillance. The results further suggest that T cell depleting cancer therapies may eliminate beneficial immune responses and that immune reconstitution of lymphopenic cancer patients could prevent metastatic recurrence of solid tumors.
 ...
PMID:Immune reconstitution prevents metastatic recurrence of murine osteosarcoma. 1714 95

To date, data are not available concerning the effectiveness of chemotherapy in the treatment of Spirocerca lupi-associated esophageal sarcomas. In the present study, we compared the effectiveness of 4 chemotherapeutic agents against S. lupi-associated osteosarcoma, using a xenograft murine model created in our lab. Samples of xenografted osteosarcoma were inoculated subcutaneously into 5 groups (n = 10 each) of 6-wk-old male and female NOD/SCID mice. Tumor-bearing mice were divided into treatment and control groups. The treatment groups were injected with either pegylated liposomal doxorubicin (6 mg/kg, intravenously, n = 9), doxorubicin (6 mg/kg, intravenously, n = 8), carboplatin (60 mg/kg, intraperitoneally, repeated twice at 1-wk intervals for a total of 2 doses, n = 9), or cisplatin (6 mg/kg, intraperitoneally, n = 8). The control group was injected with buffered saline (n = 9). Tumor size was determined by caliper measurements. Compared with the control group, the pegylated liposomal doxorubicin- and doxorubicin-treated groups, but not the carboplatin or cisplatin groups, showed significant inhibition of tumor growth. Our results indicate that doxorubicin-based drugs are effective against S. lupi-associated sarcomas in a mouse xenograft model. Because it is less toxic than doxorubicin, pegylated liposomal doxorubicin is likely the drug of choice for treatment of S. lupi-associated sarcomas. We suggest that combination of doxorubicin or its pegylated form with surgical excision will improve the prognosis of dogs with this disease.
 ...
PMID:Chemotherapeutic treatment of xenograft Spirocerca lupi-associated sarcoma in a murine model. 1760 41

Dedifferentiated chondrosarcoma is a rare, highly malignant variant of chondrosarcoma in which a high-grade sarcoma coexists with a low-grade chondroid tumor. We herein review a case of dedifferentiated chondrosarcoma with an osteosarcoma omit component that occurred in the distal femur of a 38-year-old man. We established the cell line (NDCS-1) from a pleural effusion of the metastatic lung tumor. The cell line was characterized by a the G-banded karyotype, polymerase chain reaction (PCR) single-strand conformation polymorphism analysis, spectral karyotyping, and reverse transcriptase PCR (RT-PCR). The tumor exhibited complex karyotypes and a high frequency of chromosomal amplication with p53 mutation. This tumor revealed an osteoblastic and chondroblastic character in vitro and in severe combined immunodeficiency mice. The expression and phosphorylation of platelet-derived growth factor receptor-beta, which seemed to play a major role in the malignant phenotype of chondrosarcoma, was confirmed by RT-PCR and Western blotting. To our knowledge, this is the first report of the establishment of a human dedifferentiated chondrosarcoma.
 ...
PMID:Establishment of novel human dedifferentiated chondrosarcoma cell line with osteoblastic differentiation. 1765 62

A murine model of osteosarcoma was developed to investigate the association between the expression of VEGF and the progression of osteosarcoma. Two human osteosarcoma cell lines with distinct VEGF expressions were introduced into proximal tibiae of immuno-deficient SCID mice, either by direct injection through the cortical bone or surgical exposing and drilling on the tibial metaphysis to seed tumor cells. Bone tumors were obvious on microCT within 4 weeks following osteosarcoma cell inoculation through surgical delivery. In contrast, direct injection without drilling often resulted in periosteal tumors. Although neoplasms were developed regardless of VEGF levels, orthotopic tumors derived from high VEGF-expressing cells were detected 2 weeks earlier on CT images than the ones from VEGF negative cells. At sacrifice, high VEGF tumors were distinctively larger in size and more frequently invaded the adjacent bone tissue. Multiple metastatic lesions were found in all the lung tissues at 8 weeks from high VEGF group, whereas only 1 of 7 VEGF negative tumors exhibited pulmonary metastasis. Overall, this model developed with the surgical tumor cell delivery results in histological and radiographic features more consistent with primary osteosarcoma. Interestingly, VEGF expression correlates with the early establishment, rapid tumor growth, and the development of pulmonary metastasis.
 ...
PMID:High VEGF with rapid growth and early metastasis in a mouse osteosarcoma model. 1827 12

Retrovirus-mediated sFlt-1 gene modification was performed to examine the influence of VEGF in controlling the growth of an experimental osteosarcoma in mice. Human osteosarcoma G-292 cells were in vitro infected with retroviral vectors encoding soluble Flt-1 or LacZ gene before transplanted into proximal tibiae of immune deficient SCID mice to establish experimental orthotopic osteosarcoma. Daily observation and biweekly microCT were performed to monitor tumor development and progression till sacrifice at 8 weeks after tumor cell inoculation for histological and molecular analyses. Successful transgene expression was confirmed in the culture media of sFlt-1 transduced G-292 cells using ELISA, and with positive X-gal staining of the LacZ transduced cells. Noteworthy tumors were grown in all mice on the tibiae receiving G-292 cell inoculation, with clear detection on microCT images starting 2 weeks after inoculation. Over the time period, tumors derived from sFlt-1 transduced G-292 cells were distinctively smaller in size when compared to the ones from wide-type G-292 and G-292-LacZ cells. Histology showed typical osteosarcoma characteristics including severe cellular pleomorphism, bone erosions, and neo-vascularization. Real-time polymerase chain reaction indicated significantly higher sFlt-1 expression in sFlt-1 transduced groups than the wild-type G-292 or LacZ-treated groups. Strong expression of oncogenes c-myc and c-fos were also obvious, along with the expression of VEGF in the primary tumor tissue. Overall, data suggest that retrovirus-mediated sFLT-1 gene modification decelerates the osteosarcoma tumor growth in this murine model.
 ...
PMID:VEGF blockade decelerates the growth of a murine experimental osteosarcoma. 1863 45


1 2 3 4 5 Next >>