Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microvascular proliferation, a hallmark of malignant brain tumors, represents an attractive target of anticancer research, especially because of the quiescent nonproliferative endothelium of the normal brain. Cerebral neoplasms sequester copper, a trace metal that modulates angiogenesis. Using a rabbit brain tumor model, normocupremic animals developed large vascularized VX2 carcinomas. By contrast, small, circumscribed, relatively avascular tumors were found in the brains of rabbits copper-depleted by diet and penicillamine treatment (CDPT). The CDPT rabbits showed a significant decrease in serum copper, copper staining of tumor cell nuclei, microvascular density, the tumor volume, endothelial cell turnover, and an increase in the vascular permeability (breakdown of the blood-brain barrier), as well as peritumoral brain edema. In non-tumor-bearing animals, CDPT did not alter the vascular permeability or the brain water content. CDPT also inhibited the intracerebral growth of the 9L gliosarcoma in F-344 rats, with a similar increase of the peritumoral vascular permeability and the brain water content. CDPT failed to inhibit tumor growth and the vascularization of the VX2 carcinoma in the thigh muscle or the metastases to the lung, findings that may reflect regional differences in the responsiveness of the endothelium, the distribution of copper, or the activity of cuproenzymes. Metabolic and pharmacologic withdrawal of copper suppresses intracerebral tumor angiogenesis; angiosuppression is a novel biologic response modifier for the in situ control of tumor growth in the brain.
 ...
PMID:Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by penicillamine and the depletion of copper, an angiogenic cofactor. 170 Jun 17

An elderly woman had a cerebral gliosarcoma with a single pulmonary metastasis, together with a separate pulmonary adenoid-cystic carcinoma. Spontaneous extraneural metastases of primary intracranial neoplasms are exceedingly unusual; so far, only 8 proven cases are recorded in the English language medical literature. The association of cerebral gliosarcoma and a pulmonary adenoid-cystic carcinoma is presumably coincidental.
 ...
PMID:Cerebral gliosarcoma, pulmonary adenoid-cystic carcinoma, and pulmonary metastatic gliosarcoma: report of an untreated case. 608 60

Two phenomena associated with malignant gliomas are: 1) the ability to metastasize systemically, and 2) the capacity to induce sarcomatous transformation within the supportive mesenchyma. An unusual case is presented of selective metastases of the sarcomatous elements of a mixed gliosarcoma. Immunohistochemical cell staining with glial fibrillary acidic protein was used to confirm the presence of abnormal glial elements in the primary brain tumor as well as the absence of such glial elements in the abdominal metastases.
 ...
PMID:Selective peripancreatic sarcoma metastases from primary gliosarcoma. Case report. 674

A glioma cell line, CNS-1, was developed in the inbred Lewis rat to obtain a histocompatible astrocytoma cell line with infiltrative and growth patterns that more closely simulate those observed in human gliomas. Rats were given weekly intravenous injections for a six month period with N-nitroso-N-methylurea to produce neoplasm in the central nervous system. Intracranial tumor was isolated, enzymatically and mechanically digested, and placed into culture. The tumor cell line injected subcutaneously on the flanks of Lewis rats grew extensively in situ as cohesive tumor masses but did not metastasize. Intracranially, CNS-1 demonstrated single cell infiltration of paranchyma and leptomeningeal, perivascular, and periventricular spread with expansion of the tumor within choroid plexus stroma. CNS-1 cells titrated in right frontal brain of Lewis rats at 10(5), 5 x 10(5), 10(5), 5 x 10(4) cells per group had mean survival times ranging from 20.5 to 30.2 days. CNS-1 was immunoreactive for glial fibrillary acidic protein, S100 protein, vimentin, neural cell adhesion molecule, retinoic acid receptor alpha, intercellular adhesion molecule, and neuron specific enolase. The CNS-1 cells commonly had one or more trisomies of chromosomes 11, 13 or 18; losses, possibly random, of chromosomes (3, 5, 19, 30, X or Y) were noticed, and a marker chromosome made up of approximately 3 chromosomes was usual. Comparisons of CNS-1 to 9L gliosarcoma tumor were made. The glial CNS-1 tumor model provides an excellent system in which to investigate a variety of immunological therapeutic modalities. It spreads within brain in a less cohesive mass than 9L and is accepted without rejection in non-central nervous system sites by Lewis rats.
 ...
PMID:A rat glioma model, CNS-1, with invasive characteristics similar to those of human gliomas: a comparison to 9L gliosarcoma. 776 95

Desmoplastic infantile gangliogliomas are massive cystic tumors, typically occurring in the cerebral hemispheres of infants. They are remarkable pathologically for a prominent desmoplasia and, in some cases, for a cellular mitotically active component that can be readily interpreted as a malignant neoplasm. Four children less than 1 year of age were diagnosed with desmoplastic infantile gangliogliomas in the Pediatric Oncology Group infant brain tumor study (Protocol number 8633). All had been diagnosed by their respective institutions as having malignant tumors, i.e., Grade III astrocytoma, malignant meningioma, leptomeningeal fibrosarcoma, and gliosarcoma. All had increased intracranial pressure, and two had seizures. The tumors were extremely large, with one measuring 12 x 9 x 9 cm. None had evidence of metastatic disease. One patient had a gross total resection, and the other three had debulking procedures. All four children were treated with chemotherapy (cyclophosphamide, vincristine, cisplatinum, etoposide) for periods ranging from 12 to 24 months. Of those with postoperative measurable disease, one child had a complete response, one a partial response, and one had stable disease at the conclusion of chemotherapy. No child received radiation therapy. All children are alive with progression-free survivals after diagnosis of more than 36, 42, 48, and 60 months, respectively. Although desmoplastic infantile gangliomas are rare, recognition of this tumor type is essential because, despite their massive size and pathologically malignant appearance, they may have a relatively benign clinical course. If total surgical resection can be achieved, further therapy may not be indicated. In those patients in whom residual disease is present, chemotherapy appears to be an effective form of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Desmoplastic infantile gangliogliomas: an approach to therapy. 800 54

The present study investigated the ability of a recombinant herpes simplex virus type 1 (HSV) vector to deliver genes into disseminated brain tumor foci through intrathecal injection of the vector. The animal model was designed to simulate brain tumors with cerebrospinal fluid (CSF) metastases, which are found especially in the pediatric population. 9L gliosarcoma cells were injected both into the right frontal lobe and in through the cisterna magna of adult rats. The HSV vector, hrR3, was inoculated intrathecally 5 days later. This vector is defective in the gene for ribonucleotide reductase, and, therefore, replicates preferentially in dividing cells; it retains an intact HSV-thymidine kinase gene (HSV-tk). Two days after injection of the vector, immunohistochemical staining for HSV thymidine kinase (HSV-TK) revealed expression in frontal tumors, as well as in leptomeningeal tumor foci along the entire neuroaxis. HSV-TK-immunopositive cells were most frequent in small tumors contacting the CSF pathways. Frontal lobe tumors showed the highest density of HSV-TK-immunopositive cells around their periphery with little expression in central parts. Some paraventricular neurons temporarily showed HSV-TK-immunolabeling at this early time point. The number of HSV-TK-immunopositive tumor cells markedly decreased 5 days after injection of the HSV vector. In all animals, some toxicity was observed in the first 2-4 days after virus injection with extensive leptomeningeal inflammation. In conclusion, intrathecal application of HSV vectors can mediate widespread transfer of the therapeutic HSV-tk gene into disseminated tumors throughout the brain and CSF pathways. Although there was marked toxicity associated with intrathecal injection of this vector, this mode of gene delivery offers a promising approach for treatment of CSF-metastases in conjunction with development of less toxic vectors.
 ...
PMID:Herpes vector-mediated delivery of marker genes to disseminated central nervous system tumors. 883 17

Many studies show defective immune responses in patients diagnosed with cancer. Most of the diverse nonspecific approaches used to stimulate the immune system to recognize and destroy abnormal tumor cells have limited clinical utility. Attempts to identify tumor-specific antigens and to improve the antigen presentation were equally disappointing. It appears that some of these failures can be explained by tumor-induced immunosuppression. A large number of cytokines, hormones, and other molecules secreted by tumors were demonstrated to have immunomodulating properties. The most extensively studied immunosuppressive molecules secreted by tumors are transforming growth factor-beta (TGF beta), interleukin 10 (IL-10), and prostaglandin E2 (PGE2). TGF beta in particular may play a key role in tumor-induced immunosuppression. It is the most potent immunosuppressor described to date, and it has been consistently isolated from variety of tumor cell lines and detected in plasma of tumor-bearing hosts. Level of TGF beta production by tumor cells correlates with their metastatic potential, and TGF beta neutralization not only prevents development of metastases, but also inhibits growth or completely eradicates tumors as diverse as breast cancer, melanoma, and malignant gliosarcoma in animal models. PGE2 may play significant role in early stages of tumor development, promoting the process of tumorigenesis in some tumors. Research on reversal of tumor-induced immunosuppression promises new, more powerful, and less toxic approaches to cancer therapy. Existence of molecule(s) consistently secreted by different types of tumors and responsible for tumor progression raises the possibility of a single, universal assay to monitor progression and recurrence in many malignancies, including those that currently do not have reliable plasma markers.
 ...
PMID:Reversal of tumor-induced immunosuppression: a new approach to cancer therapy. 918 55

In Jan. 97 a gliosarcoma was diagnosed in a 61-year- old man after a 6-month history with neurological deficits. A total physical examination, laboratory tests, chest x-ray and abdominal ultrasound scanning revealed no gross abnormalities. Surgery was followed by brain radiation therapy and 6 months later there were metastases to the oral cavity, right palpebra and both lungs. The histological findings of the oral and palpebral metastases revealed only the sarcomatous component. We are aware of 15 cases of gliosarcoma with extraneural metastases, and in 4 of these, the metastases contained only the sarcomatous component. We believe that our case represents the fifth case of pure sarcomatous metastases.
 ...
PMID:October 1998--61 year old male with brain tumor and oral, lung, and palpebral masses. 1021 54

Glioma invasiveness is a complex process involving recognition and attachment of tumor cells to particular extracellular matrix (ECM) molecules prior to migrating into proteolytically modified matrix and inducing angiogenesis. CD44 is a group of transmembrane adhesion molecules found on a wide variety of cells including gliomas that has been suggested as the principal mediator of migration/invasion. The aim of the present study was to demonstrate whether antibody specific for the standard form of CD44 (CD44s, 85-90 kDa) might prevent invasion, thus blocking growth of the 9L gliosarcoma in vivo. High expression of CD44s on the surface of 9L cells and brain tumors was demonstrated by immunochemistry. Fluorescence-activated cell sorting (FACS) demonstrated binding saturation of anti-CD44s monoclonal antibody (mAb) to the receptor at 1 microg/5 x 10(5) cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive, up to 95%+/-2.5% detachment of 9L cells from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in significantly reduced 9L brain tumors (2.5%+/-0.4%)--measured as the quotient: tumor surface (mm2)/brain surface (mm2) x 100--as compared to untreated (16.1%+/-2.2%) or sham-treated rats (16%+/-3.7% to 16.1%+/-3%). We conclude that CD44s-targeted treatment with specific mAb may be an effective means for preventing glioma progression.
Clin Exp Metastasis 1999 May
PMID:CD44s-targeted treatment with monoclonal antibody blocks intracerebral invasion and growth of 9L gliosarcoma. 1043 7

We report a case of gliosarcoma with areas of primitive neuroepithelial differentiation arising in the temporal lobe of a 53-year-old man. The sarcomatous component of this tumor was perivascular in its distribution and showed expression of factor VIII-related antigen, smooth muscle actin and CD34. The primitive neuroepithelial component possessed a small cell morphology and showed expression of neuronal antigens. Strong expression of p53 was demonstrated throughout the tumor with only focal weak expression of epidermal growth factor receptor. The tumor developed widespread extraneural metastases 5 months after surgical resection of the primary tumor. Histological examination of the liver metastases showed them to consist predominantly of the primitive neuroepithelial component. We believe this to be a novel pattern of differentiation in a gliosarcoma which in this case was associated with an aggressive metastatic potential.
 ...
PMID:Gliosarcoma with areas of primitive neuroepithelial differentiation and extracranial metastasis. 1214 29


1 2 3 4 Next >>