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

This article reports the results of clinical testing in pediatric patients of a new contrast agent, gadoteridol injection (ProHance), developed by Squibb Diagnostic as a nonionic gadolinium agent for use in magnetic resonance imaging (MRI). Thirteen children (four girls and nine boys) ranging in age from 10 to 18 years were enrolled in the study. The children had MR studies of the brain and/or spine with T1-weighted, T2-weighted, and postgadoteridol injection T1-weighted sequences. Five children had primary brain or spine neoplasms, three children had metastatic disease to the central nervous system, one child had a recurrent brain neoplasm and spinal canal metastasis, one child had an arteriovenous malformation, and two children were normal on the MRI studies. No minor or major reactions to gadoteridol injection developed in the 13 patients. Gadoteridol injection provided excellent delineation and enhancement of the arteriovenous malformation and all of the primary and secondary neoplasms of the central nervous system except for one case of a grade 1 glioma of the midbrain. Gadoteridol injection is a safe and excellent contrast agent for use in MRI.
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PMID:Magnetic resonance imaging of the central nervous system in children with a new nonionic gadolinium contrast agent--gadoteridol injection (ProHance). 849 90

Recent studies suggest that cysteine proteinase cathepsin L is involved in the process of tumor invasion and metastasis. We examined cathepsin L activity in brain tumor tissue samples by an enzymatic assay, and cathepsin L protein content by enzyme-linked immunoadsorbent assays and Western blotting to determine whether increased levels of cathepsin L correlate with the progression of human gliomas. Native and acid-activatable cathepsin L activities were highest in glioblastomas followed by anaplastic astrocytomas and were lowest in low-grade gliomas and normal brain tissues. Significantly higher amounts of an M(r) 29,000 cathepsin L were present in glioblastomas and anaplastic astrocytomas than in normal brain tissues and low-grade glioma tissue extracts. Using specific antibodies to cathepsin L, we also studied its cellular distribution by immunohistochemical procedures. Higher diffuse cathepsin L immunoreactivity was found in glioblastomas than in low-grade gliomas and normal brain tissue samples. Finally, the addition of cathepsin L antibody inhibits the invasion of glioblastoma cell lines through Matrigel invasion assay. These results suggest the expression of cathepsin L is dramatically upregulated in malignant gliomas and correlates with the malignant progression of human gliomas in vivo.
Clin Exp Metastasis 1996 Jan
PMID:Expression and immunohistochemical localization of cathepsin L during the progression of human gliomas. 852 13

Following pulmonary metastases, alveolar soft part sarcoma has an unexplained predisposition to metastasize to the brain. Herein, a case of alveolar soft part sarcoma solitarily metastatic to the brain is described. A 23-year old female underwent the resection of alveolar soft part sarcoma from the right thigh. Three years after the surgery, a brain tumor was resected and pathology proved it was a metastatic alveolar soft part sarcoma. She is currently alive and well 6 years after brain surgery. Our report suggests that surgical resection for solitary brain metastasis from alveolar soft part sarcoma is an effective treatment modality.
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PMID:Successful treatment for solitary brain metastasis from alveolar soft part sarcoma. 854 72

The catalytic cycle of topoisomerase II is the target of some of the most successful antitumor agents used today, e.g. etoposide (VP-16), in the treatment of testicular cancer and small-cell lung cancer. The cell kill mediated by topoisomerase II poisons can be antagonized by distinct drug types. Thus, we have demonstrated etoposide antagonism with the type-II anthracycline aclarubicin, the antimalarial drug chloroquine, and the cardioprotective agent ICRF-187. In other setups, combinations of agonist and antagonists have led to high-dose regimens for counteracting drug resistance. Thus, the exploitation of folinic acid rescue for methotrexate toxicity and the use of mesna to protect against cyclophosphamide toxicity have enabled the use of high-dose methotrexate and cyclophosphamide protocols. Using a similar approach, we have studied possible ways to apply antagonists to topoisomerase II poisons. NDF1-hybrid female mice were treated with the various drugs and drug combinations. Lethality (LD10 and LD50 values) was computed by use of the maximum-likelihood method, and the antitumor effect of the drugs was compared in mice inoculated i.p. with either L1210 cells or Ehrlich ascites tumor cells. In addition, the compounds were tested on L1210 cells inoculated intracranially. The toxicity of the various drugs was evaluated by weight and leukocyte counts. ICRF-187 rescues healthy mice from lethal doses of topoisomerase II poisons. In mice the ICRF-187 LD10 was 500 mg/kg. Within a wide non-toxic dose range (50-250 mg/kg) of ICRF-187 we found protection against m-AMSA and etoposide lethality. Thus, the LD10 of etoposide increased from 34 mg/kg for the single agent to 122 mg/kg for its combination with ICRF-187, corresponding to a 3.6-fold etoposide dose escalation. In contrast, ICRF-187 did not protect against lethal doses of the non-topoisomerase II-directed drug paclitaxel. We further investigated the anti-tumor effect of equitoxic schedules in mice inoculated i.p. with L1210 or Ehrlich ascites tumor cells. The L1210-bearing mice appeared to obtain a larger increase in life span from the etoposide and ICRF-187 combination as compared with etoposide alone, whereas this was not the case in mice inoculated with Ehrlich ascites tumor cells. As the hydrophilic ICRF-187 is not expected to cross the blood-brain barrier, in contrast to the lipophilic etoposide, we investigated the effect of the drug combination in mice inoculated intracranially with L1210 cells. We obtained a significant increase in life span in mice treated with ICRF-187 + etoposide as compared with mice treated with an equitoxic dose of etoposide alone. Thus, there appear to be potential routes by which one can benefit from this antagonism. ICRF-187 is a powerful nontoxic protector against the lethality of the topoisomerase II-directed drugs etoposide and m-AMSA in vivo. A brain tumor model demonstrates the superiority of high-dose etoposide treatment with ICRF-187 protection as compared with etoposide treatment alone. This implies that tumors in the brain can be reached by cytotoxic drug doses and that normal tissues can be protected due to differences in drug transport across the blood-brain barrier. ICRF-187 is therefore a promising lead compound for the development of schedules using high-dose topoisomerase II poisons in the treatment of brain tumors and metastases.
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PMID:ICRF-187 rescue in etoposide treatment in vivo. A model targeting high-dose topoisomerase II poisons to CNS tumors. 864 93

A 50 y.o. male presented with a right parietal tumor which was a glioblastoma on stereotactic biopsy. He was treated by radiation and steroids, with clinical improvement. Four months later, he presented with a left preauricular mass and cervical lymphadenopathy. CT scan showed destruction of the left mastoid and filling of the left tympanic cavity. One month later, he suffered progressive dyspnea. Chest X ray showed a mediastinal mass on the right side and numerous bilateral interstitial opacities in the lungs. A bronchial biopsy was inconclusive. His general condition worsened, and he died. Postmortem showed continuous neoplastic infiltration of the left part of the base of skull, extending into the neck. Numerous metastases were present in mediastinal lymph nodes, lung parenchyma, pleura and pleural aspect of the diaphragm. There were no subdiaphragmatic metastases. Neuropathological examination confirmed a poorly differentiated highly malignant glioblastoma with severe necrosis involving the internal part of the parietal lobe extending to the dura mater of the convexity and falx cerebri with invasion of the superior longitudinal sinus which was entirely occluded. The biopsy scar was not infiltrated. Visceral tumors were morphologically identical to the brain tumor. They were strongly GFAP positive and cytokeratin negative. Extraneural metastases of glioblastoma in the absence of surgery are uncommon in adults. Involvement of the dura mater and/or superior longitudinal sinus is an almost constant feature. In our case, this may have led to invasion of the base of skull and secondary regional, lymphatic, and hematogenous spread.
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PMID:[Extracerebral metastases of a glioblastoma, in the absence of surgery]. 872 51

Between May 1990, and June 1994, 79 patients with malignant tumors were treated radiosurgically using a Leksell gamma unit at Asan Medical Center. Of these patients, 57 were metastatic brain tumor, 12 were glioblastoma multiforme (GM), 4 were primitive neuroectodermal tumor, 3 were malignant germ cell tumor, 2 were recurrent lymphoma, and 1 was adenoid cystic carcinoma of the orbit. Among 57 patients with metastatic tumors, 28 patients harboring 60 tumors were followed clinically and radiographically. The median marginal dose for these tumors was 30 Gy and the median survival rate was 15 months. Twenty-one tumors disappeared and 32 tumors decreased in size during 2 to 6 months after radiosurgery on computed tomographic or magnetic resonance imaging scans. All 12 patients with GM were treated with conventional radiation (6,240 approximately 6,500 cGy) after surgical resection or biopsy prior to radiosurgery (13 approximately 15 Gy to margin). The results were varied. Radiosurgical treatment of two recurrent lymphomas and three recurrent mixed germ cell tumors after radiation and chemotherapy provided rapid clinical improvement with disappearance of the tumor. However, new lesions appeared in two lymphomas and one mixed germ cell tumor within 3 to 4 months. One patient with adenoid cystic carcinoma of the orbit, who was treated radiosurgically prior to resection, is alive without recurrence 31 months after the treatment. Gamma knife radiosurgery appears to be the best alternative method to surgical excision plus radiation therapy for single and multiple cerebral metastases. It also provides rapid palliation of symptoms due to recurrent malignant tumors. And it may have an adjuvant role in the treatment of some tumors delaying local recurrence, if given prior to resection. However, the preliminary results for the malignant gliomas were inconclusive.
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PMID:Gamma knife radiosurgery for malignant tumors. 875 65

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.
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PMID:Herpes vector-mediated delivery of marker genes to disseminated central nervous system tumors. 883 17

Fifteen patients (4 males and 11 females) developed brain metastases from well-differentiated thyroid cancer within 1 month to 14 years of the initial diagnosis. One patient presented with a brain tumor. Except for 3 patients with unique brain metastases, all the others had extensive metastases in nodes, lungs and bones in various combinations. Brain metastases generally appeared after the onset of metastases at other sites. The histology of the brain tumor matched the primary pathology in the 6 operated cases. The treatment was surgery and external radiation in 6 cases, and radioiodine or chemotherapy in the others. Survival in general was less than 6 months after the diagnosis of brain metastases. The prognosis is poor once the onset of brain metastases is evident.
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PMID:Brain metastases in well-differentiated carcinoma of the thyroid. 922 30

Patients undergoing brain tumor surgery are at high risk for the occurrence of a thromboembolic event. To identify a laboratory marker suitable for risk estimation the authors studied the perioperative time pattern of routine coagulation parameters and the specific hemostasis activation marker D-dimer in 28 consecutive patients at high risk (11 patients with glioma and eight patients with meningioma) and low risk (nine patients with metastases) for thromboembolism, as previously reported. As is typical during major surgery, most of the routine parameters declined, probably because of hemodilution, and recovered postoperatively to values higher than baseline, probably because of an acute-phase reaction. On Days 2 and 7 after surgery no difference in the routine parameters was recorded between patients at high (meningioma and glioma) and low risk (metastasis). The level of D-dimer was elevated at baseline in patients with metastasis, indicating a hemostatic hyperactivity that is usual in cancer patients. During surgery a marked increase in D-dimer levels occurred in patients with meningioma and glioma (pre- and postoperative median 90/2000 and 100/1020 ng/ml, respectively), but the increase was less pronounced in patients with metastasis (320/660 ng/ml). Postoperatively, D-dimer declined in patients with metastases to lower than preoperative levels (Day 7, 270 ng/ml); in patients with meningioma or glioma, however, D-dimer levels remained elevated until Day 7 (450 and 200 ng/ml, respectively). These results indicate that levels of D-dimer correlate with the reported high risk for thromboembolism in patients with meningioma and glioma, and D-dimer should be evaluated for its use in estimating individual risk and the efficiency of its use in the control of prophylactic treatment.
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PMID:Hemostasis activation in patients undergoing brain tumor surgery. 932 40

Cadherins are Ca(2+)-dependent cell adhesion molecules that play an important role in tissue formation and morphogenesis in multicellular organisms. In recent years, there have been reports of cadherin involvement in tumor invasion and metastasis. Twenty-two surgical specimens and some cultured cells were studied by immunohistochemical staining. No significant difference was observed in the patients with anaplastic astrocytoma, whereas decreased expression of N-cadherin was detected at the time of recurrence in those with glioblastoma. In these groups, cerebrospinal fluid dissemination was found, and contralateral cerebral metastases and extracranial metastases were observed. We conclude that decreased N-cadherin expression at the immunohistochemically demonstrated time of recurrence correlates with tumor invasion and dissemination of cerebrospinal fluid.
Brain Tumor Pathol 1997
PMID:Expression and role of cadherins in astrocytic tumors. 938 99


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