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)

The blood-brain barrier presents a major obstacle to the systemic treatment of malignant brain tumors and brain metastases. We investigated whether the direct injection of liposomes into the internal carotid artery of normal mice or mice with experimental brain-melanoma metastases could allow delivery of anticancer drugs across this barrier. Liposomes of different sizes (greater than 5 microns, less than 1 micron, 40-80 nm) and lipid compositions were injected i.v. or into the internal carotid artery. The retention of liposomes in the brain of normal C3H/HeN mice was similar to that observed in mice with experimental brain cancer metastasis. The highest accumulation of liposomes in the brain occurred with large multilamellar vesicles, which also produced severe toxicity presumably due to embolism. Smaller liposomes were not toxic but did not accumulate in the brain. Liposomes injected i.v. did not accumulate in the brain, either. Thus, neither i.v. nor intracarotid administration of liposomes produce results suitable for therapy of brain tumors/metastases.
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PMID:Arrest and retention of multilamellar liposomes in the brain of normal mice or mice bearing experimental brain metastases. 277 29

This is the second of a six-part series on metastatic spread and natural history of 18 common tumors. Part one summarized symptom/problem anticipation, cancer metastasis, and the 18 tumors that each cause more than 6,000 deaths per year in the United States. Bladder and brain cancer were discussed, with information given on tumor types, metastatic spread and invasion, and common symptoms. Part two charts the natural histories of breast, colorectal, and esophageal cancers. Each of these cancers is presented separately, with information given on mortality rates, the most common tumor types, sites of metastases, common problems, and common oncologic emergencies. Sites of spread, resulting problems (including site-specific symptoms), and assessment parameters are presented as tables. Material is presented so that clinicians will be able to anticipate the spread of these cancers and thus identify problems early in their development so that the problems are more easily managed.
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PMID:Breast cancer, colorectal cancer, and esophageal cancer. 1008 98

This is the fourth of a six-part series on the metastatic spread and natural history of 18 common tumors. Part one summarized symptom/problem anticipation, cancer metastasis, and the 18 tumors that each cause more than 6000 deaths per year in the United States. Bladder and brain cancer were discussed, with information given on tumor types, metastatic spread and invasion, and common symptoms. Parts two and three charted the natural histories, problems, and assessment parameters of advanced cancers of the breast, colon and rectum, esophagus, kidney, and liver; and leukemia. Part four provides corresponding information on lung cancer, malignant melanoma, and multiple myeloma. Each of these cancers is presented separately, with information given on mortality rates, the most common tumor types, sites of metastases, common problems, and common oncology emergencies. Sites of spread, resulting problems (including site-specific symptoms), and assessment parameters are presented as tables. Material is presented so that clinicians will be able anticipate the spread of these cancers and can thus identify problems early in their development so that the problems are more easily managed.
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PMID:Lung cancer, malignant melanoma, multiple myeloma. 1066 Oct 62

This is the fifth of a six-part series on metastatic spread and natural history of 18 common tumors. Part 1 summarized symptom/problem anticipation, cancer metastasis, and the 18 tumors that each cause more than 6000 deaths/year in the United States. Bladder and brain cancer were discussed, with information given on tumor types, metastatic spread and invasion, and common symptoms. Parts two, three, and four charted the natural histories, problems, and assessment parameters of advanced cancers of the breast, colon and rectum, esophagus, kidney, liver, and lung; and leukemia, melanoma, and multiple myeloma. Part five provides corresponding information on non-Hodgkin's lymphoma and cancers of the oral cavity (and pharynx) and ovary. Each of these cancers is presented separately, with information given on mortality rates, the most common tumor types, sites of metastases, common problems, and common oncologic emergencies. Sites of spread, resulting problems (including site-specific symptoms), and assessment parameters are presented as tables. Material is presented so that clinicians will be able to anticipate the spread of these cancers and can thus identify problems early in their development so that the problems are more easily managed.
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PMID:Non-Hodgkin's lymphoma, oral cavity and pharynx, and ovary. 1066 Oct 69

This is the last article in a six-part series on metastatic spread and natural history of the 18 most lethal tumors. The articles summarize symptom/problem anticipation, cancer metastasis, and the 18 tumors that each cause more than 6000 deaths/year in the United States. Bladder and brain cancer were discussed, with information given on tumor types, metastatic spread and invasion, and common symptoms. Parts II, III, IV, and V charted the natural histories, problems, and assessment parameters of advanced cancers of the breast, colon and rectum, esophagus, kidney, liver, and lung; and leukemia, melanoma, multiple myeloma, non-Hodgkin's lymphoma, and cancers of the oral cavity (and pharynx) and ovary. Part VI finishes the series with discussions of cancers of the pancreas, prostate, stomach, and uterus. Each of these cancers is presented separately, with information given on mortality rates, the most common tumor types, sites of metastases, common problems, and common oncology emergencies. Sites of spread, resulting problems (including site-specific symptoms), and assessment parameters are presented as tables. Material is presented so that clinicians are able to anticipate the spread of these cancers and can thus identify problems early in their development so that the problems are more easily managed.
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PMID:Metastatic spread and common symptoms. Part six: Advanced cancer of the pancreas, prostate, stomach, and uterus. 1114 71

Treatment and prognosis of neurooncolical patients are largely determined whether tumor is a primary brain neoplasm or metastasis. Out of 284 brain cancer patients treated at the Institute's Clinic, 262 had primary tumors and 22--metastases from various sites. Combined therapy was given to 273: surgery--241, radiotherapy--273 and polychemotherapy--263. Three-year survival was reported in patients with anaplastic astrocytoma stage II (90%), stage III--(51%) and stage IV--(14%). Eighty percent of cases of brain metastases have been followed up for 9 months.
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PMID:[Results of combined therapy for brain tumors of various origin]. 1468 39

Motexafin gadolinium [gadolinium (III) texaphyrin, gadolinium texaphyrin, Gd-Tex, GdT2B2, PCI 0120] is a radiosensitising agent developed for use in cancer therapy. It is cytotoxic in haematological malignancies by selectively localising in cancer cells that have high rates of metabolism. Motexafin gadolinium inhibits cellular respiration resulting in the production of reactive oxygen species and inducing apoptosis. It is being developed by Pharmacyclics in the US. Bulk motexafin gadolinium is supplied to Pharmacyclics by the US company, Celanese, through a manufacturing and supply agreement between the two companies. In June 2003, at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO-2003), the importance of having an agent for the treatment of brain metastases from lung cancer was highlighted. Results of a phase III study were presented that showed that motexafin gadolinium treatment was associated with a delay in time to neurological and neurocognitive progression in lung cancer patients. This was an important finding, as 46.6% of lung cancer patients already have brain metastases at the time of initial diagnosis, compared with only 2.7% of breast cancer patients. Brain metastases are also often the only site of metastatic disease in patients with lung cancer. In December 2002, Pharmacyclics began a phase III trial of motexafin gadolinium in patients with brain metastases (brain cancer in phase table) from lung cancer in the US, Europe, Canada and Australia. The trial is known as the Study of neurologic progression with Motexafin gadolinium And Radiation Therapy (SMART) and will compare whole-brain irradiation with whole-brain irradiation plus motexafin gadolinium in 550 patients. The primary efficacy endpoint is time to neurological progression and the secondary endpoints are survival and neurocognitive function. In January 2003, the US FDA completed its Special Protocol Assessment (SPA) of the SMART trial with a positive result and by June 2003, enrollment had begun. In addition, phase I trials are underway in children with intrinsic pontine glioma and adults with head and neck, lung and pancreatic cancers. A phase II trial is also being conducted in the US in patients with glioblastoma multiforme. Enrollment in this trial has been completed and preliminary results have been reported. Pharmacyclics has completed enrollment and follow-up of adults in its pivotal phase III trial of motexafin gadolinium as a radiation sensitiser for the treatment of brain metastases. The trial was conducted at 35 centres in Europe, Canada and the US. Full results from this initial phase III trial were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Florida, USA, held in May 2002. Pharmacyclics also announced in October 2002, at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), that motexafin gadolinium significantly prolonged time to neurological progression when added to whole brain radiation therapy and reduced the number of deaths in patients with brain tumour. Pharmacyclics announced in September 2000 that it has initiated two NCI-sponsored phase I trials conducted under a Cooperative Research and Development Agreement (CRADA) between Pharmacyclics and the NCI. The first trial, conducted in patients with stage IIIA non-small cell lung cancer, was designed to determine the safety of two different dosing regimens of motexafin gadolinium during preoperative radiotherapy after induction chemotherapy. The second study was designed to examine the use of motexafin gadolinium in combination with stereotactic Gamma Knife radiosurgery in patients with primary glioblastoma mutiforme. Two phase I clinical trials have also been conducted for the treatment of newly diagnosed glioblastoma multiforme at the UCLA Jonsson Comprehensive Cancer Center, USA. These phase I studies were sponsored by the NCI and were conducted under a CRADA with the NCI. Pharmacyclics has also completed multicentre US phase II clinical trials of motexafin gadolinium fin gadolinium in patients with metastatic tumours of the brain who require whole brain radiotherapy. Motexafin gadolinium is in a phase II trial in patients with lymphomas and multiple myeloma in the US.
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PMID:Motexafin gadolinium: gadolinium (III) texaphyrin, gadolinium texaphyrin, Gd-Tex, GdT2B2, PCI 0120. 1472 95

We have prepared the map of regional distribution of cervical cancer in Hungary. Serial HPV genotyping of sexual partners provided evidence for the sexually transmitted infections. Molecular epidemiology studies revealed activating c-kit mutation in bilateral testicular cancers. A cost-effective molecular staging method was introduced to the management of breast cancer patients. Genomic profiling identified the gene signature of Herceptin and taxane sensitivity of breast cancer. In colon cancer patients we have determined the mutational spectrum of hMLH1 and hMSH2 genes in Hungary. The prognostic power of SHMT and MTHFR polymorphism was determined in colorectal cancer patients. In head and neck cancer the gene signature of cisplatin sensitivity and the EGFR polymorphism was determined. We have introduced a cost-effective in vitro assay to determine the drug resistance of pediatric leukemias. The prognostic power of N-myc genotyping was determined in neuroblastoma patients. A phase I trial for gene therapy of brain cancer was started by using a GM-CSF adenoviral vector system. Using global genomic approaches the gene signature of malignant melanoma and its metastatic disease was determined. We have found that Ca-channel blockers and EGFR tyrosine kinase inhibitors are effective in preclinical human melanoma models in breaking the apoptosis resistance of this tumor.
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PMID:[Activity of the National Oncology R&D Consortium in 2004]. 1590 26

Glioblastoma multiforme is the most common form of primary brain cancer. In the past decade, virotherapy of tumors has gained credence, particularly in glioma management, as these tumors are not completely resectable and tend to micro-metastasize. Adenoviral vectors have an advantage over other viral vectors in that they are relatively non-toxic and do not integrate in the genome. However, the lack of coxsackie and adenovirus receptors on surface of gliomas provides for inefficient transduction of wild-type adenoviral vectors in these tumors. By targeting receptors that are overexpressed in gliomas, modified adenoviral constructs have been shown to efficiently infect glioma cells. In addition, by taking advantage of tumor-specific promoter elements, oncolytic adenoviral vectors offer the promise of selective tumor-specific replication. This dual targeting strategy has enabled specificity in both laboratory and pre-clinical settings. This review examines current trends in adenoviral virotherapy of gliomas, with an emphasis on targeting modalities and future clinical applications.
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PMID:Adenoviral virotherapy for malignant brain tumors. 1945 8

Astrocytes play a critical role in maintaining cerebral homeostasis and their dysregulation is thought to contribute to the pathogenesis of several diseases, including brain cancer and metastasis. Similar to the human disease, we found that lung and melanoma metastases in the mouse brain are accompanied by a reactive gliosis. To begin to study the biology of astrocytes and examine how these cells might contribute to metastasis formation and progression in the brain, we generated a conditionally immortal astrocyte cell line from H-2Kb-tsA58 mice. Astrocytes grown in culture expressed glial fibrillary acid protein (GFAP), glutamate receptor 1, and the N-methyl-D-aspartate (NMDA) receptor. Astrocytes also expressed the glial-specific transporters excitatory amino acid transporter 1 (EAAT1) and EAAT2. Astrocytes grown under permissive conditions (33 degrees C) expressed SV40 large T antigen and had a doubling time of 36 h, whereas expression of SV40 large T antigen was negligible in astrocytes grown at 37 degrees C for 72 h, which coincided with a plateau in cell division. In a co-culture assay with human lung adenocarcinoma cells (PC14-PE6), astrocytes activated programs in the tumor cells that signal for cell division and survival. Hence, the immortalized cell line will be useful for studying the role of astrocytes in disease processes in the brain, such as metastasis.
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PMID:Generation of an immortalized astrocyte cell line from H-2Kb-tsA58 mice to study the role of astrocytes in brain metastasis. 1972 1


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