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

Li-Fraumeni syndrome(LFS) is an autosomal dominant disorder that predisposes individuals to multiple forms of cancer including breast cancer, soft tissue sarcoma, brain tumor, osteosarcoma, leukemia, and adrenocortical carcinoma. Recently, germ-line mutation of the p53 tumor suppressor gene has been implicated in this familial disorder. We report a case of a 25-year old woman who presented with bilateral breast cancer and uterine leiomyoma. Her mother had died of early-onset bilateral breast cancer. And her younger sister had breast carcinoma as well, which was identified at the age of 22, indicating her strong familial history. To test for the presence of the p53 germ-line mutation, we analyzed the genomic DNA from the peripheral blood of the proband and her sister by PCR-SSCP analysis of exon 5 through exon 8 of the p53 gene. As a result, a p53 mutation in exon 7 was detected in an allele, and it was shared with her sister as the same pattern. Sequencing analysis determined the altered nucleotide at codon 248(CGG > TGG) which is one of the most frequent mutation sites related to LFS. Therefore, this patient has the most consistent characteristic features of LFS phenotype and it is believed that this case is the first report of a family with Li-Fraumeni syndrome carrying the p53 germ-line mutation in Korea.
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PMID:The first documentation of Li-Fraumeni syndrome in Korea. 852 48

The Li-Fraumeni syndrome was initially recognized through clinical observations at the bed side, which was followed by epidemiological studies. Children suffering from rhabdomyosarcoma were shown to have two or more of six forms of cancer in their parents, grandparents and other relatives, indicating cancer family syndrome. This syndrome has been shown to involve tumor suppressor gene p53 mutations in the germ-line. The patients in the family most often have a proband with soft tissue sarcoma or osteosarcoma, and relatives with breast cancer, brain tumor, leukemia and adrenocortical cancer. Members of the family also appear to be at risk for developing second independent malignancies during their life span. Recommendations on predictive testing for germ line p53 mutations among cancer-prone individuals have been made by the subcommittees, which were sponsored by National Cancer Institute and the National Center for Human Genome Research.
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PMID:[Li-Fraumeni syndrome]. 853 47

The biological activity of 16-epoxy side-chain analogs of 1 alpha,25-dihydroxyvitamin D3, (1 alpha,25(OH)2D3) was evaluated in vitro and in vivo. Compared to 1 alpha,25(0H)2D3, all analogs had lower affinities for the pig duodenal vitamin D receptor and also for the human serum vitamin D binding protein. The in vitro effects on cell proliferation or differentiation of human promyeloid leukemia (induction of superoxide production in HL-60 cells), human osteosarcoma MG-63 cells (osteocalcin secretion), or human breast cancer cells (incorporation of thymidine in MCF-7 cells), was markedly inhibited by several epoxy analogs, compared to 1 alpha,25(OH)2D3, but the rank order of their activity widely varied among different cancer cells. The most potent analogs (24S,25S-24-hydroxy-25,26-epoxy-22-ene-1 alpha-OHD3, 25,26-epoxy-23-yne-1 alpha-OHD3, and 25,26-epoxy-23-yne-20-epi-1 alpha-OHD3 or compounds, 16, 5, and 7, respectively) were equipotent (16 and 5) or 30-fold (compound 7 on MG-63 cells) to 40-fold (compound 7 on MCF-7 cells) more active than 1 alpha,25-(OH)2D3. These analogs were nevertheless poorly antirachitic (< 3%) when tested in vitamin D-deficient chicks (using serum and bone calcium, serum osteocalcin and duodenal calbindin D-28K, as end points). Compound 7 was also 100-fold more active than 1 alpha,25-(OH)2D3 in inhibition of proliferation of human foreskin keratinocytes. Some epoxy analogs of 1 alpha,25-(OH)2D3 thus display interesting dissociations between their receptor affinity and their potency to induce cell differentiation, whereas their effect on cell proliferation/differentiation exceed their calcemic effects more than 100- to 1000-fold.
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PMID:Biological evaluation of epoxy analogs of 1 alpha,25-dihydroxyvitamin D3. 853 86

Ketoconazole (keto) or liarozole (liaro), inhibitors of the cytochrome P450 enzymes that mediate vitamin D and A hydroxylations, could potentiate the antiproliferative effects of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and its analogs. Proliferation of MCF-7 and T47-D human breast cancer cells, MG-63 human osteosarcoma cells and HL-60 human promyeloid leukemia cells was concentration dependently inhibited by 1alpha,25(OH)2D3. The vitamin D analogs KH 1060 [20-epi-22-oxa-24,26,27-trihomo-1alpha,25(OH)2D3], RO 23-6010 [16-ene-23-yne-26-trifluoro-1,25(OH)2D2D3], ZXY 835 [20-epi-23-yne-25,26-epoxy-1alpha(OH)D3], and CD 99 [11alpha-methyl-1alpha,25(OH)2D3] were 150-,58-,16- and 7-fold more potent than 1alpha,25(OH)2D3 in inhibiting the proliferation of MCF-7 cells, respectively. A similar rank order of potency was observed in other cell lines. The antiproliferative effects of the vitamin D hormone and analogs was enhanced in MCF-7 cells when coincubated with 1 microM keto (7-, 10-, 5-, 25- and 1.3-fold more potent than in the absence of keto), respectively. The antiproliferative effect was less enhanced when 1alpha,25(OH)2D3 or its analogs KH 1060, ZXY 835 and RO 23-6010 were combined with liaro (3-, 7-, 2- and 3-fold, respectively). Keto and liaro did not markedly potentiate the activity of 1alpha,25(OH)2D3 or its analogs in MG-63 or HL-60 cells. These results suggest that differences in cellular metabolism can at least partially explain the different potency of vitamin D analogs. Moreover, the metabolism of vitamin D analogs is cell-type specific.
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PMID:Enhancement of antiproliferative activity of 1alpha,25-dihydroxyvitamin D3 (analogs) by cytochrome P450 enzyme inhibitors is compound- and cell-type specific. 864 29

Embryogenesis can be paralleled and contrasted with cancerous cell proliferation; both embryogenesis and cancer are associated with extremely rapid cell proliferation. However, unlike cancer, embryogenesis is characterized by a delicate balance of proliferative and anti-proliferative processes. We have found two chromatographically separated fractions derived from human embryonal neural tissue extracts that significantly suppress the proliferation of human breast cancer cells. The reduction in cell number was time dependent, with maximal inhibition (70%) observed after 4 days of incubation while maintaining cell viability. The anti-proliferative effect was also evidenced by decreased [3H]-thymidine incorporation. Significant inhibition of proliferation of osteosarcoma, fibrosarcoma, and Balb/c 3T3 cell lines was also obtained with a low concentration of the active fractions. Embryonal factors inhibited mouse and rat cell lines, indicating cross-species effectiveness. The SDS-PAGE of the biologically active approximately 10.7 kDa region revealed several protein bands, while the biologically active approximately 4.5 kDa fraction contained only weakly stainable bands. Thus, the embryo contains factors that control the proliferation of malignant cells. These potent and possibly novel compounds should be investigated for their potential therapeutic role in cancer and other proliferative disorders.
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PMID:Control of cell proliferation by embryonal-origin factors. 873 47

To investigate the chance of discovery of metastatic lung tumors and the five-year survival rates of patients undergoing surgical resection, we followed 99 patients who underwent initial surgical treatment at our hospital between 1979 and 1996. With regard to primary organs or sites, 32 patients had rectal cancer, 27 patients had breast cancer, 19 patients had colon cancer and 21 patients had osteosarcoma. For 22 of 99 patients (22%), discovery was due to subjective symptoms such as cough and sputum (n = 12), chest (or back) pain (n = 7) or hemosputum (n = 5). Ten of 19 patients (53%) with colon cancer experienced subjective symptoms which led to the discovery of metastases. In 76 of 99 patients (78%), metastatic lung lesions were not discovered through subjective symptoms. In 63 of those 76 patients, such lesions were initially found by plain chest roentgenography or CT. In 20 of 21 patients (95%) who had osteosarcoma, metastatic lung tumors were discovered by chest roentgenography or CT. In 14 of 76 patients, all of whom had metastatic lung carcinomas, the lesions were discovered through elevated levels of tumor markers. Therefore the importance of periodic chest roentgenography and tumor marker testing was demonstrated. Disease-free interval (DFI) was over six years in five of 32 patients (16%) with rectal cancer and 13 of 27 (48%) with breast cancer. DFI was less than five years for 15 of 19 patients (79%) with colon cancer, and less than two years for 16 of 21 (75%) with osteosarcoma. Thus, DFI differed according to the sites of the tumors. The five-year survival rates of 97 patients were examined. Patients were divided according to the sites of their primary tumors, and then subdivided according to the type of surgery they received. Patients were thus divided into five categories: I) those who underwent incomplete resection of metastatic lung lesions, II) those who underwent complete resection of both pulmonary lesions and involved mediastinal lymph nodes, III) those who had undergone previous treatment for tumors in organs other than the lung, IV) those who underwent complete resection of multiple lung lesions, and V) those who underwent complete resection of solitary lung lesions. For all primary sites, none of the patients in group I) survived for more than two years. Therefore complete resection seems very important for the treatment of metastatic lung tumors. With regard to the other groups, several facts were noted. For rectal cancer, the five-year survival rate of groups V) and III) was 55.6% in either case. Therefore complete resection of rectal cancer metastatic to the lung may improve the five-year survival rate even for patients who have previously been treated for cancers in organs other than the lung. For colon cancer, the five-year survival rate of group V) was 51.4%. Complete resection of only a solitary lung lesion may improve the five-year survival rate for colon cancer. For breast cancer, the five-year survival rate of group V) was 37.5% and that of group II) was 60.0%. This may indicate that for patients who have both pulmonary lesions and mediastinal lymph node involvement, complete resection of both is important. For osteosarcoma the five-year survival rate of group IV) was 26.0%. Thus, osteosarcoma patients have a chance of survival if they undergo complete resection of lung metastases.
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PMID:[Diagnosis and surgical treatment of metastatic lung tumors]. 883 35

In 12 patients with recurrences and metastases of different primaries (head and neck cancer, breast cancer, malignant melanoma, and osteosarcoma) who were treated with reactor fission neutrons the photon emission of irradiated tissue was measured after each radiotherapy fraction. Spectral analyses of the decay rates resulted in data for the exchange of sodium (Na) and chlorine (Cl) between the irradiated tissue and the body. About 60% of Na and Cl exchanged rapidly with a turnover half-life of 13 +/- 2 min. New defined mass exchange rates for Na and Cl amount to an average of 0.8 mval/min/kg of soft tissue. At the beginning of radiotherapy the turnover of the electrolytes in tissues with large tumor volumes was about twice that in tissues with small tumor volumes. Depending on the dose, neutron therapy led in all cases to variation in the metabolism. A maximum of Cl exchange and a minimum of Na exchange occurred after 10 Gy of neutrons (group of six previously untreated patients) or after 85 Gy (photon equivalent dose) of combined photon-neutron therapy. A significant increase in non-exchangeable fraction of Na from about 40 to 80% was observed in three tumors after a neutron dose of 10 Gy administered in five fractions correlated with a rapid reduction of tissue within 4 weeks after end of therapy. These results demonstrate for the first time the local response of the electrolyte metabolism to radiotherapy.
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PMID:In vivo neutron activation analysis of sodium and chlorine in tumor tissue after fast neutron therapy. 894 49

We report a successful resection of an osteosarcoma in the chest wall developed 25 years after irradiation. A 74-year-old woman was admitted to our hospital for her swelling in the left chest wall at August 24, 1995. At 49-year-old, she had undergone an operation and postoperative irradiation for left breast cancer. A computed tomography demonstrated a mass in the left chest wall that destructed the first rib, extending into the pleural space and invaded into the left common carotid and subclavian arteries. We planned a radical resection of the mass after repeated CT scannings, since it was histopathologically diagnosed as a chondrosarcoma and showed a rapid growth. The tumor was completely removed with radical transmediastinal forequarter amputation of the partial chest wall and total left upper extremity. The left common carotid artery was partially replaced with 6 mm EPTFE vascular prosthesis. The chest wall was reconstructed with Marlex-mesh prosthesis and a myocutaneous flap. She was discharged uneventfully and has not shown any evidence of recurrence.
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PMID:[Radiation induced osteosarcoma of the chest wall]. 895 22

To investigate the functional differences between estrogen receptor (ER) alpha and beta subtypes, we studied the expression and the transcription stimulating activities of these receptors. RT-PCR has demonstrated that ER alpha is expressed at a high level in MCF-7 cells derived from human breast cancer. Both ER alpha and ER beta were expressed at a lower level in HOS-TE85 and Saos2 cells derived from human osteosarcoma. Chloramphenicol acetyltransferase reporter assay detected the transcriptional activation by the endogenous receptor only in MCF-7 cells. Agonistic effect of tamoxifen was observed as strong as that of 17beta-estradiol on ERE activation in MCF-7 cells at the concentration of 10(-7) M when ERE-containing reporter is constructed with beta-globin promoter. The effect of tamoxifen was not apparent when the reporter was constructed with thymidine kinase promoter, suggesting that the differential gene activation between tamoxifen and estrogen may take place depending upon ERE-promoter context. Agonistic activity of tamoxifen was also detected in COS-7 and Saos-2 cells, but not in HEC-1 cells derived from human endometrial carcinoma via exogenously expressed ER. Interestingly, this effect was ER alpha specific. Thus, we demonstrate that agonistic effect of tamoxifen depends on the cell type, ERE-promoter context, and ER subtype. These parameters would explain at least a part of the tissue specific effects of antiestrogens in vivo.
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PMID:Agonistic effect of tamoxifen is dependent on cell type, ERE-promoter context, and estrogen receptor subtype: functional difference between estrogen receptors alpha and beta. 922 41

Human breast cancer cells were cultured together with their metastatic target, bone tissue, to analyze possible growth promotion effects. The coculture of human osteosarcoma cells (TE-85) with human mammary carcinoma cells (ZR-75.1) resulted in up to 8.4-fold stimulation of proliferation of the breast tumor cells. Cell contact of the two cultures was permitted through the channels of Nuclepore filters. However, physical contact turned out not to be necessary, since the proliferative stimulus was also mediated by a bone-derived diffusible factor. Conditioned medium (CM), collected from human primary bone cultures, enhanced the rate of proliferation of several breast tissue cell lines (ZR-75.1, BT-20, HBL-100), while some lines were not affected by osteoblast CM. Breast tissue lines responding to bone CM express low to intermediate levels of the c-erbB-2 gene, in contrast to nonstimulated lines, which overexpress the gene. Recent observations of metastatic spread in breast cancer patients suggest a distinctive pattern of secondary tumor distribution in association with c-erbB-2 protein expression. Bone tissue seems to be a preferential target for metastases of c-erbB-2-negative breast tumors.
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PMID:Human bone cells stimulate the growth of human breast carcinoma cells. 937 67


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