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)

Checkpoint genes, activated in response to DNA damage and other stresses, are frequently targeted for alteration in cancer. Checkpoint kinase 2 (CHK2, CDS1, RAD53) is activated by ataxia telangiectasia mutated (ATM) in response to gamma irradiation. Activated CHK2 stabilizes TP53, and acts on other cell cycle and stress regulators. These findings place CHK2 in the middle of a pathway frequently targeted in cancer. Because of this, and the observation that CHK2 mutations are inherited in some Li-Fraumeni cancer syndrome families, we decided to examine the role of CHK2 mutations in sporadic cancers. Exploiting the genomic sequence of chromosome 22, we looked for mutations in the exons and intron junctions of the CHK2 gene in DNA samples from 170 patients (57 osteosarcomas, 25 other sarcomas, 35 nonsmall-cell lung, 20 ovarian, and 33 breast cancers). Missense mutations affecting the forkhead and kinase domains were detected in four osteosarcomas and in one ovarian and one lung cancer. These findings of CHK2 gene mutations are consistent with osteosarcoma being a defining tumor of Li-Fraumeni syndrome. The occurrence of CHK2 mutations in sporadic cancers emphasizes the importance of the stress pathway which includes TP53.
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PMID:Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors. 1174 83

Although reports have been published describing clinical results in a large series of patients with metastatic brain tumors treated by stereotactic radiosurgery (SRS), clinical neuropathological correlation has rarely been available. The present paper describes three autopsy cases and one surgical case treated with linear accelerator based radiosurgery. The cases comprised a lung cancer, a rectal cancer, an osteosarcoma, and a malignant melanoma. Histological sections of each tumor were analyzed by light microscopy based on the Ohosi and Shimosato's histopathological classification of the effects of radiation therapy. In three cases (pulmonary squamous cell carcinoma, rectal adenocarcinoma and osteosarcoma), a large area of the tumors consisted of coagulation necrosis and non-viable tumor cells, while coagulation necrosis and non-viable tumor cells comprised a very small part of the malignant melanoma. Histopathological type of the metastatic brain tumor may be one of the factors influencing outcome after SRS.
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PMID:Effects of stereotactic radiosurgery on metastatic brain tumors of various histopathologies. 1183 38

In this study, we evaluated the potential of the distamycin derivative MEN 10716 as a telomerase inhibitor. Exposure of human melanoma cell extracts to MEN 10716 induced a dose-dependent inhibition of telomerase activity, with an IC50 of 24+/-3 microM. When intact JR8 melanoma cells were chronically exposed to the drug (200 microM every other day for 50 days), a marked inhibition (>80%) of the enzyme's catalytic activity was consistently observed starting from day 1. At later points in time, MEN 10716 inhibited melanoma cell proliferation and induced apoptosis. Cells surviving MEN 10716 exposure were characterised by a higher melanin content and a greater expression of p16(INK4A) protein than control cells. The effects of MEN 10716 were subsequently evaluated in different tumour cell systems. In particular, even in the H460 non-small cell lung cancer cell line, chronic exposure of the cells to the drug (100 microM every other day for 50 days) induced a consistent inhibition (>85%) of telomerase activity, a reduction of cell proliferation potential, and apoptosis. Conversely, MEN 10716 treatment did not appreciably inhibit cell proliferation in the U2-OS telomerase-negative human osteogenic sarcoma cell line. Interestingly, no variation in the mean telomere length was observed in MEN 10716-treated JR8 melanoma cells, whereas an appreciable increase in the mean telomere length was found in H460 lung cancer cells after drug exposure. Overall, the results of the study indicate that MEN 10716 is a possible telomerase inhibitor and suggest that abrogation of telomerase activity can affect cell proliferation even through pathways that are not dependent on telomere erosion.
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PMID:Inhibition of telomerase activity by a distamycin derivative: effects on cell proliferation and induction of apoptosis in human cancer cells. 1217 97

MUC2 is one of the major components of mucins that provide a protective barrier between epithelial surfaces and the gut lumen. We investigated possible alterations of MUC2 gene expression by p53 and p21(Sdi1/Waf1/Cip1) in a human colon cancer cell line, DLD-1, establishing subclones in which a tetracycline-regulatable promoter controls exogenous p53 and p21 expression. MUC2 mRNA more significantly increased in response to p53 than to p21. Unexpectedly, MUC2 expression was also induced in human osteosarcoma cells, U-2OS and Saos-2, by exogenous p53. We next performed a reporter assay to test the direct regulation of MUC2 gene expression by p53. Deletion and mutagenesis of the MUC2 promoter region showed that it contains two sites for transactivation by p53. Furthermore, an electrophoretic mobility shift assay indicated that p53 binds to those elements. We analyzed MUC2 expression in other cell types possessing a functional p53 after exposure to various forms of stress. In MCF7 breast cancer and A427 lung cancer cells, MUC2 expression was increased along with the endogenous p53 level by actinomycin D, UVC, and x-ray, but not in RERF-LC-MS lung cancer cells carrying a mutated p53. These results suggest that p53 directly activates the MUC2 gene in many cell types.
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PMID:Transcriptional activation of the MUC2 gene by p53. 1237 98

The cytotoxicities of 11 lupane series triterpenes against 3 human leukemias, 2 melanomas, 2 neuroblastomas and normal fibroblast cells were examined. Lupane triterpenes with a carbonyl group at C-17 (7-11) showed inhibitory effects on leukemia, melanoma and neuroblastoma cell growth. Lup-28-al-20(29)-en-3-one (8) markedly inhibited the cell growth of 3 leukemias to a greater extent than the other human cancers and normal lung fibroblast cells. The cytotoxicity profiles of 8 against human cancer cells showed that its cytotoxic effect against 3 lung cancer cell lines was strong and the cytotoxic effects against osteosarcoma, breast cancer and urinary bladder cancer cells were very weak. The morphological observations of leukemia nuclei and the gel electrophoresis analysis of DNA extracted from 8-treated leukemia cells revealed that 8 induced leukemia cell apoptosis. Furthermore, we investigated the cytotoxic effects of 8 on adriamycin (ADM)- and vincristine (VCR)-resistant K562 (K562/ADM and K562/VCR) cells. K562/ADM and K562/VCR cells showed greater resistance toward ADM and VCR when compared to parent K562 cells. However, 8 inhibited the drug-resistant K562 cell growth to the same extent as K562 cells by the induction of apoptosis.
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PMID:Anti-leukemia activities of Lup-28-al-20(29)-en-3-one, a lupane triterpene. 1269 74

During the past decade the clinical value of PET imaging has been investigated for many different tumors. As knowledge of the advantages and limitations of this modality increased, PET has gained acceptance in tumor imaging. (18)F-FDG PET is now successfully used and approved for procedure reimbursement in many types of cancer-for example, lung cancer, melanoma, lymphoma, head and neck tumors, brain tumors, esophageal cancer, and colorectal cancer. In osteosarcoma, the introduction of neoadjuvant chemotherapy has dramatically improved survival rates, thus changing the demands for state-of-the-art imaging to provide detailed information on tumor staging and grading, evaluating treatment, and detecting recurrences. In this review, the available literature on PET imaging in osteosarcoma patients is critically summarized with respect to diagnosis, staging, therapy monitoring, and follow-up focusing on the clinically used tracers (18)F-FDG and (18)F-fluoride ion. Potential and probable indications are outlined. Because of the relatively small number of patients enrolled in clinical trials published to date, further research needs to be done in larger, prospective patient series to determine the full utility of PET in osteosarcoma.
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PMID:PET imaging of osteosarcoma. 1529 71

Breast cancer is the commonest malignancy in women. However, metastatic involvement of the breast is relatively rare. Metastatic disease of the breast is therefore often an unexpected diagnosis in a female patient presenting with a breast mass. The commonest cause is spread from a contralateral breast carcinoma. Of solid tumors at other sites, the most common cancers to metastasize to the breast are, in declining order of frequency, malignant melanoma, lymphoma, lung cancer, ovarian carcinoma, soft tissue sarcoma, and gastrointestinal and genitourinary tumors. Besides these, metastases from osteosarcoma, thyroid neoplasms, and cervical, vaginal and endometrial carcinomas to the breast have been sporadically reported in the literature. A clinical presentation with pain, tenderness and discharge is distinctly unusual. A solitary lesion is the most common clinical presentation. Lesions that metastasize to the breast may produce changes that look similar to those of primary breast cancer on mammography, but they are more likely to be multiple, are frequently bilateral, and form a nidus of tumor cells that are usually round with fairly well-defined margins. Microcalcifications are not a distinguishing feature, and although their margins may be ill defined, spiculations are not commonly found. Diagnosis is generally achieved by means of fine-needle aspiration cytology or open biopsy of the breast masses. In recent reports, particular importance has been attached to the performance of fine-needle aspiration cytology diagnosis, to differentiate a metastasis from a second primary tumor, thus making it possible to avoid unnecessary mastectomy and ensure that appropriate chemotherapy and radiotherapy are implemented.
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PMID:Metastatic disease in the breast. 1496 21

Second malignant neoplasms (SMNs) after treatment of children and adolescent cancers have been extensively studied. Lung cancer as an SMN is rare in all type of primary cancer in children and in osteosarcoma as well. The authors reviewed all cases of osteosarcomas treated at their institution from 1975 to 2000 and found 22 cases of SMN, only 1 involving lung cancer. The authors describe this latter case, a 17-year-old girl with a localized osteosarcoma of the tibia who developed simultaneously lung metastases of osteosarcoma and a primitive lung adenocarcinoma only 18 months from the diagnosis. Lung cancer is unusual in youths as a primary malignancy or as a second primary malignancy. The occurrence of a primitive lung cancer together with lung metastases from osteosarcoma is even more unusual, and examination of all new lung nodules is highly recommended.
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PMID:Simultaneous osteosarcoma lung metastasis and second primary lung cancer. 1521 24

A humanized monoclonal antibody against parathyroid hormone-related protein (PTHrP) was generated from the mouse monoclonal antibody raised against the peptide corresponding to the N-terminal 34 amino acids of the human PTHrP [(PTHrP(1-34)]. The humanized antibody interacted with the PTHrP(1-34) with a kD value of 1.90 x 10(-10) M, and the epitope resides between the amino acids 20 and 30 of the PTHrP. PTHrP(1-34) significantly increased the intracellular cAMP levels in the rat osteosarcoma cells that expressed PTHR1, and the 5 microg/mL or higher concentrations of the humanized antibody almost completely blocked the PTHrP-induced cAMP production even in the presence of 2 microg/mL PTHrP(1-34), demonstrating its ability to fully neutralize PTHrP function. There was no significant difference in the potency of the mouse, chimera, or the humanized antibodies to suppress the PTHrP-induced increase in the intracellular cAMP in ROS cells. Furthermore, at the same doses, the administration of the chimera or the humanized antibody was equally effective in reducing the blood ionized calcium levels of hypercalcemic mice bearing the PAN-7-JCK human pancreatic cancer xenograft or the LC-6-JCK human lung cancer xenograft that secreted PTHrP. Thus, humanized anti-PTHrP may be useful for the treatment of the humoral hypercalcemia of malignancy in humans.
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PMID:Generation of a humanized monoclonal antibody against human parathyroid hormone-related protein and its efficacy against humoral hypercalcemia of malignancy. 1551 71

Lung cancer is usually diagnosed at an advanced stage and metastases are present in 50% of patients. Small bowel metastases from lung cancer are rare, being more frequent in patients with melanoma, uterine, ovarian, kidney or gastrointestinal cancer, or osteosarcoma. From November 1998 to August 2003, 740 cases of lung cancer (641 non-small-cell lung cancer and 99 neuroendocrine tumours) were diagnosed. We also observed 64 patients with malignant pleural mesothelioma and performed 23 pleuropneumonectomies. Over the same period we admitted 4 patients (one recurrent) with small bowel metastases, three from lung cancer and one from malignant mesothelioma. The clinical symptoms were bowel occlusion and intestinal bleeding. Radiological techniques such as small bowel enema and CT enteroclysis were used with positive results. In one patient with intestinal bleeding capsular endoscopy revealed a bleeding metastasis. All patients were operated on. Neither mortality nor morbidity were observed. All patients were discharged after a median stay of 10 days. One patient is still alive and disease-free 39 months after the first intestinal surgery for metastases. Intestinal metastases from lung cancer are rare and the diagnosis is often late. In some cases the clinical manifestations of the metastases are observed before those of the primitive tumour. However, in the presence of small bowel occlusion and intestinal bleeding of uncertain origin, clinical history-taking is very important and diagnostic procedures must be performed to exclude a secondary pathology.
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PMID:[Small bowel metastases from lung cancer]. 1555 34


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