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)

A cohort mortality study was conducted of 15,727 white men employed by the Los Alamos National Laboratory, a nuclear research and development facility. Some of the workers at this facility have been exposed to various forms of ionizing radiation and other potentially hazardous materials. These analyses focused on whole-body ionizing radiation exposures and internal depositions of plutonium. The results indicated that overall mortality among this cohort is quite low, even after nearly 30 y of follow-up. No cause of death was significantly elevated among plutonium-exposed workers when compared with their unexposed coworkers; however, a rate ratio for lung cancer of 1.78 (95% CI = 0.79-3.99) was observed. A case of osteogenic sarcoma, a type of cancer related to plutonium exposure in animal studies, was also observed. Dose-response relationships for whole-body dose from external ionizing radiation and tritium were observed for cancers of the brain/central nervous system, the esophagus, and Hodgkin's disease.
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PMID:Mortality through 1990 among white male workers at the Los Alamos National Laboratory: considering exposures to plutonium and external ionizing radiation. 796 Jul 79

We reviewed the clinical course and the results of various treatment modalities of 80 patients with rare pulmonary neoplasms, who constituted 0.8% of all patients with primary lung cancer treated at the Mayo Clinic from 1980 through 1990. The 50 male and 30 female patients had a median age of 60 years (range, 20 to 87). The histopathologic types of these rare pulmonary neoplasms were non-Hodgkin's lymphoma (41%), carcinosarcoma (20%), mucoepidermoid carcinoma (15%), malignant fibrous histiocytoma (5%), malignant melanoma (4%), fibrosarcoma (4%), leiomyosarcoma (4%), angiosarcoma (2%), hemangiopericytoma (2%), osteosarcoma (1%), and blastoma (1%). Follow-up was complete in all 80 patients, and the median duration of follow-up was 59 months (range, 15 to 130). Of the 80 patients, 63 (79%) underwent pulmonary resection. Of the other 17 patients, 8 underwent only bronchoscopy for diagnosis, 4 had unresectable disease at thoracotomy, 3 had metastatic disease on initial assessment, and 2 had mediastinal involvement detected on mediastinoscopy. Fifty-four patients (68%) received chemotherapy or radiation treatment (or both). The overall 5-year survival was 39%. The strongest factors that influenced survival were cell type and extent of disease at time of initial examination.
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PMID:Rare pulmonary neoplasms. 838 92

Two patients with metastatic tumors invading the left atrium are described. One is a 52-year-old woman with osteosarcoma; the other is a 77-year-old man with lung cancer. The first patient presented with severe dyspnea 1 year after treatment for a primary tumor. Cardiac metastasis was suspected, then documented by transesophageal echocardiography. The study of pulmonary vein flow showed decreased systolic forward and increased diastolic components of pulmonary venous flow. The second patient presented with chronic cough without dyspnea. Although a huge tumor invaded the left atrium, as in the first patient, a normal pattern of pulmonary vein flow with higher systolic than diastolic velocities was shown by transesophageal echocardiography. Thus, transesophageal echocardiography is not only a useful tool to diagnose left atrial metastatic tumors, but also the study of pulmonary venous flow patterns can delineate causes of dyspnea in patients with metastatic tumors invading the left atrium.
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PMID:Role of transesophageal echocardiography in the management of metastatic tumors invading the left atrium. 909 25

Halichondrin B and homohalichondrin B are novel tubulin-interacting agents isolated from marine sponges. The in vivo antitumor activities of these compounds were examined in human tumor models in immunodeficient mice and rats. In nude mice, regression or pronounced delay of subcutaneous tumor growth was obtained with both halichondrins, at a maximum tolerable dose of 20 micrograms/kg Q2Dx5, in three of four vinblastine-sensitive tumors, including two melanomas and one osteosarcoma; one small-cell lung cancer line was resistant. The halichondrins as well as vinblastine showed only marginal activity against KM20L colon carcinoma xenografts. In a LOX melanoma lung colony formation assay in groups of six nude mice, all control animals were sacrificed because of respiratory symptoms 38 days after cell injection, and likewise one vinblastine-treated mouse after 53 days. All halichondrin-treated mice in the lung colony assay appeared healthy throughout an observation period of 112 days (p = 0.002). Upon necropsy all vinblastine-treated animals, and two of six mice in the halichondrin group, had macroscopic lung tumor colonies. In a nude rat model for LOX bone marrow metastases, the mean lifespan of untreated control animals was 15 days. Whereas vinblastine had only a marginal effect (17 days) in this model, halichondrin B prolonged the lifespan of the animals to 32 days, representing a significant (p = 0.0016) difference between the two compounds. In conclusion, the halichondrins, which comprise a subtype of tubulin-interactive anti-mitotic agents, showed distinct antitumor activity profiles in human tumor models, thereby encouraging their further preclinical development and possible clinical evaluation.
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PMID:Comparative antitumor activities of halichondrins and vinblastine against human tumor xenografts. 941 95

We constructed an adenoviral vector containing human p16 cDNA in order to evaluate the cytotoxic effects of exogenous p16 expression on cancer cell proliferation and to explore the potential use of p16 in cancer gene therapy. Following infection of human breast (MCF-7, MDA-MB-231, and BT549), osteosarcoma (U-2 OS and Saos-2), cervical (C33a), and lung cancer (H358) cell lines with the recombinant adenovirus Adp16, high levels of p16 expression were observed in all cell lines. Cancer cell lines which were mutant or null for p16 but wild-type for the retinoblastoma gene product (pRb) (MCF-7, MDA-MB-231, BT549 and U-2 OS) were 7-22-fold more sensitive to the cytotoxic effects of Adp16 than to a control virus. In contrast, cancer cell lines which were wild-type for p16 but mutant or null for pRb (Saos-2, C33a and H358) were <threefold more sensitive to Adp16 when compared to a control virus. Analysis of 5-bromodeoxyuridine incorporation into DNA following infection with Adp16 showed a loss of S phase in those cell lines which were null or mutant for p16 but expressed a functional pRb. This cell cycle arrest was associated with binding of the p16 protein to cyclin-dependent kinase 4 and dephosphorylation of pRb. In contrast, human cancer cell lines expressing a wild-type p16 and a mutant pRb or no pRb showed no substantial loss of S phase following Adp16 infection. Based on these studies, we conclude that p16-mediated cytotoxicity is tightly associated with the presence of functional pRb in human cancer cells, and that tumor cells which are mutant or null for p16 are candidates for Adp16 mediated cancer gene therapy.
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PMID:Effects of adenovirus-mediated p16INK4A expression on cell cycle arrest are determined by endogenous p16 and Rb status in human cancer cells. 946 45

The expression of Bfl-1 gene, a novel Bcl-2 related gene, was determined by Northern blot analysis using a radiolabeled cDNA specific for Bfl-1 gene in 82 surgically resected tissue specimens of 28 gastric cancers, 15 colon cancers, nine breast cancers, eight bone and soft tissue sarcomas, five ovarian cancers, nine colon adenomas and eight gastric adenomas. A high rate of expression was observed in gastric and colon cancer, at 86 and 93%, respectively. In breast cancer, bone and soft tissue sarcoma and ovarian cancer, the expression rate was 33, 25 and 40%, respectively. In stomach cancer, the expression rate of Bfl-1 gene in metastatic lymph nodes was 82%, which was higher than 50% of the primary sites (p < 0.02). The intensity of RNA bands of the gastric cancer specimens was compared according to the stage, demonstrating that there was no difference in the expression levels of Bfl-1 gene between the stages in both primary sites and metastatic lymph nodes. Bfl-1 gene was expressed in three (33%) out of nine adenomas of the colon, while it was not detected in all eight gastric adenomas, We also examined the RNA expression of Bfl-1 gene in 22 human cancer cell lines consisting of five stomach cancer, four squamous cell carcinoma, three lung cancer, three cervical cancer, two colon cancer, two brain cancer, two leukemia and one osteosarcoma cell lines. Bfl-1 gene band was detected in one (5%) cervical cancer cell line, SiHa. The results of cancer tissue specimens indicate that Bfl-1 gene may play an important role in carcinogenesis of human cancers and may be involved in a relatively early phase of the adenoma-carcinoma sequence in colon cancer development. However, the mechanism responsible for the very low rate of expression in established cell lines is not clearly understood and further investigation is necessary to clarify the mechanism involved.
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PMID:Expression of a novel Bcl-2 related gene, Bfl-1, in various human cancers and cancer cell lines. 949 79

Normal human cells stop proliferation after a certain number of cell divisions. This phenomenon is called cellular aging. The fact that the senescence phenotype is dominant and the immortal one is recessive indicates that immortalization of human cells may be caused by loss of functions of certain genes in normal cells. Based on this evidence, several cDNA clones whose expression was down-regulated during the immortalization process of human cells were isolated by the representative difference analysis (RDA) system in our laboratory. One of them, which was named REIC, was expressed to a lower degree in three human immortalized cell lines as compared with their parental normal counterparts. In addition, the expression of REIC was markedly lower in eight human tumor-derived cell lines (Hep3B and HuH-7 hepatocellular carcinomas, HuH-6 Clone 5 hepatoblastoma, HuCCT-1 cholangiocarcinoma, A549 lung cancer, HaCaT immortalized keratinocyte, HeLa cervical carcinoma, and Saos-2 osteosarcoma). In contrast, among the human tissues examined, the heart and brain, which contain a large number of post-mitotic cells, showed the highest expression of REIC. The full-length REIC cDNA revealed that the predicted protein is 350 amino acids in length and possesses coiled-coil tertiary structures in each of the amino- and carboxyl-termini. Furthermore, a search of the protein database revealed a match of this gene product with Dkk-3, which is a novel inhibitor of Wnt oncogene. These results indicate that the REIC cloned by us may function as a tumor suppressor.
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PMID:A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines. 1065 5

In the past years, clinical research performed by cooperative groups achieved important results. The trials of adjuvant chemotherapy in breast and colorectal cancer or neoadjuvant treatment in osteosarcoma are cornerstones in the history of medical oncology and highlight the importance of research performed by cooperative groups. However, there are many difficulties for the functioning of cooperative groups: financial support, slow enrollment of patients in clinical trials, insurance related problems and quality control of clinical research. In the last few years, our group focused its interest on lung cancer, both small cell and non-small cell. The group is composed of experts from various disciplines in oncology. The clinical interest of the group has focused on two aspects of lung cancer: quality of life and treatment of elderly patients. Our group is giving significant contributions to the field of lung cancer. Today, large controlled clinical trials are ongoing.
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PMID:Originality, benefits and difficulties of clinical research performed by cooperative groups: the experience of an Italian Lung Cancer Study Group. 1099 18

The differential diagnosis of an osteoblastic vertebral lesion (ivory vertebra) includes metastatic prostate cancer, lung cancer, lymphoma, osteosarcoma and Paget's disease. We report a case of a man who was initially diagnosed with Paget's disease on vertebral biopsy. He failed to respond to conventional bisphosphate therapy. The review of the original biopsy specimen showed metastatic carcinoid tumor involving the bone marrow. The various features of carcinoid tumors metastasizing to the skeleton are briefly reviewed.
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PMID:Case of an ivory vertebra. 1102 70

Introduction of the herpes simplex type I thymidine kinase (HSV-TK) gene into tumor tissue, followed by ganciclovir, initiates a phosphorylation cascade that induces formation of a toxic ganciclovir triphosphate. Animal trials suggest that this ganciclovir triphosphate has antitumor activity. Here we report application of the HSV-TK transfection approach using a retroviral construct. Sixteen patients (median age 61.5 years) with refractory carcinoma (13 melanoma, 1 breast cancer, 1 nonsmall-cell lung cancer, and 1 osteogenic sarcoma) received intratumoral injection of HSV-TK retroviral vector at escalating doses (0.2x10(7) cfu per injection x 5 daily doses) and we evaluated them for toxicity and activity. We observed grade III pain associated with cellulitis in one patient following injection. Analysis of blood samples drawn between 3 and 28 weeks from 14 patients for replication-competent retrovirus by PCR analysis of the amphotrophic envelope revealed no replication-competent retrovirus. We injected 21 lesions. We identified no tumor responses of the injected lesions. Of 13 patients with advanced melanoma, 6 survived over one year. Thus, injection of retroviral delivered HSV-TK in patients with refractory cancer was well-tolerated.
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PMID:Toxicity assessment of intratumoral injection of the herpes simplex type I thymidine kinase gene delivered by retrovirus in patients with refractory cancer. 1148 88


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