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)

Cancer chemotherapy has developed rapidly over the last twenty years. The majority of patients with cancer die from metastatic disease, so the major therapeutic advance now must be better systemic therapy. From its early beginning in the 1940's with oestrogen therapy for prostatic cancer, nitrogen mustards in the lymphomas, and folic acid antagonists in childhood leukaemia, there are now between thirty and forty active anti-cancer agents in clinical use. The main clinical pharmacological points of the major agents are briefly reviewed, together with their main dose-limiting toxic effects and their activity as single agents. Clinical chemotherapy has developed by the introduction of newer agents from the drug screening programmes and a better understanding of the scheduling to avoid serious toxicity. Although drug-resistance is still a major problem, by combining different active agents there has been a dramatic improvement in survival of patients with selected tumours. More recently, treatment of patients early, before they have gross clinical recurrence, has already shown some benefit in pre-menopausal patients with carcinoma of the breast and in patients with osteosarcoma. The limitations of clinical measurements in monitoring therapy are clear, and a major improvement could well be realised if therapy could be monitored on the basis of quantitative markers. The clinical impact of cancer chemotherapy has already been dramatic in drug-sensitive tumours, but these only contribute a small proportion of the total. Some of the common tumours fall into the group that are relatively drug sensitive where the lives of patients can be prolonged, but there is still a significant fraction of tumours which are insensitive to existing drugs and which will probably require the development of newer agents before chemotherapy can make any impact on the survival of patients with these tumours.
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PMID:The current role of cancer chemotherapy. 36 Nov 39

Spontaneous pneumothorax is an uncommon complication of lung metastatic disease. In most of the cases reported until today, the primary disease was a sarcoma (osteogenic sarcoma, soft tissue sarcoma, hemangioendotheliosarcoma, and Ewing's sarcoma). An exceptional case of spontaneous pneumothorax in a patient suffering from carcinoma of the breast with lung metastases, is herein presented. The pneumothorax developed immediately after regression of lung metastases during administration of combined chemotherapy. Some etiological factors, as well as the rarity of this complication and its treatment, are also discussed.
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PMID:Spontaneous pneumothorax complicating lung metastases from carcinoma of the breast. 83 Mar 15

Postirradiation and Paget's osteosarcomas are high-grade malignancies. The five-year survival was only 10% in recent experience at the author's institution. Progressive pain is an important clinical feature in both conditions. Careful roentgenographic studies demonstrate cortical destruction and a soft-tissue mass in virtually all patients. Metastasis was present in 25% of both groups of patients at presentation. In contrast to previous series, more than 80% of the patients with postirradiation osteosarcoma had had irradiation for malignant entities and more than 70% had been treated with modern radiotherapy regimens (cobalt-60 or linear accelerator). Twice as many patients with postirradiation osteosarcoma were evaluated and treated in the 1980s than in the previous decade. The initial indication for irradiation often was carcinoma of the breast, uterus, or cervix, or lymphoma. Two-thirds of the patients had progressive disease that was not controllable within six months after diagnosis. Early detection may be the only effective means of improving survival with postirradiation or Paget's osteosarcoma. These patients require lifelong follow-up evaluations.
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PMID:Survival and management considerations in postirradiation osteosarcoma and Paget's osteosarcoma. 188 30

The data on 26 patients with solitary metastatic lesions arising in cortical bone were studied. Nineteen patients were over 50 years of age. In 19 patients, the cortical metastasis was the first indication of the presence of a primary malignant condition. In seven cases, cortical metastases developed in patients with a known primary tumor. The primary tumors involved were eight renal cell carcinomas, six bronchogenic carcinomas, two carcinomas of the gastrointestinal tract, one osteosarcoma, one neuroblastoma, one melanoma, one hepatoma, one carcinoma of the breast, and one thyroid carcinoma. In four cases, the primary tumor remained unknown. A metastatic origin should be considered in the differential diagnosis of an osteolytic lesion arising in the cortex of a long bone, especially in older patients and in patients with a known primary malignant condition. The cortical bone metastases encountered in this study did not originate solely from bronchogenic carcinoma, as has been reported by other authors. Cortical metastases are probably less rare than has been hitherto assumed.
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PMID:Cortical bone metastases. 317 2

Ionizing radiations have been shown to be carcinogenic to man as well as experimental animals. Malignancies following therapeutic radiation occur rarely. Over the past 10 years the authors recorded 10 cases of tumours in irradiated tissues. 3 occurred in patients irradiated for nasopharyngeal carcinoma, 3 were irradiated for tuberculosis adenitis, 2 for carcinoma of the cervix, 1 for carcinoma of the breast and 1 for basal cell carcinoma. The latent period for tumour induction following the irradiation varied from 5 years to 31 years. All these cases showed no evidence of recurrence or metastases of the original primary lesion; and the histology of the second primary differed from the first. Evidence of radiation damage was seen in all cases except for 2 patients who were treated for tuberculosis adenitis. The doses received varied from 900r to about, 9000r. Among the tumours produced, there were 3 cases of squamous cell carcinoma of the oral & postcricoid region, 2 cases of papillary carcinoma of the thyroid, 2 cases of adenocarcinoma of the rectum, 1 case of adenocarcinoma of the ethmoid, 1 case of osteosarcoma of the mandible and 1 case of extraskeletal osteosarcoma. The clinical features of these cases are discussed and other cases reported in the literature are reviewed.
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PMID:Radiation induced cancer: a report of 10 cases. 627 26

Spindle cell (sarcomatoid) carcinoma of the breast is a rare variant of breast cancer that has been classified under the broad rubric of metaplastic carcinoma. Because the term "metaplastic carcinoma" comprises a heterogeneous group of tumors, it has been difficult to reliably predict biologic potential or to determine optimal therapy. To better characterize the spindle cell subset of metaplastic breast carcinomas, we reviewed 29 cases. All patients were adult females ranging from 40 to 96 years of age (median, 68 years). Tumor size ranged from 1.5 to 15 cm (median, 4 cm). Treatment was by excision and/or mastectomy with axillary node evaluation in most cases, often combined with postoperative radiation and/or chemotherapy. All cases were clinically of breast origin, showed >or=80% spindled/sarcomatoid morphology, and demonstrated keratin positivity and/or close association with ductal carcinoma in situ. Immunohistochemical studies showed evidence suggesting myoepithelial differentiation as exhibited by immunoreactivity for smooth muscle actin, cytokeratin 14, and p63 in a subset of cases (39%). Twenty-seven cases exhibited pure spindled or sarcomatoid morphology of variable appearance and nuclear grade, whereas 2 contained high-grade invasive ductal carcinoma comprising <or=20% of the tumor mass. Two cases exhibited heterologous elements (1 rhabdomyosarcoma and 1 with both chondrosarcoma and osteosarcoma) and 4 were associated with ductal carcinoma in situ. Follow-up data were available on 24 of 29 patients (range, 1-120 months; median, 20 months). Of 20 cases in which axillary nodes were biopsied, definitive nodal metastases were identified in only 1 (5%), and this was in a case with a significant component of invasive ductal carcinoma. Three patients developed local recurrences. Extranodal metastases occurred in 11 of 24 patients (46%), most commonly to the lungs. Ten of 24 patients (42%) died of disease at a median interval of 11.5 months (range, 1-46 months) and 3 patients were alive with metastatic disease. Eight patients were alive with no evidence of recurrent or metastatic disease (median, 29.5 months). Based on this series, spindle cell/sarcomatoid carcinoma of the breast is a highly aggressive neoplasm with a high rate of extranodal metastases. Purely spindled/sarcomatoid tumors have a significantly lower rate of nodal metastases than conventional ductal and lobular breast carcinomas.
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PMID:Spindle cell (sarcomatoid) carcinoma of the breast: a clinicopathologic and immunohistochemical analysis of 29 cases. 1725 81

Small bowel obstruction in an oncology patient is a common and serious medical problem which is associated with diagnostic as well as therapeutic dilemmas. While the condition is most commonly caused by postoperative adhesions and peritoneal carcinomatosis, other causes have been reported [Cormier WJ, Gaffey TA, Welch JM, et al. Linitis plastica caused by metastatic lobular carcinoma of the breast. Mayo Clinical Proceedings 1980;55:747-53; Clavien P-A, Laffer U, Torhos J, et al. Gastrointestinal metastases as first clinical manifestation of the dissemination of a breast cancer. European Journal of Surgical Oncology 1990;16:121-6; Bender GN, Maglinte DD, McLarney JH, et al. Malignant melanoma: patterns of metastasis to the small bowel, reliability of imaging studies, and clinical relevance. American Journal of Gastroenterology 2001;96:2392-400; Gatsoulis N, Roukounakis N, Kafetzis I, et al. Small bowel intussusception due to metastatic malignant melanoma. A case report. Technical Coloproctology 2004;8:141-3; Hung GY, Chiou T, Hsieh YL, et al. Intestinal metastasis causing intussusception in a patient treated for osteosarcoma with history of multiple metastases: a case report. Japanese Journal of Clinical Oncology 2001;31(4):165-7; Chen TF, Eardley I, Doyle PT, Bullock KN. Rectal obstruction secondary to carcinoma of the prostate treated by transanal resection of the prostate. British Journal of Urology 1992;70(6):643-7; Kamal HS, Farah RE, Hamzi HA, et al. Unusual presentation of rectal adenocarcinoma. Roman Journal of Gastroenterology 2003;12(1):47-50; Hofflander R, Beckes D, Kapre S, et al. A case of jejunal intussusception with gastrointestinal bleeding caused by metastatic testicular germ cell cancer. Digestive Surgery 1999;16(5):439-40]. One of these, reported thus far in only very few patients, is obstruction caused by secondary tumors, i.e. metastases from other organs to the small bowel wall. As cancer patients live longer with improved therapy, physicians are more likely to cope with rare phenomena of neoplasms, such as small bowel obstruction caused by secondary tumors. We hereby present a review of the relevant medical literature. The goal of this article is to define current knowledge on this phenomenon, with emphasis on its epidemiology and clinical characteristics, and to increase the awareness of the clinician treating cancer patients of such possibility.
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PMID:Small bowel obstruction caused by secondary tumors. 1690 10

Dihydrofolate reductase (DHFR) is an essential enzyme involved in de novo purine and thymidine biosynthesis. For several decades, selective inhibition of DHFR has proven to be a potent therapeutic approach in the treatment of various cancers including acute lymphoblastic leukemia, non-Hodgkin's lymphoma, osteogenic sarcoma, carcinoma of the breast, and head and neck cancer. Therapeutic success with DHFR inhibitor methotrexate (MTX) has been compromised in the clinic, which limits the success of MTX treatment by both acquired and intrinsic resistance mechanisms. We report that benzamide riboside (BR), via anabolism to benzamide adenine dinucleotide (BAD) known to potently inhibit inosine monophosphate dehydrogenase (IMPDH), also inhibits cell growth through a mechanism involving downregulation of DHFR protein. Evidence to support this second site of action of BR includes the finding that CCRF-CEM/R human T-cell lymphoblasic leukemia cells, resistant to MTX as a consequence of gene amplification and overexpression of DHFR, are more resistant to BR than are parental cells. Studies of the mechanism by which BR lowers DHFR showed that BR, through its metabolite BAD, reduced NADP and NADPH cellular levels by inhibiting nicotinamide adenine dinucleotide kinase (NADK). As consequence of the lack of NADPH, DHFR was shown to be destabilized. We suggest that, inhibition of NADK is a new approach to downregulate DHFR and to inhibit cell growth.
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PMID:A second target of benzamide riboside: dihydrofolate reductase. 2295 84

Notch 1 to 4 receptors are important determinants of cell fate and function, and Notch signaling plays an important role in skeletal development and bone remodeling. After direct interactions with ligands of the Jagged and Delta-like families, a series of cleavages release the Notch intracellular domain (NICD), which translocates to the nucleus where it induces transcription of Notch target genes. Classic gene targets of Notch are hairy and enhancer of split (Hes) and Hes-related with YRPW motif (Hey). In cells of the osteoblastic lineage, Notch activation inhibits cell differentiation and causes cancellous bone osteopenia because of impaired bone formation. In osteocytes, Notch1 has distinct effects that result in an inhibition of bone resorption secondary to an induction of osteoprotegerin and suppression of sclerostin with a consequent enhancement of Wnt signaling. Notch1 inhibits, whereas Notch2 enhances, osteoclastogenesis and bone resorption. Congenital disorders of loss- and gain-of-Notch function present with severe clinical manifestations, often affecting the skeleton. Enhanced Notch signaling is associated with osteosarcoma, and Notch can influence the invasive potential of carcinoma of the breast and prostate. Notch signaling can be controlled by the use of inhibitors of Notch activation, small peptides that interfere with the formation of a transcriptional complex, or antibodies to the extracellular domain of specific Notch receptors or to Notch ligands. In conclusion, Notch plays a critical role in skeletal development and homeostasis, and serious skeletal disorders can be attributed to alterations in Notch signaling.
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PMID:Notch Signaling and the Skeleton. 2707 49

Notch (Notch1 through 4) are transmembrane receptors that play a fundamental role in cell differentiation and function. Notch receptors are activated following interactions with their ligands in neighboring cells. There are five classic ligands termed Jagged (Jag)1 and Jag2 and Delta-like (Dll)1, Dll3, and Dll4. Recent work has established Notch as a signaling pathway that plays a critical role in the differentiation and function of cells of the osteoblast and osteoclast lineages and in skeletal development and bone remodeling. The effects of Notch are cell-context dependent, and the four Notch receptors carry out specific functions in the skeleton. Gain- and loss-of-function mutations of components of the Notch signaling pathway result in a variety of congenital disorders with significant craniofacial and skeletal manifestations. The Notch ligand Jag1 is a determinant of bone mineral density, and Notch plays a role in the early phases of fracture healing. Alterations in Notch signaling are associated with osteosarcoma and with the metastatic potential of carcinoma of the breast and of the prostate. Controlling Notch signaling could prove useful in diseases of Notch gain-of-function and in selected skeletal disorders. However, clinical data on agents that modify Notch signaling are not available. In conclusion, Notch signaling is a novel pathway that regulates skeletal homeostasis in health and disease.
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PMID:Notch in skeletal physiology and disease. 3034 67


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