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)

Since the introduction of bone scans in 1951, there have been many studies comparing biologic and physical characteristics of new bone-imaging agents and the results of scintigraphy and radiology in large numbers of patients. Relatively speaking, there have been fewer studies detailing the health benefits and financial cost associated with the use of skeletal scintigraphy. This review concerns these aspects in patients with malignancies of various sites and stages. About 2% of patients with stage I or II breast cancer have bone metastases at the time they first present, whereas nearly 28% of patients with stage III disease have bone metastases. A large percentage of patients with initially negative scans develop bone metastases during the first 3--4 yr; many of them develop them within the first 12--18 mo after initial diagnosis. For patients with lung cancer, the use of bone scans in staging their disease is somewhat controversial. Several studies indicate that the yield of positive bone scans may range from as low as 2% to as high as 35%. Data on the use of bone scans in staging prostatic cancer initially are similar to those in patients with breast cancer, that is, yields of 7% in patients with stage I or II disease and a yield of about 20% with stage III disease. Children with osteosarcoma or Ewing's sarcoma rarely have bone disease distant from the site of their primary bone lesion at presentation. However, a large percentage of them (30%--40% or so) develop bone metastases during the follow-up period. As in the case with patients with breast cancer, about half of these bone metastases are evident by 12--18 mo.
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PMID:Rationale for the use of bone scans in selected metastatic and primary bone tumors. 11 84

Based on our prior experience in treating children with metastatic osteogenic sarcoma, a multidrug regimen was developed. Nine children with evaluable osteogenic sarcoma were treated with vincristine 1.5 mg/m2 on day 1, highdose methotrexate 200-300 mg/kg i.v. on day 2, with p.o. citrovorum factor "rescue" 9 mg every 6 hours x 12, followed in 2 weeks by cyclophosphamide 40 mg/kg i.v., then 2 weeks later Adriamycin 1.5 mg/kg/day x 2; in 2 weeks cyclophosphamide was repeated. After a 2-week rest, the 56-day cycle was repeated for a total period of 1 year. Oropharyngeal mucositis was the most frequent severe manifestation of gastrointestinal toxicity. Hematologic depression was mild to severe. Nine patients with clinically evaluable osteogenic sarcoma and no previous chemotherapeutic treatment were treated with this regimen. One patient had only a transient shrinkage in tumor mass, and one patient had no progression of multiple pulmonary and bone metastases for 16 months while on therapy. Of the remaining seven patients, all had clinically significant responses with tumor regression demonstrated for from 5 to 20+ months. Four of these patients (three presenting with primary tumor and pulmonary metastases) demonstrated regression of their primary tumor. In an attempt to increase the cure rate in osteogenic sarcoma, chemotherapy that has proven to be effective against metastatic osteogenic sarcoma should now be employed as prophylactic therapy, after amputation, at cancer treatment centers where it can be safely and effectively administered.
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PMID:The rationale for multiple drug chemotherapy in the treatment of osteogenic sarcoma. 107 42

Although the radiopharmaceuticals used for bone scintigraphy are of very high quality, the search for an "ideal" agent continues. To optimise the detectability of bone lesions, we analysed 244 different 99mTc-labeled phosphonates in animal experiments. In osteosarcoma-carrying rats 99mTc-labeled 1-Hydroxy-3-methyl-phosphinic-1, 1-propanediphosphonic acid (HMPD) was shown to produce the best lesion/normal bone ratio. 99mTc-MDP was used as reference. The ratio was found to be 1.28 for 99mTc-HMPD. The transferability of our results in animals to the situation in man was studied in 10 patients with bone metastases. There was for 99mTc-HMPD an improvement of the lesion/normal bone ratio by more than 60% but also an additional reduction of the soft tissue contrast by about 40%. 15% of the metastases were detected by scintigraphy using 99mTc-HMPD only and not with 99mTc-MDP. The new agent should make possible a better and earlier discrimination of bone lesions in the scintigram.
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PMID:[A phosphine-substituted diphosphonic acid (HMPD) for improved scintigraphic detection of bone lesions]. 146 53

Bromodeoxyuridine (BrdU) labeled human prostatic cancer cells, PC-3, and murine osteosarcoma cells, POS-1 were injected into the tail veins of male mice under concomitant temporal occlusion of inferior vena cava. Five minutes after release of the venous occlusion, animals were sacrificed and various tissues, organs and the vertebral bones were examined immunohistochemically using an application of BrdU-anti-BrdU methods. Obvious BrdU labeled tumor cells, isolated or clumped, were demonstrated within the venous channels along the vertebral column, the epidural venous channels around spinal nervous tissues, in the bone marrow of lumbo-sacral vertebrae and intra- and peri-prostatic venous channels. The results suggest that a blockade of short duration of venous flow at the inferior vena cava can result in the bypassing of tumor cells through the vena cava to the vertebral venous system, which has a close connection with the peri-prostatic venous plexus. Thus, the vertebral venous system may play an important role in the metastasis of prostatic carcinoma to bone. In addition this experimental procedure is a very valuable model for studying mechanisms and prevention of bone metastases from prostatic carcinoma.
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PMID:Role of the vertebral venous system in metastatic spread of cancer cells to the bone. 149 28

Twenty-two dogs with appendicular osteosarcoma were treated by amputation (n = 17) or limb-sparing surgery (n = 5). All dogs were given cisplatin (60 mg/m2 of body surface, IV) at 3-week intervals, beginning 1 week after surgery. Number of cisplatin treatments ranged from 1 to 6. Survival data for the 22 dogs were compared with survival data from a historical control group consisting of 162 dogs with appendicular osteosarcoma treated by amputation alone. Median survival time for the 22 dogs given cisplatin was estimated to be 46.4 weeks, and 1- and 2-year survival rates were estimated to be 45.5 and 20.9%, respectively. Survival time was significantly (P less than 0.0001) longer for treated dogs than for control dogs. Statistically significant relation was not found between survival time and number of cisplatin treatments. Three dogs were alive with no evidence of disease at the time of reporting. Of the remaining 19 dogs, 14 (73.4%) were euthanatized for problems documented to be related to metastases. Nine (47.4%) dogs were euthanatized because of bone metastases, and 5 (26.3%) were euthanatized because of pulmonary metastases. The proportion of dogs euthanatized because of bone metastases was significantly (P less than 0.0001) higher for treated than for control dogs. Median survival times for dogs developing bone and lung metastases were estimated to be 51.2 weeks and 21.2 weeks, respectively; however, this difference was not statistically significant. One local tumor recurrence was observed among dogs that had limb-sparing surgery. Significant difference in survival time was not observed between dogs that had limb-sparing surgery and dogs that underwent amputation.
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PMID:Treatment of dogs with osteosarcoma by administration of cisplatin after amputation or limb-sparing surgery: 22 cases (1987-1990). 163 15

Multiple foci of osteosarcoma are found in several pathological conditions: skip metastases, late bone metastases from osteosarcoma, so called metachronous osteosarcoma and multicentric osteosarcoma. The authors describe five cases with multicentric osteosarcoma of the skeleton. These lesions differ from classic osteosarcoma for their clinical and radiographical features. They generally arise in younger patients and are always sclerotic on X-rays and histological evaluation. Our data, as reported in literature, underline the poor prognosis of this disease.
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PMID:Multicentric osteosarcoma. Report of 5 cases. 175 71

36 patients with advanced malignancy were studied in a phase I trial of continuous 24-h infusion of floxuridine (FUdR) plus etoposide plus cisplatin (FEP) administered for 5 consecutive days at 4-week intervals. Study design fixed the dose rate of etoposide and cisplatin with escalation of FUdR only. Dose rate-limiting toxicity related to the FUdR component was stomatitis and diarrhoea and was invariably associated with leukopenia and thrombocytopenia when grade 3 or 4 level gastrointestinal toxicity was observed. Only 3 of 64 courses were associated with transient renal failure related to cisplatin. Drug-related deaths occurred (leukopenia-associated sepsis) in 4 patients with poor performance status (ECOG 3 and 4). Responses occurred in 15 of 26 evaluable patients (all previously treated minimally or untreated) including 5/11 non-small cell lung cancer; 3/3 oesophageal; 2/2 breast; 4/5 gastric; 1 osteogenic sarcoma; and 1 unknown primary (probably ovary). The recommended dose rates for a 5-day infusion of the three agents for good risk patients is 20 mg/m2 per day of each drug. For poor risk patients including age greater than 65 years; performance status 2 or greater; or extensive bone metastases or prior radiation; the recommended starting dose rates are: FUdR 15 mg/m2 per day; etoposide 15 mg/m2 per day; and cisplatin 20 mg/m2 per day. Dose escalation of FUdR to a maximum of 25 mg/m2 daily is feasible in selected patients demonstrating optimal tolerance.
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PMID:Infusion of floxuridine plus etoposide plus cisplatin in human malignancies. 183 61

Preoperative intraarterial (IA) cisplatin (CDP) was administered to 92 patients with nonmetastatic osteosarcoma. The ages of the patients ranged from 4 to 28 years. Sixty-four patients (70%) received 2 or 3 preoperative courses and 28 (30%) received 4 or more. Sixty-two specimens were available for pathologic examination to assess the degree of tumor necrosis. More than 90% tumor destruction was observed in 16 of 42 patients (38%) who received 1 to 3 preoperative courses as opposed to 17 of 20 (85%) who received 4 or more courses. Patients who received 4 or more courses had a 2-fold probability of achieving more than 90% tumor necrosis, and 68% underwent conservative surgery. Of those who received 3 or less courses, 23% underwent conservative surgery. Postoperatively, patients were treated with intravenous (IV) CDP alternating with doxorubicin (ADR) (Adriamycin, Adria Laboratories, Columbus, OH). Pulmonary metastases developed in 36 patients, bone metastases in 2, and local recurrence in 6. Two patients died of cardiac failure without evidence of disease. Thus, 46 patients (50%) were continuously free of disease 18 to 78 months after diagnosis. Univariate and multivariate analyses showed that male sex, low grade preoperative chemotherapy-induced necrosis, and nonosteoblastic histologic condition were prognostic factors predictive of recurrence, while male sex and large tumor size were prognostic factors predictive of death. These results are comparable with those reported by other centers and are superior to our previous experiences that yielded survival rates of 5% to 10%. A substantial number of patients also had the opportunity to achieve tumor removal with conservative surgery.
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PMID:Increased survival, limb preservation, and prognostic factors for osteosarcoma. 185 72

Bisphosphonates are compounds with a high affinity for bone and other calcified tissues. They inhibit tumor-induced bone destruction and the associated hypercalcemia by hindering the activity of the osteoclasts. Owing to a long biological half-life of bisphosphonates in the bone, a treatment using a prophylactic regimen seems possible. This paper summarizes preclinical studies with the bisphosphonate 3-amino-1-hydroxypropylidene-1,1-diphosphonic acid and two methyl derivatives; 3-N,N-dimethylamino-1-hydroxypropylidene-1,1-diphosphonic acid and 4-N,N-dimetyhlamino-1-hydroxybutylidene-1,1-diphosphonic acid with respect to their bone-protecting activity in therapy as well as in prophylaxis. To find substances that are useful for the treatment of primary tumor, as well as bone metastasis, we synthesized and tested cis-diammine[nitrilotris(methylphosphonato)(2-)-O1,N1]platin um(II) and cis-diammine[( bis-(phosphonatomethyl)amino]acetato(2-)-O1,N1)platinum(II), which contain both an osteotropic and an antineoplastic moiety. Experiments were carried out: (a) in the intratibial transplanted Walker carcinosarcoma 256B of the rat, which mimics osteolytic bone metastasis, and (b) in the transplantable osteosarcoma of the rat, which shows a histology and metastatic pattern similar to that found in man. These investigations indicate that it is possible to effect adjuvant therapy of bone metastases by combination of two compounds with different properties into one structure without losing the therapeutic characteristics of the parent compounds. They thus provide evidence that it may be possible to design compounds well suited for the therapeutic or prophylactic treatment of bone-related malignancies.
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PMID:Anticancer-agent-linked phosphonates with antiosteolytic and antineoplastic properties: a promising perspective in the treatment of bone-related malignancies? 215 96

General considerations about the possible mechanisms of action of rather low dose ionizing radiation with bone metastases and stimulated nerve fibers reveal that only minute amounts of chemicals are produced by direct interaction of energetic electrons. Thus changes of the chemical milieu due to direct interaction must be ruled out in favour of a radiation-induced trigger reaction which may then initiate a cascade of cellular responses. Organ distribution studies of a series of radioiodinated benzylidenediphosphonates with H-, HO- and H2N- in the alpha- and p-position revealed best results for pHO-NH2 (BDP3). The microscopic distribution of 131I-DBP3 in bone tissue was monitored by autoradiography. Elevated uptake in normal (tibia) and neoplastic bone (experimental osteosarcoma) corresponded with the degree of vascularization and formation of new hydroxylapatite. Unlike the uptake in human osteoblastic bone metastases the experimental osteosarcoma of SD-rats accumulated 131I-BDP3 less than normal bone. This was due to the short volume doubling time, the delay of hydroxyl-apatite deposition and the formation of necroses. Theoretical replacement of 131I in iodinated BDP3 with radioisotopes emitting higher energy electrons yielded best bone metastasis/organ ratios for 32P labeled BDP3. The bone metastasis/bone marrow dose ratio by comparison with 131I labeled BDP3 is, however, almost equal. The isotopes 130I and 133I are not suited to the achievement of higher tumor/background doses although they are higher energy beta- -emitters than 131I. Because of their short physical half life and absence of different kinetics in normal and neoplastic bone no dose enhancement in bone metastases can be attained.
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PMID:Iodine-131-labeled diphosphonates for the palliative treatment of bone metastases--III. Considerations of interaction, binding and absorbed dose. 302 76


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