Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The clinical records and histopathologic features in 26 cases of extraskeletal osteosarcoma (ESOS) diagnosed at M.D. Anderson Cancer Center (Houston) between 1950 and 1987 were reviewed. Presentation was usually that of an enlarging soft tissue mass. The thigh (11 cases), upper extremity/shoulder girdle (three cases), and retroperitoneum (three cases) were the most common anatomic sites. Tumor size ranged from 2.5 to 30 cm. The predominant histologic pattern was osteoblastic in four cases, chondroblastic in two, fibroblastic or pleomorphic malignant fibrous histiocytoma (MFH)-like in four, giant cell type MFH-like in one, and small cell in one. Various mixtures of these patterns were seen in the remaining 14 tumors. The telangiectatic pattern was not seen as the predominant component in any primary tumor but was observed as a minor component. Thirteen tumors recurred locally and 16 metastasized; five patients had distant metastases at presentation. The lungs, bone, and soft tissue were the most frequent metastatic sites. Sixteen patients died of disease at 2 to 54 months, one patient died of unrelated causes at 61 months, seven patients were alive with no evidence of disease (NED) at 30 to 122 months, and two patients were alive with disease at 28 and 54 months, respectively. Tumor size (less than 5 cm versus greater than or equal to 5 cm) was the main prognostic factor; all patients alive with NED for whom accurate tumor measurements were available (six of seven) had neoplasms measuring less than 5 cm that were amenable to complete surgical excision. Histologic pattern and other clinicopathologic features did not significantly affect outcome.
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PMID:Extraskeletal osteosarcoma. A clinicopathologic review of 26 cases. 216 Mar 17

Between March 1983 and September 1988, 22 patients with non-metastatic malignant fibrous histiocytoma MFH of bone of the extremities were treated with two regimens of neo-adjuvant chemotherapy successively activated. Preoperatively, the patients received moderate doses of methotrexate and cisplatinum-Regimen 1- or high dose methotrexate, cisplatinum and adriamycin-Regimen 2. Cisplatinum was delivered intraarteriously, the other drugs intravenously. Limb salvage surgery was performed in 20 patients, and 2 patients were amputated. The surgical margins were adequate (radical or wide) in 18 cases and inadequate (marginal) in 4. The histologic response to chemotherapy was good (90% or more tumor necrosis) in 8 patients. In both regimens postoperative chemotherapy was tailored according to the grade of necrosis determined by preoperative treatment on the primary tumor. At an average follow-up of 40 months (15-70), 15 patients (68%) remained continuously disease-free and 7 relapsed with metastases. No local recurrences were observed. Regimen 2 was slightly more effective than Regimen 1 in terms of good histologic response (5/10 vs 1/12) and continuous disease-free survival (8/10 vs 7/127). The results demonstrate that, as in osteosarcoma, in non-metastatic malignant fibrous histiocytoma of bone in the extremities a high percentage of patients can be cured with neoadjuvant chemotherapy and that in most of them limb sparing surgery is possible and safe.
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PMID:Primary chemotherapy and delayed surgery for malignant fibrous histiocytoma of bone in the extremity. 217 84

Bone scintigraphy was performed as part of an initial diagnostic evaluation of 70 dogs admitted with primary bone tumors during a 2-year period. Tumors involved major long bones of the appendicular skeleton and included 62 osteosarcomas, 6 fibrosarcomas, and 2 chondrosarcomas. All dogs were free of radiographically detectable pulmonary metastases. Bone scintigraphy was not of value in distinguishing among various types of primary tumors. One dog with an ulnar chondrosarcoma had a scintigraphically detectable occult osseous metastasis or synchronous primary tumor, and 1 dog with osteosarcoma had a scintigraphically detectable lymph node metastasis. Pulmonary metastases were not detected scintigraphically. Of the 70 dogs, 44.3% had areas of increased isotope uptake associated with nonneoplastic disease processes.
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PMID:Bone scintigraphy in the initial evaluation of dogs with primary bone tumors. 231 89

Of 33 surgical specimens of osteosarcoma obtained from 24 patients, eight were established as transplantable tumor lines in immune-deprived CBA/CaJ inbred mice. Each line retained the histological characteristics of the corresponding primary tumor and produced human lactate dehydrogenase isozymes. Volume doubling times, which ranged from a mean of 12.3 +/- 5.6 to 39.3 +/- 9.8 days, were stable for individual lines over multiple passages. Flow cytometric analysis indicated similar cellular DNA content values in the primary human tumors and established xenograft lines; the presence of two separate stem lines, as in the original tumors, was observed in the laboratory models. Comparison of two methods of immune deprivation indicated that thymectomy, whole-body irradiation, and bone marrow reconstitution was associated with a higher rate of successful engraftment than was thymectomy, 1-beta-D-arabinofuranosylcytosine treatment, and whole-body irradiation. Bone marrow-reconstituted mice also showed less variability in tumor volume doubling time. We conclude that osteosarcoma can be heterotransplanted into bone marrow-reconstituted mice with a relatively high success rate and that the xenografts retain features characteristic of the tumors of origin. The availability of these models should prove useful in the development of new therapeutic regimens and in understanding the biology of osteosarcoma.
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PMID:Development and characterization of pediatric osteosarcoma xenografts. 232 4

In this study, 25 dogs each with a histopathologically diagnosed appendicular or axial osteosarcoma were prospectively and consecutively examined by methylene diphosphate nuclear scintigraphy. Scannings that revealed scintigraphically enhanced focal increased activity via bone uptake of the 99mTc methylene diphosphate radionuclide at sites other than the primary tumor site were compared with scintigrams obtained from dogs without osteosarcoma. Secondary scintigraphic sites were evaluated by survey radiography and, if possible, by histologic examination (biopsy or necropsy specimens). On the basis of our findings, scintigraphy seems to be more efficient than physical examination and radiographic bone survey for the diagnosis of multicentric, metachronous, or metastatic canine osteosarcoma.
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PMID:Single-phase methylene diphosphate bone scintigraphy in the diagnostic evaluation of dogs with osteosarcoma. 234 21

Twenty-one cases in which sarcomas metastasized to the ovaries are reported. The patients ranged from 18 to 79 (average 42) years of age; only five of them were over 50 years old. Eleven tumors were primary in the uterus and 10 outside the genital tract. Three uterine tumors were leiomyosarcomas, and eight, endometrial stromal sarcomas. The extragenital primary tumors were leiomyosarcoma of the stomach (1) and small intestine (2), retrovesical leiomyosarcoma (1), fibrosarcoma of the anterior abdominal wall (1), sarcoma of the mesentery of smooth muscle or neural type (1), hemangiosarcoma probably primary in the heart (1), osteosarcoma of the maxilla (1), chondrosarcoma of the rib (1), and Ewing's sarcoma of the pubic bone (1). The ovarian tumors, most of which were large, were discovered at the same time as the primary tumors in 11 cases; in seven cases, the ovarian tumor was discovered 7 months to 9 years after diagnosis of the primary tumor. In three cases, the ovarian tumors were discovered 4, 7, and 10 months before detection of the primary neoplasm. Two of these tumors were endometrial stromal sarcomas, and one, an epithelioid leiomyosarcoma of the stomach. Eleven ovarian metastases were bilateral. On microscopic examination, the greatest difficulty in pathologic interpretation was posed by the metastatic endometrial stromal sarcomas because of their simulation of sex cord-stromal tumors. Features helpful in their distinction from these tumors included the frequent presence of extra-ovarian disease, bilaterality, and a characteristic content of small arteries resembling the spiral arteries of the late secretory endometrium. The other tumor that caused major diagnostic difficulty was the metastatic epithelioid leiomyosarcoma from the stomach, which had a pattern that initially suggested the solid-tubular pattern of a Sertoli cell tumor.
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PMID:Sarcomas metastatic to the ovary: a report of 21 cases. 237 88

Six patients with extremity osteosarcoma initially underwent successful treatment of the primary tumor with four to seven courses of intraarterial cis-diamminedichloroplatin-II (IA-CDP; 100 to 150 mg/m2/course). The primary tumors in two patients were then extirpated by limb salvage. However, a local soft tissue recurrence occurred in both patients several months later. The other four patients refused surgical intervention and later also developed local bony recurrences. Reinstatement of three to five courses of IA-CDP in all six patients induced a complete response in five. The local recurrences (bony and soft tissue) in all six patients were excised. This included limb-salvage procedures in three patients. Additional postoperative chemotherapy was administered. Four patients remain alive and continuously free of disease 3.5+ to 4.5+ years after retreatment with IA-CDP.
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PMID:Pediatric osteosarcoma. Successful retreatment of relapsed primary tumor and soft tissue recurrence with intraarterial cis-diamminedichloroplatin-II. 238 6

Between April and September 1986, 60 patients with osteosarcoma have been treated according to the T10 protocol in the Pediatrics Department of the Gustave Roussy Institute in Villejuif, France. Limb sparing could be achieved in 49 patients and amputation was necessary in 11. The necrosis of the primary tumor was total or subtotal in 33 cases and incomplete in the 27 others. With a median follow-up of 28 months, the actuarial survival is 85% at 48 months and the actuarial disease-free survival is 58%; the disease-free survival of "good responders" is 75% and 32% for "bad responders".
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PMID:[Experience with protocol T10 in the pediatric service at the Gustave-Roussy Institute]. 245 56

Twelve patients with telangiectatic osteogenic sarcoma (TOS) of the extremities were treated with neoadjuvant chemotherapy, according to two different protocols. Preoperatively the patients received high-dose methotrexate(HD-MTX)/cisplatinum(CPD) or HD-MTX/CPD/adriamycin(ADM). CPD was delivered intra-arterially, the other drugs intravenously. Limb salvage surgery was performed in eight instances and four patients underwent amputation. Post operative chemotherapy was tailored according to the grade of necrosis determined by preoperative treatment on the primary tumor. In ten cases (83%) the grade of necrosis resulted higher than 95%. The mean length of follow-up was 3.5 years with a range of 18 to 72 months. Ten patients (83%) remained continuously disease-free, while two patients developed lung metastases and died of uncontrolled disease. No local recurrences were observed. These results are better than those observed in 167 contemporary cases of conventional osteosarcoma treated with the same protocols. This study confirms that TOS is not always a lethal tumor as suggested by prior reports. Employing neoadjuvant chemotherapy a high percentage of patients with TOS can be cured and in most of them, limb sparing surgery is possible and safe.
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PMID:Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for telangiectatic osteogenic sarcoma of the extremities. 247 10


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