Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with peripheral T-cell Lymphoma and acquired, systemic osteosclerosis is described. Bone histology showed a spectacular activation of osteoblasts accompanyed by massive new bone formation. Alkaline phosphatase in serum was elevated and increased to greater than 2000 U/l when the lymphoma became refractory to chemotherapy. In the patient's serum an osteoblast-activating factor could be demonstrated using a rat osteogenic osteosarcoma cell line (ROS 17/2.8). The factor was absent during remission of the tumor. We conclude that osteosclerosis was a paraneoplastic syndrome in this patient due to the secretion of an osteoblast-stimulating factor by the T-cell lymphoma. This situation is similar to the secretion of osteoclast-activating factors described in B-cell lymphomas, particularly multiple myeloma. The characterization of such a factor could be of therapeutic relevance.
 ...
PMID:Evidence for an osteoblast-activating factor in a patient with peripheral T-cell lymphoma and osteosclerosis. 278 45

A total of 70 patients with conventional osteosarcoma underwent preoperative chemotherapy, and here we report the histopathological effects of the chemotherapy on the tumors. The changes in the tumors since pre-chemotherapy observed at resection were classified as: (1) non-degeneration, (2) degeneration, (3) coagulation necrosis, (4) granulation, (5) fibrosis, or (6) osteosclerosis, It was thought that any coagulation necrosis was due to ischemia, while any degeneration in the tumor tissue was mainly caused by the chemotherapy. Coagulation necrosis was found at the center of the tumor, while degeneration, fibrosis, and osteosclerosis tended to be present mainly at the periphery. Coagulation necrosis was less prominent in these patients with a longer period between preoperative chemotherapy and resection. The above results suggest that coagulation necrosis was not a change caused directly by the chemotherapy, and there is a possibility that the tumor cells in these regions survived until just before resection. Accordingly, when evaluating the effects of preoperative chemotherapy, it may be inappropriate to include any area of coagulation necrosis in the calculation of the necrotic ratio.
 ...
PMID:[Histopathological study of the effect of preoperative chemotherapy on osteosarcoma]. 818 97

Sodium fluoride is a white, crystalline, water-soluble powder used in municipal water fluoridation systems, in various dental products, and in a variety of industrial applications. Toxicology and carcinogenesis studies were conducted with F344/N rats and B6C3F1 mice of each sex by incorporating sodium fluoride into the drinking water in studies lasting 14 days, 6 months, and 2 years. In addition, genetic toxicology studies were performed with Salmonella typhimurium, with mouse L5178Y cells, and with Chinese hamster ovary cells. 14-Day Studies: Rats and mice received sodium fluoride in drinking water at concentrations as high as 800 ppm. (Concentrations are expressed as sodium fluoride; fluoride ion is 45% of the sodium salt by weight.) In the high-dose groups, 5/5 male and 5/5 female rats and 2/5 male mice died; one female rat was given 400 ppm in the drinking water also died before the end of the studies. No gross lesions were attributed to sodium fluoride administration. 6-Month Studies: Rats received concentrations of sodium fluoride in drinking water as high as 300 ppm, and mice as high as 600 ppm. No rats died during the studies; however, among the mice, 4/9 high-dose males, 9/11 high-dose females, and 1/8 males in the 300 ppm group died before the end of the studies. Weight gains were less than those of controls for rats receiving 300 ppm and mice receiving 200 to 600 ppm. The teeth of rats and mice receiving the higher doses of sodium fluoride were chalky white and chipped or showed unusual wear patterns. Mice and male rats given the higher concentrations had microscopic focal degeneration of the enamel organ. Rats receiving 100 or 300 ppm sodium fluoride had minimal hyperplasia of the gastric mucosa of the stomach, and one high-dose rat of each sex had an ulcer. Acute nephrosis and/or lesions in the liver and myocardium were observed in mice that died early, and minimal alterations in bone growth/remodeling were observed in the long bones of mice receiving sodium fluoride at concentrations of 50 to 600 ppm. The sodium fluoride concentrations selected for the 2-year studies in both rats and mice were 0, 25, 100, and 175 ppm in the drinking water. These concentrations were selected based on the decreased weight gain of rats at 300 ppm and of mice at 200 ppm and above, on the incidence of gastric lesions in rats at 300 ppm in the 6-month studies, and on the absence of significant toxic effects at sodium fluoride concentrations as high as 100 ppm in an earlier 2-year study. Body Weights and Survival in the 2-Year Studies: Mean body weights of dosed and control groups of rats and mice were similar throughout the 2-year studies. Survival of rats and mice was not affected by sodium fluoride administration. Survival rates after 2 years were: male rats-control, 42/80; 25 ppm, 25/51; 100 ppm, 23/50; 175 ppm, 42/80; female rats-59/80; 31/50; 34/50; 54/81; male mice-58/79; 39/50; 37/51; 65/80; female mice-53/80; 38/52; 34/50; 52/80. Neoplastic and Nonneoplastic Effects in the 2-Year Studies: The teeth of rats and mice has a dose-dependent whitish discoloration, and male rats had an increased incidence of tooth deformities and attrition leading on occasion to malocclusion. The teeth of male and, to a lesser degree, female rats had areas of microscopic dentine dysplasia and degeneration of ameloblasts. Dentine dysplasia occurred in both dosed and control groups of male and female mice; the incidence of this lesion was significantly greater in high-dose than in control male mice. Osteosclerosis of long bones was increased in female rats given drinking water containing 175 ppm sodium fluoride. No other significant nonneoplastic lesions in rats or mice appeared related to sodium fluoride administration. Osteosarcomas of bone were observed in 1/50 male rats in the 100 ppm group and in 3/80 male rats in the 175 ppm group. None were seen in the control or 25 ppm dose groups. One other 175 ppm male rat had an extraskeletal osteosarcoma arising in the subcutaneous tissue. Osteosarcomas occur in historical control male rats at an incian incidence of 0.5% (range 0-6%). The historical incidence is not directly comparable with the incidences observed in this study because examination of bone was more comprehensive in the sodium fluoride studies than in previous NTP studies of other chemicals, and the diet used in previous studies was not controlled for fluoride content. In the current study, although the pairwise comparison of the incidence in the 175 ppm group versus that in the controls was not statistically significant, osteosarcomas occurred with a statistically significant dose-response trend, leading to the conclusion that a weak association may exist between the occurrence of these neoplasms and the administration of sodium fluoride. No other neoplastic lesions in rats or mice were considered possibly related to chemical administration. Genetic Toxicology: Sodium fluoride was negative for gene mutation induction in Salmonella typhimurium strains TA100, TA1535, TA1537, and TA98 with and without S9. In two laboratories, sodium fluoride was tested for induction of trifluorothymidine resistance in mouse L5178Y lymphoma cells; results were positive both with and without S9. Sodium fluoride was tested for cytogenetic effects in Chinese hamster ovary (CHO) cells in two laboratories. In the first laboratory, the sister chromatid exchange (SCE) test was negative with and without S9, and the chromosomal aberration (Abs) test was positive in the absence of S9; in the second laboratory, the SCE test was positive with and without S9, but no induction of Abs was observed. The laboratory that reported a negative result for Abs tested at doses below that shown to be positive at the other laboratory. Similarly, the positive SCE result was obtained at a higher dose and longer harvest time than used by the laboratory reporting the negative SCE response. Conclusions: Under the conditions of these 2-year dosed water studies, there was equivocal evidence of carcinogenic activity of sodium fluoride in male F344/N rats, based on the occurrence of a small number of osteosarcomas in dosed animals. "Equivocal evidence" is a category for uncertain findings defined as studies that are interpreted as showing a marginal increase of neoplasms that may be related to chemical administration. There was no evidence of carcinogenic activity in female F344/N rats receiving sodium fluoride at concentrations of 25, 100, or 175 ppm (11, 45, or 79 ppm fluoride) in drinking water for 2 years. There was no evidence of carcinogenic activity of sodium fluoride in male or female mice receiving sodium fluoride at concentrations of 25, 100, or 175 ppm in drinking water for 2 years. Dosed rats had lesions typical of fluorosis of the teeth and female rats receiving drinking water containing 175 ppm sodium fluoride had increased osteosclerosis of long bones.
 ...
PMID:NTP Toxicology and Carcinogenesis Studies of Sodium Fluoride (CAS No. 7681-49-4)in F344/N Rats and B6C3F1 Mice (Drinking Water Studies). 1263 66

The case of 52-year-old man is presented, who had suffered from pains in his right brachial region and in whom, upon admission to the Lower Silesia Centre of Oncology, a tumour of 20 cm in diameter and restricted mobility was disclosed in the right brachial region and proximal 1/3 of his right arm. Radiograms of his right humerus disclosed non-uniform restructuring of the osseous tissue, dominated by osteosclerosis in the upper half of his right humerus, while in the surrounding dift tissues of the proximal portion non-uniform shades were seen of calcified appearance. The patient was qualified to surgical biopsy and histopathological examination of the sample disclosed Chondrosarcoma G II. Following amputation of the right upper extremity together with the scapula, the tumour was subjected to histopathological and immunocytochemical examination in the Department of Pathomorphology, Lower Silesia Centre of Oncology. In numerous samples of the tumour dedifferentiated chondrosarcoma was diagnosed with a dominating component of malignant fibrous histiocytoma (MFH), which was confirmed by detecting a high expression of alpha-1-antichymotrypsin (ACT) within the spindle-shaped cell component of the chondrosarcoma. Spindle-shaped elements in dedifferentiated chondrosarcoma (DChSa) may represent patterns of fibrosarcoma, osteosarcoma or the malignant fibrohistiocytoma (MFH) type and they are present as if in the form of restricted fields with no reciprocal infiltrates. Moreover, due to the worse prognosis in the case of the MFH component in dedifferentiated chondrosarcoman as compared to that in classical chondrosarcoma, common evaluation of the material was made by a surgeon, radiologist and histopathologist, accompanied by a minimum panel of immunocytochemical tests (ACT, Vimentyna, Desmina, S-100). This enabled a final diagnosis for all tumour components to be established and prognosis to be made regarding the further fate of the patient.
 ...
PMID:The expression of selected immunocytochemical diagnostic markers in the case of chondrosarcoma with a mesenchymal component. 1465 55

The carcinogenic potential of human parathyroid hormone 1-84 (PTH) was assessed by daily subcutaneous injection (0, 10, 50, 150 microg/kg/day) for 2 years in Fischer 344 rats. Histopathological analyses were conducted on the standard set of soft tissues, tissues with macroscopic abnormalities, selected bones, and bones with abnormalities identified radiographically. All PTH doses caused widespread osteosclerosis and significant, dose-dependent increases in femoral and vertebral bone mineral content and density. In the mid-and high-dose groups, proliferative changes in bone increased with dose. Osteosarcoma was the most common change, followed by focal osteoblast hyperplasia, osteoblastoma, osteoma and skeletal fibrosarcoma. The incidence of bone neoplasms was comparable in control and low-dose groups providing a noncarcinogenic dose for PTH of 10 microg/kg/day at a systemic exposure to PTH that is 4.6-fold higher than for a 100 microg dose in humans. The ability of PTH to interact with and balance the effects of both the PTH-1 receptor and the putative C-terminal PTH receptor, may lead to the lower carcinogenic potential observed with PTH than reported previously for teriparatide.
 ...
PMID:Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1-84 in a 2-year study in Fischer 344 rats. 1809 50

Malignant transformation of giant cell tumor of bone (GCTB) without radiotherapy exposure is exceptionally rare, occurring in less than 1% of GCTBs. The safety and efficacy of denosumab in patients with GCTB was recently reported. We herein report a case of a benign recurrent GCTB with an H3F3A mutation that underwent secondary malignant transformation during treatment with denosumab. A 29-year-old woman underwent curettage of a GCTB of the left ischium in 2005. Ten years after the first surgery, the GCTB recurred locally. We started treatment with denosumab. During the first 5 months of treatment, we observed a demarcated area of osteosclerosis in the recurrent lesion, and the patient's clinical condition improved. At 6 months, however, the patient developed pain, and a rapidly growing mass was detected by computed tomography. An incisional biopsy was performed. Histologic analysis showed a high-grade osteosarcoma. The patient developed lung metastases and died soon after beginning chemotherapy. The mechanism of sarcomatous transformation of GCTB during denosumab therapy is unclear. These findings suggest that the scientific community should be aware of the possible malignant transformation of GCTB during denosumab treatment.
 ...
PMID:Development of high-grade osteosarcoma in a patient with recurrent giant cell tumor of the ischium while receiving treatment with denosumab. 2904 79

The skeleton is affected by numerous primary and metastatic solid and hematopoietic malignant tumors, which can cause localized sites of osteolysis or osteosclerosis that can weaken bones and increase the risk of fractures in affected patients. Chemotherapeutic drugs can eliminate some tumors in bones or reduce their volume and skeletal-related events, but adverse effects on non-target organs can significantly limit the amount of drug that can be administered to patients. In these circumstances, it may be impossible to deliver therapeutic drug concentrations to tumor sites in bones. One attractive mechanism to approach this challenge is to conjugate drugs to bisphosphonates, which can target them to bone where they can be released at diseased sites. Multiple attempts have been made to do this since the 1990s with limited degrees of success. Here, we review the results of pre-clinical and clinical studies made to target FDA-approved drugs and other antineoplastic small molecules to bone to treat diseases affecting the skeleton, including osteoporosis, metastatic bone disease, multiple myeloma and osteosarcoma. Results to date are encouraging and indicate that drug efficacy can be increased and side effects reduced using these approaches. Despite these successes, challenges remain: no drugs have gone beyond small phase 2 clinical trials, and major pharmaceutical companies have shown little interest in the approach to repurpose any of their drugs or to embrace the technology. Nevertheless, interest shown by smaller biotechnology companies in the technology suggests that bone-targeting of drugs with bisphosphonates has a viable future.
 ...
PMID:Targeting anti-cancer agents to bone using bisphosphonates. 3258 21