Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three model systems involving LOX human malignant melanoma cells in nude rats were used to compare the chemosensitivity of tumors growing in different tissues. Groups of 4-18 rats with either s.c. xenografts, lung tumor colonies, or bone metastases were treated with cisplatin, doxorubicin, dacarbazine, or mitozolomide. The antitumor effect in the s.c. model was expressed as specific growth delay, and in the experimental metastasis studies as relative increase in life span (RILS), calculated on the basis of observed disease-free survival. Cisplatin had a moderate but significant effect on the progression of LOX tumor growth in all three systems. Doxorubicin was clearly more efficacious, but for both drugs tumor-free survivors were rare or absent. Importantly, for each of the compounds the levels of response were roughly the same in all three models, with specific growth delay and RILS values in the range of 0.2-0.3 for cisplatin and 0.5-0.9 for doxorubicin. In contrast, a significant site-dependent difference in sensitivity of the LOX tumors was observed for two alkylating agents. Thus, dacarbazine, which temporarily caused complete regression of s.c. xenografts (specific growth delay = 21.0), showed a moderate activity in the lung tumor model (RILS = 1.0) but had only a limited effect (RILS = 0.4) on bone metastases. Mitozolomide gave a curative effect in 6 of 10 animals with s.c. and in 4 of 4 animals with lung tumors, whereas in the bone metastasis model it was only slightly superior to doxorubicin (RILS = 1.1). In preliminary attempts to elucidate the underlying mechanisms, no site-dependent differences in drug distribution and in two cellular detoxifying systems were detected. The data demonstrate the usefulness of the LOX models for studying the clinically relevant problem of site-dependent tumor response to chemotherapy.
 ...
PMID:Site-dependent differences in sensitivity of LOX human melanoma tumors in nude rats to dacarbazine and mitozolomide, but not to doxorubicin and cisplatin. 173 96

The present review is concerned with the value of bone scanning in the follow-up of patients with malignant tumors. The scintigraphic sensitivity depends on the type of bone metastases. Osteoplastic metastases (e.g., from prostatic cancer) can be detected much more easily than purely osteolytic foci (e.g., of multiple myeloma). One controversial point is the role of bone scans in the follow-up of patients with breast carcinoma. This particular malignancy is used as an example to point out irrationalities in the recommendations on the selection of imaging modalities in routine follow-up. Such recommendations are based on the present knowledge of the tumor growth kinetics, which is still inadequate. In view of this, follow-up strategies should not be based solely on statistical and epidemiological considerations and cost-benefit ratios.
 ...
PMID:[The importance of bone scintigraphy in the aftercare of patients with malignancies]. 225 52

The dose of gallium chloride required to inhibit tumor growth after oral and chronic administration depends on the stage of the cancer disease and of the type of metastases. A dose regimen of 800 mg/24 h of gallium chloride will provide serum gallium concentrations greater than or equal to 600 micrograms/l in lung cancer patients with a small and limited disease. A dose of 1,400 mg/24 h is well tolerated in metastatic patients but may not be high enough to reach the desired serum gallium concentrations especially in patients with bone metastases. Radiotherapy and/or a chemotherapy will permit one to increase the serum gallium concentrations and the tumor gallium uptake by reducing the volume of the tumor. After chronic, oral administration of gallium a decrease in RBC Mg is noted. To avoid the Mg deficiency, the treatment must not be interrupted and may perhaps be decreased with care and slowly without resulting in a decrease of the serum gallium concentrations provided the treatment has been prolonged over a sufficient time to enable one to induce intratumor biological modifications and a decrease in the number of the malignant cells. Acute pharmacokinetic data are related to the histologic type of the tumor and may not be used to predict the serum gallium concentrations after chronic administration. The serum gallium concentrations required to inhibit the tumor growth may be higher in small cell lung carcinomas than in nonsmall cell lung carcinomas. Frequent Mg and Ga blood determinations are necessary to manage effective gallium treatment.
 ...
PMID:Magnesium alterations and pharmacokinetic data in gallium-treated lung cancer patients. 254 71

Radical surgery in malignant bone tumors can either be limited by anatomical structures or seems inadequate in the palliative stabilization of bone metastases. Incomplete removal of the tumor and stabilization by compound osteosynthesis or endoprosthesis contains two problems: 1) the wide spread of malignant cells by manipulation in the tumor bearing area; 2) progressive destruction of bone due to remaining tumor. To overcome these problems we developed methotrexate bone cement (MTX-Palacos) with the aim to obtain high local concentrations of methotrexate in order to destroy remaining tumor cells and avoid systemic side effects. In vitro studies showed that methotrexate is released continuously from this cement without relevant changes of its biomechanical properties. Animal studies with transplanted osteosarcomas and mamma carcinomas in mice showed a considerable decrease of tumor growth when a plug of MTX-Palacos was inserted in the center of the tumor. Histological findings showed that in the surroundings of the plug the tumor was destroyed considerably contrary to normal bone cement which had no effect on the tumor at all. The results are discussed with regard to clinical application of MTX-Palacos.
 ...
PMID:[Bone cement containing cytostatic drugs: new aspects in the treatment of malignant bone tumors. I. Experimental studies]. 347 46

On the basis of 8 patients of our own and a survey of the literature, the present state of chemotherapy of thyroid carcinoma is discussed. Chemotherapy is only indicated in cases of progressing disease after exhaustion of all conventional therapies. Only in cases of undifferentiated giant- or spindle-cell thyroid carcinomas can chemotherapy following conventional treatment be approved right from the beginning. The three most widely applied cytostatics are adriamycin, bleomycin and cis-platinum, and it seems that adriamycin monotherapy, is superior to all other therapies, even combinations, except probably for the undifferentiated thyroid carcinoma. In addition to the patient's general condition, a sufficiently high single dose of adriamycin, which should be increased in case of nonresponse, appears to be essential for the therapeutical effect. Due to its low toxicity, especially cardiotoxicity, 4'-epi-adriamycin, which, while being almost as effective, can be applied at higher doses and over longer periods, seems to be promising. Approximately 1/3 of thyroid carcinomas respond to adriamycin monotherapy, the response rate probably being highest for medullary types and lowest for undifferentiated thyroid carcinomas. The highest response is observed in the case of pulmonary metastases, followed by bone metastases and local tumor growth. If thyroid carcinomas respond to chemotherapy--even by no-change behavior only--a prolongation of median survival rates from 3-5 months (nonresponders) to 15-20 months (responders) can be achieved.
 ...
PMID:Chemotherapy of thyroid carcinoma. 362 2

Intratibial inoculation of a Moloney strain of Murine Sarcoma Virus (MSV-M) in neonatal Wistar-Lewis rats produced osteosarcoma in 96% of animals and resulted in a median survival of 20 days. Intraperitoneal (i.p.) administration of doxorubicin (adriamycin) (1-2 mg/kg/d, on day 10-12) resulted in reduced tumor growth and prolonged median survival to 95+ and 64 days, respectively. Higher dose doxorubicin (3-4 mg/kg/d, on day 10-12) caused early lethal toxicity. Autopsy data revealed a characteristic sarcomatous tumor producing osteoid. Gross pulmonary nodules appeared in 30% of both treated and untreated animals. Microscopic evaluation of lung tissue revealed anaplastic tumors without osteoid in as many as 90% of rats. Hepatosplenomegaly was usually present but microscopic sections of the spleen did not reveal tumor. Long bone metastases were increased in frequency in those animals receiving doxorubicin. Cell mediated immunity (CMI) to osteosarcoma cells by peripheral blood lymphocytes of tumor-bearing animals was detectable between days 21-48. This was bimodal with an early peak at day 21 (CMI = 56%) and a late peak at day 39 (CMI = 48%). CMI in rats given 1 mg/kg/d x 3d of doxorubicin was similar, with peak cytotoxicity (CMI = 61%) on day 26. Two mg/kg/d x 3d of doxorubicin did not significantly suppress either the early response (CMI = 50% on day 22) or the second peak (CMI = 38% and 50% on day 40 and 46, respectively). Thus, doxorubicin was effective in decreasing the growth of an MSV-M induced osteosarcoma and prolonging survival in the rat while usually failing to suppress CMI against rat osteosarcoma cells.
 ...
PMID:Antitumor effects of doxorubicin against a virally-induced rat osteosarcoma with minimal immunosuppression. 693 62

The use of standard assessment criteria to evaluate therapeutic responses in patients with advanced prostate cancer is confounded by the high percentage of patients with bone-only metastatic disease. In an effort to develop a reliable means of assessing the activity of various therapeutic interventions, the role of prostate-specific antigen (PSA) as a response parameter is being actively evaluated. The precise role of PSA in this setting remains undefined as there is limited and sometimes conflicting findings in the literature. Additionally, there is emerging data to suggest that various therapeutic agents may influence PSA expression in a manner unrelated to the impact on tumor growth. Given the high percentage of patients with bone metastases, investigators have been actively evaluating a series of new markers of bone turnover; however, the lack of acceptable specificity limits the clinical usefulness of this approach. The role of palliative endpoints such as pain and quality of life measures have been shown to be both feasible and clinically relevant in the assessment of response in patients with symptoms of advanced disease. The emergence of an enlarging subset of asymptomatic patients with PSA-only evidence of metastatic disease presents a new and pressing challenge to clinicians to develop reliable new methods of assessing disease response to therapeutic interventions.
 ...
PMID:Metastatic prostate cancer: assessment of response to systemic therapy. 905 Jan 37

Only limited data are available on chromosomes specifically involved in the multistep tumorigenesis of prostate cancer. To investigate the cytogenetic status at different stages of prostatic tumor development, we have applied interphase in situ hybridization (ISH) with a set of (peri) centromeric DNA probes--specific for chromosomes 1, 7, 8, and Y--to routinely processed tissue sections of prostatic specimens from 75 different individuals. Our panel consisted of: 16 normal/benign prostatic hyperplasia specimens; 23 primary, localized, prostatic tumors (N0M0 stage); 20 regional lymph node metastases (M0 stage); and 16 distant metastases. Numerical aberrations of at least one chromosome were not observed in normal/benign prostatic hyperplasia cases, but were present in localized tumors (39%), regional lymph node metastases (40%), and distant metastases (69%). Within the different pTNM groups, we observed the following aberrations (listed, within each series, in decreasing order of frequency): -Y, +8, -8, +7 in primary tumors; +8, +7, -Y, +Y, -8 in regional lymph node metastases; and +8, +7, +1, -Y, -8 in distant metastases. In primary tumors, the number of aberrant cases increased significantly with local tumor stage (p < 0.05). A significant increase in gain of chromosome 8 was also observed (p < 0.02). Gain of chromosome 7 and/or 8 showed a significant increase with progression of local tumor stage (p < 0.02). Specific involvement of chromosome 8 was seen in bone metastases, but not in hematogenous metastases to other sites (p = 0.02). Comparative genomic hybridization analysis of these bone metastases disclosed centromere 8 gains as amplifications of the (whole) 8q arm, whereas centromeric loss appeared to be due to loss of 8p sequences. With progression toward metastatic disease, an accumulation of genetic changes was seen as exemplified by gain of chromosome 1, which was solely observed in distant metastases. With tumor progression, gain of chromosomes 7 and/or 8 significantly increased (p = 0.03), whereas the number of cases with aberrations of the Y chromosome did not change. Furthermore, ploidy status determined by ISH revealed a significant increase in the number of aneuploid cases along with advancement of pTNM stage (p = 0.04). Collectively, the data strongly suggest that: (a) gain of chromosome 7 and/or 8 sequences is implicated in prostatic tumor progression; (b) gain of chromosome 8 sequences is related to local tumor growth; (c) overrepresentation of 8q sequences, most likely by isochromosome 8q formation, is involved in metastatic spread to the bone; and (d) changes in the centromeric copy number, as detected by interphase ISH, might in some cases represent structural alterations, such as an isochromosome.
 ...
PMID:Interphase cytogenetics of prostatic tumor progression: specific chromosomal abnormalities are involved in metastasis to the bone. 938 87

Angiogenesis inhibitor TNP-470, 6-O-(N-chloroacetyl-carbamoyl)-fumagillol, semisynthetic analogue of fumagillin, has strong inhibitory activities against in vivo tumor growth and metastasis in a wide variety of tumors. However, it is still unknown whether this agent inhibits bone metastasis. We examined the effects of TNP-470 in a bone metastasis model in nude mice in which intracardiac injection of the human breast cancer cell line MDA-MB-231 (MDA-231) produced osteolytic bone metastasis. After inoculation of MDA-231 cells into the left heart ventricle, TNP-470 (30 mg/kg, three times a week) or PBS was s.c. administrated for 4 weeks. After this period, the TNP-470 had reduced not only the number and area of osteolytic bone metastases (approximately 60 and 70%, respectively) but also their radiolucency. Histological examination of the femurs of the untreated group revealed that most of the cancellous bone had been replaced by the metastatic cancer. Numerous active osteoclasts were present along the trabecular bone surface surrounded by the metastatic MDA-231 cancer cells aggressively invading the bone marrow. In contrast, in the bone from TNP-470-treated mice, bone destruction was markedly inhibited, and there were much fewer osteoclasts. In a murine bone marrow culture under 1,25-dihydroxyvitamin D3 in which mature functional osteoclasts formed in vitro, TNP-470 significantly inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclast-like cells. And also, TNP-470 suppressed the in vivo bone resorption in calvaria treated with interleukin-1beta, an osteoclast stimulator. These data suggested that TNP-470 inhibited bone metastasis through not only antitumor action by its angiogenesis inhibition but also by the inhibition of osteoclastic bone resorption. Our results indicate that TNP-470 should be a potentially beneficial drug to be used in the treatment of osteolytic metastasis.
 ...
PMID:Angiogenesis inhibitor TNP-470 inhibits human breast cancer osteolytic bone metastasis in nude mice through the reduction of bone resorption. 945 90

A breast cancer patient with bone metastases showed a marked response to treatment with a bisphosphonate, an inhibitor of osteoclastic bone resorption. The patient was admitted to our hospital with hypercalcemia, widespread bone metastases and severe disseminated intravascular coagulation (DIC). We treated her conservatively with pamidronate and gabexate mesilate, because the patient had refused any anti-cancer chemotherapy. She showed marked improvement in performance status, hypercalcemia, DIC and tumor markers, whereas splenomegaly due to metastasis progressed. These results suggest that pamidronate has the potential to suppress metastatic tumor growth selectively in bone.
 ...
PMID:A remarkable improvement of clinical manifestations in a breast cancer patient with widespread bone metastases after administration of pamidronate. 947 53


1 2 3 4 5 6 7 8 9 10 Next >>