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

The 5 years' survival rate of all cancer patients is 35-45%. In that survival rate radiotherapy takes part in 15%. By further development of radiological methods and techniques radiotherapy gains significance in the recent time. Optimizing radiation planning and tactics, all modern imaging techniques are applied consequently. The radiotherapist must be able to asses their immanent specifity which should remain object of the radiological training, even if separated into therapy and diagnostics. Dose distribution is calculated by computer; three-dimensional planning is done in tumors of the mediastinum, oesophagus carcinoma and paraaortic lymphomas. Critical description of radiation techniques, results, problems and prognoses are given by results in tumors of the epipharynx and gastric cancer. After-loading, done until now only in gynaecological tumors, is performed in recurrences of pharyngeal tumors by individually shaped applicators. Reducing the number of therapy failures as well as possible, the application of higher tumor doses, new kinds of rays as neutrons and combinations with physical and chemical methods is outlined. Modifications of radiation volumes are discussed, especially the irradiation of the complete abdomen in ovarian cancer, the irradiation of the complete body surface by electrons in mycosis fungoides, and the total body irradiation prior to autologue bone marrow transplantation. Modifications of fractionation are shown in short-time radiation of bone metastases and single-time radiation of brain lesions. Low penetrating electron therapy facilitates intraoperative single-time irradiation. Because of higher biological efficiency neutrons and heavy ions allow to irradiate low sensible tumors or recurrences embedded in fibrotic tissue respectively. The combination with hyperthermia yields good results in tumors of the head and neck with better local response and total remissions of 59%. There are potentials in synchronising with chemotherapeutics. Remissions of different duration were achieved in 190 patients. Because of neutrotoxicity there are still problems in applicating radiosensitizers. New methods are applied treating endocrine active tumors by labelled hormone precursers.
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PMID:Perspectives of radiotherapy. 310 47

Studies have demonstrated abnormalities of the CD3/T-cell antigen receptor (TCR) and pathways of signal transduction in T lymphocytes from animals and patients with advanced malignancy. Diminished expression of TCRzeta and p56(lck) that are associated with the TCR and reduced nuclear localization of RelA containing nuclear factor kappaB (NFkappaB) complexes have been noted. These defects have been described in T cells from patients with malignant melanoma, renal cell carcinoma (RCC), ovarian cancer, and colorectal cancer. Preliminary observations also indicate possible correlation with clinical variables such as stage in selected instances. To further characterize altered expression of TCRzeta, p56(lck), and impaired activation of NFkappaB, T lymphocytes were obtained from 65 patients with RCC, the majority of whom were receiving combination cytokine therapy [interleukin (IL)-2, IFN alpha-containing regimens] and 37 control individuals. In 29 of these patients, levels of TCRzeta and p56(lck) were determined by Western blots of T-cell lysates and semiquantitated using densitometry. Relative levels were then correlated with a series of clinical variables including response to therapy, performance status, survival, disease sites, age, and others. In another group of 28 patients (three individuals from the first group), the frequency of abnormal NFkappaB activation was studied using electrophoretic mobility shift assays after activation of T cells with phorbol myristate acetate/ionomycin or anti-CD3 monoclonal antibody. Changes in these signaling molecules during cytokine treatment were also investigated. TCRzeta and p56(lck) were detected in the peripheral blood T cells in 27 of 29 patients, and overall, reduced levels were noted visually in 12 of 29 (41%) and 13 of 29 (45%) individuals, respectively. When levels were semiquantitated using densitometry, significant decreases of TCRzeta (P = 0.029) and p56(lck) (P = 0.029) but not CD3epsilon (P = 0.131), compared with control levels, were found. In patients treated with IL-2/IFN alpha-based therapy, relative levels of TCRzeta increased significantly (P = 0.002) on day 15 of cycle one compared with the baseline. Correlations of TCRzeta or p56(lck) levels with response or disease variables, except for lower TCRzeta levels (P < 0.001) in the presence of bone metastases, were not found. Abnormal NFkappaB activation after stimulation with phorbol myristate acetate/ionomycin and/or anti-CD3 monoclonal antibody was found in 59% of patients (17 of 28) and was not accounted for by the advanced age of the study cohort. Activation of NFkappaB in peripheral blood T cells was inducible during cytokine therapy in four of six individuals who displayed impaired NFkappaB activity prior to therapy. Moreover, impaired activation of NFkappaB does not appear linked to a reduction of TCRzeta expression, because in five patients, normal TCRzeta levels were present although kappaB binding was not inducible. In the majority of patients with advanced RCC, peripheral blood T cells express TCRzeta and p56(lck), and in a subset, reduced levels of these TCRzeta associated molecules are seen that may increase during cytokine-based therapy. Abnormal activation of NFkappaB is also present in >50% of patients and may also revert to normal during IL-2/IFN alpha-based treatment. This alteration in NFkappaB activation occurred in the presence of normal expression of TCRzeta-associated signaling elements. The clinical significance of these findings remains unclear.
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PMID:Signal transduction abnormalities in T lymphocytes from patients with advanced renal carcinoma: clinical relevance and effects of cytokine therapy. 979 63

The paper presents a retrospective evaluation of 47 patients with bone metastases treated surgically during the last 10 years at our ward. The mean age of the patients was 62.5 years. There were 31 females (mean age: 62.8 years) and 16 males (mean age: 62.3 years). In 37 cases (78.8%) it as possible to establish the primary localization of the tumour: breast carcinoma--16 cases, ovary cancer 5 cases, lung cancer--5 cases, prostate cancer--5 cases, kidney cancer--2 cases, stomach cancer--1 case, vagina cancer--1 case, hepatocarcinoma--1 cases and plasmocytoma--1 cases. In 10 cases (21.1%) we were unable to establish the primary focus of the tumour. The localization of the metastases was as follows: femur--32 cases, humerus--6 cases, tibia--3 cases, lumbar spine--1 case. Patients treated very briefly after qualification for surgery, in some cases during emergency service. In 2 cases of metastases to the tibia amputations at the femur were performed. The remaining patients were treated by local excisions of the metastatic tumours, followed by: in 33 cases internal osteosynthesis and bone cement application; in 7 cases osteosynthesis, in 4 cases hip arthroplasties and posterior spine instrumentation in 1 case. In 6.4% we had poor results because of the death of 3 patients. The mean follow-up was three months. In 93.6% we had good and very good results--no pain, good function and independence during daily activities. Mean survival time was 13.5 month (range 5-28 months).
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PMID:[Efficacy of operative treatment for pathological fractures in bone metastases in relation to length and comfort of survival]. 1138 15

The role of lysophosphatidic acid (LPA) in cancer is poorly understood. Here we provide evidence for a role of LPA in the progression of breast cancer bone metastases. LPA receptors LPA(1), LPA(2), and LPA(3) were expressed in human primary breast tumors and a series of human breast cancer cell lines. The inducible overexpression of LPA(1) in MDA-BO2 breast cancer cells specifically sensitized these cells to the mitogenic action of LPA in vitro. In vivo, LPA(1) overexpression in MDA-BO2 cells enhanced the growth of subcutaneous tumor xenografts and promoted bone metastasis formation in mice by increasing both skeletal tumor growth and bone destruction. This suggested that endogenous LPA was produced in the tumor microenvironment. However, MDA-BO2 cells or transfectants did not produce LPA. Instead, they induced the release of LPA from activated platelets which, in turn, promoted tumor cell proliferation and the LPA(1)-dependent secretion of IL-6 and IL-8, 2 potent bone resorption stimulators. Moreover, platelet-derived LPA deprivation in mice, achieved by treatment with the platelet antagonist Integrilin, inhibited the progression of bone metastases caused by parental and LPA(1)-overexpressing MDA-BO2 cells and reduced the progression of osteolytic lesions in mice bearing CHO-beta3wt ovarian cancer cells. Overall, our data suggest that, at the bone metastatic site, tumor cells stimulate the production of LPA from activated platelets, which enhances both tumor growth and cytokine-mediated bone destruction.
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PMID:Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. 1559 91

Endothelin axis deregulation triggers a series of events that ultimately activate proliferation, invasion, escape from programmed cell death, new vessel formation, abnormal osteogenesis and alteration of nociceptive stimuli. Atrasentan is a novel agent that effectively targets this pathway and is able to inhibit and/or reverse several of those events. Biologic and clinical activity in patients with prostate cancer has been demonstrated in a Phase III, placebo-controlled setting by the suppression of markers of biochemical prostate cancer progression and a delay in time to disease progression. Atrasentan represents a new therapeutic option in the management of prostate cancer, especially in those patients with bone metastases. However, its precise role in other diseases such as ovarian cancer is yet to be defined.
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PMID:Atrasentan: a novel and rationally designed therapeutic alternative in the management of cancer. 1600 50

Platelet-derived lysophosphatidic acid (LPA) supports the progression of breast and ovarian cancer metastasis to bone. The mechanisms through which LPA promotes bone metastasis formation are, however, unknown. Here we report that silencing of the type 1 LPA receptor (LPA(1)) in cancer cells blocks the production of tumor-derived cytokines that are potent activators of osteoclast-mediated bone destruction and significantly reduces the progression of osteolytic bone metastases. Moreover, functional blockade of LPA action on its cognate receptor LPA(1) using a pharmacological antagonist mimics the effects of silencing LPA(1) in tumor cells in vitro and substantially reduces bone metastasis progression in animals. Overall, these results suggest that inhibition of platelet-derived LPA action on LPA(1) expressed by tumor cells may be a promising therapeutic target for patients with bone metastases.
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PMID:The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases. 1676 91

Bisphosphonates are now well established as successful agents for the prevention and treatment of postmenopausal osteoporosis and corticosteroid-induced bone loss. Bisphosphonates have also recently become important in the management of cancer-induced bone disease, and they now have a widely recognized role for patients with multiple myeloma and bone metastases secondary to breast cancer and prostate cancer. Recent studies suggest that, besides the strong antiosteoclastic activity, the efficacy of such compounds in the oncological setting could also be due to direct anti-tumor effect. However, the effect of bisphosphonates to ovarian and endometrial cancers has not been elucidated. Thus, we examined the direct effect of bisphosphonates on the various ovarian cancer cell lines. Except for etidronate, all of bisphosphonates examined had the direct inhibitory effects on proliferation of all ovarian cancer cell lines used. Especially, pamidronate had the most marked inhibitory effect and inhibited dose-dependently the proliferation of ovarian cancer cell lines. KFr 13 cells among ovarian cancer cell lines used was the most sensitive to pamidronate and the caspase 3 activity was markedly stimulated by treatment with pamidronate, suggesting induction of apoptosis.
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PMID:Inhibitory effects of bisphosphonates on the proliferation of human ovarian cancer cell lines and the mechanism. 1694 67

The painful shoulder is a very common condition encountered in the rheumatology clinic with rotator cuff disorders, glenohumeral disorders, acromioclavicular joint disease and referred neck pain being the most common causes. Other rare causes have to be considered in the presence of "red flag" indicators. We describe a case of a patient with mild rheumatoid arthritis and a past medical history of stage 2C epithelial ovarian carcinoma who presented to the rheumatology clinic with a painful shoulder and who was initially diagnosed with rotator cuff tendinopathy. When seen 3 months later she was found to have a 15 x 10-cm firm, non-tender soft tissue mass over the right scapula and X-rays showed a large lytic mass destroying much of the upper border of the scapula, suggestive of metastasis. Bone metastases in patients with ovarian carcinoma are very rare; they occur in about 2% of cases and are invariably predictors of poor prognosis. To our knowledge, this is the first case of ovarian cancer metastasised to the scapula. We suggest that rheumatologists should be aware of the differential diagnosis of painful shoulder and look for "red flag" indicators in patients with known rheumatic conditions.
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PMID:Unusual cause of painful shoulder in an elderly woman with rheumatoid arthritis. 1716 May 29

The endothelin axis (ET axis), comprising the three peptides endothelin (ET)-1, -2, -3 and their receptors ET(A)R and ET(B)R, is expressed in various cells and tissues. The biologically active ET-1 is formed by endothelin-converting enzyme (ECE) from inactive big-ET-1. ET-1 has emerged as an important peptide in a host of biological functions, including development, cellular proliferation, apoptosis and angiogenesis, thereby playing an important physiological and pathophysiological role. As these effects are mediated by ET(A)R, activation of ET(B)R prevents apoptosis, inhibits ECE expression and mediates the clearance of ET-1. Emerging data indicate that the ET axis is involved in tumourigenesis and tumour progression of various cancers. Expression of the ET axis has been demonstrated in a wide range of human tumours. Since most data have been reported for female malignancies, this review will focus on the role of the ET axis in cancers of the ovary, the cervix and the breast. In ovarian cancer, activation of ET(A)R by ET-1 is a key mechanism in the cellular signalling network promoting cancer growth and progression. Similar effects have been shown for cervical and endometrial cancer. In breast cancer, ET-1 via ET(A)R promotes proliferation and invasion, mediates bone metastases and predicts unfavourable response to chemotherapy. The outstanding role of ET-1 and ET(A)R in carcinogenesis and tumour progression has led to an extensive search for interfering agents, resulting in the development of selective ET(A)R antagonists on the one hand and inhibitors of the endothelin-converting enzyme (ECE) on the other. Targeting the ET axis via ET(A)R or ECE blockade seems to be a promising approach in the treatment of female malignancies.
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PMID:The endothelin axis: a novel target for pharmacotherapy of female malignancies. 1762 67

Targeted alpha therapy is an advancing experimental therapy that holds promise to deliver high cytotoxicity to targeted cancer cells. Initially thought to be indicated for leukaemia and micrometastases, there is now evidence that solid tumours can also be regressed. Alpha therapy may be molecular or physiological in its targeting. Alpha emitting radioisotopes such as Bi-212, Bi-213, At-211 and Ac-225 are used to label monoclonal antibodies or proteins that target specific cancer cells. Alternatively, radium-233 is used for palliative therapy of breast and prostate cancers as it is a bone seeking element. Progress in the development of clinical trials of alpha therapy is examined for leukaemia, lymphoma, melanoma, glioblastoma multiforme, bone metastases, ovarian cancer, pancreatic cancer and other cancers. Results of past and current trials are reviewed, and the bases of some proposed trials are presented.
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PMID:Clinical trials of targeted alpha therapy for cancer. 1878 76


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