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 purpose of this prospective study was to define the value of bone scintigraphy (BS), bone marrow scintigraphy (BMS) and the new fast spin-echo (FSE) magnetic resonance imaging (MRI) sequences in screening for bone metastases in patients with solid malignant tumours. It was our particular interest to classify patients into a group with and a group without bone metastases, and not only to compare the absolute number of metastases detected by each method. Thirty-two patients were examined using technetium-99m dicarboxy propane diphosphonate bone scintigraphy, 99Tc-labelled monoclonal anti-granulocyte antibodies for bone marrow scintigraphy and 1.5 T MRI using T1-weighted and FSE T2-weighted sequences. Against a reference standard obtained by re-evaluation of all clinical and imaging data 1 year after prospective BS, BMS and MRI had been performed, the three imaging modalities were falsely positive in two, eight and two cases and falsely negative in zero and four cases, respectively. BMS was falsely positive in eight patients because of vertebral marrow degeneration which caused photopenic defects which could not be differentiated from metastases. MRI showed these lesions to unequivocally contain fat. BMS and MRI were falsely negative in four cases because of the limited field of examination. In our study the key factor in classifying a patient as bone M1 or M0 was the possibility of surveying the entire skeleton, as is the case in BS, and not that MRI had a higher sensitivity compared to BS when analysis was on a lesion-by-lesion basis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The value of bone scintigraphy, bone marrow scintigraphy and fast spin-echo magnetic resonance imaging in staging of patients with malignant solid tumours: a prospective study. 828 74

Bone marrow scintigraphy using 99Tcm-labelled chimeric anti-granulocyte antibody (anti-NCA-95) was performed in 17 patients with haematological disorders and skeletal metastases. Chimeric anti-NCA-95 antibody (chNCA95 Ab, 0.2 mg) labelled with 444 MBq 99Tcm was administered to obtain bone marrow images 4 h post-injection. One week later, an 111In-chloride bone marrow scan was performed on nine patients with haematological disorders. Lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B) uptake ratios were calculated for each scan. In six patients with suspected skeletal metastases, 99Tcm-HMDP bone scans were performed. No patient had any adverse reaction or any immune reaction over 20 weeks. In the patients with haematological disorders, the L/B and I/B ratios of the 99Tcm-chNCA95 Ab scan were 3.41 +/- 0.90 and 1.23 +/- 0.31, whereas those of the 111In-chloride scan were 1.58 +/- 0.32 and 1.00 +/- 0.32, respectively. In assessing findings of irregular central bone marrow uptake and peripheral expansion of the bone marrow, the 99Tcm-chNCA95 Ab scan was much better than the 111In-chloride scan. In the six patients with suspected skeletal bone metastases, three true-positive and two true-negative results were observed. This preliminary study has revealed that 99Tcm-chNCA95 Ab scanning is safe and useful in the diagnosis of haematological disorders and skeletal metastases.
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PMID:99Tcm-labelled chimeric human/mouse anti-granulocyte antibody bone marrow scintigraphy: a preliminary clinical study. 985 36

Mouse bone marrow cells cultured with human breast cancer MCF-7 cell-conditioned media showed osteoclastogenesis with an increment of bone resorption, although conditioned media from an adriamycin-selected MCF-7 clone (MCF-7ADR) had no effect. Consistently, MCF-7 cells induced 5-fold more in vivo experimental osteolytic bone metastases, with no soft tissue lesions, compared to MCF-7ADR cells. Paracrine factors stimulating (interleukin (IL)-6, IL-1beta, tumor necrosis factor-alpha (TNF-alpha)) or inhibiting (IL-12, IL-18, granulocyte macrophage-colony stimulating factor (GM-CSF)) osteoclastogenesis were significantly increased in MCF-7ADR relative to MCF-7 cells, suggesting that the inhibitory cytokines could selectively overwhelm the effects of the stimulatory ones. Treatment of osteoblast primary cultures with MCF-7-conditioned medium induced a selective upregulation of IL-6 expression, suggesting an indirect stimulation of osteoclastogenesis via the osteoblasts. MCF-7 and MCF-7ADR showed no difference in proliferation rate. However, a higher ability to migrate and invade gelatin and matrigel was observed in MCF-7ADR. Enhanced invasiveness might result from increased metalloproteinase (MMP) activity and cytoskeleton rearrangement. MCF-7ADR cells expressed higher levels of c-Src, focal adhesion kinase (FAK), and protein tyrosine kinase 2 (PYK2) involved in cell adhesion and motility. MCF-7 and MCF-7ADR expressed high and faint levels of functional estrogen receptor alpha (ERalpha), respectively. MCF-7ADR also showed significantly higher levels of the protein kinase C (PKC) alpha and beta2 and a selective activation of PKC compared to MCF-7, where the most abundant isoforms were beta1 and delta. Heat shock protein 27 (Hsp27) was more abundant in MCF-7 cells, but failed to translocate to the nucleus in response to heat shock. In conclusion, we have demonstrated that despite the fact that MCF-7ADR cells showed a more invasive phenotype relative to MCF-7, they have low potential to induce osteolytic bone lesions and stimulate osteoclastogenesis and osteoclast activity. Therefore, we believe that reduced aggressiveness of breast carcinomas could correlate with a greater osteolytic activity featuring their bone metastases.
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PMID:In vivo bone metastases, osteoclastogenic ability, and phenotypic characterization of human breast cancer cells. 1505 Sep 1

Hematopoietic growth factors are used to reverse chemotherapy-induced leukopenia. However, some factors such as granulocyte macrophage colony-stimulating factor (GM-CSF) induce osteoclast-mediated bone resorption that can promote cancer growth in the bone. Accordingly, we evaluated the ability of GM-CSF to promote bone metastases of breast cancer or prostate cancer in a mouse model of chemotherapy-induced leukopenia. In this model, GM-CSF reversed cyclophosphamide-induced leukopenia but also promoted breast cancer and prostate cancer growth in the bone but not in soft tissue sites. Bone growth was associated with the induction of osteoclastogenesis, yet in the absence of tumor GM-CSF, it did not affect osteoclastogenesis. Two osteoclast inhibitors, the bisphosphonate zoledronic acid and the RANKL inhibitor osteoprotegerin, each blocked GM-CSF-induced tumor growth in the bone but did not reverse the ability of GM-CSF to reverse chemotherapy-induced leukopenia. Our findings indicate that it is possible to dissociate the bone-resorptive effects of GM-CSF, to reduce metastatic risk, from the benefits of this growth factor in reversing leukopenia caused by treatment with chemotherapy.
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PMID:Reversal of chemotherapy-induced leukopenia using granulocyte macrophage colony-stimulating factor promotes bone metastasis that can be blocked with osteoclast inhibitors. 2050 34

Pneumocystis jirovecii (formerly carinii) pneumonia (PJP) is an opportunistic infection well-recognized in patients with profound T cell immunodeficiency. It is much less common in patients with solid tumors unless they have other major predisposing factors such as prolonged treatment with corticosteroids or T4 lymphocyte counts of less than 200 cells/mm(3). We present a previously unreported case of fatal PJP in a breast cancer patient with bone metastases who was receiving a first-line treatment with weekly paclitaxel, trastuzumab, and dexamethasone as premedication for paclitaxel. She had received eight doses of paclitaxel at 80 mg/m(2), trastuzumab 2 mg/m(2), and dexamethasone 10 mg for just over 7 weeks when she was diagnosed with PJP. While the patient's granulocyte counts were normal throughout her treatment, the total lymphocyte counts reached the nadir of 400 cells/mm(3) a few days after the eighth dose of chemotherapy - around the time of PJP diagnosis. Both dexamethasone and the total lymphocyte nadir predisposed this patient to PJP.
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PMID:A fatal case of Pneumocystis jirovecii pneumonia in a breast cancer patient receiving weekly paclitaxel and trastuzumab. 2191 78