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Bone Metastasis (bone + metastasis)
Kinds of Bone Metastasis Selected AbstractsEarly (mucosal) gastric cancer with synchronous osteosclerotic bone metastases: a case reportEUROPEAN JOURNAL OF CANCER CARE, Issue 4 2010G. ANAGNOSTOPOULOS md ANAGNOSTOPOULOS G., SAKORAFAS G.H., KOSTOPOULOS P., MARGANTINIS G., TSIAKOS S. & PAVLAKIS G. (2010) European Journal of Cancer Care Early (mucosal) gastric cancer with synchronous osteosclerotic bone metastases: a case report Early gastric cancer (EGC) is defined as an adenocarcinoma confined to the gastric mucosa or submucosa, regardless of the presence of lymph node metastases. Early gastric cancer carries an excellent prognosis, with a 5-year survival rate at least 85% in most series. However, there are rare cases where distant metastases exist. Bone metastases are rare in gastric cancer; osteoblastic bone metastases are even rarer. We report a patient with EGC (mucosal) and synchronous osteosclerotic bone metastasis. To our knowledge, this is the first reported case of submucosal EGC with synchronous bone metastases. The patient was operated and he received adjuvant chemotherapy and radiotherapy. He died 18 months after gastric surgery from generalized disease. [source] Feasibility and long-term results of autologous PBSC transplantation in recurrent undifferentiated nasopharyngeal carcinomaHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2001Mario Airoldi MD Abstract Background Recurrent undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive illness. Here we report long-term results of high-dose chemotherapy (HDC) as late intensification, with autologous peripheral blood stem cell (PBSC) support. Methods Six patients (5 men, 1 woman; median age 41years; median ECOG PS = 0) with recurrent UNPC (local, 2; local + nodal, 2; bone metastasis, 2) have been enrolled. All patients had been previously treated with neoadjuvant chemotherapy and radiotherapy; 3 of 4 local relapses had received a re-irradiation. Every patient received three courses of cisplatin + epirubicin and 1 cycle of epirubicin followed by PBSC collection. A median of 7.2 × 106/kg (range, 4.5,18) CD34+ cells were reinfused. HDC was according ICE scheme: ifosfamide, 2.5 g/m2/d, + carboplatin, 300 mg/m2/d, + VP-16, 300 mg/m2/d days 1 through 4. Results After conventional chemotherapy, we had 1 CR (16%), 3 PR (50%), and 2 NC (34%). After HDC, we had 4 CR (66%) ,1 PR (17%), and 1 MR (17%). Toxicity was manageable. After a median follow-up of 30 months (range, 14,50), two patients are alive without disease (34%), one is alive with bone disease (16%), and three (50%) died of disease at 16, 18, and 24 months. Conclusions HDC has an acceptable toxicity, can convert PR in CR, and seems effective, with long-lasting CRs. © 2001 John Wiley & Sons, Inc. Head Neck 23: 799,803, 2001. [source] Sustained delivery and efficacy of polymeric nanoparticles containing osteopontin and bone sialoprotein antisenses in rats with breast cancer bone metastasisINTERNATIONAL JOURNAL OF CANCER, Issue 7 2010Victoria Elazar Abstract Poor prognosis in mammary carcinoma is associated with a certain expression profile of a defined set of genes including osteopontin and bone sialoprotein. Efficient and specific delivery of antisenses (AS) and a protection of the sequences from degradation are the crucial conditions for AS therapeutic efficiency. We hypothesized that effective and safe AS delivery direceted against these genes could be achieved by polymeric nanoparticles (NP) fabricated from a biocompatible polymer. Due to their nano-size range and small negative charge, AS-NP can overcome the absorption barrier offering increased resistance to nuclease degradation, sustained duration of AS administration, and consequently, prolonged antisense action. The ASs designed against OPN and BSP-II were successfully encapsulated in NP composed of the biodegradable and biocompatible polylactide- co -glycolide polymer (PLGA), exhibiting sustained release and stability of the ASs. The therapeutic efficacy of the AS-NP delivery system was examined in vitro, and in a breast cancer bone metastasis animal model of MDA-MB-231 human breast cancer cells in nude rats. Treatment with OPN-AS or BSP-AS loaded NP in comparison with osmotic mini-pumps (locoregional injection and SC implants, respectively) resulted in a significant decrease in both, tumor bone metastasis incidence and in the size of the lesions in rats with metastases. Despite its smaller dose, AS-NP exhibited a better therapeutic efficacy than osmotic mini-pumps in terms of lesion ratio at later time periods (8,12 weeks). It may be concluded that AS delivery by NP is a promising therapeutic modality providing stability of the encapsulated AS and a sustained release. [source] Identification of prospective factors promoting osteotropism in breast cancer: a potential role for CITED2INTERNATIONAL JOURNAL OF CANCER, Issue 4 2010Wen Min Lau Abstract Breast cancer metastases develop in the bone more frequently than any other site and are a common cause of morbidity in the form of bone pain, pathological fractures, nerve compression and life-threatening hypercalcemia. Despite ongoing research efforts, the molecular and cellular mechanisms that regulate breast cancer cell homing to and colonization of the bone as well as resultant pathological bone alteration remain poorly understood. To identify key mediators promoting breast cancer metastasis to bone, we utilized an immunocompetent, syngeneic murine model of breast cancer metastasis employing the mammary tumor cell line NT2.5. Following intracardiac injection of NT2.5 cells in neu-N mice, metastases developed in the bone, liver and lung, closely mimicking the anatomical distribution of metastases in patients with breast cancer. Using an in vivo selection process, we established NT2.5 sublines demonstrating an enhanced ability to colonize the bone and liver. Genome-wide cDNA microarray analysis comparing gene expression between parental NT2.5 cells and established sublines revealed both known and novel mediators of bone metastasis and osteolysis, including the transcriptional co-activator CITED2. In further studies, we found that expression of CITED2 was elevated in human primary breast tumors and bone metastasis compared to normal mammary epithelium and was highest in breast cancer cell lines that cause osteolytic bone metastasis in animal models. In addition, reducing CITED2 expression in NT2.5 cells inhibited the establishment of bone metastasis and osteolysis in vivo, suggesting a potential role for CITED2 in promoting breast cancer bone metastasis. [source] Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastasesINTERNATIONAL JOURNAL OF CANCER, Issue 5 2008Guojun Bu Abstract Most breast cancer metastases in bone form osteolytic lesions, but the mechanisms of tumor-induced bone resorption and destruction are not fully understood. Although it is well recognized that Wnt/,-catenin signaling is important for breast cancer tumorigenesis, the role of this pathway in breast cancer bone metastasis is unclear. Dickkopf1 (Dkk1) is a secreted Wnt/,-catenin antagonist. In the present study, we demonstrated that activation of Wnt/,-catenin signaling enhanced Dkk1 expression in breast cancer cells and that Dkk1 overexpression is a frequent event in breast cancer. We also found that human breast cancer cell lines that preferentially form osteolytic bone metastases exhibited increased levels of Wnt/,-catenin signaling and Dkk1 expression. Moreover, we showed that breast cancer cell-produced Dkk1 blocked Wnt3A-induced osteoblastic differentiation and osteoprotegerin (OPG) expression of osteoblast precursor C2C12 cells and that these effects could be neutralized by a specific anti-Dkk1 antibody. In addition, we found that breast cancer cell conditioned media were able to block Wnt3A-induced NF-kappaB ligand reduction in C2C12 cells. Finally, we demonstrated that conditioned media from breast cancer cells in which Dkk1 expression had been silenced via RNAi were unable to block Wnt3A-induced C2C12 osteoblastic differentiation and OPG expression. Taken together, these results suggest that breast cancer-produced Dkk1 may be an important mechanistic link between primary breast tumors and secondary osteolytic bone metastases. © 2008 Wiley-Liss, Inc. [source] Multifocal metastases of recurrent renal cell carcinoma successfully treated with a combination of low dose interleukin-2, ,-interferon and radiotherapyINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2005NORIFUMI SAWADA Abstract ,A 59-year-old man presented with a 2-month history of left ,ank pain and a possibility of gross hematuria. Left renal cell carcinoma stage II was diagnosed and radical left nephrectomy was performed. Twenty-two months postoperatively, lung metastases were demonstrated and 6 × 106 units of ,-interferon (IFN-,) were administered for 9 months, only to keep the sizes of the metastases unchanged. Thirty-four months after the operation, liver metastases and bone metastasis in the left sacroiliac joint were revealed. The combination cytokine therapy was performed with 1.4 × 106 U of interleukin-2 (IL-2) and 3 × 106 U of IFN-, for 16 weeks, and the left sacroiliac joint metastasis was treated with radiation therapy of 4 Gy per day for 7 days. Six months after the 16 weeks of immunotherapy, computed tomography and bone scintigraphy revealed that the metastases of the lung, liver and bone substantially disappeared and this complete response is still kept after 16 months. [source] Early Detection of Bone Metastases in a Murine Model Using Fluorescent Human Breast Cancer Cells: Application to the Use of the Bisphosphonate Zoledronic Acid in the Treatment of Osteolytic LesionsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2001Olivier Peyruchaud Abstract A very common metastatic site for human breast cancer is bone. The traditional bone metastasis model requires human MDA-MB-231 breast carcinoma cell inoculation into the left heart ventricle of nude mice. MDA-MB-231 cells usually develop osteolytic lesions 3,4 weeks after intracardiac inoculation in these animals. Here, we report a new approach to study the formation of bone metastasis in animals using breast carcinoma cells expressing the bioluminescent jellyfish protein (green fluorescent protein [GFP]). We first established a subclone of MDA-MB-231 cells by repeated in vivo passages in bone using the heart injection model. On stable transfection of this subclone with an expression vector for GFP and subsequent inoculation of GFP-expressing tumor cells (B02/GFP.2) in the mouse tail vein, B02/GFP.2 cells displayed a unique predilection for dissemination to bone. Externally fluorescence imaging of live animals allowed the detection of fluorescent bone metastases approximately 1 week before the occurrence of radiologically distinctive osteolytic lesions. The number, size, and intensity of fluorescent bone metastases increased progressively with time and was indicative of breast cancer cell progression within bone. Histological examination of fluorescent long bones from B02/GFP.2-bearing mice revealed the occurrence of profound bone destruction. Treatment of B02/GFP.2-bearing mice with the bisphosphonate zoledronic acid markedly inhibited the progression of established osteolytic lesions and the expansion of breast cancer cells within bone. Overall, this new bone metastasis model of breast cancer combining both fluorescence imaging and radiography should provide an invaluable tool to study the effectiveness of pharmaceutical agents that could suppress cancer colonization in bone. [source] Femur window,a new approach to microcirculation of living bone in situJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2005N. Hansen-Algenstaedt Abstract Background: The processes of osteogenesis, bone remodelling, fracture repair and metastasis to bone are determined by complex sequential interactions involving cellular and microcirculatory parameters. Consequently studies targeting the analysis of microcirculatory parameters on such processes should mostly respect these complex conditions. However these conditions could not yet be achieved in vitro and therefore techniques that allow a long-term observation of functional and structural parameters of microcirculation in bone in vivo at a high spatial resolution are needed to monitor dynamic events, such as fracture healing, bone remodelling and tumor metastasis. Methods: We developed a bone chamber implant (femur window) for long-term intravital microscopy of pre-existing bone and its microcirculation at an orthotopic site in mice preserving the mechanical properties of bone. After bone chamber implantation vascular density, vessel diameter, vessel perfusion, vascular permeability and leukocyte-endothelial interactions (LEIs) in femoral bone tissue of c57-black mice (n = 11) were measured quantitatively over 12 days using intravital fluorescence microscopy. Furthermore a model for bone defect healing and bone metastasis in the femur window was tested. Results: Microvascular permeability and LEIs showed initially high values after chamber implantation followed by a significant decrease to a steady state at day 6 and 12, whereas structural parameters remained unaltered. Bone defect healing and tumor growth was observed over 12 and 90 days respectively. Conclusion: The new femur window design allows a long-term analysis of structural and functional properties of bone and its microcirculation quantitatively at a high spatial resolution. Altered functional parameters of microcirculation after surgical procedures and their time dependent return to a steady state underline the necessity of long-term observations to achieve unaltered microcirculatory parameters. Dissection of the complex interactions between bone and microcirculation enables us to evaluate physiological and pathological processes of bone and may give new insights especially in dynamic events e.g. fracture healing, bone remodeling and tumor metastasis. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] The role of surgery in breast cancer patients with isolated bone metastases at the time of diagnosisJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2009Sevim Turanli MD Abstract Background Surgery for the primary tumor in breast cancer patients with synchronous isolated bone metastasis is applied for palliation. The aim was to determine whether surgical removal of the primary tumor provides a better survival and disease progression. Methods Forty-four patients were diagnosed between the dates June 2004 and January 2007 and these patients are classified according to the removal of the primary tumor or not. Patients and tumor characteristics, removal of the primary tumor, and response to systemic therapy are examined as the factors that were affecting overall survival and time to progression of the disease. Results The median follow-up time was 37.5 months. Mean time to progression and overall survival was longer for the patients who received surgery than the patients who did not (20.4 vs. 18.4 months and 57.6 vs. 44.5 months, respectively), but these were not significant (P,=,0.58, P,=,0.39). In multivariate analysis, response to systemic treatment [(P,=,0.03), hazard ratio,=,0.44, 95% confidence interval,=,0.20,0.93] was independent factor associated with overall survival. Conclusion The response to systemic therapy is the major factor on survival in the breast cancer patients with isolated bone metastasis. Excision of the primary tumor has no effect on time to progression and overall survival. J. Surg. Oncol. 2009;100:95,99. © 2009 Wiley-Liss, Inc. [source] Neuroblastoma of unknown primary site with periorbital bone metastasis in a child,PEDIATRIC BLOOD & CANCER, Issue 2 2010Darren Salmi MS Abstract Neuroblastoma is the second most common solid tumor in children. Most tumors arise in the adrenal glands or paravertebral region. Rarely, patients present with metastatic disease but no primary site can be found despite extensive imaging. We report here a patient with a large periorbital bone metastasis and bone marrow involvement but with no known primary site. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc. [source] RANKL inhibition is an effective adjuvant for docetaxel in a prostate cancer bone metastases modelTHE PROSTATE, Issue 8 2008K. M. Woods Ignatoski Abstract BACKGROUND Docetaxel induces an anti-tumor response in men with advanced prostate cancer (PCa); however, the side effects associated with docetaxel treatment can be severe, resulting in discontinuation of therapy. Thus, identification of an effective adjuvant therapy to allow lower doses of docetaxel is needed. Advanced PCa is typically accompanied by skeletal metastasis. Receptor activator of NFkB ligand (RANKL) is a key pro-osteoclastic factor. Targeting RANKL decreases establishment and progression of PCa growth in bone in murine models. METHODS The efficacy of inhibiting RANKL, using a recombinant soluble RANK extracellular domain fused with the immunoglobulin Fc domain (RANK-Fc), was tested as an adjuvant therapy with docetaxel for PCa bone metastasis in a murine intra-tibial model. RESULT The combination of RANK-Fc and docetaxel reduced tumor burden in bone greater than either treatment alone. CONCLUSION The combination of docetaxel with a RANKL-inhibiting agent merits further investigation for treatment of advance PCa. Prostate 68:820,829, 2008. © 2008 Wiley-Liss, Inc. [source] Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancerTHE PROSTATE, Issue 4 2007Jin Gao Abstract BACKGROUND Prostate cancer (PCa) and bone cell interactions are critical in the metastatic phase. Kallikrein 4 (KLK4/hK4) is expressed in both PCa and mineralized tissues. We determined if KLK4/hK4 expression was associated with, and influenced by, the bone environment of metastatic PCa. METHODS Immunohistochemistry, in vitro co-culture, cell migration, and attachment assays. RESULTS hK4 was localized to tumor cells and osteoblasts in bone metastases. KLK4/hK4 increased in LNCaP and PC3 cells co-cultured with SaOs2 cells; SaOs2 KLK4/hK4 was unchanged. Co-culture did not affect cell proliferation but altered alkaline phosphatase activity/mRNA levels in SaOs2 cells. KLK4 -transfected PC3 cells had increased migration towards SaOs2 conditioned medium and greater attachment to the bone-matrix proteins, collagens I and IV. CONCLUSIONS hK4 expression and interaction with both tumor cells and osteoblasts suggests a role for hK4 in PCa bone metastasis. Whether this observation is unique to bone metastasis or reflects a role for hK4 in PCa metastasis generally is yet to be established. Prostate 67: 348,360, 2007. © 2007 Wiley-Liss, Inc. [source] In vivo real-time imaging of TGF-,-induced transcriptional activation of the RANK ligand gene promoter in intraosseous prostate cancerTHE PROSTATE, Issue 4 2004Jian Zhang Abstract BACKGROUND Current animal models of prostate cancer (CaP) bone metastasis do not allow measurement of either tumor growth in bone over time or activation of gene promoters in intraosseous tumors. To develop these methods, we used bioluminescent imaging (BLI) to determine if expression of receptor activator of NF-,B ligand (RANKL), a pro-osteoclastogenic factor that promotes CaP bone metastases, is modulated by the bone matrix protein transforming growth factor-, (TGF-,) in vivo. METHODS C4-2B human CaP cells were treated with TGF-, in vitro and RANKL mRNA and protein production were measured by polymerase chain reaction (PCR) and ELISA, respectively. Then C4-2B cells stably transfected with the RANKL promoter driving luciferase (lux) were injected intra-tibially into severe combined immundeficient (SCID) mice. Tumors were subjected to BLI every 2 weeks for 6 weeks and serum prostate specific antigen (PSA) was measured using ELISA. Vehicle (V), 1,25 dihydroxyvitamin D (VitD), or TGF-, was administered to mice with established tumors and BLI to measure RANKL promoter activity was performed. Tumors were then subjected to immunohistochemistry for lux and assayed for RANKL mRNA levels. RESULTS TGF-, induced RANKL protein and mRNA expression and activated the RANKL promoter activity in a dose-dependent manner in vitro. BLI demonstrated an increase in intraosseous tumor size over time, which correlated with serum PSA levels. Administration of TGF-, and VitD to mice with established intraosseous tumors increased lux activity compared to V. Intratibial tumor RANKL mRNA expression paralleled the increased promoter activity. Immunohistochemistry confirmed the presence of lux in the intraosseous tumors. CONCLUSIONS These results demonstrate the ability to measure intraosseous tumor growth over time and gene promoter activation in an established intraosseous tumor in vivo and also demonstrate that TGF-, induces activates the RANKL promoter. These results provide a novel method to explore the biology of CaP bone metastases. © 2004 Wiley-Liss, Inc. [source] Is palliative resection of the primary tumour, in the presence of advanced rectal cancer, a safe and useful technique for symptom control?ANZ JOURNAL OF SURGERY, Issue 4 2004Nasser Al-Sanea Introduction: At some time, every general surgeon will be faced with the task of trying to decide what to do with a patient who presents with rectal cancer and unresectable distant metastases. How safe is resectional surgery? What sort of palliation may be expected following resection of the primary tumour? In an attempt to answer these questions, the management and outcomes of all patients with rectal cancer and distant metastases, who were primarily referred to the colorectal unit at King Faisal Specialist Hospital were examined. Methods: All patients who underwent primary surgery for rectal cancer in the presence of metastatic disease were identified. The charts of these patients were examined and their morbidity, mortality and survival were determined. Results: Over an 8-year period 22 patients (average age 54 years) underwent rectal resectional surgery in the presence of metastatic disease. There were 13 men and nine women. The commonest complaint was rectal bleeding. All patients had chest radiographs. Pulmonary metastases were identified in four patients. Nineteen abdominal and pelvic computed tomography scans were performed and eight showed evidence of metastases. Skeletal radiographs in two patients showed evidence of bone metastasis. At operation, intraperitoneal metastases were found in 18 patients. Nine of these were not identified preoperatively. Six patients underwent abdomino-perineal resection, nine anterior resection and seven a Hartmann's procedure. Eight patients developed a significant postoperative complication and one died 42 days after surgery. The mean length of hospital stay was 18.6 days. Nine patients received preoperative radiotherapy. Four patients had palliative radiotherapy, two for bony, one for liver and one for peritoneal metastases. Patients were followed up for a mean of 1.1 years. During follow up, 11 returned to the emergency room on 24 occasions. Two patients required readmission. No patient had further rectal bleeding. The mean survival was 1.3 years. Conclusion: Patients with rectal cancer and unresectable distant metastases can be successfully palliated by resection of the primary tumour with low morbidity and mortality. The early involvement of a palliative care team facilitates patient management and helps patients enjoy what remains of the rest of their lives at home, in comfort and with good symptom control. [source] Crystallization and preliminary X-ray analysis of mouse RANK and its complex with RANKLACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 6 2009Thomas S. Walter The interaction between the TNF-family molecule receptor activator of NF-,B ligand (RANKL) and its receptor RANK induces osteoclast formation, activation and survival in the process of bone remodelling. RANKL,RANK also plays critical roles in T-cell/dendritic cell communication and lymph-node formation and in a variety of pathologic conditions such as tumour-cell migration and bone metastasis. Both the ectodomain of mouse RANKL and the extracellular domain of mouse RANK have been cloned, expressed and purified. Crystals of RANK alone and of RANK in complex with RANKL have been obtained that are suitable for structure determination. [source] State-of-the-art approaches to detecting early bone metastasis in prostate cancerBJU INTERNATIONAL, Issue 3 2004Ramesh Thurairaja First page of article [source] Pathogenesis of osteoblastic bone metastases from prostate cancer,CANCER, Issue 6 2010Toni Ibrahim MD Abstract Prostate cancer is the second leading cause of cancer-related death in men. A typical feature of this disease is its ability to metastasize to bone. It is mainly osteosclerotic, and is caused by a relative excess of osteoblast activity, leading to an abnormal bone formation. Bone metastases are the result of a complex series of steps that are not yet fully understood and depend on dynamic crosstalk between metastatic cancer cells, cellular components of the bone marrow microenvironment, and bone matrix (osteoblasts and osteoclasts). Prostate cancer cells from primary tissue undergo an epithelial-mesenchymal transition to disseminate and acquire a bone-like phenotype to metastasize in bone tissue. This review discusses the biological processes and the molecules involved in the progression of bone metastases. Here we focus on the routes of osteoblast differentiation and activation, the crosstalk between bone cells and tumor cells, and the molecules involved in these processes that are expressed by both osteoblasts and tumor cells. Furthermore, this review deals with the recently elucidated role of osteoclasts in prostate cancer bone metastases. Certainly, to better understand the underlying mechanisms of bone metastasis and so improve targeted bone therapies, further studies are warranted to shed light on the probable role of the premetastatic niche and the involvement of cancer stem cells. Cancer 2010. © 2010 American Cancer Society. [source] Percutaneous radiofrequency ablation of painful osseous metastasesCANCER, Issue 4 2010A multicenter American College of Radiology Imaging Network trial Abstract BACKGROUND: The study was conducted to determine whether radiofrequency ablation (RFA) can safely reduce pain from osseous metastatic disease. METHODS: The single-arm prospective trial included patients with a single painful bone metastasis with unremitting pain with a score >50 on a pain scale of 0-100. Percutaneous computed tomography-guided RFA of the bone metastasis to temperatures >60°C was performed. Endpoints were the toxicity and pain effects of RFA before and at 2 weeks, 1 month, and 3 months after RFA. RESULTS: Fifty-five patients completed RFA. Grade 3 toxicities occurred in 3 of 55 (5%) patients. RFA reduced pain at 1 and 3 months for all pain assessment measures. The average increase in pain relief from pre-RFA to 1-month follow-up is 26.3 (95% confidence interval [CI], 17.7-34.9; P < .0001), and the increase from pre-RFA to 3-month follow-up is 16.38 (95% CI, 3.4-29.4; P = .02). The average decrease in pain intensity from pre-RFA to 1-month follow-up was 26.9 (P < .0001) and 14.2 for 3-month follow-up (P = .02). The odds of lower pain severity at 1-month follow-up were 14.0 (95% CI, 2.3-25.7; P < .0001) times higher than at pre-RFA, and the odds at 3-month follow-up were 8.0 (95% CI, 0.9-15.2; P < .001) times higher than at pre-RFA. The average increase in mood from pre-RFA to 1-month follow-up was 19.9 (P < .0001) and 14.9 to 3-month follow-up (P = .005). CONCLUSIONS: This cooperative group trial strongly suggests that RFA can safely palliate pain from bone metastases. Cancer 2010. © 2010 American Cancer Society [source] Detection of tumor specific gene expression in bone marrow and peripheral blood from patients with small cell lung carcinomaCANCER, Issue 4 2003Masato Shingyoji M.D. Abstract BACKGROUND Small cell lung carcinoma (SCLC) has the propensity to grow rapidly and metastasize extensively. Detection of micro-dissemination of SCLC may have clinical relevance. For its detection, tumor-specific gene expressions were examined in peripheral blood and bone marrow aspirate from patients with SCLC. METHODS Expression of prepro-gastrin-releasing peptide (preproGRP), neuromedin B receptor (NMB-R) and gastrin-releasing peptide receptor (GRP-R) were examined by reverse transcriptase polymerase chain reaction (RT-PCR) in peripheral blood and bone marrow aspirate from 40 untreated patients with SCLC. Control samples consisted of peripheral blood samples from 5 patients with nonsmall cell lung cancer (NSCLC) and 20 healthy volunteers. RESULTS Positive rates of preproGRP, NMB-R, and GRP-R in bone marrow aspirate of patients with SCLC were 23% (9/40), 8% (3/40), and 10% (4/40), respectively. Those rates in peripheral blood were 11% (4/38), 5% (2/38), and 29% (11/38), respectively. Although GRP-R expression was detected in patients with NSCLC and in healthy volunteers, preproGRP and NMB-R expressions were not detected in patients with NSCLC and in healthy volunteers. All three gene expressions in bone marrow were more frequently observed in patients with bone marrow metastasis, accessed by biopsy, than in patients without. PreproGRP gene expression in bone marrow was also more frequent in patients with bone metastasis, accessed by bone scintigram, than in patients without, and was related to poorer survival. CONCLUSIONS Micro-dissemination of SCLC was detectable by RT-PCR of preproGRP and NMB-R, both specific for SCLC. These gene expressions in bone marrow may be related to disease extent and prognosis. Cancer 2003;97:1057,62. © 2003 American Cancer Society. DOI 10.1002/cncr.11108 [source] Clinical importance of serum interleukin-18 and nitric oxide activities in breast carcinoma patientsCANCER, Issue 3 2002Nazan Günel M.D. Abstract BACKGROUND Interleukin-18 (IL-18) is a novel immunoregulatory cytokine that was known previously as interferon-,,inducing factor. IL-18 levels can be used as a serum indicator for monitoring the clinical course of patients with hematologic malignancies and gastric carcinoma. Nitric oxide (NO) is a pleiotropic molecule that participates in the multistep processing of carcinogenesis. METHODS In the current study, we measured serum IL-18 and nitrate and nitrite levels in 38 metastatic and 26 nonmetastatic breast carcinoma patients and 16 healthy control subjects. Serum nitrate and nitrite levels were measured as an index of NO generation. RESULTS The levels of serum IL-18 and nitrate and nitrite were increased significantly in breast carcinoma patients compared with control subjects (P < 0.001). Serum IL-18 levels were significantly higher in the metastatic patients compared with the nonmetastatic patients (P < 0.001). There was no difference in serum nitrate and nitrite levels between metastatic and nonmetastatic patients (P > 0.05). Patients with bone metastasis have higher serum IL-18 levels and lower serum nitrate and nitrite levels compared with patients with liver, lung, and local metastasis (P < 0.001). There was no correlation among serum IL-18, nitrate and nitrite, CA 15-3, and carcinoemybryonic antigen levels (P > 0.05). CONCLUSIONS These findings suggest that serum IL-18 and nitrate and nitrite levels may be useful markers in monitoring metastatic breast carcinoma pateints. IL-18 and NO activities in breast carcinoma patients with bone metastasis may be more valuable in the follow-up of these patients. Cancer 2002;95:663,7. © 2002 American Cancer Society. DOI 10.1002/cncr.10705 [source] A multiinstitutional, concurrent chemoradiation trial of strontium-89, estramustine, and vinblastine for hormone refractory prostate carcinoma involving boneCANCER, Issue 6 2002Wallace Akerley M.D. Abstract BACKGROUND Estramustine phosphate (EMP) and vinblastine have radiosensitizing properties and significant activity against hormone refractory prostate carcinoma. Strontium-89 is a palliative agent that acts as a selective radiation source for bone metastasis. The combination of EMP, vinblastine, and strontium-89 was developed to exploit the potential for radiosynergy. PATIENTS AND METHODS Forty-four patients at the Brown Oncology Group affiliated hospitals were treated with oral EMP 600 mg/m2 daily on Weeks 1,4 and 7,10, vinblastine 4 mg/m2 intravenously once each week on Weeks 1,4 and 7,10, and strontium-89 2.2 MBq/kg on Day 1. Courses were repeated every 12 weeks. Response assessment was based on a change in the serum prostate specific antigen (PSA) levels, correlated with change in measurable disease and bone scan appearance. RESULTS A greater than or equal to 50% decline in PSA for at least 6 weeks was observed in 21 patients (48%, 95% confidence interval, 33,62%). Median duration of response was 23 weeks (range, 6,70.8 weeks). The median survival was 13 months with 1- and 2-year survival rates of 55% and 25%, respectively. After completion of protocol therapy, a retrospective review showed that only nine patients received subsequent palliative external beam radiation after progression. CONCLUSIONS The addition of strontium-89 to the regimen of EMP and vinblastine can be delivered safely and in repeated doses, provides effective palliation, and may decrease the need for future radiation therapy. A randomized trial is necessary to quantify these effects. Cancer 2002;94:1654,60. © 2002 American Cancer Society. DOI 10.1002/cncr.10437 [source] Bone morphogenetic protein-10 (BMP-10) inhibits aggressiveness of breast cancer cells and correlates with poor prognosis in breast cancerCANCER SCIENCE, Issue 10 2010Lin Ye Our recent study showed that a novel member of bone morphogenetic protein (BMP) family, BMP-10, was decreased in prostate cancer. In the present study, we investigated the implication of BMP-10 in breast cancer, particularly the relation of its expression with clinical aspects. The expression of BMP-10 was examined in a cohort of human breast cancer specimens (normal, n = 23; cancer, n = 97), using both quantitative real-time PCR and immunohistochemical staining. The full-length human BMP-10 was cloned into a mammalian expression plasmid vector and then transfected into breast cancer cells. The effect on growth, cell matrix adhesion, motility, and invasion of MDA-MB-231 cells by BMP-10 was then investigated using in vitro growth assays. Immunohistochemical staining and quantitative real-time PCR revealed a decreased expression of BMP-10 in breast cancer. Further analysis of BMP-10 transcript level against the clinical aspect demonstrated that the decreased BMP-10 expression correlated with disease progression, bone metastasis, and poor prognosis. The disease-free survival of the patients with a higher level of BMP-10 was 132.8 (95% CI, 122.0,143.5) months, significantly longer compared to 93.7 (95% CI, 60.3,127.2) months for patients with a lower level of BMP-10 expression (P = 0.043). The overexpression of BMP-10 has broad inhibitory effects on the in vitro growth, invasion, and motility of breast cancer cells. Taken together, BMP-10 can inhibit the cell growth of breast cancer cells, and decreased BMP-10 expression correlates to poor prognosis and disease progression, particularly the lymphatic and bone metastasis. Bone morphogenetic protein-10 (BMP-10) may function as a tumor suppressor in breast cancer. (Cancer Sci 2010) [source] Osteoclast-targeting small molecules for the treatment of neoplastic bone metastasesCANCER SCIENCE, Issue 11 2009Makoto Kawatani Osteoclasts are highly specialized cells that resorb bone, and their abnormal activity is implicated in a variety of human bone diseases. In neoplastic bone metastasis, the bone destruction caused by osteoclasts is not only associated with the formation and progression of metastatic lesions, but also could contribute to frequent complications such as severe pain and pathological fractures, which greatly diminish the quality of life of patients. Bisphosphonates, potent antiresorptive drugs, have been shown to have efficacy for treating bone metastases in many types of cancer, and the development of various molecularly targeted agents is currently proceeding. Thus, inhibition of osteoclast function is now established as an important treatment strategy for bony metastases. This review focuses on promising small molecules that disrupt osteoclast function and introduces our chemical/biological approach for identifying osteoclast-targeting small molecular inhibitors. (Cancer Sci 2009) [source] Transforming growth factor-, signaling at the tumor,bone interface promotes mammary tumor growth and osteoclast activationCANCER SCIENCE, Issue 1 2009Mitsuru Futakuchi Understanding the cellular and molecular changes in the bone microenvironment is important for developing novel therapeutics to control breast cancer bone metastasis. Although the underlying mechanism(s) of bone metastasis has been the focus of intense investigation, relatively little is known about complex molecular interactions between malignant cells and bone stroma. Using a murine syngeneic model that mimics osteolytic changes associated with human breast cancer, we examined the role of tumor,bone interaction in tumor-induced osteolysis and malignant growth in the bone microenvironment. We identified transforming growth factor-, receptor 1 (TGF-,RI) as a commonly upregulated gene at the tumor-bone (TB) interface. Moreover, TGF-,RI expression and activation, analyzed by nuclear localization of phospho-Smad2, was higher in tumor cells and osteoclasts at the TB interface as compared to the tumor-alone area. Furthermore, attenuation of TGF-, activity by neutralizing antibody to TGF-, or TGF-,RI kinase inhibitor reduced mammary tumor-induced osteolysis, TGF-,RI expression and its activation. In addition, we demonstrate a potential role of TGF-, as an important modifier of receptor activator of NF-,B ligand (RANKL)-dependent osteoclast activation and osteolysis. Together, these studies demonstrate that inhibition of TGF-,RI signaling at the TB interface will be a therapeutic target in the treatment of breast cancer-induced osteolysis. (Cancer Sci 2009; 100: 71,81) [source] CXCR6 is expressed in human prostate cancer in vivo and is involved in the in vitro invasion of PC3 and LNCap cellsCANCER SCIENCE, Issue 7 2008Weidong Hu In spite of the clinical importance of prostate cancer (PCa) bone metastasis, the precise mechanisms for the directed migration of malignant cells remain unclear. In the present study, the expression of CXCR6 in human PCa and benign prostatic hyperplasia samples, and the expression of CXCL16 in human osseous tissues were determined by immunohistochemistry. It was found that the level of CXCR6 protein expression was elevated in human malignant prostate tumors, and CXCL16 was expressed positively by human osteocytes in vivo. The in vitro experiments further confirmed that the PCa cell lines PC3 and LNCap expressed CXCR6 at both the mRNA and protein levels, and exogenous CXCL16 has the potential to stimulate the invasion of PC3 and LNCap. To further elucidate the role of the CXCL16,CXCR6 axis in PCa progression, we compared the expression of CXCR6 and CXCR4 in human PCa tissues and the effects of CXCL16 and CXCL12 on the in vitro invasion of PC3 and LNCap cells. It was shown that CXCR6 and CXCR4 proteins were coexpressed and elevated in human PCa samples, and CXCL16 and CXCL12 promoted the invasion of PC3 and LNCap via their respective receptors. Furthermore, in contrast to CXCL12, which enhanced the activity of matrix metalloproteinase (MMP) 9 and MMP2 in PC3 and LNCap, CXCL16 ligation resulted in stronger MMP9 and MMP2 activity in LNCap but not in PC3. Our results suggest that besides CXCL12/CXCR4, CXCL16/CXCR6 might be another important factor involved in PCa bone metastasis. (Cancer Sci 2008; 99: 1362,1369) [source] NF-,B activation in development and progression of cancerCANCER SCIENCE, Issue 3 2007Jun-ichiro Inoue Nuclear factor-,, (NF-,B) binds specifically to NF-,B-binding sites (,B sites, 5,-GGGRNNYYCC-3,; R, purine; Y, pyrimidine; N, any nucleotide) present in enhancer regions of various genes. Binding of various cytokines, growth factors and pathogen-associated molecular patterns to specific receptors activates NF-,B and expression of genes that play critical roles in inflammation, innate and acquired immunity, bone remodeling and generation of skin appendices. Activation of NF-,B is also involved in cancer development and progression. NF-,B is activated in cells that become malignant tumors and in cells that are recruited to and constitute the tumor microenvironment. In the latter scenario, the TLR-TRAF6-NF-kB pathways seem to play major roles, and NF-,B activation results in production of cytokines, which in turn induce NF-,B activation in premalignant cells, leading to expression of genes involved abnormal growth and malignancy. Furthermore, NF-,B activation is involved in bone metastasis. Osteoclasts, whose generation requires the RANK-TRAF6-NF-,B pathways, release various growth factors stored in bone, which results in creation of microenvironment suitable for proliferation and colonization of cancer cells. Therefore, NF-,B and molecules involved its activation, such as TRAF6, are attractive targets for therapeutic strategies against cancer. (Cancer Sci 2007; 98: 268,274) [source] | |||||||||||||||||||||||||||||||