OBJECTIVETo examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis.

METHODSThe osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0.08 mmol/L), or 10 μmol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-β1 (TGF-β1), nuclear factor-kappa B (NF-κB) and Hes1 were determined by enzyme-linked immunosorbent assay.

RESULTSCompared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells (P<0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-β1, NF-κB and Hes1 (P<0.05 or P<0.01).

CONCLUSIONBrucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.

Animals ; Bone Neoplasms ; metabolism ; prevention & control ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Female ; Humans ; Jagged-1 Protein ; metabolism ; Macrophages ; drug effects ; physiology ; Mice ; Osteoclasts ; drug effects ; physiology ; Receptor, Notch1 ; metabolism ; Signal Transduction ; drug effects ; Strychnine ; analogs & derivatives ; pharmacology ; therapeutic use

Cytokines are believed to be involved in a "vicious circle" of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose (30 μg/mL) iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.
Animals ; Apoptosis ; drug effects ; Bone Neoplasms ; complications ; drug therapy ; pathology ; secondary ; Bone Resorption ; complications ; drug therapy ; pathology ; Breast Neoplasms ; complications ; drug therapy ; genetics ; pathology ; Carcinogenesis ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Chromones ; administration & dosage ; Female ; Humans ; Interleukin-6 ; biosynthesis ; genetics ; MCF-7 Cells ; Neoplasm Invasiveness ; genetics ; pathology ; Rats ; Sulfonamides ; administration & dosage ; Transcription Factor RelA ; biosynthesis ; genetics

The occurrence of hepatocellular carcinoma (HCC) is closely associated with viral hepatitis or alcoholic hepatitis. Although active surveillance is ongoing in Korea, advanced or metastatic HCC is found at initial presentation in many patients. Metastatic HCC presents with a hypervascular intrahepatic tumor and extrahepatic lesions such as lung or lymph node metastases. Cases of HCC presenting as carcinoma of unknown primary have been rarely reported. The authors experienced a case of metastatic HCC in a patient who presented with a metastatic bone lesion but no primary intrahepatic tumor. This case suggests that HCC should be considered as a differential diagnosis when evaluating the primary origin of metastatic carcinoma.
Antineoplastic Agents/therapeutic use ; Bone Neoplasms/*diagnosis/diagnostic imaging/secondary ; Carcinoma, Hepatocellular/*diagnosis/drug therapy ; Cervical Cord/pathology ; Chemoembolization, Therapeutic ; Gamma Rays ; Humans ; Liver Neoplasms/*diagnosis/drug therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasms, Unknown Primary/pathology ; Niacinamide/analogs & derivatives/therapeutic use ; Pelvic Bones/pathology ; Phenylurea Compounds/therapeutic use ; Tomography, X-Ray Computed

We reviewed and analyzed the clinical data for a patient with metastatic castration-resistant prostate cancer (mCRPC) from September, 2009 to December, 2014. After the treatment with abiraterone, patient's performance status improved, pain relieved, total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) markedly decreased. tPSA or fPSA fluctuated between 
30 and 50 ng/mL or between 10 and 20 ng/mL. MRI showed the left peripheral zone reduced. MRI and bone single photon emission computed tomography (SPECT) scan showed no new metastasis. These results indicated that application of abiraterone for patient with mCRPC not only decreased prostate specific antigen (PSA) levels and tumor volume, but also blocked bone metastasis progression and enhanced pain relief.
Androstenes ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Disease Progression ; Humans ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Endostatins ; therapeutic use ; Epirubicin ; administration & dosage ; Feasibility Studies ; Female ; Follow-Up Studies ; Hemangiosarcoma ; drug therapy ; pathology ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Pubic Bone ; pathology ; Taxoids ; administration & dosage

OBJECTIVEThe aim of this study was to analyze the clinical characteristics, treatment and prognosis of advanced urothelial carcinoma of the bladder (AUCB).

METHODSThe clinicopathological data of 117 patients with AUCB admitted in our hospital from 1998 to 2009 were reviewed. All patients received first-line chemotherapy. The survival rate was calculated by Kaplan-Meier analysis and log-rank test.

RESULTSThe median age of all patients was 56 years and the male-to-female ratio was 3.33:1. Their 6-, 12-, 24-, 36- and 60-month survival rates were 90.3%, 61.3%, 32.3%, 24.2% and 8.1%, respectively. In the first-line chemotherapy regimen, the effectiveness rate of gemcitabine + platinum drugs was 49.3% (37/75), the median progression-free survival(PFS) was 7.9 months and overall survival (OS) was 18.7 months. The effectiveness of cyclophosphamide + epirubicin + platinum drug regimen was 45.5% (10/22), Median PFS was 7.1 months and OS was 15.3 months. The effectiveness of paclitaxel + platinum drug regimen was 47.1% (8/17), median PFS was 6.5 months and OS was 13.7 months. Among them, the effectiveness rate of the gemcitabine + cisplatin regimen in 67 patients was 47.8%, the median PFS was 7.0 months and OS was 15.3 months. In the 13 patients who received paclitaxel + carboplatin regimen, the effectiveness rate was 53.8%, median PFS was 7.7 months and OS was 16.0 months. The major side effects were leucopenia and thrombocytopenia, mostly were tolerable, of grade I to II.

CONCLUSIONSIn advanced unresectable and metastatic urothelial carcinoma of the bladder, GC regimen is recognized as a standard first-line chemotherapy, with a higher effectiveness and tolerable side effects. Taxane and molecular targeted drugs may further improve the therapeutic effect of the treatment of advanced urothelial carcinomas of the bladder in the future.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Transitional Cell ; drug therapy ; pathology ; secondary ; Cisplatin ; administration & dosage ; adverse effects ; Cyclophosphamide ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Disease-Free Survival ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; adverse effects ; Retrospective Studies ; Survival Rate ; Thrombocytopenia ; chemically induced ; Urinary Bladder Neoplasms ; drug therapy ; pathology ; Urothelium ; pathology

The standard first-line treatment of castration-resistant prostate cancer (CRPC) is docetaxel-based chemotherapy. However, CRPC may not respond to docetaxel due to drug resistance or other causes. Several new therapeutic agents have been developed, some of which are approved by FDA or on clinical trials. The mechanisms of action of these agents include stabilizing microtubules, inhibiting hormone synthesis, blocking androgen receptor, bone targeting or immune regulation. In this article we review the novel therapeutic options for CPRC after docetaxel failure.
Bone Neoplasms ; drug therapy ; secondary ; Drug Resistance, Neoplasm ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology ; Taxoids ; therapeutic use

Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process of bone metastasis, the roles of the Wnt signaling, and the available experimental models and treatments.
Animals ; Bone Neoplasms ; drug therapy ; metabolism ; radiotherapy ; secondary ; surgery ; Breast Neoplasms ; metabolism ; pathology ; Disease Models, Animal ; Drug Delivery Systems ; Female ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Prostatic Neoplasms ; metabolism ; pathology ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway ; beta Catenin ; metabolism

PURPOSE: Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients. MATERIALS AND METHODS: The medical records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis. RESULTS: The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 [95% confidence interval (CI), 38.6-71.9] months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment [hazard ratio=0.18; 95% CI, 0.07-0.43], estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor. CONCLUSION: Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.
Adult ; Antineoplastic Agents/therapeutic use ; Bone Neoplasms/drug therapy/genetics/*secondary ; Breast Neoplasms/drug therapy/genetics/*pathology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Regression Analysis ; Retrospective Studies ; Survival Analysis

OBJECTIVETo investigate the clinical features and prognosis of bone metastases in colorectal cancer patients.

METHODSThe clinical data of 104 cases of colorectal cancer with bone metastasis were collected and retrospectively analyzed.

RESULTSAmong all the 104 patients included, 45 (43.3%) patients had multiple bone metastases, and 59 (56.7%) patients had single bone metastasis. Pelvis (46.1%) was the most common site, followed by thoracic vertebrae (41.3%), lumbar vertebrae (40.4%), sacral vertebrae (29.8%) and ribs (29.8%). One hundred and two patients (98.1%) were complicated with other organ metastases. The median time from colorectal cancer diagnosis to bone metastasis was 16 months, and the median time from bone metastasis to first skeletal-related events (SREs) was 1 month. The most common skeletal-related events (SREs) were the need for radiotherapy (44.2%), severe bone pain (15.4%) and pathologic fracture (9.6%). The median survival time of patients with bone metastases was 10.0 months, and 8.5 months for patients with SREs. ECOG score, systemic chemotherapy and bisphosphonate therapy were prognostic factors by univariate analysis (all P < 0.05). ECOG score and systemic chemotherapy were independent prognostic factors by Cox multivariate analysis.

CONCLUSIONSBone metastasis in colorectal cancer patients has a poor prognosis and the use of chemotherapy and bisphosphonates may have a benefit for their survival.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Density Conservation Agents ; therapeutic use ; Bone Neoplasms ; drug therapy ; radiotherapy ; secondary ; Colorectal Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Diphosphonates ; therapeutic use ; Female ; Follow-Up Studies ; Fractures, Bone ; etiology ; Humans ; Lumbar Vertebrae ; pathology ; Male ; Middle Aged ; Pain ; etiology ; Pelvic Bones ; pathology ; Prognosis ; Retrospective Studies ; Ribs ; pathology ; Sacrum ; pathology ; Spinal Cord Compression ; etiology ; Spinal Neoplasms ; drug therapy ; radiotherapy ; secondary ; Thoracic Vertebrae ; pathology ; Young Adult