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

ADP-ribosyl Cyclase 1 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Biopsy ; Bone Neoplasms ; drug therapy ; metabolism ; pathology ; CD56 Antigen ; metabolism ; Humans ; Ilium ; Interferon Regulatory Factors ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; metabolism ; pathology ; Syndecan-1 ; metabolism

OBJECTIVETo study the histogenesis of giant cell tumor (GCT) and factors related to tumor recurrence, invasiveness and malignant transformation.

METHODSThe clinical features, radiologic classification, surgical approach, pathologic findings, immunophenotypes and follow-up data of 123 cases of GCT were analyzed.

RESULTSThere was a significant correlation between tumor recurrence and radiographic classification (P = 0.032), over-expression of CD147 (P = 0.034) and p53 (P = 0.005), and surgical approach (P = 0.0048) in GCT. The biologic behavior showed no correlation with intramedullary infiltration, cortical bone involvement, parosteal soft tissue extension, tumor thrombi, fusiform changes of mononuclear tumor cells, mitotic count, Ki-67 index, coagulative tumor necrosis, secondary aneurysmal bone cyst formation, and adjoining bony reaction. The positive rate of p63 in stromal cells of GCT (79.7%, 94/118) was significantly higher than that in chondroblastoma (44.7%, 21/47), osteosarcoma (22.2%, 10/45) and other giant cell-rich tumors.

CONCLUSIONSGCT is a bone tumor of low malignant potential. It is sometimes characterized by locally invasive growth, active proliferation, coagulative necrosis, secondary aneurysmal bone cyst and surrounding bony reaction. It is difficult to predict the biologic behavior of GCT. Over-expression of p53 in the tumor cells and CD147 in all components of GCT correlate with tumor invasiveness, recurrence and malignant transformation. Selection of suitable surgical approach with reference to radiologic classification is considered as an important factor in reducing the recurrence rate.

Adolescent ; Adult ; Aged ; Basigin ; metabolism ; Bone Neoplasms ; diagnostic imaging ; drug therapy ; metabolism ; pathology ; surgery ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Giant Cell Tumor of Bone ; diagnostic imaging ; drug therapy ; metabolism ; pathology ; surgery ; Humans ; Male ; Membrane Proteins ; metabolism ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Osteosarcoma ; pathology ; Phosphoglucomutase ; metabolism ; Radiography ; Tumor Suppressor Protein p53 ; metabolism ; Young Adult

OBJECTIVETo analyze the clinicopathological features and prognostic factors of breast cancer patients with inguinal lymph node metastases.

METHODSSeventeen breast cancer patients with inguinal lymph node metastases were treated from January 1999 to December 2010 in our cancer center. All of the patients had a history of breast cancer without other primary cancer. Their clinicopathological characteristics and prognostic factors were surveyed.

RESULTSThe frequency of breast cancer cases with inguinal lymph node metastaseis consisted of 0.11% of the total number of breast cancer patients in the same period. Two patients (11.8%) had inguinal lymph node metastasis only, and multi-site metastases were observed in the remaining 15 (88.2%) patients. The number of ER- and/or PR-positive and negative were 10 (58.8%) and 7 (41.2%) cases, respectively, and among the 13 cases who underwent HER-2 test, the number of HER-2-positive was 4 (30.8%). For the 16 patients who underwent surgery, 9 patients were detected with metastatic axillary lymph nodes equal or greater than 4. All of the 17 patients were treated with chemotherapy.The median follow-up time was 156 months. The 5-year overall survival rate was 49.9%. Univariate analysis revealed that metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, disease stage as III/IV at diagnosis and the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis ≤ 36 months were predictors of shorter PFS (P < 0.05). Metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, primary recurrence as multiple distant metastases, the period from diagnosis of breast cancer to the occurrence of inguinal lymph nodes metastasis ≤ 36 months and pleural effusion were predictors of shorter OS (P < 0.05). Multivariate analysis revealed that the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis was an independent prognostic factor concerning PFS (P < 0.05).

CONCLUSIONSThe prognostic factors of breast cancer patients with inguinal lymph node metastases include the number of metastatic axillary lymph nodes, ER and(or) PR status, the cycles of adjuvant chemotherapy, type of primary recurrence, the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis and pleural effusion. Regular and complete physical examination after surgery as well as prompt intensive treatment for high-risk patients may have positive significance in the treatment of such type of patients. However, a type of more reasonable and individualized treatment is warranted in future studies.

Adult ; Aged ; Axilla ; Bone Neoplasms ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Groin ; Humans ; Liver Neoplasms ; secondary ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Recurrence, Local ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Survival Rate

OBJECTIVETo evaluate the cardioprotective effects of dexrazoxane (DEX) on breast cancer patients who received anthracycline-containing chemotherapy.

METHODSA total of 122 breast cancer patients after operation were randomly divided into two groups: The experimental group of 61 cases treated with EPI plus DEX (DEX:EPI = 10:1) as adjuvant chemotherapy regimen, and the control group of 61 cases treated with EPI but without DEX. All patients received four cycles of adjuvant chemotherapy and their changes of specific cardiac functional status and hematology status before and after chemotherapy, as well as non-cardiac toxicity were observed and analyzed.

RESULTSBrain natriuretic peptide (BNP) before chemotherapy and after four cycles of chemotherapy in the control group was (106.78 ± 4.52)×10(-6) µg/ml and (187.19 ± 8.71)×10(-6) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (102.34 ± 8.76)×10(-6) µg/ml and (105.29 ± 7.21)×10(-6) µg/ml, respectively, without a significant difference (P > 0.05). Cardiac troponin T (cTnT) before chemotherapy and after four cycles of chemotherapy in the control group was (12.55 ± 2.73)×10(-3) µg/ml and ( 31.05 ± 7.10 )×10(-3) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (12.70 ± 2.15)×10(-3) µg/ml and (13.65 ± 7.82)×10(-3) µg/ml, respectively, without a significant difference (P > 0.05). The hart rate (HR) before chemotherapy and after four cycles of chemotherapy in the control group, was 75.32 ± 7.14 bpm and 89.60 ± 9.21 bpm, respectively, with a significant difference (P < 0.05). It in the experimental group was 78.60 ± 6.29 bpm and 83.10 ± 7.56 bpm, respectively, without a significant difference (P > 0.05). The left ventricular ejection fraction (LVEF) before chemotherapy and after four cycles of chemotherapy in the control group was (65.23 ± 7.82)% and (55.21 ± 7.23)%, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (64.12 ± 6.25)% and (59.6 ± 4.72)%, respectively, without a significant difference (P > 0.05). The absolute neutrophil count before chemotherapy and after four cycles of chemotherapy in the control group was (3.95 ± 1.36)×10(9)/L and (3.50 ± 1.52)×10(9)/L, respectively, without a significant difference (P > 0.05). It in the experimental group, was (4.96 ± 1.41)×10(9)/L and (3.10 ± 1.26)×10(9)/L, respectively, with a significant difference (P < 0.05). The incidence of grade I-IV bone marrow suppression in the experimental group was 21.3%, 16.4%, 24.6%, and 4.9%, respectively. It in the control group was 16.4%, 11.5%, 9.8%, and 5.5%, respectively, with a significant difference (P < 0.05).

CONCLUSIONSCardiac toxicity after anthracycline treatment in breast cancer patients may be significantly reduced by DEX, without increase of non-cardiac and and non-hematologic toxicity. DEX combined with anthracycline increases the risk of bone marrow suppression, therefore, peripheral blood picture should be monitored or routine bone marrow support may be needed.

Adolescent ; Adult ; Aged ; Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; Bone Marrow ; drug effects ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; physiopathology ; surgery ; Cardiovascular Agents ; adverse effects ; therapeutic use ; Chemotherapy, Adjuvant ; Epirubicin ; adverse effects ; therapeutic use ; Female ; Follow-Up Studies ; Heart Rate ; drug effects ; Humans ; Leukocyte Count ; Middle Aged ; Natriuretic Peptide, Brain ; metabolism ; Neutrophils ; cytology ; Razoxane ; adverse effects ; therapeutic use ; Stroke Volume ; drug effects ; Young Adult

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

OBJECTIVETo study the effect and mechanisms of quercetin (Qu) on proliferation and apoptosis of human methotrexate resistant osteosarcoma cell U-2OS/MTX300.

METHODMTT assay was used to observe cell proliferation. The apoptosis was examined by using Annexin V/PI staining. Western blot of mitochondrial membrane potential and cytochrome c were used to detect mitochondria spoptosis pathway. The protein expressions related to Akt pathway was detected by continuous activated Akt transient transfection and western blot.

RESULTQu can obviously inhibit the growth of human MTX resistant osteosarcoma cell U-2OS/MTX300 cells in a dose- and time-dependent manner. Annexin V/PI staining showed obvious cell apoptosis. Reduction of mitochondrial membrane potential, release of mitochondrial cytochrome c to cytosol and dephoshorylation of Akt were observed after Qu treatment.

CONCLUSIONQu can inhibit proliferation and induce apoptosis of human MTX resistant osteosarcoma cell U-2OS/MTX300, which may be related with mitochondrial apoptosis pathway and Akt activity.

Apoptosis ; drug effects ; Bone Neoplasms ; drug therapy ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Osteosarcoma ; drug therapy ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Quercetin ; pharmacology

OBJECTIVETo investigate the prognostic values of HIF-1α, APE1, VEGF, and COX-2 protein expressions and their predictive value of tumor necrosis rate and prognosis in osteosarcoma, as well as their interrelationships.

METHODSFormalin-fixed paraffin-embedded tissue samples were obtained from patients with osteosarcoma. Immunohistochemical assay was performed in pre-chemotherapy samples to determine the HIF-1α, VEGF, APE1, and COX-2 protein expression levels. Hematoxylin-eosin staining was used in post-operative samples to determine the tumor necrosis rate. Univariate and multivariate analyses were used to assess the impact of protein expression on prognosis.

RESULTSTumor tissues were obtained from 49 patients. Their median follow up was 29 months. HIF-1α was significantly correlated to every protein we tested: VEGF (P = 0.032), APE1 (P < 0.001), and COX-2 (P < 0.001). HIF-1α protein expression had a significant impact on disease free survival (P = 0.006). Expression of HIF-1α had a sensitivity of 64.7% and a specificity of 71.9% for poor pathological response (< 90% of tumor necrosis) versus good pathological response to chemotherapy (≥ 90% necrosis).

CONCLUSIONExpression of HIF-1α is a predictor of tumor response to neoadjuvant chemotherapy and outcome in osteosarcoma and is correlated with VEGF, APE1, and COX-2 expression.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; drug therapy ; metabolism ; pathology ; Chemotherapy, Adjuvant ; Child ; Cyclooxygenase 2 ; metabolism ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; metabolism ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Osteosarcoma ; drug therapy ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

OBJECTIVETo characterize the sites of distant recurrence and clinical outcomes in a cohort of Chinese patients with metastatic triple-negative breast cancer (TNBC).

METHODSOne hundred and thirty-four patients with metastatic TNBC treated at Cancer Hospital of CAMS from January 1999 to December 2007 were included in this study. The clinicopathological features and long-term survival of the patients were retrospectively analyzed.

RESULTSThe median age of the patients was 45 years. Most patients (72.7%) had a higher predilection for visceral metastasis and early recurrence within the first two years of follow-up. Six patients (4.5%) presented with stage IV disease, 14 patients were diagnosed with locoregional recurrence after mastectomy, 75 patients with distant metastases, and 45 patients with both locoregional recurrence and distant metastasis. The most common site of first recurrence was the lung, and 62(51.7%)of the patients had more than two sites of metastasis. By July 30, 2009, 75 patients died of breast cancer (56.0%). The median overall survival (OS) was 26.5 months [95% confidence interval (CI), 20.5 - 32.6 months]. The 1-, 3- and 5-year overall survivals (OS) were 80.9%,37.1% and 30.1%, respectively. The median overall survival time of 58 patients with single site of metastasis was 28.5 months, longer than that of patients with more than two sites of metastases. Patients whose initial distant recurrence was bone metastasis only (7 patients) had better prognosis, with a median OS of 84.2 months. The median OS (28.5 vs. 12.6 months, P = 0.0001) differed significantly between patients who received first-line chemotherapy and those who did not. Forty-five of the 96 patients with measurable disease achieved complete/partial response (CR/PR), 39 patients had stable disease (SD), and 12 patients had disease progression (PD). The median OS was 36.1 months in patients with CR/PR, 20.8 months with SD, and 14 months with PD, respectively. The median OS of patients with CR/PR was significantly longer than that of patients with SD/PD (P = 0.0108). Distant metastasis, first-line chemotherapy and clinical response were significantly related with OS by univariate analysis. Furthermore, first-line chemotherapy and the clinical response were demonstrated to be an independent prognostic factor by multivariate analysis.

CONCLUSIONSRecurrence risk and mortality are considerably higher in TNBC patients within the early years of follow-up. TNBC patients have a higher risk of multiple and visceral metastases, and poorer survival, which might attribute to its aggressive clinical behavior and lack of effective regimens. Our findings also suggest that chemotherapy can effectively improve the clinical outcome of those patients.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Remission Induction ; Retrospective Studies ; Survival Rate ; Young Adult

Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients. The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases. Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells. Here, we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha (PDGFRα) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFRα in a ligand-independent fashion. Finally, we offer pre-clinical evidence that this receptor is a viable target for therapy.
Animals ; Antibodies, Monoclonal ; therapeutic use ; Bone Marrow ; enzymology ; pathology ; Bone Neoplasms ; prevention & control ; secondary ; Enzyme Activation ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; enzymology ; pathology ; Receptor, Platelet-Derived Growth Factor alpha ; antagonists & inhibitors ; genetics ; immunology ; metabolism ; Signal Transduction ; Transcriptional Activation