miR-200c inhibits metastasis of breast cancer cells by targeting HMGB1.

miR-200c has been shown to regulate the epithelial-mesenchymal transition (EMT) by inhibiting ZEB1 and ZEB2 expression in breast cancer cells. This study further examined the role of miR-200c in the invasion and metastasis of breast cancer that goes beyond the regulation on ZEB1 and ZEB2 expression. In this study, the bioinformatics software (miRanda) was used to predict the target gene of miR-200c and Renilla luciferase assay to verify the result. The metastatic breast cancer cells MDA-MB-231 were cultured and transfected with the miR-200c mimic or inhibitor. The expressions of miR-200c and HMGB1 were detected by RT-PCR and Western blotting, respectively. Transwell assay and wound healing assay were employed to examine the invasive and migrating ability of transfected cells. Target prediction and Renilla luciferase analysis revealed that HMGB1 was a putative target gene of miR-200c. After transfection of MDA-MB-231 cells with the miR-200c mimic or inhibitor, the expression of miR-200c was significantly increased or decreased when compared with cells transfected with the miR-200c mimic NC or inhibitor NC. Moreover, the expression of HMGB1 was reversely correlated with that of miR-200c in transfected cells. Tranwell assay showed that the number of invasive cells was significantly reduced in miR-200c mimic group when compared with miR-200c inhibitor group. It was also found that the migrating ability of cells transfected with miR-200c mimics was much lower than that of cells transfected with miR-200c inhibitors. It was suggested that miR-200c can suppress the invasion and migration of breast cancer cells by regulating the expression of HMGB1. miR-200c and HMGB1 may become useful biomarkers for progression of breast cancer and targets of gene therapy.

Hypoxia-induced autophagy contributes to radioresistance via c-Jun-mediated Beclin1 expression in lung cancer cells.

Reduced radiosensitivity of lung cancer cells represents a pivotal obstacle in clinical oncology. The hypoxia-inducible factor (HIF)-1α plays a crucial role in radiosensitivity, but the detailed mechanisms remain elusive. A relationship has been suggested to exist between hypoxia and autophagy recently. In the current study, we studied the effect of hypoxia-induced autophagy on radioresistance in lung cancer cell lines. A549 and H1299 cells were cultured under normoxia or hypoxia, followed by irradiation at dosage ranging from 0 to 8 Gy. Clonogenic assay was performed to calculate surviving fraction. EGFP-LC3 plasmid was stably transfected into cells to monitor autophagic processes. Western blotting was used to evaluate the protein expression levels of HIF-1α, c-Jun, phosphorylated c-Jun, Beclin 1, LC3 and p62. The mRNA levels of Beclin 1 were detected by qRT-PCR. We found that under hypoxia, both A549 and H1299 cells were radio-resistant compared with normoxia. Hypoxia-induced elevated HIF-1α protein expression preferentially triggered autophagy, accompanied by LC3 induction, EGFP-LC3 puncta and p62 degradation. In the meantime, HIF-1α increased downstream c-Jun phosphorylation, which in turn upregulated Beclin 1 mRNA and protein expression. The upregulation of Beclin 1 expression, instead of HIF-1α, could be blocked by SP600125 (a specific inhibitor of c-Jun NH2-terminal kinase), followed by suppression of autophagy. Under hypoxia, combined treatment of irradiation and chloroquine (a potent autophagy inhibitor) significantly decreased the survival potential of lung cancer cells in vitro and in vivo. In conclusion, hypoxia-induced autophagy through evaluating Beclin1 expression may be considered as a target to reverse the radioresistance in cancer cells.

[Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport].

OBJECTIVE: To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer. METHODS: Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival. RESULTS: Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively. CONCLUSIONS: Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

Pituitary metastasis from a renal cell carcinoma progressed after sorafenib treatment.

Pituitary metastasis from renal cell carcinoma is rare and has never been reported for renal cell carcinoma primarily treated with sorafenib. Herein, we present a case of an advanced clear-cell renal cell carcinoma in which pituitary metastasis progressed but extracerebral metastases showed partial response to sorafenib treatment.

Whether, when, and who to disclose bad news to patients with cancer: a survey in 150 pairs of hospitalized patients with cancer and family members in China.

OBJECTIVE: The purpose of this study is to determine how to disclose bad news to patients with cancer in China. METHODS: One hundred fifty pairs of hospitalized patients and their family members were investigated using a self-designed questionnaire. RESULTS: More patients than their families believed that patients should be informed of their illnesses (98.0% vs. 66.7%, p < 0.001), that patients should be informed of their condition completely (69.3% vs. 18.7%, p < 0.001), that patients should be informed as soon as the diagnoses were confirmed (49.3% vs. 14.7%, p < 0.001), and that patients should be informed by doctors (55.3% vs. 10.7%, p < 0.001). κ coefficients between patients and their families on "whether, when and who to disclose" ranged from -0.084 to 0.004. Univariate logistic analyses demonstrated that farmer patients and patients with lower education and lower income were less likely to prefer to be informed completely; farmer patients and patients without an intended curative operation history were less likely to prefer to be informed immediately and directly by doctors. Multivariate analyses showed that farmer patients were less likely to prefer to be informed completely, immediately, and directly by doctors. CONCLUSIONS: There was poor or slight concordance in disclosure preferences between patients with cancer and their families. More patients than their families wanted to be informed completely, immediately, and directly by doctors. Farmer patients with cancer were less likely to prefer to be informed completely, immediately, and directly by doctors.

MicroRNA-10b targets E-cadherin and modulates breast cancer metastasis.

BACKGROUND: Recent studies have suggested that microRNA-10b (miR-10b) acts as a promoter of metastasis in breast cancer, although the underlying mechanism remains largely unknown. In this study, we provide the first evidence that E-cadherin (E-cad) is a potential target of miR-10b. MATERIAL/METHOD: By applying gain-of-function and loss-of-function approaches in the metastatic breast cancer cell line MDA-MB-231, we demonstrated that miR-10b is necessary and sufficient to regulate the cellular expression of E-cad and in vitro tumor cell invasion. RESULTS: Comparative expression analysis of miR-10b in benign breast lesions (N=16), primary breast cancers (N=21), and metastatic breast carcinomas (N=23) revealed that miR-10b transcription was uniquely up-regulated in metastatic cancers. The expression level of miR-10b positively correlated with tumor size, pathological grading, clinical staging, lymph node metastasis, Her2-positivity and tumor proliferation, but was negatively associated with estrogen receptor-positivity, progesterone receptor-positivity and E-cad mRNA and protein levels. CONCLUSIONS: These findings indicate the existence of a novel E-cadherin-related mechanism by which miR-10b modulates breast cancer metastasis. In addition, miR-10b may be a useful biomarker of advanced progression and metastasis of breast cancer.

[Chinese HER2 positive early breast cancer trastuzumab adjuvant therapy: preliminary outcomes].

OBJECTIVE: To evaluate the efficacy and safety of 1-year adjuvant trastuzumab (herceptin) versus 1-year non-trastuzumab observation in Chinese patients with HER2-positive early breast cancer during a median follow-up of 1 year. METHODS: The HERA trial was an international, multicenter, randomized, open-label, phase III trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard adjuvant chemotherapy, radiotherapy or both in patients with HER2-positive node-positive or high-risk node-negative early breast cancer. The primary endpoint was disease-free survival. Secondary end points included recurrence-free survival, distant disease-free survival, overall survival and cardiac safety. The first planned interim analysis comparing the efficacy and safety of treatment with trastuzumab for 1 year versus observation were completed in April 2005. Only the outcomes of recruited Chinese patients were reported. RESULTS: A total of 122 Chinese patients from 8 participating centers were included for planned interim analysis. And they were divided into trastuzumab (n = 68) and observation (n = 54) groups. Three and eight disease-free survival events were observed in the trastuzumab and observation groups respectively. Two-year disease-free survival rates were 92.9% and 81.4% respectively (P = 0.0489); 2-year recurrence-free survival and distant disease-free survivals were 98.1% vs 81.4% (P = 0.0064) and 98.1% vs 83.3% (P = 0.0117) respectively. Trastuzumab was generally well-tolerated with a decent safety profile. Severe cardiotoxicity was not observed. CONCLUSION: One-year treatment with adjuvant trastuzumab improves disease-free survival, recurrence-free survival and distant disease-free survival in Chinese patients with HER2-positive early breast cancer.

Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients.

Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial.

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.

Morphine Suppresses Liver Cancer Cell Tumor Properties In Vitro and In Vivo.

Morphine is an analgesic widely adopted to relieve cancer pain. A number of discrepancies, however, are presented by the published literature, with reports suggesting that opioids may either promote or inhibit the spread of cancer. It is of great significance to determine whether morphine may increase the risk of metastasis while utilized in liver cancer surgical treatment. In this study, we explore the effects of morphine on liver cancer cells in vitro and in vivo. Our results showed that morphine does not promote proliferative ability to cultured liver cancer cells. While morphine could increase the apoptosis rate of Hep3B/HepG2 cells. Furthermore, morphine could significantly inhibit the migratory and invasion ability of Hep3B/HepG2 cells. Subsequent investigations disclosed that morphine could inhibit sphere formation ability of Hep3B/HepG2 cells by using sphere formation assay. Based on nude mouse models, we demonstrated that morphine significantly reduced pulmonary tumorigenicity of Hep3B/HepG2 cells. In conclusion, our results found that morphine at clinical concentrations could suppress liver cancer cell tumor properties in vitro and in vivo, indicating the safety of morphine utilization in HCC patients' pain management.

Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study.

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways may delay therapeutic resistance in advanced non-small cell lung cancer (NSCLC). This phase 3 study investigated the efficacy and safety of an erlotinib plus bevacizumab regimen in untreated patients with advanced NSCLC. In total, 311 patients received bevacizumab plus erlotinib (n = 157) or erlotinib only (n = 154). Progression-free survival (PFS) was 17.9 months (95% confidence interval [CI], 15.2-19.9) for bevacizumab plus erlotinib and 11.2 months (95% CI, 9.7-13.8) for erlotinib only (hazard ratio [HR] = 0.55; 95% CI, 0.41-0.73; p < 0.001). A brain metastases subgroup treated with bevacizumab plus erlotinib also showed improved PFS (HR = 0.48; 95% CI, 0.27-0.84; p = 0.008). Grade ≥3 treatment-related adverse events occurred in 86 (54.8%) and 40 (26.1%) patients, respectively. Bevacizumab plus erlotinib significantly improved PFS in patients with untreated metastatic EGFR-mutated NSCLC, including those with brain metastases at baseline.

Postmarketing surveillance study of OxyContin tablets for relieving moderate to severe cancer pain.

OBJECTIVE: To evaluatethe efficacy and safety of OxyContin tablets (controlled-release oxycodone hydrochloride: 5, 10, 20, and 40 mg) in relieving moderate to severe cancer pain. METHOD: A multicenter, open-label, prospective, self-controlled clinical trial was used. RESULTS: Pain was relieved in 89.1% of patients within 1 h after drug administration. OxyContin tablets showed good clinical efficacy in relieving both moderate and severe cancer pain. Compared with baseline average pain scores of 6.9 +/- 1.4, subjects had lower average pain scores after administration of OxyContin tablets: 2.7 +/- 1.8 after 1 week and 2.1 +/- 1.5 after 2 weeks. Response rate reached 75.0% at the end of the 1st week and was maintained at approximately 90% from the 3rd to the 8th week. The most common adverse drug reactions (ADRs) caused by OxyContintablets were, in descending order of incidence rate: constipation (25.5%), nausea (13.3%), vomiting (6.2%), lethargy (3.7%), and dysuria (2.1%). All these ADRs could be decreased by preventive medications. CONCLUSION: OxyContin tablets demonstrated fast onset of cancer pain control, superior efficacy in relieving both moderate and severe cancer pain and a good safety profile.

Gemcitabine and cisplatin treatment over a 3-week versus a 4-week dosing schedule: a randomized trial conducted in Chinese patients with nonsmall cell lung cancer.

BACKGROUND: Gemcitabine plus cisplatin is a standard treatment for stages IIIB and IV nonsmall cell lung cancer (NSCLC). This randomized phase II study evaluated a 3-week versus a 4-week schedule of gemcitabine-cisplatin as first line treatment for Chinese patients with advanced NSCLC. METHODS: Patients were randomized to receive cisplatin 75 mg/m(2) on day 1 plus either gemcitabine 1250 mg/m(2) on days 1 and 8 of a 21-day cycle (3-week group) or gemcitabine 1000 mg/m(2) on days 1, 8 and 15 of a 28-day cycle (4-week group). RESULTS: One hundred patients were enrolled in this study. The response rate was 24% (12/51 patients) in the 3-week group and 27% (13/49 patients) in the 4-week group. There were no statistically significant differences between the two treatment groups in survival (hazard ratio: 1.19; 95% CI: 0.68 - 2.09) with a median survival of 12.1 months and 13.8 months in the 3-week group and the 4-week group respectively. The rate of grade 3/4 toxicity in the 3-week group was 55% compared with 86% in the 4-week group (P = 0.001). The difference in the incidence of grade 3/4 haematological toxicities did not reach statistical significance (3-week: 37%, 4-week: 57%), however grade 3/4 drug related neutropenia (3-week: 27%, 4-week: 51%) and thrombocytopenia (3-week: 8%, 4-week: 31%) were significantly lower in the 3-week group. Grade 3/4 nonhaematological toxicities were less in the 3-week group (33% cf 63%; P = 0.005). CONCLUSIONS: The differences in the efficacy endpoints were all in favour of the 4-week schedule of gemcitabine plus cisplatin, however these differences did not reach statistical significance. Fewer grade 3/4 toxicities were observed in the 3-week group compared with the 4-week group.

[Chemokine receptor CXCR4 gene silencing with shRNA inhibits breast cancer metastasis to the lung in nude mice].

OBJECTIVE: To construct a CXCR4 specific recombinant plasmid vector and study its inhibiting effect on invasion capacity in vitro of human breast cancer MDA-MB-231 cell line and its metastatic potential to the lung in nude mice. METHODS: A CXCR4 specific recombinant plasmid vector was constructed and transfected into the cultured MDA-MB-231 cell line with lipofectamine 2000. RT-PCR and Western blot were used to detect the mRNA and protein expression of CXCR4, respectively. Invasion capability in vitro of the cells was evaluated by Boyden chamber. The cell proliferation capacity was detected by MTT method. The nude mouse model of lung metastasis was established by injection of MDA-MB-231 cells into the tail vein. The animals were sacrificed at 6 weeks after the tumor cells injection. Whole lung tissues were harvested, embedded in paraffin, sectioned serially, and the HE-stained paraffin sections were examined pathologically to evaluate the presence and number of metastatic tumors. RESULTS: The CXCR4 mRNA expression rate was 29.5% +/- 3.8% in the CXCR4-shRNA group, significantly lower than that of the control group (69.7% +/- 2.6%, P < 0.01) and mock-control group (67.8% +/- 3.5%, P < 0.01). The CXCR4 protein expression rate was 15.4% +/- 1.1% in the CXCR4-shRNA group, significantly lower than that of the control group (39.0% +/- 2.4%, P < 0.01) and mock-control group (35.9% +/- 3.9%, P < 0.01). Silencing of CXCR4 by shRNA lead to a significant decrease in breast cancer cell invasion and proliferation capacity in vitro. Furthermore, tumor cells with CXCR4 shRNA permanent transfcetion had a much lower lung metastatic potential in nude mice than control cells and mock control cells in vivo. CONCLUSION: CXCR4 shRNA can inhibit the expression of CXCR4 and decrease the invasion and lung metastatic potential of human breast cancer cells.

[Correlation of aquaporin 1 with hypoxia-inducible factor 1 in breast cancer].

OBJECTIVE: To determinate the correlation of aquaporin 1 (AQP1) and hypoxia-inducible 1 (HIF-1). METHODS: 155 samples of breast cancer obtained during radical mastectomy underwent immunohistochemistry to detect the expression of AQP1 and HIF-1. RESULTS: The positive rates of AQP1 in the HIF1 positive group was 297 +/- 25, significantly higher than that of HIF1 negative group (168 +/- 38, P < 0.001). CONCLUSION: AQP1 is positively correlated with HIF1. The interaction of AQP1 and HIF1 may co-regulate the progress of breast cancer.

Local analgesic effect of a bioadhesive barrier-forming oral liquid in cancer patients with oral mucositis caused by chemotherapy and/or radiotherapy: a randomized multicenter, single-use, positive-controlled, open-label study.

OBJECTIVE: CAM2028 (Episil®; Camurus AB, Lund, Sweden) is a liquid for use in the oral cavity to treat various pains associated with mouth injuries. Upon contact with the swollen oral mucosa, the oral liquid forms a thin protective film that acts as a mechanical barrier to relieve pain. This study was the first in China to evaluate the local analgesic effect of oral liquid in cancer patients who developed oral mucositis following chemotherapy and/or radiotherapy. METHODS: A total of 60 patients were randomized in a 1:1 ratio to the CAM2028 group (the pump device was firmly pressed three times and the fluid was distributed to the painful area of the oral cavity) or KS (a mucoadhesive oral wound rinse, Kangsu™; Luye Pharmaceutical Co. Ltd, Nanjing, China) group (5 mL of the oral rinse was poured into and kept in the oral cavity for at least 1 minute). The primary endpoint was the area under the oral mucosal pain score-time curve (AUC) within 6 hours of treatment in the trial and control groups. Medical device adverse events were assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. Statistical analyses were performed using the chi-squared test (Fisher's exact test), independent-samples t-test, and analysis of covariance. RESULTS: Sixty patients were included in the per-protocol set population analysis. The average (mean ± SD) 6-hour AUC of the CAM2028 group and the KS group was 14.20±10.29 and 24.46±14.15, respectively. The difference between the groups was statistically significant (P=0.0022). The incidence of adverse events in the trial group and the control group was 16.67% and 30.0%, respectively, and there was no statistical difference. CONCLUSIONS: CAM2028 displayed an efficacious local analgesic effect in cancer patients who developed oral mucositis following chemotherapy and/or radiotherapy. The results demonstrated its potential value in clinical applications.

Anti-rheumatic drug iguratimod protects against cancer-induced bone pain and bone destruction in a rat model.

The bone is one of the most common sites of metastasis in patients with cancer. Current treatments for bone metastases include bisphosphonates, denosumab, non-steroidal anti-inflammatory drugs and analgesics, but each of them has certain limitations. Cytokines and mediators released from various cells in the bone microenvironment may drive a vicious cycle of osteolytic bone metastases. Iguratimod (T-614), a novel disease-modifying anti-rheumatic drug, has demonstrated therapeutic effects by suppressing the production of inflammatory cytokines in rats and patients with rheumatoid arthritis. Therefore, the current study evaluated the hypothesis that iguratimod may protect against cancer-induced bone pain and bone metastasis in a rat model. For this purpose, rats inoculated with Walker 256 cells were treated with iguratimod from days 11-17 post-surgery. Mechanical paw withdrawal thresholds and expression levels of phosphorylated extracellular signal-related kinase (pERK) and c-Fos in the spinal cord were investigated to detect changes in bone pain. Bone destruction levels were detected using X-rays, hematoxylin and eosin and tartrate-resistant acid phosphatase staining. The results revealed that mechanical paw withdrawal thresholds and the expression levels of pERK and c-Fos declined in a dose-dependent manner in rats treated with iguratimod, and bone destruction severity was also reduced. These findings may provide important new insights into the treatment of bone metastasis symptoms.

Iguratimod prevents ovariectomy­induced bone loss and suppresses osteoclastogenesis via inhibition of peroxisome proliferator­activated receptor­Î³.

Iguratimod is known for its anti­inflammatory activities and therapeutic effects in patients with rheumatoid arthritis. It has previously been demonstrated that iguratimod attenuates bone destruction and osteoclast formation in the Walker 256 rat mammary gland carcinoma cell­induced bone cancer pain model. Therefore, it was hypothesized that iguratimod may additionally exhibit therapeutic effects on benign osteoclast­associated diseases including postmenopausal osteoporosis. In the present study, ovariectomized mice were used to investigate the effects of iguratimod in vivo. Bone marrow mononuclear cells were cultured to detect the effects of iguratimod on receptor activator of nuclear factor­κB ligand (RANKL)­induced osteoclastogenesis in vitro and the molecular mechanisms involved. It was demonstrated that iguratimod may prevent ovariectomy­induced bone loss by suppressing osteoclast activity in vivo. Consistently, iguratimod may inhibit RANKL­induced osteoclastogenesis and bone resorption in primary bone marrow mononuclear cells. At the molecular level, peroxisome proliferator­activated receptor­Î³ (PPAR­Î³)/c­Fos pathway, which is essential in RANKL­induced osteoclast differentiation, was suppressed by iguratimod. Subsequently, iguratimod decreased the expression of nuclear factor of activated T cells c1 and downstream osteoclast marker genes. The results of the present study demonstrated that iguratimod may inhibit ovariectomy­induced bone loss and osteoclastogenesis by modulating RANKL signaling. Therefore, iguratimod may act as a novel therapeutic to prevent postmenopausal osteoporosis.

Managing Pain in Patients With Cancer: The Chinese Good Pain Management Experience.

PURPOSE: The number of cancer cases in China has increased rapidly from 2.1 million in 2000 to 4.3 million in 2015. As a consequence, pain management as an integral part of cancer treatment became an important health care issue. In March 2011, the Good Pain Management (GPM) program was launched to standardize the treatment of cancer pain and improve the quality of life for patients with cancer. With this work, we will describe the GPM program, its implementation experience, and highlight key lessons that can improve pain management for patients with cancer. METHODS: We describe procedures for the selection, implementation, and assessment procedures for model cancer wards. We analyzed published results in areas of staff training and patient education, pain management in practice, analgesic drugs administration, and patient follow-up and satisfaction. RESULTS: Pain management training enabled medical staff to accurately assess the level of pain and to provide effective pain relief through timely dispensation of medication. Patients with good knowledge of treatment of pain were able to overcome their aversion to opioid drugs and cooperate with nursing staff on pain assessment to achieve effective drug dose titration. Consumption of strong opioid drugs increased significantly; however, there was no change for weaker opioids. Higher pain remission rates were achieved for patients with moderate-to-severe pain levels. Proper patient follow-up after discharge enabled improved outcomes to be maintained. CONCLUSION: The GPM program has instituted a consistent and high standard of care for pain management at cancer wards and improved the quality of life for patients with cancer.

A consensus on liquid biopsy from the 2016 Chinese Lung Cancer Summit expert panel.

The diagnosis and treatment of lung cancer have evolved into the era of precision medicine. Liquid biopsy, a minimally invasive approach, has emerged as a promising practice in genetic profiling and monitoring of lung cancer. Translating liquid biopsy from bench to bedside has encountered various challenges, including technique selection, protocol standardisation, data analysis and cost management. Regarding these challenges, the 2016 Chinese Lung Cancer Summit expert panel organised a trilateral forum involving oncologists, clinicians, clinical researchers, and industrial expertise on the 13th Chinese Lung Cancer Summit to formally discuss these controversies. Six consensuses were reached to guide the use of liquid biopsy and perform precision medicine in both clinic and research.