[Epidemiological survey of asthma among children aged 0-14 years in 2010 in urban Zhongshan, China].

OBJECTIVE: To investigate the prevalence, current treatment, and clinical characteristics of asthma, as well as the risk factors for this disease, among children aged 0-14 years in 2010 in urban Zhongshan, China. METHODS: A total of 10 336 children aged 0-14 years were selected from urban Zhongshan by cluster random sampling. The Third National Childhood Asthma Epidemiological Questionnaire 2010 was used to analyze the prevalence, current treatment, and clinical characteristics of childhood asthma, as well as the risk factors for this disease. RESULTS: Asthma was diagnosed in 179 cases (1.73%). The prevalence of asthma in male children was significantly higher than that in female children (2.25% vs 1.16%; P<0.01). Of the 179 patients, severe attacks were common in 104 cases (58.1%), 110 cases (61.5%) had slow onset, 102 cases (57.0%) had gradually relieved conditions, 61 cases (34.1%) suffered from asthma during seasonal transition, and 150 cases (83.8%) developed asthma due to respiratory tract infection. Among all asthmatic children, 71.5% had been treated with inhaled corticosteroids, and 71.5% had been treated with bronchodilator. The multivariate logistic regression analysis showed that a history of penicillin allergy, a family history of allergy, food allergy, eczema, allergic rhinitis, cesarean delivery, family mould, and perinatal passive smoking were independent risk factors for childhood asthma. CONCLUSIONS: The prevalence of childhood asthma in urban Zhongshan is on a high level, and is associated with gender. The treatment of asthma has been standardized, but still needs further improvement. The onset of asthma attack is influenced by various factors.

Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer.

BACKGROUND: Accumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of HOTAIR in gastric carcinogenesis remains largely unknown. METHODS: HOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. RESULTS: HOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers. CONCLUSIONS: HOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.

Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition.

BACKGROUND: Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis. These lncRNAs are found to be dysregulated in a variety of cancers. BRAF activated non-coding RNA (BANCR) is a 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. The clinical significance of BANCR, and its' molecular mechanisms controlling cancer cell migration and metastasis are unclear. METHODS: Expression of BANCR was analyzed in 113 non-small cell lung cancer (NSCLC) tissues and seven NSCLC cell lines using quantitative polymerase chain reaction (qPCR) assays. Gain and loss of function approaches were used to investigate the biological role of BANCR in NSCLC cells. The effects of BANCR on cell viability were evaluated by MTT and colony formation assays. Apoptosis was evaluated by Hoechst staining and flow cytometry. Nude mice were used to examine the effects of BANCR on tumor cell metastasis in vivo. Protein levels of BANCR targets were determined by western blotting and fluorescent immunohistochemistry. RESULTS: BANCR expression was significantly decreased in 113 NSCLC tumor tissues compared with normal tissues. Additionally, reduced BANCR expression was associated with larger tumor size, advanced pathological stage, metastasis distance, and shorter overall survival of NSCLC patients. Reduced BANCR expression was found to be an independent prognostic factor for NSCLC. Histone deacetylation was involved in the downregulation of BANCR in NSCLC cells. Ectopic expression of BANCR impaired cell viability and invasion, leading to the inhibition of metastasis in vitro and in vivo. However, knockdown of BANCR expression promoted cell migration and invasion in vitro. Overexpression of BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression. CONCLUSION: We determined that BANCR actively functions as a regulator of EMT during NSCLC metastasis, suggesting that BANCR could be a biomarker for poor prognosis of NSCLC.

[Incidence of wheezing and chronic cough in children aged 3-14 years in rural and urban areas of Zhongshan, China: a questionnaire survey].

OBJECTIVE: To investigate the incidence of wheezing and chronic cough in children aged 3-14 years in different living areas of Zhongshan, China. METHODS: According to the unified program of the 2010 national epidemiological survey of asthmatic children aged 0-14 years, a questionnaire survey of the children aged 3-14 years in rural and urban areas of Zhongshan was conducted. RESULTS: A total of 15 763 children were included in the survey. Among all participants, 8 248 were from the urban area, and 7 515 from the rual area; 8 306 were boys, and 7 457 were girls. The percentage of children with a history of wheezing was significantly higher in the urban group than in the rural group (6.6% vs 3.2%; P<0.05), and it was significantly higher in boys than in girls for each group (P<0.05). The urban group had a significantly higher percentage of individuals who had wheezing in the past one year than the rural group (2.8% vs 1.5%; P<0.05), and this percentage was significantly higher in boys than in girls for each group (P<0.05). Compared with the rural group, the urban group had a significantly higher percentage of individuals who had chronic cough (duration 1 year) (7.9% vs 3.1%; P<0.05). The above indices were relatively high in children under 6 years of age, and all but the percentage of girls who had wheezing in the past one year in both rural and urban areas showed significant differences between all age groups. CONCLUSIONS: The incidence of wheezing and chronic cough varies with age, sex, and living area for children aged 3-14 years in Zhongshan, and it is relatively high under 6 years of age, in the urban area, and among boys.

Low-loss optical waveguides and Y-branch splitters in lithium niobate fabricated by MeV oxygen ions with low dose.

Single-mode optical waveguides in LiNbO(3) substrate with loss as low as 0.17dB/cm were fabricated by a multi-energy low-dose ion implantation technology and cumulative annealing treatment. A waveguide Y-Branch splitter was demonstrated. Index profile in waveguide is described based on the ion implantation-induced damage profile, and propagation property in waveguide is simulated. Simulation results show a good consistence with the measured ones.

High-efficiency second-harmonic generation in doubly-resonant χ(²) microring resonators.

By directly simulating Maxwell's equations via the finite-difference time-domain (FDTD) method, we numerically demonstrate the possibility of achieving high-efficiency second harmonic generation (SHG) in a structure consisting of a microscale doubly-resonant ring resonator side-coupled to two adjacent waveguides. We find that ≳ 94% conversion efficiency can be attained at telecom wavelengths, for incident powers in the milliwatts, and for reasonably large bandwidths (Q ∼ 1000s). We demonstrate that in this high efficiency regime, the system also exhibits limit-cycle or bistable behavior for light incident above a threshold power. Our numerical results agree to within a few percent with the predictions of a simple but rigorous coupled-mode theory framework.

Optical waveguides in TiO2 formed by He ion implantation.

We report on the formation and the optical properties of the planar and ridge optical waveguides in rutile TiO2 crystal by He+ ion implantation combined with micro-fabrication technologies. Planar optical waveguides in TiO2 are fabricated by high-energy (2.8 MeV) He+-ion implantation with a dose of 3 × 10¹6 ions/cm² and triple low energies (450, 500, 550) keV He+-ion implantation with all fluences of 2 × 10¹6 ions/cm² at room temperature. The guided modes were measured by a modal 2010 prism coupler at wavelength of 1539 nm. There are damage profiles in ion-implanted waveguides by Rutherford backscattering (RBS)/channeling measurements. The refractive-index profile of the 2.8 MeV He+-implanted waveguide was analyzed based on RCM (Reflected Calculation Method). Also ridge waveguides were fabricated by femtosecond laser ablation on 2.8 MeV ion implanted planar waveguide and Ar ion beam etching on the basis of triple keV ion implanted planar waveguide, separately. The loss of the ridge waveguide was estimated. The measured near-field intensity distributions of the planar and ridge modes are all shown.

MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5.

BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs (~22 nt) that play important roles in the pathogenesis of human diseases by negatively regulating gene expression. Although miR-196a has been implicated in several other cancers, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of miR-196a in NSCLC and its clinical significance, as well as its biological role in tumor progression. METHODS: Expression of miR-196a was analyzed in 34 NSCLC tissues and five NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of DNA methylation on miR-196a expression was investigated by 5-aza-2-deoxy-cytidine treatment and bisulfite sequencing. The effect of miR-196a on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Analysis of target protein expression was determined by western blotting. Luciferase reporter plasmids were constructed to confirm the action of miR-196a on downstream target genes, including HOXA5. Differences between the results were tested for significance using Student's t-test (two-tailed). RESULTS: miR-196a was highly expressed both in NSCLC samples and cell lines compared with their corresponding normal counterparts, and the expression of miR-196a may be affected by DNA demethylation. Higher expression of miR-196a in NSCLC tissues was associated with a higher clinical stage, and also correlated with NSCLC lymph-node metastasis. In vitro functional assays demonstrated that modulation of miR-196a expression affected NSCLC cell proliferation, migration and invasion. Our analysis showed that miR-196a suppressed the expression of HOXA5 both at the mRNA and protein levels, and luciferase assays confirmed that miR-196a directly bound to the 3'untranslated region of HOXA5. Knockdown of HOXA5 expression in A549 cells using RNAi was shown to promote NSCLC cell proliferation, migration and invasion. Finally, we observed an inverse correlation between HOXA5 and miR-196a expression in NSCLC tissues. CONCLUSIONS: Our findings indicate that miR-196a is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell proliferation, migration and invasion, partially via the down-regulation of HOXA5. Thus, miR-196a may represent a potential therapeutic target for NSCLC intervention.

[Effects of electroacupuncture at PC6 and BL15 on nerve electrical activity in spinal dorsal root and norepinephrine and dopamine contents in paraventricular nucleus of hypothalamus in rats with acute myocardial ischemia].

OBJECTIVE: To investigate the effects of electroacupuncture (EA) at Neiguan (PC6) and Xinshu (BL15) on the nerve electrical activity in spinal dorsal root and norepinephrine (NE) and dopamine (DA) concentrations in the paraventricular nucleus of the hypothalamus in rats with acute myocardial ischemia (AMI). METHODS: A total of 100 male Sprague-Dawley rats were randomly divided into sham-operation, model, EA at PC6, EA at BL15 and EA at both PC6 and BL15 groups with 20 rats in each group. The nerve electrical activity in spinal dorsal roots was recorded by bipolar electrodes. NE and DA concentrations in the paraventricular nucleus of the hypothalamus were detected by high-performance liquid chromatography. RESULTS: When compared with the sham-operation group, the nerve electrical activity in spinal dorsal roots was significantly increased while the NE and DA concentrations in the paraventricular nucleus of the hypothalamus were decreased in the model group (P<0.01). The nerve electrical activity in spinal dorsal roots was decreased and the NE and DA concentrations were increased in the paraventricular nucleus of the hypothalamus in the EA at PC6 group, the EA at BL15 group and the EA at both PC6 and BL15 group in comparison to those in the model group (P<0.01). The nerve electrical activity in spinal dorsal roots and the NE and DA concentrations in paraventricular nucleus of hypothalamus of the EA at both PC6 and BL15 group were significantly improved when compared to those of the EA at PC6 and EA at BL15 groups (P<0.05). CONCLUSION: EA at both PC6 and BL15 acupoints exhibits the synergistic protective effects against AMI. The possible mechanism is related to regulating the nerve electrical activity in spinal dorsal roots and the concentrations of NE and DA in paraventricular nucleus of the hypothalamus.

[Effects of acupuncture at Shenmen (HT7) or Taiyuan (LU9) on P3a and P3b of event-related potentials in healthy young adults].

OBJECTIVE: To investigate the effects of manual acupuncture at Shenmen (HT7) or Taiyuan (LU9) on the attention function of the brain, and to lay an experimental foundation for researching brain function and integration mechanisms of the human brain in relation to acupuncture stimulation. METHODS: Ten healthy young college students were selected as experimental subjects. P3a and P3b potentials were induced by novel stimulation and target stimulation with vision and were observed using Neuroscan event-related potentials system at time windows of ms 330-430 or 400-600 ms for observing the change of intensity distribution of P300 after manual acupuncture at HT7 or LU9. RESULTS: The amplitude of P3a and P3b decreased significantly after manual acupuncture at HT7 or LU9, but the degree of decreases affected by the acupoints was different. The decrease of the amplitude of P3a due to acupuncture at HT7 was more significant than acupuncture at LU9 (P<0.05). CONCLUSION: The attention function of the brain is affected by manual acupuncture at HT7 or LU9 and manual acupuncture at HT7 has a greater influence on the attention function of the brain.

Adenovirus-mediated siRNA targeting c-Met inhibits proliferation and invasion of small-cell lung cancer (SCLC) cells.

BACKGROUND: The hepatocyte growth factor receptor c-Met and its ligand hepatocyte growth factor (HGF) have been reported to be involved in cellular motility, growth, and invasion by activating mitogenic signaling pathways. The overexpression of c-Met gene has been found in many malignant cancers, but the roles of c-Met overexpression in SCLC tumors still remain unclear. The aim of the present study was to explore its roles and potential as a therapeutic target for SCLC. METHODS: Quantitative real-time RT-PCR and immunohistochemistry assays were performed to detect the expression of c-Met mRNA and protein in SCLC tissue or corresponding non-tumor lung tissue samples. Adenovirus-mediated small interfering RNA (siRNA) was employed to down-regulate the expression of c-Met gene in SCLC cell line (NCI-H446). MTT and colony formation assays were performed to detect in vitro proliferation of NCI-H446 cells. In vitro wound-healing and transwell invasion assays were performed to detect in vitro invasion and metastasis of NCI-H446 cells. Finally, in vivo tumorigenicity and metastasis assays were done to analyze in vivo proliferation and metastasis of NCI-H446 cells in a xenograft model. RESULTS: We showed that the levels of c-Met mRNA expression were significantly higher in SCLC tissue samples (0.97±0.08) than those in corresponding non-tumor lung tissue samples (0.21±0.02; P<0.05). Additionally, the immunostaining of c-Met protein in SCLC tissues was stronger than that in corresponding non-tumor tissues. Adenovirus-mediated siRNA targeting c-Met could significantly down-regulate c-Met expression, and the specific down-regulation of c-Met expression in SCLC cells could strongly inhibit proliferation of SCLC cells both in vitro and in vivo. Moreover, c-Met down-regulation could also reduce invasion capacity in vitro and metastasis capacity in vivo of SCLC cells. CONCLUSIONS: Taken together, our results indicated that the overexpression of c-Met gene played an important role in the progression and development of SCLC, and adenovirus-mediated siRNA targeting c-Met could potentially be an experimental approach for SCLC gene therapy.

Prognostic significance of serum miRNA-21 expression in human non-small cell lung cancer.

BACKGROUND: Deregulation of microRNAs (miRNAs) plays important roles in tumor progression. The aim of this study was to investigate miR-21 expression in serum of non-small cell lung cancer (NSCLC) and its correlation with prognosis of NSCLC patients. METHODS: Dysregulated miRNAs in NSCLC serum were identified by microarray. MiR-21 expression in NSCLC and control serum was detected by TaqMan RT-PCR assay. The correlation of serum miR-21 with clinicopathological factors of NSCLC patients was analyzed. Furthermore, the prognostic significance of serum miR-21 was analyzed by using Kaplan-Meier curves with log-rank tests and a Cox proportional hazard model. RESULTS: The level of miR-21 expression was higher in NSCLC serum samples than in control serum samples (P < 0.01). High serum miR-21 was significantly correlated with tumor-node metastases stage and lymph node metastasis of NSCLC patients (P = 0.016 and 0.026, respectively). The 3-year actuarial overall survival rates in NSCLC patients with high serum miR-21 expression (39.8%) was significantly shorter than those with low serum miR-21 expression (58.2%; P < 0.001). Furthermore, univariate and multivariate analyses for overall survival showed that serum miR-21 expression was an independent prognostic factor for NSCLC patients (P = 0.015, RR = 2.01, 95% CI: 1.78-3.26). CONCLUSION: Serum miR-21 expression might be useful as a prognostic marker for NSCLC patients.

Optical properties of a single mode planar waveguide in Nd:YVO4 fabricated by multienergy He ion implantation.

We fabricated a single-mode planar waveguide in z-cut Nd:YVO(4) by multienergy He ion implantation in total fluence of 4.5×10(16) ions/cm(2) at room temperature and investigated optical properties of Nd:YVO(4) before and after He ion implantation by measuring transmission, confocal microluminescence, and confocal Raman spectra. Absorption bands and the photoluminescence features of the bulk Nd:YVO(4) crystal have been preserved after He ion implantation. In Raman spectra, most of the peak positions and peak widths had no obvious change before and after He ion implantation. The guiding mode and near-field image in the waveguide were measured by the prism coupling method and end-face coupling method, respectively. We investigated the damage behavior of a Nd:YVO(4) waveguide after implantation, annealing treatment by the Rutherford backscattering/channeling technique. The minimum yield of the virgin z-cut Nd:YVO(4) was 1.98%, which increased to 4.73% after He ion implantation and decreased to 3.20% after annealing at 600 K for 30 minutes.

[Etiology and risk factors of infantile wheezing].

OBJECTIVE: To study the etiology and risk factors of infantile wheezing. METHODS: The clinical data of 180 infants with wheezing were retrospectively studied. The risk factors for wheezing attacks were investigated by logistic regression analysis. RESULTS: Viral infection (33.3%) was the most common cause for wheezing attacks, followed by asthma (19.4%), parental smoking and special environments (15.6%), gastroesophageal reflux disease (12.8%), premature delivery (7.8%), Mycoplasma infection (6.7%), and bronchopulmonary dysplasia (4.4%). The multivariate logistic regression analysis showed 7 factors that significantly correlated with wheezing attacks: allergic history of parents, sensitization to alimentary or inspiratory allergens, viral or Mycoplasma infection, premature delivery and special environments. CONCLUSIONS: The commonest cause of infantile wheezing is viral infection, followed by asthma. Genetic factors, individual atopic constitution and environmental factors play important roles in wheezing attacks.

Planar and ridge waveguides formed in LiNbO3 by proton exchange combined with oxygen ion implantation.

We report on the fabrication of planar and ridge waveguides in lithium niobate by proton exchange combined with oxygen ion implantation. The implanted energy ranges from 600 to 1400 keV with a dose of 1 x 10(15) ions/cm(2). The modes in proton exchanged waveguide can be modulated by O ion implantation. There are different damage profiles in proton-exchanged and ion-implanted waveguides in Rutherford backscattering/channeling spectra. The refractive index profile in single-mode waveguide in lithium niobate has been obtained based on Intensity Calculation Method. Also ridge waveguide was fabricated on the basis of planar waveguide by Ar ion beam etching. The measured near-field intensity distributions of the ridge waveguide modes show a reasonable agreement with the simulated ones. The estimated propagation loss was approximately 2.2 dB/cm.

BTEB2-Activated lncRNA TSPEAR-AS2 Drives GC Progression through Suppressing GJA1 Expression and Upregulating CLDN4 Expression.

Long non-coding RNAs (lncRNAs) are characterized as key layers of the genome in various cancers. TSPEAR-AS2 was highlighted to be a candidate lncRNA potentially involved in gastric cancer (GC) progression. However, the clinical significance and mechanism of TSPEAR-AS2 in GC required clarification. The clinical significance of TSPEAR-AS2 was elucidated through Kaplan-Meier Plotter. The mechanism of TSPEAR-AS2 in GC was clarified in vitro and in vivo using luciferase reporter, chromatin immunoprecipitation, RNA immunoprecipitation assays, and animal models. TSPEAR-AS2 elevation was closely correlated with overall survival of GC patients. A basic transcription element-binding protein 2 (BTEB2)-activated TSPEAR-AS2 model was first explored in this study. TSPEAR-AS2 silencing substantially reduced tumorigenic capacities of GC cells, while TSPEAR-AS2 elevation had the opposite effect. Mechanistically, TSPEAR-AS2 bound with both polycomb repressive complex 2 (PRC2) and argonaute 2 (Ago2). TSPEAR-AS2 knockdown significantly decreased H3K27me3 levels at promoter regions of gap junction protein alpha 1 (GJA1). Ago2 was recruited by TSPEAR-AS2, which was defined to sponge miR-1207-5p, contributing to the repression of claudin 4 (CLDN4) translation. The axis of EZH2/GJA1 and miR-1207-5p/CLDN4 mediated by BTEB2-activated-TSPEAR-AS2 plays an important role in GC progression, suggesting a new therapeutic direction in GC treatment.

Annealing effect on mono-mode refractive index enhanced RbTiOPO4 waveguides formed by ion implantation.

We reported on the annealing features of the RbTiOPO4 planar waveguides fabricated by 6.0 MeV C3+ ion implantation. The thermal stability of the ion-implanted RbTiOPO4 waveguide was investigated by annealing at different temperatures ranging from 260 degrees C to 650 degrees C. Results revealed that when temperatures are higher than 550 degrees C, annealing caused the refractive indices of both ny and nz a saturation behavior. An increase of the ny refractive index in waveguide region was observed after proper annealing. The low loss planar mono-mode waveguides have been achieved in RbTiOPO4 crystals by applying appropriate ion implantation and annealing conditions.

Optical waveguide in stoichiometric lithium niobate formed by 500 keV proton implantation.

We report on the fabrication of planar waveguide in stoichiometric lithium niobate by 500 keV proton implantation with a dose of 1x10(17) ions/cm(2). The formation of n(e) enhancement planar waveguide in the crystal was disclosed by the dark mode spectra and the subsequent endface coupling measurement. The absorption spectra show that the postannealing treatments above 400 masculineC temperature can remove the color centers induced by implantation efficiently. The propagation loss and near-field profiles of the planar waveguide were obtained with an end-face coupling system.

Atlantoaxial Misalignment Causes High Blood Pressure in Rats: A Novel Hypertension Model.

Atlantoaxial disorders are often correlated with hypertension in practice. In order to study the relationship between atlantoaxial disorder and hypertension, we attempted to construct an animal model. In this work, we presented an animal model where their atlantoaxial joints were misaligned. We investigated the changes of blood pressure before and after treatments of the modeled rats. We had the following results. (1) SBP and DBP of each surgery group were significantly higher than those of control and sham groups. (2) After the second operation (the fixture was removed), SBP and DBP of both surgery groups decreased and got closer to the control and sham groups after 7 days. (3) Heart rates got significantly higher in both surgery groups, compared to control and sham groups. (4) The blood Ach levels of the surgery groups were significantly lower than those of control and sham groups. With these results, we concluded that we successfully constructed cervical atlantoaxial disorder models in rats that showed hypertension symptom. However, the underlying mechanism connecting atlantoaxial disorder and hypertension still requires further study.

Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer: a multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial.

BACKGROUND: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. METHODS: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. RESULTS: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3-4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). CONCLUSION: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium.