Fabrication of vascular smooth muscle-like tissues based on self-organization of circumferentially aligned cells in microengineered hydrogels.

Circumferential alignment of vascular smooth muscle cells (vSMCs) is critical to form an in vivo-like vascular smooth muscle layer in vitro. Although many techniques to elicit such an alignment on 3D substrates have been demonstrated, it remains a challenge to recapitulate the circumferential cellular alignment of vascular smooth muscle tissues in 3D hydrogels. Here, we propose a spring-like gelatin methacrylate (GelMA) structure formed by semi-automated reeling of a core-shell microfiber at the micro-scale. The resulting structures facilitate circumferential alignment and self-organization of encapsulated human mesenchymal stem cells (MSCs) into multilayer spring-like cellular structures. Based on the permeable tubular lumens of these structures, a perfusion culture micro-system is developed to further facilitate the vSMC differentiation of MSCs under the effect of TGF-ß1. We also evaluated the MSC contraction-induced shrinkage of the resulting cellular structures. These results demonstrate the successful in vitro regeneration of vascular smooth muscle (vSM)-like tissues in 3D environments. Compared with the substrate surface, the porous structure in hydrogels is more similar to cell microenvironments in vivo. Thus, this approach may be used to develop an in vitro model for the study of vascular tissue regeneration and the mechanism of vascular remolding during hypertension.

Template-based fabrication of spatially organized 3D bioactive constructs using magnetic low-concentration gelation methacrylate (GelMA) microfibers.

Low concentrations of gelatin methacrylate (GelMA) microfibers are more favorable for cellular activity compared with high concentrations. However, applying low-concentration GelMA microfibers as building blocks for higher-order cellular assembly remains challenging owing to their poor mechanical properties. Herein, we report a new template-based method to solve this problem. GelMA microfibers (5%, w/v) containing magnetic nanoparticles were synthesized by a microfluidic spinning method. A 9 × 9 micropillar array surrounded by a magnetic substrate was constructed to form 8 × 8 microgaps arranged in a crisscross pattern as a magnetic template. In DMEM solution, magnetic attraction facilitated efficient arrangement of the microfibers according to the template with micron assembly accuracy, with a microgrid-like construct (microGC) generated after removing all micropillars. MicroGCs were shown to effectively support the activities of surface seeded or encapsulated cells and be flexibly constructed with various organized spatial patterns. Owing to the low mechanical property requirements of assembled microfibers and the easy-to-implement operation, the proposed method provides a versatile pathway for the assembly of various microfluidic spun microfibers. Furthermore, the resulting 3D microgrid-like cellular constructs with organized spatiotemporal composition offer a convenient platform for the study of tissue engineering.

An open label, multicenter, noninterventional study of apatinib in advanced gastric cancer patients (AHEAD-G202).

BACKGROUND: Apatinib has been proved to be effective and well tolerated among patients in phase II and III studies. Here, we evaluated the safety and effectiveness of apatinib in advanced gastric cancer patients in a real-world setting. METHODS: This study enrolled advanced gastric cancer patients who had progressed or relapsed despite systemic chemotherapy. The primary outcome was safety and the secondary outcomes included overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 337 patients were included. In total, 62 (18.4%), 102 (30.3%), and 173 (51.3%) patients received first, second, and third or higher line apatinib therapy, respectively. Grade 3/4 treatment-emergent adverse events (AEs) were infrequent (<5%), with hypertension (6.8%) being the only grade 3/4 AE occurring in more than 5% of the patients and across the low-dose (250 mg, 7.3%), mid-dose (425-500 mg, 6.1%), and high-dose group (675-850 mg, 2/15, 13.3%). The median OS and PFS were 7.13 months (95% CI, 6.17-7.93) and 4.20 months (95% CI, 4.60-4.77), respectively, and were comparable among the low-, mid-, and high-dose groups. CONCLUSION: Lower daily doses of apatinib achieved comparable OS and PFS versus higher daily doses of apatinib while maintaining a more benign safety profile in advanced gastric cancer patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02668380.

Clinical features and prognostic factors in 190 cancer patients with brain metastases.

BACKGROUND: Brain metastases significantly reduce the survival of cancer patients. However, detailed researches on the clinical manifestations and prognoses of patients with brain metastases are lacking. The aim of this study was to investigate the clinical features and prognostic factors of cancer patients with brain metastases. METHODS: A retrospective study was conducted on patients with brain metastases who were treated in our hospital between January 2014 and January 2019. Comparison of overall survival (OS) was performed by the Kaplan-Meier method. Multivariate Cox regression models was used to identify prognostic factors for OS. RESULTS: A total of 190 patients with complete data and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 were enrolled. Patients with brain metastases from different primary sites had significantly different survival time (P=0.001). Patients who had a longer survival time included female patients (47.4%) (34 vs. 19 months, P=0.002), those with age <65 years (63.7%) (29 vs. 18 months, P=0.002), with ECOG 0 or 1 (44.2%) (32 vs. 21 months, P=0.005), with ≤3 brain lesions (61.1%) (29 vs. 20 months, P=0.041), and with small molecular targeted therapy (48.4%) (21 vs. 18 months, P=0.006). Furthermore, multivariate analysis revealed that female, age <65 years, ≤3 brain lesions, small molecular targeted therapy were independent favorable prognostic factors of OS. CONCLUSIONS: Female, younger patients with ≤3 brain metastases predicted a better survival. To improve the poor outcomes of these patients, it is necessary to find clinically significant genetic abnormalities and administer the small molecular targeted therapy early in the course of treatment.

Engineered tissue micro-rings fabricated from aggregated fibroblasts and microfibres for a bottom-up tissue engineering approach.

Tissue rings with incorporated microscaffolds have been engineered as promising building blocks for constructing biological tubes from the bottom up. However, the microscaffolds available for incorporation are very limited at present. In this paper we provide an efficient strategy to first incorporate microfluidic spun Ca-alginate microfibres encapsulating magnetic nanoparticles into self-assembled fibroblast micro-rings. Based on the surface modification, microfibres with a size of ∼40 µm allowed fibroblasts to spread and proliferate along the long axis. The optimal cell seeding density was obtained by evaluating the degree of coverage of fibroblasts on microfibres after 3 days of culture. Then we designed a magnetically guided culture apparatus with multiple annular micro-wells to facilitate cell-driven assembly of microfibres. A manipulation strategy dependent on surface tension was used to pattern microfibres along the micro-wells prior to cell seeding, and magnetic attraction further kept the patterned microfibres from being deposited in the micro-wells during cultivation. Within 3 days of culture, microfibre-incorporated tissue micro-rings were formed in the micro-wells. Quantitative analysis of the formation process revealed liquid-like aggregating behaviours, and incorporated microfibres showed the potential to promote the directed organization of cells in tissue micro-rings. Furthermore, magnetically driven manipulation was used robotically to assemble the micro-rings on a micropillar inserted into the centre of the culture apparatus. After 5 days of culture to allow cell fusion, a biological tubular microstructure was achieved. Microfluidic spinning can generate fibres with a variety of shapes, geometries, and compositions; therefore, our proposed method greatly enriches the variety of microscaffolds available for incorporation into tissue rings to engineer complex artificial organs for tissue engineering and regenerative medicine.

The role of miR-92b in cholangiocarcinoma patients.

PURPOSE: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. METHODS: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan-Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. RESULTS: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.

[Clinical Efficacy of Decitabine Combined with or without Cytarabine-based Low Dose Regimen for Senile patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the therapeutic effectiveness and side effects of decitabine combined with or without cytarabine-based low dose regimen for acute myeloid leukemia in geratic patients. METHODS: Clinical data of 8 geratic patients (aged over 70 years) suffered from acute myeloid leukemia from September 2009 to March 2012 were analyzed retrospectively, including age, sex, peripheral blood and bone marrow characteristics and so on. These patients were treated by an 1-hour intravenous infusion of decitabine 20 mg/m2 per day for 5 consecutive days every 4 weeks combined with or without low dose regimen dominantly consisting of cytarabine 20 mg per day as subcutaneous injection for seven consecutive days. The therapeutic effectiveness and side-effects were evaluated. RESULTS: Among 8 patients, incinding 3 males and 5 females aged between 71-84 years old, their median white blood cell count was 31.2(1.38-179)× 109/L, and median bone marrow blast cell ratio was 42.7(23-94)% at the initial diagnosis.The median treatment courses was 2.5 (1-20).After treatment by this protocol,2 patients achieved complete remission(CR) (25%), 2 patients achieved partial remission (PR)(25%), 3 were not relieved, and 1 died, thus the overall response rate reached to 50% (4/8). The median overall survival time was 9.5 (2-36) months, and the overall survival time of 3 patients reached 1 year or more. The main side-effects of treatment were grade III-IV of myelosuppression (87.5%) and pneumonia (50%). CONCLUSION: Decitabine combined with or without cytarabine-based low dose regimen is promising for the treatment of geriatric acute myeloid leukemia, thus improving the overall response rate, and prolonging overall survival time.

[Screening of key molecules of HAb18G/CD147 signal transduction pathway in human hepatoma cells].

Objective To screen the differentially expressed key molecules of HAb18G/CD147 signal transduction pathway in human hepatoma cells. Methods The total RNA was extracted from SMMC-7721 and T7721 cells, which were stably transfected and overexpressed HAb18G/CD147, and then detected by signal transduction-related microarray to identify differentially expressed key molecules. Results The microarray data indicated that there were 13 differentially expressed genes between T7721 and SMMC-7721 cells. In T7721 cell line which overexpressed HAb18G/CD147, the down-regulated genes included bone morphogenetic protein-2 (BMP-2), BMP-5, endothelin-1 (ET-1), Wnt1-induced signaling proteins-2/CCN5 (WISP-2), cysteine-rich 61/CCN1 (Cyr61), prostate stem cell antigen (PSCA), and the up-regulated genes included interleukin-10 receptor α (IL-10Rα), IL-6, IL-8, CXCL2, mitochondrial superoxide dismutase 2 (SOD2), B factor and ßig-h3.Conclusion The study identified totally 13 differentially expressed genes which were related to HAb18G/CD147 signal transduction pathway. These genes are involved in the regulation of various hepatoma biological processes, such as immune microenvironment remolding, angiogenesis, cell proliferation, invasion and metastasis.

Synergistic inhibitory effects of an engineered antibody-like molecule ATF-Fc and trastuzumab on tumor growth and invasion in a human breast cancer xenograft mouse model.

The overexpression of the oncogene human epidermal growth factor receptor 2 (HER-2) has been associated with decreased disease-free survival and is a marker of poor prognosis of invasive breast cancer. Although the high efficacy of trastuzumab, a drug that targets the HER-2 oncogene, has been widely recognized, the efficiency of the treatment remains at ~30%. Therefore, novel effective treatments are required for patients with recurrent metastatic breast cancer. The present study aimed to investigate the effects of an engineered antibody-like molecule administered alone or in combination with trastuzumab on the tumor growth and metastasis of HER-2-positive breast cancer. Another aim was to investigate novel cancer therapies for HER-2-positive breast cancer. The engineered antibody-like molecule consists of the amino-terminal fragment (ATF) of human urokinase-type plasminogen (uPA) and is conjugated with the Fc fragment of human immunoglobulin G1 (ATF-Fc). The anti-cancer effect of ATF-Fc (alone and in combination with trastuzumab) on tumor cells and in a nude mouse tumor model was evaluated by detecting the expression of uPA, urokinase plasminogen activator receptor (uPAR) and HER-2. In vitro experiments demonstrated that specifically blocking the uPA-uPAR and HER-2 signaling pathways may effectively promote the apoptosis of breast cancer cells. Additionally, ATF-Fc-induced cell death in HER-2-positive breast cancer cells was observed in vivo. When ATF-Fc was administered in combination with trastuzumab, cell death was increased and breast cancer metastasis was reduced. The novel engineered antibody-like molecule ATF-Fc was able to inhibit HER-2-positive breast cancer cell growth and metastasis by interfering with uPA and its receptor (uPA-uPAR) system. Additionally, the antibody-like molecule exhibits a synergistic inhibitory effect when administered in combination with trastuzumab.

12-O-tetradecanoylphorbol-13-acetate (TPA) increases murine intestinal crypt stem cell survival following radiation injury.

Radiation enteropathy is a common complication in cancer patients following radiation therapy. Thus, there is a need for agents that can protect the intestinal epithelium against radiation. 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown to induce differentiation and/or apoptosis in multiple cell lines and primary cells. In the current report, we studied the function of TPA in radiation induced enteropathy in cultured rat intestinal epithelial cell line IEC-6 after ionizing radiation (IR) and in mice after high dose total-body gamma-IR (TBI). In IEC-6 cells, there were reduced apoptosis and cell cycle arrest in TPA treated cells after IR. We detected a four-fold increase in crypt cell survival and a two-fold increase in animal survival post TBI in TPA treated mice. The beneficial effects of TPA were accompanied by upregulation of stem cells markers and higher level of proteins that are involved in PKC signaling pathway. In addition, TPA also decreased the TBI-augmented levels of the DNA damage indicators. The effects were only observed when TPA was given before irradiation. These results suggest that TPA has the ability to modulate intestinal crypt stem cells survival and this may represent a promising countermeasure against radiation induced enteropathy.

Mesenchymal stem cell-conditioned medium promotes MDA-MB-231 cell migration and inhibits A549 cell migration by regulating insulin receptor and human epidermal growth factor receptor 3 phosphorylation.

Various in vitro and in vivo studies have linked mesenchymal stem cells (MSCs) with cancer, but little is known about the effect of MSCs on tumor progression. The present study aimed to analyze the role of the MSCs from different tissues, consisting of human bone marrow, adipose and the umbilical cord tissues, and the heterogeneity of tumors in tumor progression. By collecting the culture supernatants of MSCs as MSC-conditioned media (CMs), the present study found that MSC-CM produces no significant effect on the proliferation of MDA-MB-231 and A549 tumor cells. The migration of MDA-MB-231 cells was enhanced upon incubation with MSC-CM, while that of A549 cells was inhibited. Furthermore, the phosphorylation of insulin receptors (IRs) was upregulated in MSC-CM-treated MDA-MB-231 cells, while in MSC-CM-treated A549 cells, the phosphorylation of human epidermal growth factor receptor 3 (Her3) was downregulated. Taken together, the findings suggest that the phosphorylation of IR and Her3 may contribute to the discrepant effects of MSC-CM on the migration of the 2 cell lines.

Research Advances in Bacteria-based Microrobot.

The concept of bacteria-based microrobot has been well recognized. It has shown great advantages and potentials for the early diagnosis and early treatment of malignant tumor and in reducing chemotherapy toxicities. In this article we review the concept,structure,and potential clinical applications of bacteria-based microrobot.

CTNNA1 hypermethylation, a frequent event in acute myeloid leukemia, is independently associated with an adverse outcome.

The aim of this study is to evaluate the frequency of CTNNA1 hypermethylation in acute myeloid leukemia (AML) patients in an attempt to improve molecular prognostic model. CTNNA1 promoter methylation levels in 319 newly diagnosed AML patients were detected using quantitative methylation-specific polymerase chain reaction (qMS-PCR). Furthermore, hematological characteristics, cytogenetic abnormalities, and genetic mutation status were analyzed, followed by assessment of clinical impact. Our findings demonstrated that CTNNA1 hypermethylation was observed in 25% AML patients. Hypermethylation of the CTNNA1 promoter was associated with unfavorable karyotype, and also possessed the higher frequency of coexisting with ASXL1 and RUNX1 mutations. Patients with CTNNA1 hypermethylation exhibited the shorter relapse-free survival (RFS) and overall survival (OS) in the whole AML and non-M3 AML patients. Moreover, patients with the higher methylation levels had more aggressive course than those with relative lower levels. In multivariate analyses, CTNNA1 hypermethylation was an independent factor predicting for poor RFS, but not for OS. In conclusion, CTNNA1 hypermethylation may be a reliable factor for improving prognostic molecular model for AML.

Higher expression levels of the HOXA9 gene, closely associated with MLL-PTD and EZH2 mutations, predict inferior outcome in acute myeloid leukemia.

BACKGROUND: Although the biological insight of acute myeloid leukemia (AML) has increased in the past few years, the discovery of novel discriminative biomarkers remains of utmost value for improving outcome predictions. Systematical studies concerning the clinical implications and genetic correlations of HOXA9 aberrations in patients with AML are relatively promising. MATERIALS AND METHODS: Here, we investigated mutational status and the mRNA levels of the HOXA9 gene in 258 patients with AML. Furthermore, hematological characteristics, chromosome abnormalities, and genetic mutations associated with AML were analyzed, followed by the assessment of clinical survival. Besides, the expression level and mutational status of MEIS1, a cofactor of HOXA9, were also detected in patients with AML with the aim of a deeper understanding about the homeodomain-containing transcription factors associated with hematological characteristics. RESULTS: HOXA9 and MEIS1 mutations were detected in 4.26% and 3.49% AML cases, respectively. No correlations were detected between mutation status and clinical characteristics, cytogenetic and genetic aberrations, and clinical survival. Higher HOXA9 expression levels were correlated with white blood cell count and closely associated with unfavorable karyotype as well as MLL-PTD and EZH2 mutations, whereas, there was an inverse correlation with the French-American-British M3 subtype. Compared with patients with lower HOXA9 expression levels, those with higher HOXA9 expression levels had a lower complete remission rate and inferior survivals in both AML and cytogenetically normal AML. CONCLUSION: HOXA9 expression may serve as a promising biomarker to ameliorate a prognostic model for predicting clinical outcome and consummating individualized treatment in patients with AML.

CHFR hypermethylation, a frequent event in acute myeloid leukemia, is independently associated with an adverse outcome.

The CpG island of the promoter region of the checkpoint with fork-head associated and ring finger gene (CHFR), a mitotic checkpoint gene with tumor-suppressor functions, is hypermethylated in various human cancers. The objective of this study was to evaluate the frequency of aberrant CHFR promoter methylation in acute myeloid leukemia (AML) patients in an attempt to improve prognostication. CHFR promoter methylation levels were analyzed in 358 newly diagnosed AML cases and 30 healthy donors by the use of quantitative methylation-specific polymerase chain reaction. In addition, we analyzed possible association between CHFR hypermethylation and hematological characteristics, chromosome abnormalities, genetic mutations, and survival. Hypermethylation of the CHFR promoter was observed in 24% (85 of 358) AML patients, but not in healthy individuals. CHFR hypermethylation correlated significantly with SRSF2 and DNMT3A mutations. Patients with hypermethylation exhibited lower overall survival and shorter relapse-free survival than nonmethylated cases. In multivariate analysis, CHFR hypermethylation was an independent factor predicting poor overall survival but not relapse-free survival. In conclusion, hypermethylation of the CHFR promoter, frequent in AML, is associated with adverse outcome, and can thus be used for risk stratification.

[Effect of brentuximab vedotin combined with chlormethine hydrochloride on the treatment of 6 patients with relapsed and refractory Hodgkin lymphoma].

OBJECTIVE: To observe the clinical efficacy and side effects of brentuximab vedotin (BV) plus chlormethine hydrochloride (CH) in patients with relapsed and refractory Hodgkin lymphoma (HL) after failure with BV alone. METHODS: From March, 2014 to December, 2014, 6 patients who failed with BV monotherapy were enrolled in this study. The chemotherapy regimen consisted of BV (1.2-1.8 mg/kg, iv. gtt, d1) and CH (6 mg/m2, iv. gtt, d1) was given for 3 weeks as one course, and all patients received about 3-8 courses of chemotherapy, with an median of 4 courses. Clinical efficacy and adverse events were assessed and observed by radiographic examination and serological detection. RESULTS: Among 6 patients, the overall response rate was 100% with 2 complete remission and 4 partial remission. The main adverse events were grade I (2 patients) and IV (2 patients) bone marrow depression, grade II (2 patients)gastrointestinal reaction, grade I (1 patient) increase of transaminase and myocardial enzyme and grade I (1 patient) mouth ulcers. CONCLUSION: The combination of BV and CH in the treatment of relapsed and refractory HL after failure with BV alone was high effective and the toxicities were well tolerable.

The LPS-Pretreated MSCs Supply a Positive Microenvironment for Tumor Cell Proliferation and Clone Formation.

In this study, the culture supernatant of LPS-treated MSCs was collected and served as a conditioned medium (CM). It was found that the LPS-CM promoted the proliferation of tumor cells (SKBR3, MDA-MB-231, A549, 95D and HepG2). In addition, the colony formation ability was also enhanced by LPS-CM incubation. The inflammatory cytokines, IL-6 and IL-8, were demonstrated to be up-regulated in the LPS-CM, which we supposed to function in the tumor-growth promotion in vitro.

[Application of multiplex nested RT- PCR assay for screening the fusion genes in acute myeloid leukemia and its clinical significance].

OBJECTIVE: To investigate the clinical value of multiplex nested reverse transcription PCR (RT-nPCR) in screening acute myeloid leukemia(AML)fusion genes. METHODS: A novel multiplex RT-nPCR assay was developed to detect 16 AML-related fusion genes (AML1-EVI1, AML1-ETO, AML1-MDS1, AML1-MTG16, MLL-AF9, MLL-AF6, MLL-AF10, MLL-ENL, MLL-MLL, PML-RARα, PLZFRARα, NPM1-RARα, CBFB-MYH11, DEK-CAN, SET-CAN and TLS-ERG) according to 2008 WHO classification of AML. The chromosome reciprocal translocations of 356 AML cases were detected by multiplex RT-nPCR and karyotyping. The positive samples were further confirmed by split- out PCR and FISH. RESULTS: The fusion genes were detected in 172 patients with the positive detection rate of 48.31%(172/356), which was higher than that of karyotyping (31.46%) (χ²=70.314, P<0.01). Multiplex RT-nPCR is superior to karyotyping and FISH in identifying the rare, cryptic chromosome translocation (χ²=96.074, P<0.01). CONCLUSION: The multiplex RT-nPCR used in this study can quickly, effectively and accurately screen the fusion genes in AML patients, which can provide important evidence for assessing diagnosis and treatment, and also provide necessary information for minimal residual disease (MRD) and prognosis.

Paclitaxel nanosuspension coated with P-gp inhibitory surfactants: II. Ability to reverse the drug-resistance of H460 human lung cancer cells.

PURPOSE: The present studies evaluated the ability of paclitaxel (PTX) nanosuspension coated with TPGS to reverse drug-resistance of P-glycoprotein (P-gp)-overexpressing H460 human lung cancer cells. METHOD: P-gp expression level of H460 cells was detected by western blot method. MTT assay was used to investigate in vitro cytotoxicity of PTX formulations and the resistance index (RI) of H460/RT cells. At last the antitumor efficacy of PTX nanosuspension was evaluated in resistant H460 cells xenograft Balb/c mice. RESULTS: The P-gp expression level of H460/RT cells was four times more than that of sensitive H460 cells. TPGS could reduce the P-gp expression by 25.41% at a concentration of 100 µg/ml after 24h exposure. Both PTX solution and nanosuspension exhibited obvious cytotoxicity against sensitive H460 cells. When H460/RT cells were treated, PTX nanosuspension showed significantly higher cytotoxicity compared with PTX solution, with much lower IC50 value and RI at each time point. After intravenous administration PTX nanosuspension exhibited about 5-fold increase in the inhibition rate of tumor growth compared with the mixed solution of PTX and TPGS. CONCLUSIONS: PTX nanosuspension coated with TPGS could effectively reverse drug resistance of H460/RT cells. The usage of TPGS as stabilizers on the surface of nanocrystals of insoluble anticancer drugs may be an effective approach to overcome the multi-drug resistances (MDR).

Curcumin inhibits lung cancer progression and metastasis through induction of FOXO1.

Recent population studies provide clues that the use of curcumin may be associated with reduced incidence and improved prognosis of certain cancers. In the present study, we demonstrated that curcumin acted as a growth inhibitor for lung cancer cells. Our results found that curcumin inhibited cell proliferation, which was associated with upregulation of the cyclin-dependent kinase inhibitors, p27 and p21, and downregulation of cyclin D1. In addition, we showed that curcumin induced the expression of forkhead box protein O1 (FOXO1) through activation of extracellular signal-regulated kinase 1/2 signaling. These findings provide evidence for a mechanism that may contribute to the antineoplastic effects of curcumin and justify further work to explore potential roles for activators of FOXO1 in the prevention and treatment of lung cancer.