Human Mesenchymal Stem Cell-Derived Exosomes Promote the Proliferation and Melanogenesis of Primary Melanocytes by Attenuating the H2O2-Related Cytotoxicity in vitro.

Background: Mesenchymal stem cell-derived exosomes (MSC-Exo) have therapeutic potential. However, the impact of MSC-Exo on the survival and melanogenesis of human primary melanocytes following H2O2-induced damage has not been clarified. We therefore investigated the effects of MSC-Exo on the H2O2-affected survival of human primary melanocytes and their proliferation, apoptosis, senescence, and melanogenesis in vitro. Methods: MSC-Exo were prepared from human MSCs by sequential centrifugations and characterized by Transmission Electron Microscopy, Western blot and Nanoparticle Tracking Analysis. Human primary melanocytes were isolated and treated with different concentrations of MSC-Exo, followed by exposing to H2O2. Furthermore, the impact of pretreatment with MSC-Exo on the proliferation, apoptosis, senescence and melanogenesis of melanocytes were tested by CCK-8, flow cytometry, Western blot, L-Dopa staining, tyrosinase activity and RT-qPCR. Results: Pretreatment with lower doses of MSC-Exo protected human primary melanocytes from the H2O2-triggered apoptosis, while pretreatment with higher doses of MSC-Exo enhanced the H2O2-induced melanocyte apoptosis. Compared with the untreated control, pretreatment with a lower dose (1 µg/mL) of MSC-Exo enhanced the proliferation of melanocytes, abrogated the H2O2-increased p53, p21, IL-1ß, IL-6 and IL-8 expression and partially rescued the H2O2-decreased L-dopa staining reaction, tyrosinase activity, MITF and TRP1 expression in melanocytes. Conclusion: Our findings indicate that treatment with a low dose of MSC-Exo promotes the proliferation and melanogenesis of human primary melanocytes by ameliorating the H2O2-induced apoptosis and senescence of melanocytes. MSC-Exo may be a promising therapeutic strategy of vitiligo.

The Effect of Carbon Doping on the Crystal Structure and Electrical Properties of Sb2Te3.

As a new generation of non-volatile memory, phase change random access memory (PCRAM) has the potential to fill the hierarchical gap between DRAM and NAND FLASH in computer storage. Sb2Te3, one of the candidate materials for high-speed PCRAM, has high crystallization speed and poor thermal stability. In this work, we investigated the effect of carbon doping on Sb2Te3. It was found that the FCC phase of C-doped Sb2Te3 appeared at 200 °C and began to transform into the HEX phase at 25 °C, which is different from the previous reports where no FCC phase was observed in C-Sb2Te3. Based on the experimental observation and first-principles density functional theory calculation, it is found that the formation energy of FCC-Sb2Te3 structure decreases gradually with the increase in C doping concentration. Moreover, doped C atoms tend to form C molecular clusters in sp2 hybridization at the grain boundary of Sb2Te3, which is similar to the layered structure of graphite. And after doping C atoms, the thermal stability of Sb2Te3 is improved. We have fabricated the PCRAM device cell array of a C-Sb2Te3 alloy, which has an operating speed of 5 ns, a high thermal stability (10-year data retention temperature 138.1 °C), a low device power consumption (0.57 pJ), a continuously adjustable resistance value, and a very low resistance drift coefficient.

Tumor Size Is an Independent Prognostic Factor for Stage I Ovarian Clear Cell Carcinoma: A Large Retrospective Cohort Study of 1,000 Patients.

Objective: The aim of this study was to investigate the prognostic value and stratification cutoff point for tumor size in stage I ovarian clear cell carcinoma (OCCC). Methods: This was a retrospective cohort study using the Surveillance, Epidemiology, and End Results database (version: SEER 8.3.9). Patients diagnosed with stage I OCCC from 1988 to 2018 were included for further analysis. X-Tile software was used to identify the potential cutoff point for tumor size. Stratification analysis, propensity score matching, and inverse probability weighting analysis were used to balance the potential confounding factors. Results: A total of 1,000 stage I OCCC patients were included. Of these 1,000 patients, median follow-up was 106 months (95% confidence interval [CI]: 89-112 months). Multivariate analysis showed that tumor size, age at diagnosis, and stage IC were significantly associated with stage I OCCC patients. Eight centimeters is a promising cutoff point that can divide stage I OCCC patients into a good or a poor prognosis group. After controlling potential confounding factors with propensity score matching and inverse probability weighting, we demonstrated that stage I OCCC patients with tumor size ≤ 8 cm enjoyed a significantly better 5-year overall survival (OS, 89.8% vs. 81%, p < 0.0001). Tumor size ≤ 8 cm was an independent prognostic factor of stage I OCCC patients (hazard ratio [HR] 0.5608, 95% CI: 0.4126-0.7622, p = 0.0002). Conclusions: Tumor size is an independent prognostic factor for stage I OCCC, and 8 cm is a promising cutoff point for tumor size for risk stratification. However, using tumor size in the stratification management of stage I OCCC patients warrants further investigation.

Inhibitory Effects of Compounds from Plumula nelumbinis on Biofilm and Quorum Sensing Against P. aeruginosa.

Quorum sensing (QS), which controls the survival and virulence of Pseudomonas aeruginosa, including the formation of biofilm, is considered to be a new target to overcome pathogens. The aim of this study was to identify new QS inhibitors against P. aeruginosa and provide potential treatments for clinical infections. In this study, 25 compounds were isolated from Plumula nelumbini. Among these compounds, C25 showed the most significant biofilm inhibition activity, reaching 44.63% at 100 µM without inhibiting bacterial growth. Furthermore, C25 showed significant inhibition activity of rhamnolipid, pyocyanin, and elastase. Further mechanistic studies have confirmed that C25 could downregulate key genes in the QS system, including lasI, lasR, lasA, lasB, and pqsR, and Molecular docking studies have shown that C25 can bind to the active sites of the LasR and PqsR receptors. The present study suggests that C25 is a promising QS inhibitor for treating P. aeruginosa infections.

Woolly hair nevus caused by somatic mutation and Costello syndrome caused by germline mutation in HRAS: Consider parental mosaicism in prenatal counseling.

Germline mutations in HRAS cause Costello syndrome (CS), while mosaic mutations in HRAS show a variability of phenotypes, ranging from mild features such as keratinocytic epidermal nevus (KEN), sebaceous nevus (SN), woolly hair nevus (WHN) with KEN, to severe manifestations of CS with cutis laxa. We report two individuals. The first was a 2-year-old boy with woolly hair nevus (WHN) without any other cutaneous involvement, in whom somatic HRAS mutation (c.34G>A; p.Gly12Ser) was identified in his affected scalp and hair follicle specimens. This is the first reported WHN type 1 (no cutaneous involvement) patient caused by somatic HRAS mutation. The other individual was a 12-year-old girl with CS caused by germline HRAS mutation (c.34G>A), that manifested with coarse face, palmoplantar keratoderma, deep palmar and plantar creases, hyperpigmented patches, asymmetry and deformity of lower limbs, atopic dermatitis, as well as mental retardation. Of note, a linear hyperpigmented plaque was observed in her father's lumbosacral region. Although the father refused to provide semen and skin tissue for further examination, this reminds us of possible mosaicism in parents of individuals with germline de novo HRAS mutation and underlines the importance of parental evaluation for prenatal counseling.

Multi-level phase-change memory with ultralow power consumption and resistance drift.

By controlling the amorphous-to-crystalline relative volume, chalcogenide phase-change memory materials can provide multi-level data storage (MLS), which offers great potential for high-density storage-class memory and neuro-inspired computing. However, this type of MLS system suffers from high power consumption and a severe time-dependent resistance increase ("drift") in the amorphous phase, which limits the number of attainable storage levels. Here, we report a new type of MLS system in yttrium-doped antimony telluride, utilizing reversible multi-level phase transitions between three states, i.e., amorphous, metastable cubic and stable hexagonal crystalline phases, with ultralow power consumption (0.6-4.3 pJ) and ultralow resistance drift for the lower two states (power-law exponent < 0.007). The metastable cubic phase is stabilized by yttrium, while the evident reversible cubic-to-hexagonal transition is attributed to the sequential and directional migration of Sb atoms. Finally, the decreased heat dissipation of the material and the increase in crystallinity contribute to the overall high performance. This study opens a new way to achieve advanced multi-level phase-change memory without the need for complicated manufacturing procedures or iterative programming operations.

Large magnetodielectric response of PST/LSMO/LCMO film over a wide temperature range.

Pb0.6Sr0.4TiO3/La0.7Sr0.3MnO3/La0.7Ca0.3MnO3 (PST/LSMO/LCMO) film is grown on Si substrate by chemical solution deposition method. The film crystallizes perfectly into perovskite phases with a random crystalline orientation. The La0.7Sr0.3MnO3/La0.7Ca0.3MnO3/Si layer exhibits low resistivity and obvious negative magnetoresistivity (MR); the PST/LSMO/LCMO film shows notable magnetocapacitance (MC) above 350 K, from 102.9% to 29.5%. Near room temperature, there is no distinguished magnetoelectric coupling; the MC is 34.3% @ 250 K, 29.5% @ 300 K and 32.8% @ 350 K respectively. The mechanism can be explained in light of the Maxwell-Wagner (MW) model and the enhanced MR origin from the successive mixed manganite phases and spin dependent tunneling across the junctions of PST/LSMO/LCMO. This work provides a new approach for designing and developing novel composites with promising MC.

Feasibility of Bone Marrow Mesenchymal Stem Cell-Mediated Synthetic Radiosensitive Promoter-Combined Sodium Iodide Symporter for Radiogenetic Ovarian Cancer Therapy.

Ovarian cancer is the most lethal gynecological cancer, most patients relapse within 12-24 months, and eventually die, especially platinum-resistant patients. Gene therapy has been one of the most potential methods for tumor treatment. Bone marrow mesenchymal stem cells (BMSCs) have been used for systemic delivery of therapeutic genes to solid tumors. Sodium iodide symporter (NIS) is an intrinsic membrane glycoprotein and can concentrate 131I, which is important for radionuclide therapy and nuclear medicine imaging in recent years. However, the rapid iodine efflux has become a bottleneck for NIS-mediated radionuclide gene therapy. Our previous studies found that the early growth response-1 (Egr1) promoter containing CC(A/T)6GG (CArG) elements had an 131I radiation-positive feedback effect on the NIS gene. Other research showed the synthesized Egr1 promoter containing four CArG elements, E4, was nearly three times as sensitive as the Egr1 promoter. In our study, BMSC-E4-NIS was engineered to express NIS under the control of E4 promoter using lentivirial vectors. After BMSC-E4-NIS implantation, no tumors were seen in BALB/c nude mice and BMSC-E4-NIS did not promote the growth of SKOV3 tumor. BMSCs migrated toward ovarian cancer samples in chemotaxis assays and to ovarian tumors in mice. Using micro-single-photon emission computed tomography/computed tomography (SPECT/CT) imaging, we found that E4 promoter produced a notable increase in 125I uptake after 131I irradiation, the radionuclide uptake is almost three and six times more than Egr1 and cytomegalovirus (CMV) promoters. These studies confirmed the feasibility of using BMSCs as carriers for lentivirus-mediated E4-NIS gene therapy for ovarian cancer. Further research on BMSC-E4-NIS gene therapy for ovarian cancer in vivo will also be carried on, and if successful, this might provide a new adjuvant therapeutical option for platinum-resistant ovarian cancer patients and provide a new method for dynamic evaluation of curative effect.

Correction to: LncRNA MEG3 promotes melanoma growth, metastasis and formation through modulating miR-21/E-cadherin axis.

[This corrects the article DOI: 10.1186/s12935-019-1087-4.].

Long non-coding RNA MIAT promotes the growth of melanoma via targeting miR-150.

Melanoma is a common skin cancer and it can lead to high mortality probably by early invasion and metastasis. LncRNA MIAT is involved in tumor proliferation, invasion and epithelial-to-mesenchymal transition (EMT). However, the roles of MIAT in melanoma still require further investigation. Thus, the aim of the study is to investigate the roles of MIAT in melanoma, especially the effects of MIAT on EMT of melanoma cancer cells. The results showed that the expression of MIAT was significantly upregulated in melanoma tissue and cells compared with the normal skin and normal melanocytes; moreover, miR-150 was confirmed as a target of MIAT. Furthermore, knockdown of MIAT inhibited cell proliferation and invasion in melanoma cancer cells and transfection of miR-150 inhibitors partial abrogated the anti-tumor effects of MIAT siRNA. In addition, MIAT siRNA also inhibited the EMT of melanoma cells, while miR-150 inhibitors can reverse the effects of MIAT siRNA. Finally, knockdown of MIAT also inhibited the carcinogenic effects of melanoma in vivo by targeting miR-150. In conclusion, we reported that MIAT promotes the proliferation, invasion and EMT of melanoma cells via targeting miR-150, which suggested that MIAT might be a therapeutic target for the treatment of melanoma.

Y-Doped Sb2Te3 Phase-Change Materials: Toward a Universal Memory.

The disadvantages of high power consumption and slow operating speed hinder the application of phase-change materials (PCMs) for a universal memory. In this work, based on a rigorous experimental scheme, we synthesized a series of YxSb2-xTe3 (0 ≤ x ≤ 0.333) PCMs and demonstrated that Y0.25Sb1.75Te3 (YST) is an excellent candidate material for the universal phase-change memory. This YST PCM, even being integrated into a conventional T-shaped device, exhibits an ultralow reset power consumption of 1.3 pJ and a competitive fast set speed of 6 ns. The ultralow power consumption is attributed to the Y-reduced thermal and electrical conductivity, while the maintained crystal structure of Sb2Te3 and the grain refinement provide the competitive fast crystallization speed. This work highlights a novel way to obtain new PCMs with lower power consumption and competitive fast speed toward a universal memory.

Development of a four-gene prognostic model for pancreatic cancer based on transcriptome dysregulation.

We systematically developed a prognostic model for pancreatic cancer that was compatible across different transcriptomic platforms and patient cohorts. After performing quality control measures, we used seven microarray datasets and two RNA sequencing datasets to identify consistently dysregulated genes in pancreatic cancer patients. Weighted gene co-expression network analysis was performed to explore the associations between gene expression patterns and clinical features. The least absolute shrinkage and selection operator (LASSO) and Cox regression were used to construct a prognostic model. We tested the predictive power of the model by determining the area under the curve of the risk score for time-dependent survival. Most of the differentially expressed genes in pancreatic cancer were enriched in functions pertaining to the tumor immune microenvironment. The transcriptome profiles were found to be associated with overall survival, and four genes were identified as independent prognostic factors. A prognostic risk score was then proposed, which displayed moderate accuracy in the training and self-validation cohorts. Furthermore, patients in two independent microarray cohorts were successfully stratified into high- and low-risk prognostic groups. Thus, we constructed a reliable prognostic model for pancreatic cancer, which should be beneficial for clinical therapeutic decision-making.

Paeoniflorin alleviates lipopolysaccharide-induced disseminated intravascular coagulation by inhibiting inflammation and coagulation activation.

Lipopolysaccharide (LPS) is a toxic component of the outer membrane of gram-negative bacteria that can activate the blood coagulation system, leading to disseminated intravascular coagulation (DIC). DIC is a syndrome characterized by thromboembolism and multiple organ failure. Herein, the beneficial effect of paeoniflorin (PF) on the alleviation of LPS-induced DIC was investigated with an experimental DIC mouse model. Briefly, mice were randomly divided into the following six groups: (1) control; (2) LPS; (3) heparin; (4) low-PF treatment; (5) medium-PF treatment; and (6) high-PF treatment. The histological morphology of the liver and kidney was observed, and the coagulation indicators (such as prothrombin time), function indicators (such as alanine transferase), and inflammatory factors (such as TNF-α) were detected. Additionally, an in vitro cell inflammation model using RAW 264.7 murine macrophages was established. Activation of the nuclear factor kappa B (NF-κB) signaling pathway and tumor necrosis factor-α (TNF-α) were determined by western blotting. Based on our findings, PF could significantly improve the histological morphology of the liver and kidney, indicating that PF protects the liver and kidney against damage induced by LPS. Additionally, PF improved the function and coagulation indicators and reduced the production of inflammatory factors. In vitro, PF inhibited the expression of TNF-α by suppressing NF-κB signaling pathway activation. Collectively, our findings support the hypothesis that PF has anti-inflammatory and anticoagulation effects for the alleviation of LPS-induced DIC. PF is thus a potential co-treatment option for DIC.

LncRNA MEG3 promotes melanoma growth, metastasis and formation through modulating miR-21/E-cadherin axis.

BACKGROUND: Melanoma is the most aggressive type of skin cancer with high mortality rate and poor prognosis. lncRNA MEG3, a tumor suppressor, is closely related to the development of various cancers. However, the role of lncRNA MEG3 in melanoma has seldom been studied. METHODS: RT-PCR was used to examine the expressions of lncRNA MEG3 and E-cadherin in melanoma patients and cell lines. Then, the biological functions of lncRNA MEG3 and E-cadherin were demonstrated by transfecting lncRNA MEG3-siRNA, lncRNA MEG3-overexpression, E-cadherin-siRNA and E-cadherin-overexpression plasmids in melanoma cell lines. Moreover, CCK8 assay and colony formation assay were utilized to assess the cell proliferation; Transwell assay was performed to evaluate the cell invasive ability; and tumor xenografts in nude mice were applied to test the tumor generation. Additionally, the target interactions among lncRNA MEG3, miR-21 and E-cadherin were determined by dual luciferase reporter assay. Finally, RT-PCR and WB were further conducted to verify the regulatory roles among lncRNA MEG3, miR-21 and E-cadherin. RESULTS: The clinical data showed that lncRNA MEG3 and E-cadherin expressions were both declined in carcinoma tissues as compared with their para-carcinoma tissues. Moreover, lncRNA MEG3 and E-cadherin expressions in B16 cells were also higher than those in A375 and A2058 cells. Subsequently, based on the differently expressed lncRNA MEG3 and E-cadherin in these human melanoma cell lines, we chose B16, A375 and A2058 cells for the following experiments. The results demonstrated that lncRNA MEG3 could suppress the tumor growth, tumor metastasis and formation; and meanwhile E-cadherin had the same effects on tumor growth, tumor metastasis and formation. Furthermore, the analysis of Kaplan-Meier curves also confirmed that there was a positive correlation between lncRNA MEG3 and E-cadherin. Ultimately, dual luciferase assays were further used to verify that lncRNA MEG3 could directly target miR-21 which could directly target E-cadherin in turn. Additionally, the data of RT-PCR and WB revealed that knockdown of lncRNA MEG3 in B16 cells inhibited miR-21 expression and promoted E-cadherin expression, but overexpression of lncRNA MEG3 in A375 and A2058 cells presented completely opposite results. CONCLUSION: Our findings indicated that lncRNA MEG3 might inhibit the tumor growth, tumor metastasis and formation of melanoma by modulating miR-21/E-cadherin axis.

Mesenchymal stem cells promote human melanocytes proliferation and resistance to apoptosis through PTEN pathway in vitiligo.

BACKGROUND: Vitiligo is an acquired chronic and recurrent skin disease that causes a depigmentation disorder, resulting in selective destruction of melanocytes (MC). However, the mechanism that leads to melanocyte dysfunction and death remains unclear. METHODS: We performed RNA sequencing, immunohistochemistry, and immunoblotting to characterize the patterns of phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway activation in vitiligo. We also cocultured primary melanocytes with mesenchymal stem cells (MSCs) in a Transwell system to explore how MSCs inhibit the PTEN/PI3K/AKT pathway in melanocytes. RESULTS: We identified that vitiligo normal-lesional junction skin presented with high expression of PTEN, which led to the inhibition of AKT phosphorylation (p-AKT) at S-473. Furthermore, PTEN overexpression led to oxidative stress-induced apoptosis in melanocytes. Coculturing with MSCs enhanced the cell proliferation of human melanocytes and repressed PTEN expression, which inhibited oxidative stress-induced apoptosis. CONCLUSION: We report that vitiligo patients present with high PTEN expression, which may play a role in the impairment of melanocytes. Furthermore, our study provides evidence that MSCs target the PTEN/PI3K/AKT pathway to regulate cell proliferation and apoptosis in human melanocytes, indicating that MSCs may serve as a promising therapy for vitiligo.

MicroRNA-139-5p modulates the growth and metastasis of malignant melanoma cells via the PI3K/AKT signaling pathway by binding to IGF1R.

The relation between microRNAs (miRNAs) and malignant melanoma has been demonstrated in previous studies, while there was little research about miR-139-5p and malignant melanoma. The aim of this study is to investigate the ability of miR-139-5p in malignant melanoma cells via the modulation of the PI3K/AKT signaling pathway by targeting IGF1R. MiR-139-5p expression in malignant melanoma tissues and 5 malignant melanoma cell lines was detected. The melanoma cells were transfected with miR-139-5p mimic negative control (NC) sequence, miR-139-5p mimic, IGF1R overexpressed recombinant plasmid NC or IGF1R overexpressed sequence. The expression of Akt signaling pathway-related protein was evaluated. The biological functions in malignant melanoma cells were evaluated by a string of experiments. MiR-139-5p expressed a poor level in tissues and cell lines of malignant melanoma. Overexpressed miR-139-5p suppressed the cell proliferation, migration, and invasion, and contributed to the promoted apoptosis of malignant melanoma cells by decreasing IGF1R. MiR-139-5p down-regulated the IGF1R expression, and IGF1R accelerated the activation of the PI3K/AKT signaling pathway. miR-139-5p reversed the promotive impacts of IGF1R on the PI3K/AKT signaling pathway. The study validates that miR-139-5p could suppress malignant melanoma progression through the repression of the PI3K/AKT signaling pathway by down-regulating IGF1R. Therefore, miR-139-5p could pave a new way for the treatment of malignant melanoma.

The fusion landscape of hepatocellular carcinoma.

Most cases of hepatocellular carcinoma (HCC) are already advanced at the time of diagnosis, which limits treatment options. Challenges in early-stage diagnosis may be due to the genetic complexity of HCC. Gene fusion plays a critical function in tumorigenesis and cancer progression in multiple cancers, yet the identities of fusion genes as potential diagnostic markers in HCC have not been investigated. Here, we employed STAR-Fusion and identified 43 recurrent fusion events in our own and four public RNA-seq datasets. We identified 2354 different gene fusions in two hepatitis B virus (HBV)-HCC patients. Validation analysis against the four RNA-seq datasets revealed that only 1.8% (43/2354) were recurrent fusions. Comparison with the four fusion databases demonstrated that 19 recurrent fusions were not previously annotated to diseases and three were annotated as disease-related fusion events. Finally, we validated six of the novel fusion events, including RP11-476K15.1-CTD-2015H3.2, by RT-PCR and Sanger sequencing of 14 pairs of HBV-related HCC samples. In summary, our study provides new insights into gene fusions in HCC and may contribute to the development of anti-HCC therapy.

Identification of the molecular relationship between intravenous leiomyomatosis and uterine myoma using RNA sequencing.

The purpose of this study was to explore the potential relationship between intravenous leiomyomatosis (IVL) and uterine myoma (UM) at the molecular level. RNA-sequencing was performed on IVL tumours, UM tumours, and adjacent normal uterine muscle. We compared the gene expression levels between IVL and normal uterine muscle, UM and normal uterine muscle, to identify differentially expressed genes (DEGs). Then we used Gene Ontology Enrichment Analysis to determine the functions of the DEGs and performed specimen cluster analysis. We obtained 98 DEGs between IVL and adjacent normal uterine muscle, and 61 DEGs between UM and adjacent normal uterine muscle. Functional enrichment of both IVL and UM DEGs showed that they are associated with hormone stimulus, extracellular matrix, and cell adhesion. Unsupervised clustering analysis showed that IVL and UM could not be separated completely. Among these dysregulated genes, we found that HOXA13 showed a distinct dysregulated status between IVL and UM. HOXA13 may therefore serves as a biomarker to distinguish IVL and UM. Our results showed that IVL and UM may have similar dysregulated gene networks. They may be closely related, and HOXA13 may serves as a biomarker to distinguish between IVL and UM.

CMTTdb: the cancer molecular targeted therapy database.

BACKGROUND: The cancer molecular targeted therapy has achieved unprecedented progress in the past decade and is thought to be the most promising direction for cancer treatment in future. As the fast growing of the clinical trials of targeted anticancer agents for different cancer types, it is critical to collect and integrate such information to guide clinical practice. METHODS: We constructed the Cancer Molecular Targeted Therapy database (CMTTdb) to store and retrieve molecular targeted therapy data about randomized clinical trials (RCTs) of targeted agents and also accompanied targets, biomarkers, targeted cancer subtypes, etc. RESULTS: Different with some existing resources, CMTTdb particularly focuses on clinical application of the trails. Design of the trails, such as treatment modalities (monotherapy or combination with other therapies), as well as results on clinical efficacy parameters, adverse events are also collected. In this current version, CMTTdb contains data for 1,088 clinical trials which cover 165 agents, 80 targets, 15 cancer types (95 molecular subtypes and 56 histological or cytological subtypes) from public literatures. This database is freely available at http://www.biosino.org/CMTTdb. A user-friendly web interface was designed so that these data can be easily retrieved. CONCLUSIONS: CMTTdb will be a valuable source for providing access to information of clinical trials on the rapidly growing number of novel targeted agent and be useful in guiding oncologists for the optimization of the therapy strategy for cancer treatment.