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Lung cancer has the highest mortality of any cancer worldwide, and cisplatin is a first-line chemotherapeutic agent for lung cancer treatment. Unfortunately, cisplatin resistance is a common cause of therapeutic failure. The ability to overcome chemoresistance is crucial to the effective treatment of lung cancer. Recently, epigallocatechin gallate (EGCG), a type of polyphenol extracted from tea, has been shown to suppress the rapid proliferation of cancer cells, including lung cancer. We tested whether nanoparticles (NPs) carrying a dual drug load, cisplatin and EGCG, could overcome chemoresistance to cisplatin, by working together to kill lung cancer cells. Self-assembling gelatin/EGCG nanoparticles (GE) were synthesized, and cisplatin was then incorporated, to construct a dual drug nanomedicine (EGCG/cisplatin-loaded gelatin nanoparticle, named as GE-Pt NP). The particle size and zeta potential were examined by dynamic light scattering (DLS). The morphological structure of GE-Pt NPs was observed by transmission electron microscopy (TEM). In vitro testing was performed using a human lung adenocarcinoma cell line (A549). A cytotoxicity examination was performed, using a WST-8 cell proliferation assay. Intracellular cisplatin content was quantified by inductively coupled plasma mass spectrometry (ICP-MS). In conclusion, we successfully prepared GE-Pt NPs, as spherical structures, approximately 75 nm in diameter, with a positive charge (+19.83±0.25 mV). The encapsulation rate of cisplatin in GE-Pt was about 63.7%, and the EGCG loading rate was around 89%. A relatively low concentration of GE-Pt NPs (EGCG 5 μg/mL : cisplatin 2 μg/mL) exhibited significant cytotoxicity, compared to cisplatin alone. The GE-Pt NPs are freely taken up by cells via endocytosis, raising the intracellular cisplatin concentration to a therapeutic level. We consider that combination therapy of cisplatin and EGCG in nanoparticles (GE-Pt NPs) may help overcome cisplatin resistance and could effectively be used in the treatment of lung cancer.

Chemotherapy resistance is a huge barrier for head and neck cancer (HNC) patients and therefore requires close attention to understand its underlay mechanisms for effective strategies. In this review, we first summarize the molecular mechanisms of chemotherapy resistance that occur during the treatment with cisplatin, 5-fluorouracil, and docetaxel/paclitaxel, including DNA/RNA damage repair, drug efflux, apoptosis inhibition, and epidermal growth factor receptor/focal adhesion kinase/nuclear factor-κB activation. Next, we describe the potential approaches to combining conventional therapies with previous cancer treatments such as immunotherapy, which may improve the treatment outcomes and prolong the survival of HNC patients. Overall, by parsing the reported molecular mechanisms of chemotherapy resistance within HNC patient’s tumors, we can improve the prediction of chemotherapeutic responsiveness, and reveal new therapeutic targets for the future.

Vascular leiomyosarcoma is an extremely rare tumor and is associated with poor prognosis among leiomyosarcoma. Surgical resection remains the main treatment option. But outcome of definitive treatment with chemoradiotherapy in inoperable patients is not clear. Here, we report treatment and outcome of definitive chemoradiotherapy in a case of vascular leiomyosarcoma. A 64-year-old man with the initial presentation of pulsatile right neck mass was diagnosed with right carotid body leiomyosarcoma. He refused surgical intervention due to risk of carotid body injury and ischemic stroke. Successful tumor control was achieved with carboplatin-based concurrent chemoradiotherapy. Investigational liquid biopsy for circulating sarcoma cells was also performed to analyze drug sensitivity profile of this rare tumor. One year after treatment, the disease remained well controlled and there was no evidence of baroreflex failure or treatment-related late toxicities. To our best knowledge, this is the first case report of right carotid body leiomyosarcoma controlled with definitive concurrent chemoradiotherapy. The approach of personalized multi-modality treatment will be a focus of our future investigation.

Cisplatin is the first-line chemotherapy agent for head and neck cancer (HNC), but its therapeutic effects are hampered by its resistance. In this study, we employed systemic strategies to overcome cisplatin resistance (CR) in HNC. CR cells derived from isogenic HNC cell lines were generated. The CR related hub genes, functional mechanisms, and the sensitizing candidates were globally investigated by transcriptomic and bioinformatic analyses. Clinically, the prognostic significance was assessed by the Kaplan&ndash, Meier method. Cellular and molecular techniques, including cell viability assay, tumorsphere formation assay, RT-qPCR, and immunoblot, were used. Results showed that these CR cells possessed highly invasive and stem-like properties. A total of 647 molecules was identified, and the mitotic division exhibited a novel functional mechanism significantly related to CR. A panel of signature molecules, MSRB3, RHEB, ULBP1, and spindle pole body component 25 (SPC25), was found to correlate with poor prognosis in HNC patients. SPC25 was further shown as a prominent molecule, which markedly suppressed cancer stemness and attenuated CR after silencing. Celastrol, a nature extract compound, was demonstrated to effectively inhibit SPC25 expression and reverse CR phenotype. In conclusion, the development of SPC25 inhibitors, such as the application of celastrol, maybe a novel strategy to sensitize cisplatin for the treatment of refractory HNC.

Tissue-specific microenvironmental factors contribute to the targeting preferences of metastatic cancers. However, the physical attributes of the premetastatic microenvironment are not yet fully characterized. In this research, we develop a transwell-based alginate hydrogel (TAH) model to study how permeability, stiffness, and roughness of a hanging alginate hydrogel regulate breast cancer cell homing. In this model, a layer of physically characterized alginate hydrogel is formed at the bottom of a transwell insert, which is placed into a matching culture well with an adherent monolayer of breast cancer cells. We found that breast cancer cells dissociate from the monolayer and home to the TAH for continual growth. The process is facilitated by the presence of rich serum in the upper chamber, the increased stiffness of the gel, as well as its surface roughness. This model is able to support the homing ability of MCF-7 and MDA-MB-231 cells drifting across the vertical distance in the culture medium. Cells homing to the TAH display stemness phenotype morphologically and biochemically. Taken together, these findings suggest that permeability, stiffness, and roughness are important physical factors to regulate breast cancer homing to a premetastatic microenvironment.

Piperlongumine (PL), a natural product of Piper longum, inhibits multiple malignant phenotypes. Therefore, the present study examined whether PL suppresses cancer stemness in oral cancer. The cellular effects of PL were determined by examining alterations in tumor sphere formation, cell migration, invasion, proliferation ability, chemosensitivity and radiosensitivity. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting were performed in order to determine molecular expression levels. The present study revealed that PL inhibited cancer stem cell-forming ability and suppressed the expression of the stemness-related transcription factors SRY-Box 2, POU class 5 homeobox 1, and Nanog homeobox. However, it increased the expression of the differentiation marker cytokeratin 18. PL also suppressed cell migration and invasion, resulting in the elimination of the epithelial-mesenchymal transition. Furthermore, PL increased chemo- and radiosensitivity and suppressed tumor growth in vitro and in vivo. The results of the present study suggested that PL inhibits malignant phenotypes via the suppression of cancer stemness in oral cancer. Thus, PL may serve as an effective therapeutic agent for oral cancer.

This work demonstrates a fast process to decorate silver (Ag) nanoparticles onto the functionalized few-walled carbon nanotubes (f-FWCNTs) and graphene nanosheets (f-GNs). The Ag-coated carbon nanomaterials were used as fillers, which mixed with poly(3,4-ethylenedioxythiophene)-poly(4-stryensulfonate) (PEDOT:PSS) for preparing high optoelectronic performances of flexible transparent conductive films (TCFs). The Ag nanoparticles with a particle size of approximate 5 nm were uniformly distributed on the surfaces of the f-FWCNTs (Ag@f-FWCNTs) and the f-GNs (Ag@f-GNs). The Ag ions play the role of electron acceptors during the reduction process, which increases the hole concentrations in PEDOT:PSS, f-FWCNTs, and f-GNs, therefore enhancing the electrical conductivity of the TCFs. Additionally, the Schottky barrier was decreased because of the increase of work functions of the carbon fillers caused by Ag decoration. The X-ray diffraction spectrum of Ag@f-GNs depicts the formations of the face-centered cubic Ag nanoparticles, and the peak of the (002) graphene plane slightly shifted to the lower frequency, indicating that the f-GN interlayer was intercalated with Ag ions or Ag nanoparticles. When the mixture of 2.0 wt % Ag@f-FWCNTs and 8.0 wt % Ag@f-GNs containing PEDOT:PSS dispersant was coated onto a poly(ethylene terephthalate) (PET) substrate, outstanding optoelectronic properties with a sheet resistance of 50.3 Ω/sq and a transmittance of 79.73% at a wavelength of 550 nm were achieved.

To develop novel electromagnetic interference (EMI) shielding materials, polyaniline (PAni) composites filled with graphene, graphene decorated with silver nanoparticles (Ag@graphene), and graphene decorated with nickel nanoparticles (Ni@graphene) were prepared, and the microstructures, morphologies, electrical conductivities, and EMI shielding efficiencies (EMI SEs) of the composites with different filler loadings (0.5, 1.0, 3.0, and 5.0 wt.%) were investigated. The PAni composite containing 5.0 wt.% Ag@graphene showed the best electrical conductivity of 20.32 S/cm and highest EMI SE of 29.33 dB. The uniform dispersion of fillers significantly enhanced the formation of conductive pathways in the PAni matrix, and the presence of metal nanoparticles on the graphene surface and between the graphene layers also increased the electrical conductivity. The results of this study show that absorption is the primary factor governing EMI shielding, which is attributed to the high permittivity of the composites. This study reveals that the Ag@graphene/PAni composite is promising for applications as an EMI shielding material.

This work demonstrates the fabrications and characterizations of polyaniline (PAni) composites containing single-walled carbon nanotubes (SWCNTs), graphite nanosheets (GNS), or hybrid fillers (SWCNTs/GNS). The characterization of microstructure, examination of fracture surface morphologies, and measurement of electric conductivity and electromagnetic interference shielding efficiency (EMI SE) were performed. It was found that both the electric conductivity and the EMI SE increase with filler loading, and the nanocomposites filled with 1.0 wt.% SWCNTs/GNS possessed the highest electric conductivity of 16.2 S/cm and total EMI SE of 27.0 dB. The experimental results also show that absorption is the primary mechanism of EMI SE for all of the loadings and fillers.

Objectives: There is no plasma marker for detecting nasopharyngeal cancer (NPC). We developed a bead-based affinity fractionated proteomic method to search potential plasma markers for NPC. Design and methods: Affinity purification of heparinized plasma with Cu-chelated beads and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis were used to screen potential NPC markers. We compiled MS protein profiles for 47 patients with NPC and compared them to profiles from 28 healthy controls. The spectra were statistically analyzed using flexAnalysis ™ and ClinProt ™ bioinformatics software. Diagnostic efficacy was evaluated by determination of the assay sensitivity and specificity of each marker. Results: Twelve mass fingerprint markers differing between cancer and control spectra were found. The sensitivities of these NPC markers are various ranging from 36% to 83%, and the specificities were all over 90%. Combine use of these markers significantly increases diagnostic efficacy. In which, the combined markers (2020 Da and 4635 Da) possess best discriminator with high sensitivity (94%) and specificity (93%). We further identify a C3 fragment, C3f, that may serve as a biomarker for NPC. Conclusion: The combined use of mass fingerprint markers in plasma proteome will enhance diagnostic efficacy for NPC. This method can be applied to search for novel plasma markers for cancers.

Five new sesquiterpenes, parahigginols A-D (1-4) and parahigginic acid (5), have been isolated from a Taiwanese marine sponge Parahigginsia sp. The structural assignments of the new compounds were based on their spectral data, including 1D and 2D NMR. Biological studies revealed that compounds 2-5 exhibited cytotoxicity against murine P-388 and human KB16, A549, and HT-29 tumor cells.

Two new β-carboline alkaloids, xestomanzamine A ( 1) and xestomanzamine B ( 2), and a new manzamine-type alkaloid, manzamine X ( 3), were isolated as cytotoxic constituents from an Okinawan marine sponge of Xestospongia sp. Another new manzamine-type alkaloid, manzamine Y( 4), was isolated from an Okinawan marine sponge of Haliclona sp. The structures of these alkaloids were elucidated on the bases of 2D-NMR and X-ray analyses.

We report a facile method of preparing few-layer graphene nanosheets (FLGs), which can be soluble in ethanol. Atomic force microscopy and high-resolution transmission electron microscopy studies reveal that FLGs have average thicknesses in the range of 2.6‐2.8 nm, corresponding to 8‐9 layers. A graphene/nafion composite film has a sheet resistance of 9.70 k�/ sq at the transmittance of 74.5% (at 550 nm) while the nafion film on polyethylene terephthalate has a sheet resistance of 128 k�/ sq at transmittance of 90.0%. For the cycling/bending test, almost no change in resistance was exhibited when the film was bent at an angle up to 140 ◦ , and no obvious deviation in resistance could be found after 100 bending cycles was applied. In addition, an FLGs-poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) composite layer was demonstrated as the effective hole transporting layer to improve the hole transporting ability in an organic photovoltaic device, with which the power conversion efficiency was enhanced from 3.10% to 3.70%. The results demonstrated the promising applications of FLGs on graphene-based electronics, such as transparent electrode and flexible conducting film. S Online supplementary data available from stacks.iop.org/Nano/22/295606/mmedia (Some figures in this article are in colour only in the electronic version)

Three new 11(15-->1)-abeo-taxanes, taxumairols U-W (1-3), have been isolated from extracts of the stem bark of Formosan Taxus mairei. The structures of 1-3 were identified as 5alpha,7beta,9alpha,13alpha,20-pentaacetoxy-2alpha,10beta,15-trihydroxy-11(15-->1)-abeo-taxene, 5alpha,7beta,9alpha,20-tetraacetoxy-2alpha,10beta,13alpha,15-tetrahydroxy-11(15-->1)-abeo-taxene, and 2alpha,4alpha,7beta,10beta-tetraacetoxy-5beta,20-epoxy-9alpha,13alpha,15-trihydroxy-11(15-->1)-abeo-taxene, respectively, on the basis of 2D NMR techniques including COSY, HSQC, HMBC, and NOESY experiments as well as chemical reactions of compounds 1-3 to give 4 (5alpha,7beta,9alpha,10beta,13alpha,20-hexaacetoxy-2alpha,15-dihydroxy-11(15-->1)-abeo-taxene) and 5 (4alpha,7beta,10beta-triacetoxy-9alpha,13alpha-dibenzoxy-5beta,20-epoxy-2alpha,15-dihydroxy-11(15-->1)-abeo-taxene), which are also novel taxane derivatives. Taxumairols U (1) and V (2) exhibited significant cytotoxicities against human hepatoma tumor cells, while taxumairol W (3) was inactive.

The NS5A protein of the hepatitis C virus (HCV) is an integral component of the viral replicase. It also modulates cellular signaling and perturbs host interferon responses. The multifunctional characteristics of NS5A are mostly attributed to its ability to interact with various cellular proteins. This study aimed to identify the novel cellular factors that interact with NS5A and decipher the significance of this interaction in viral replication. The NS5A-interacting proteins were purified by the tandem affinity purification (TAP) procedure from cells expressing NS5A and identified by mass spectrometry. The chaperone protein Hsp72 was identified herein. In vivo protein-protein interaction was verified by co-immunoprecipitation and an in situ proximity ligation assay. In addition to NS5A, Hsp72 was also associated with other members of the replicase complex, NS3 and NS5B, suggesting that it might be directly involved in the HCV replication complex. Hsp72 plays a positive regulatory role in HCV RNA replication by increasing levels of the replicase complex, which was attributed either to the increased stability of the viral proteins in the replicase complex or to the enhanced translational activity of the internal ribosome entry site of HCV. The fact that the host chaperone protein Hsp72 is involved in HCV RNA replication may represent a therapeutic target for controlling virus production.

Background: There is no plasma marker for detecting oral cancer, one of the most frequent cancers worldwide. We developed a bead-based affinity-fractionated proteomic method to discover a novel plasma marker for oral cancer.Methods: Affinity purification of heparinized plasma with magnetic beads and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis were used to screen potential oral cancer markers. We compiled MS protein profiles for 57 patients with oral cancer and compared them with profiles from 29 healthy controls. The spectra were analyzed statistically using flexAnalysis™ and ClinProt™ bioinformatic software. In each MS analysis, the peak intensities of interest were normalized with an internal standard (adrenocorticotropic hormone 18–39). For identification, affinity bead–purified plasma protein was subjected to MALDI TOF/TOF analysis followed by Mascot identification of the peptide sequences and a search of the National Center for Biotechnology Information protein database.Results: To optimize MALDI-TOF analysis based on the best discriminator of the cancer and control spectra, copper-chelated beads were used for plasma protein profiling. The within- and between-run CVs for assays were Conclusion: The high specificity and sensitivity of the fibrinogen α-chain fragment suggest that it may be a clinical useful tumor marker.

Aragusteroketals A (1) and C (2), two new marine steroids having dimethylketal structure, were isolated from an Okinawan marine sponge of Xestospongia sp. The chemical structures of 1 and 2 were determined on the basis of spectroscopic analysis and chemical evidence. Compounds 1 and 2 showed potent cytotoxic activity with the same IC50 value of 4 ng/ml against KB cells.

The taxoid chinentaxunine has been isolated from the seeds of Chinese yew Taxus chinensis, and its structure determined on the basis of spectral and chemical methods. In addition, the known taxol C, paclitaxel, 10-deacetyl taxol A, 10-deacetyl-7-epitaxol, 10-deacetyl-10-oxo-7-epi-taxol, taxinine M, taxchinin A, 10-deacetyl taxinine B and taxuspine X were also isolated and identified from this source.

In addition to taxol A (1), 10-deacetyltaxol A (2), 10-deacetyl-7-epi-taxol A (3), 10-deacetylbaccatin III (5), taxuspine Z, taxezopidine G, 5 alpha-cinnamoyloxy-9 alpha,10 beta,13 alpha-triacetoxytaxa-4(20)11-diene, taxinine J, and taxinine M, a new bicyclic taxoid named taxumairol M (4), has been isolated from the seeds of Taxus mairei. The structure of 4 was determined on the basis of spectral analysis.

Two new taxoids, 2alpha-acetoxy-2',7-dideacetoxyaustrospicatine (1) and decinnamoyltaxinine E (2), have been isolated from the extracts of the seeds of the Chinese yew Taxus chinensis (Pilg.) Rehd. in addition to taxuspine Z (3), taxin B (4), taxezopidine G (5), 7, 2'-bisdeacetoxyaustropicatine (6), 5alpha-cinnamoyl-9alpha,10beta, 13alpha-triacetoxytaxa-4(20),11-diene (7), taxachitriene A, 20-deacetyltaxachitriene A, 13-O-acetylbrevifoliol, taxinines A and J, and taxacin. The structures of these compounds were elucidated on the basis of spectral analysis and chemical derivatizations.