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Spoof surface plasmon (SSP) meta-couplers that efficiently integrate other diversified functionalities into a single ultrathin device are highly desirable in the modern microwave and terahertz fields. However, the diversified functionalities, to the best of our knowledge, have not been applied to circular polarization meta-couplers because of the spin coupling between the orthogonal incident waves. In this paper, we propose and numerically demonstrate a terahertz spin-decoupled bifunctional meta-coupler for SSP excitation and beam steering. The designed meta-coupler is composed of a coupling metasurface and a propagating metasurface. The former aims at realizing anomalous reflection or converting the incident waves into SSP under the illumination of the left or right circular polarization waves, respectively, and the latter are used to guide out the excited SSP. The respective converting efficiency can reach 82% and 70% at 0.3THz for the right and left circular polarization incident waves. Besides, by appropriately adjusting the reflection phase distribution, many other diversified functionalities can also be integrated into the meta-coupler. Our study may open up new routes for polarization-related SSP couplers, detectors, and other practical terahertz devices.

In this paper, a linear polarization-controlled (LPC) spoof surface plasmon polaritons (SSPPs) meta-coupler with high efficiency and directionality is proposed and demonstrated in the terahertz (THz) regime. By changing the polarization (TE or TM polarization) of the incident electromagnetic (EM) waves, the corresponding SSPPs can be directionally excited towards opposite directions. The meta-coupler is composed of a coupling metasurface (CM) and two propagating metasurfaces (PMs) on both sides of CM. Under the illumination of specified polarization Gaussian beam, the unit cells of the CMs have the similar electric field distribution with that of PMs, which can realize a smooth and efficient transition between the surface waves and SSPPs. The respective excitation efficiency of the TE and TM polarization can reach up to 87% and 90% at the frequency of 0.355 THz. Besides, the PMs are designed to support the propagation of the specified TE or TM mode SSPPs. This guarantees a relatively high directionality (> 24 dB) in the frequency range of 0.325-0.375 THz. Our study may open up new routes for polarization-related antennas, detectors and other practical THz devices.

An efficiency way to enhance the excitation efficiency of spoof surface plasmons (SSP) is proposed and demonstrated in this work. Under the rigorous theoretical deduction, it is found that almost perfect transmission through transmissive metallic grating can be realized when the Fabry–Perot (FP) resonance occurs. A significantly high conversion efficiency 92% between incident waves and surface waves is achieved by transmissive metallic gratings under the situation of FP resonances. Further studies show that tuning the direction of excited SSP and compressing the thickness of coupler are also realized by tilting the incident waves and filling high-index dielectric, respectively. This work may provide technical supports for plasmonic applications.

Background With the rapid development of the high throughput detection techniques, tumor-related Omics data has become an important source for studying the mechanism of tumor progression including breast cancer, one of the major malignancies worldwide. A previous study has shown that the G2 and S phase-expressed-1 (GTSE1) can act as an oncogene in several human cancers. However, its functional roles in breast cancer remain elusive. Method In this study, we analyzed breast cancer data downloaded from The Cancer Genome Atlas (TCGA) databases and other online database including the Oncomine, bc-GenExMiner and PROGgeneV2 database to identify the molecules contributing to the progression of breast cancer. The GTSE1 expression levels were investigated using qRT-PCR, immunoblotting and IHC. The biological function of GTSE1 in the growth, migration and invasion of breast cancer was examined in MDA-MB-231, MDA-MB-468 and MCF7 cell lines. The in vitro cell proliferative, migratory and invasive abilities were evaluated by MTS, colony formation and transwell assay, respectively. The role of GTSE1 in the growth and metastasis of breast cancer were revealed by in vivo investigation using BALB/c nude mice. Results We showed that the expression level of GTSE1 was upregulated in breast cancer specimens and cell lines, especially in triple negative breast cancer (TNBC) and p53 mutated breast cancer cell lines. Importantly, high GTSE1 expression was positively correlated with histological grade and poor survival. We demonstrated that GTSE1 could promote breast cancer cell growth by activating the AKT pathway and enhance metastasis by regulating the Epithelial-Mesenchymal transition (EMT) pathway. Furthermore, it could cause multidrug resistance in breast cancer cells. Interestingly, we found that GTSE1 could regulate the p53 function to alter the cell cycle distribution dependent on the mutation state of p53. Conclusion Our results reveal that GTSE1 played a key role in the progression of breast cancer, indicating that GTSE1 could serve as a novel biomarker to aid in the assessment of the prognosis of breast cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1157-4) contains supplementary material, which is available to authorized users.

Imaging below the diffraction limit is always a public interest because of the restricted resolution of conventional imaging systems. To beat the limit, evanescent harmonics decaying in space must participate in the imaging process. Here, we introduce the method of spatial spectrum sampling, a novel far-field superresolution imaging method for microwave and terahertz regime. Strong dispersion and momentum conservation allow the spoof surface plasmon polaritons (SSP) structure to become a sensitive probe for spatial harmonics. This enables that the spatial information of the targets including both propagating and evanescent components, can be extracted by tuning and recording SSP in the far field. Then, the subwavelength resolution is constructed by the inversed Fourier transform of the sampled spatial spectrum. Using the modified subwavelength metallic grating as the spoof plasmonic structure, a far-field resolution of 0.17 wavelength is numerically and experimentally verified, and two-dimensional imaging ability is also fully discussed. The imaging ability and flexibility can be further optimizing the SSP structures. We are confident that our working mechanism will have great potentials in the superresolution imaging applications in the microwave and terahertz frequency range, Comment: 7 figures,48 reference,24 pages

Terahertz imaging has recently attracted great attention owing to the abilities of high penetration and low ionizing damages. However, the low resolution and low contrast resulting from the diffraction limit and unwanted background illumination significantly hinder the extensive usage. In this Letter, we propose and numerically demonstrate a terahertz subwavelength imaging method capable of extracting only the edges and fine features of the targets. The underlying physics is the efficient transmission of the scattering evanescent waves related to key geometric information while blocking the propagating components. By exploiting the structurally induced plasmons in a bounded metallic waveguide, the transmission channel for evanescent waves is realized by hyperbolic metamaterials through periodically stacking dielectric layers. On this basis, high-contrast edge detection with a resolution up to 0.1 λ is demonstrated at terahertz wavelengths. The proposed terahertz imaging method may find important applications in non-destructive testing, weak scattering object detection, and high-contrast microscopy.

Terahertz wireless communication has emerged as a fast-growing research area. Routing, which is designed to control the propagation of terahertz wave, is of great importance for building the terahertz all-optical communication network. Metamaterials provide a good method for manipulating the terahertz wave, which can be used to realize the wave router. To steer the input wave in different directions, for example negative refraction angle, some structures have been proposed, such as stacked structures and nanowire arrays. However, in these metamaterials, the incident wave is generally limited to transverse magnetic polarization. Here, a new terahertz routing method for transverse electric wave is put forward with using graphene magnetic metamaterials. Theoretical analysis is performed to show that this metamaterial has negative components not only in effective permittivity tensor but also in effective permeability tensor. Routing is realized by topological transitions between different dispersion regimes in this metamaterial. Our finding provides a new candidate for signal routing of terahertz wave.

Based on phased-gradient metasurfaces, an efficient method is developed to convert waveguide modes in a parallel-plate waveguide. An effective wavevector is imparted to the incident mode at each interaction with matesurfaces, resulting in the mode conversion. The numerical simulation indicates that the efficiency and purity of TE1-to- TE2 conversion can significantly reach up to 99.98% and 99.99% at 9GHz. The conversion between TM3 and TM4 is also achieved, which gives a fair verification of the polarization insensitivity. This work can provide technical guidance for compact modes control.

A plasmonic band-stop reflective filter based on periodic graphene patch is proposed and numerically investigated using the FDTD method. The proposed filter has a simple three-layer structure, which is composed of graphene, dielectric layer, and metal. Simulated results exhibit that significant absorption peak can be achieved. The absorption spectra can be freely tuned in a broad frequency range by changing the chemical potential. Compared with traditional active filters, this filter does not require mechanical motion, which is suitable for many high-performance situations where stability is a primary concern. Besides, the structure of the filter is ultrathin and reduces the requirements of size and weight. The filter is valid for both transverse electric and transverse magnetic polarization. The filter can be used as a high-sensitivity sensor.

An ultra-broadband subwavelength resolution probe that consists of a Teflon rod and six metallic strips is developed for the near-field imaging system. The slit between two metallic strips maintains quasi-TEM modes, avoiding the problem of low coupling efficiency caused by the cutoff effect. The numerical calculations visualize the process of energy compression into a 0.047λ diameter spot with great field enhancement at the taper apex, and the probe holds subwavelength focusing behavior from 10 GHz to 0.25 THz. Although limited by the fabrication, the resolution of 0.16 and 0.25λ are still experimentally demonstrated at 14 GHz and 0.1 THz. The properties of easy fabrication and no cutoff frequency would lower the threshold of a high-resolution near-field imaging system.

The controversy of (p53) in nasopharyngeal carcinoma persists, despite the fact that many studies have been conducted on its correlation with latent membrane protein 1 (LMP1), bcl-2, and prognosis. To better understand this postulated relationship, a meta-analysis was performed based on existing relevant studies. A total of 19 individual studies with a total of 1189 patients were included in the meta-analysis. Overall, the results revealed a significant association of p53-positive status with a poor 5-year survival of nasopharyngeal carcinoma (NPC) patients as the risk difference (RD) was -0.17 (95% CI, -0.31, -0.03; P=0.02, Pheterogeneity =0.01).The overall odds ratio (OR) for LMP1 in the p53 positive group vs. negative group revealed that a significantly elevated risk of positive LMP1 in the former was achieved (OR 5.52 95% CI, 2.66-11.46; P0.00001, Pheterogeneity =0.78). Similarly, a strong correlation between bcl-2 and p53 was found with an OR 6.85 (95% CI, 2.37-19.74; P=0.0004, Pheterogeneity =0.48). However, there did not appear to be any correlations with clinical parameters such as gender, tumor site, lymph node metastasis,pathological type and TNM stage. In conclusion, p53 expression is related to the survival of nasopharyngeal carcinoma. It can be considered as the auxiliary detection index in treatment and prognosis of nasopharyngeal carcinoma.

A gradient index (GRIN) lens is proposed and demonstrated for efficiently focusing incident waves in terahertz regime. This lens is composed of three layers of metamaterial based on annular slots, allowing a large variation of the effective refractive index in both two bands. Thus we manage to design a dual-band focusing lens which can focus the terahertz radiation to a spot size smaller than the wavelength.

The high-order operating modes in gyrotrons are always converted into Gaussian beam for transmission. However, the Gaussian beam radiated from the gyrotrons is frequently non-ideal, which may result in poor coupling to the fundamental HE 11 mode in corrugated waveguides and high attenuation in the transmission line. Therefore, a back-to-back corrugated horn structure is designed in this paper for Gaussian mode filtering This structure is capable of enhancing the coupling coefficient from 82% to nearly 98%. Besides, the high coupling coefficient maintains during a broadband frequency range of $\mathbf{200 GHz }\leq J \leq 240$ GHz.

We theoretical and simulated demonstrate frequency scanning can be an effective approach to realize terahertz far-field subwavelength imaging. The imaging device composed of metallic gratings and coupler has the ability of coupling evanescent wave and transforming them to corresponding propagating waves so that the subwavelength details will be conserved in the imaging process. By carrying out frequency scanning simulation and a simple data processing from 0.1 THz to 0.24 THz, the operating spatial spectrum is dramatically extended to 5k0 (k is the wavenumber of 0.24 THz) in the far-field, which is well verified our method. Better spatial spectrum range can be expected by decreasing period of grating and increasing scanning frequency points. We are confident this method will find useful applications in terahertz imaging area.

A terahertz polarization converter composed of graphene patch is demonstrated. It can convert circularly polarized wave to linearly polarized wave from 4.6THz to 5.6THz with a transmission intensity more than 40%. The effect of the geometry on the transmitted circularly polarized waves is investigated. This periodic structure is then used in double layer structure to realize a polarization converter with twice the bandwidth compared with the single layer design. This offers a further step in developing ultrathin terahertz polarization components.

Based on the mode expansion theory, a detailed derivation of light transmission properties through fanshaped metallic grating (FMG) is presented. We confirm that all harmonics have considerable transmission coefficients through FMG under limited theoretical assumptions. This means FMG have ability to transmit an image with subwavelength resolution from inner face to outer face. Subsequent simulated results indicate a far-field surperlens by FMG with a resolution better than λ/10 can be obtained. The simulated results are in good agreement with the results of theoretical derivation. Lastly, we demonstrate that clearer image can be reconstructed on the condition of Fabry-Perot resonance, where both the propagating and evanescent waves almost hold same transmission coefficients. This theory can be applied in designing far-field imaging, highly sensitive detector in biosensing, and research in light-matter interactions.

The tunable plasmon-induced transparency (PIT) metamaterial structures composed of periodically patterned graphene microholes and microribbons are presented and numerically investigated. The interaction between plasmonic modes that lead to the PIT effect is studied in detail by analyzing the field distributions. A coupled Lorentz oscillator model is used to explain the mechanism of the PIT effect. The transparency window of PIT structures can be dynamically tuned by varying the Fermi level of the graphene. The tunable graphene PIT device may have potential applications in designing optical switching devices, ultra-compact sensors and slow light devices in the THz region.

Nasopharyngeal carcinoma (NPC), which originates from the nasopharynx, is highly prevalent in Southern China and Southeast Asia, and more than 90% of all NPCs are non-keratinizing undifferentiated cells or poorly differentiated squamous cells. Cancer stem cells (CSCs) are capable of self-renewal and have differentiation potential. These properties form the basis of cancer initiation, development, and radiochemoresistance. However, the molecular mechanisms underlying NPC CSC maintenance remain poorly understood. Here, genomic expression profiling using our previously established monoclonal cellular and animal models revealed that interferon regulatory factor 6 (IRF6) was downregulated in highly metastatic NPC cells, cancer stem-like NPC cells and animal models. Functional assays revealed that elevated IRF6 expression suppressed cell proliferation, growth, CSCs properties and enhanced cell chemotherapeutic sensitivity. However, silencing IRF6 resulted in opposing effects. Moreover, we determined that as a tumor suppressor gene and transcription factor, IRF6 directly bound the upstream region of the ATP-binding cassette sub-family G member 2 (ABCG2) DNA element and suppressed target ABCG2 expression in NPC cells. Consistently, an inverse correlation was observed between the mRNA levels of IRF6 and ABCG2 in clinical NPC samples. With these results, we provide the first evidence that IRF6 directly targets the ABCG2 gene and selectively kills CSCs in NPC and that IRF6 may be a valuable tool for developing new CSC-targeted treatment strategies for undifferentiated NPC patients.

The resolution of conventional terahertz (THz) imaging techniques is limited to about half wavelength, which is not fine enough for applications of biomedical sensing and nondestructive testing. To improve the resolution, a new superlens, constructed by a monolayer graphene sheet combining with a grating voltage gate, are proposed in this paper to achieve deep super-resolution imaging in the THz frequency range. The main idea is based on the Fabry-Perot resonance of graphene edge plasmon waves. By shaping the voltage gate into a radial pattern, magnified images of subwavelength targets can be obtained. With this approach, the finest resolution can achieve up to λ/150. Besides, the superlens can be conveniently tuned to work in a large frequency band ranging from 4.3 THz to 9 THz. The proposal could find potential applications in THz near-field imaging systems.

Emerging evidence confirms that cancer stem cells (CSCs) are responsible for the chemoradioresistance of malignancies. EBV-encoded latent membrane protein 1 (LMP1) is associated with tumor relapse and poor prognosis of nasopharyngeal carcinoma (NPC). However, whether LMP1 induces the development of CSCs and the mechanism by which this rare cell subpopulation leads to radioresistance in NPC remain unclear. In the present study, LMP1-transformed NPC cells showed significant radioresistance compared to the empty vector control. We found that LMP1 up-regulated the expression of several stemness-related genes, increased the cell number of side population (SP) by flow cytometry analysis, enhanced the self-renewal properties of the cells in a spherical culture and enhanced the in vivo tumor initiation ability. We also found that LMP1 positively regulated the expression of the CSC marker CD44. The CD44(+/High) subpopulation of the LMP1-transformed NPC cells displayed more significant CSC characteristics than the CD44(-/Low) subpopulation of the LMP1-transformed NPC cells; these characteristics included the upregulation of stemness-related genes, in vitro self-renewal and in vivo tumor initiation ability. Importantly, the CD44(+/High) subpopulation displayed more radioresistance than the CD44(-/Low) subpopulation. Our results also demonstrated that phosphorylation of the DNA damage response (DDR) proteins, ATM, Chk1, Chk2 and p53, was inactivated in the LMP1-induced CD44(+/High) cells in response to DNA damage, and this was accompanied by a downregulation of the p53-targeted proapoptotic genes, which suggested that the inactivation of the p53-mediated apoptosis pathway was responsible for the radioresistance in the CD44(+/High) cells. Taken together, we found that LMP1 induced an increase in CSC-like CD44(+/High) cells, and we determined the molecular mechanism underlying the radioresistance of the LMP1-activated CSCs, highlighting the need of CSC-targeted radiotherapy in EBV-positive NPC.

A beam-scanning terahertz (THz) radiation mechanism in a free-electron-driven grating system is proposed for THz applications. By loading a period-asynchronous rod array above the grating, the spoof surface plasmon (SSP) originally excited by the electron changes its radiation characteristics owing to the rod-induced Brillouin zone folding effect. The rod array functions as an antenna and converts the SSP into a spatial coherent THz radiation. The radiation frequency and direction can be precisely controlled by the electron energy. The field intensity of the radiation is increased approximately 20 times compared with that of the conventional Smith-Purcell radiation in the same frequency range. In addition, a microwave-band scaling prototype is fabricated and the frequency-controlled radiation is measured. Excellent agreement between the experimental and simulated results is obtained. This study paves the way for the development of on-chip THz sources for advanced communication and detection applications.

A new scenario to realize superfocusing of terahertz waves based on a gradient index (GRIN) metasurface is proposed. To design the GRIN material, a robust algorithm is presented and numerically demonstrated to retrieve the constitutive effective parameters (permittivity and permeability) of the metasurface from the measurement of S parameters. In addition, a new kind of unit cell with a simple structure is designed to verify the theory of effective parameters. By computing the effective refractive index of the unit cell using the algorithm, we design a plate with a thickness of approximately 0.11λ0 (free-space wavelength) at 0.967 THz to superfocus terahertz waves in one dimension. We also revise the theory of superfocusing to make full use of the coupling effect among the cells in the plate and are able to demonstrate it. Comprehensive simulations of focusing are provided, and the full width at half-maximum beam width reaches up to 0.167λ0 at a distance of 0.2λ0. The focusing depth can be further enhanced by decreasing the cell size of the metasurface. This work is beneficial for metasurface design, super-resolution imaging, and other applications in the near field.

In this paper, we propose and numerically demonstrate a new way to realize superfocusing of terahertz waves via the spoof surface plasmons (SSP). With the assist of a modified subwavelength metallic grating, a near-field rapid oscillation can be formed, originating from the Fabry-Perot resonances due to the reflection of SSP waves at terminations. We show that the field pattern of oscillation on textured metallic surface can be engineered by adjusting groove width and grating number. This produces a desired modulation of phase and amplitude for the radiationless electromagnetic interference (REI) focusing. The effective focusing depth through the corrugated metal is evaluated by the full-width-half-maximum (FWHM) beamwidth. At the situation of third-order Fabry-Perot resonance, the FWMH reaches up to 0.069λ at a distance of 0.1λ, improving the beamwidth by more than 540% compared with a single slit. The FWHM is optimized to 0.06λ as the order of Fabry-Perot resonance becomes seven, leading to the superfocusing metric of 1.67. On the basis of this, we further show the focusing ability can be held on the ultra-thin metallic grating. Two-dimensional subwavelength focusing behavior is also numerically verified. Our study may extend the working distance of sensing and super-resolution imaging devices at terahertz frequency.

A perfect lens made from negative refraction (NR) materials is utilized to overcome the diffraction limit. However, these NR lenses are realized by metamaterials, which suffer from high losses, and the volume is bulky. In this Letter, we propose a terahertz NR lens by using a four-wave mixing (FWM) process in graphene. NR is demonstrated because of the phase matching along the surface of graphene. Evanescent waves that store high spatial frequency information can be converted into propagating waves in the nonlinear NR process. An image with subwavelength resolution is reconstructed at the FWM wavelength. Theoretical analysis and numerical simulations are performed to demonstrate the capability of such imaging. The lens has a subwavelength resolution of around λ/5. The lens needs low field intensity due to the strong nonlinear response of graphene in the terahertz frequency. This Letter may have applications in terahertz microscopy.

Objective: To construct a fine map of the loss of chromosome Ipter-p36.11 region in nasopharyngeal carcinoma (NPC) using PCR-LOH technique. Methods: DNA extracted from separated cancerous cells and their mated noncancerous lymphocytes from 47 cases of NPC biopsies were analyzed by means of PCR-LOH to detect 20 loci spanning chromosome Ipter-p36.11 region in NPC. Results: In 47 NPC cases, 37 (82.2%) cases showed at least one loci LOH. The highest frequency of less of heterozygosity (LOH) at all 20 loci was found at loci DIS234 (50. 0%) on 1p36.13 and loci DIS2644 (37.5%) on 1p36.22. There was a statistically significant difference between DIS234 LOH frequency (60%, 9/15) in early stage and that (50. 0%, 8/16) in advanced stage (P>0.05). Of all 20 STSs (sequence tqgged-site, STS), DIS243 (37.5%) and DIS199 (30.2%) showed the highest frequency of MI (microsatellite instability) on 1p36.33 and 1p36.21, respectively. In addition, several cases showed a contiguous stretch of allelic loss in a different level. Conclusion: Two minimal deletion regions (MDR) on the short arm of chromosome 1 were seated at 1p36.13 (DIS234, 2.0 cm) and 1p36.22 (DIS436-DIS2644, 6.3 cm) respectively, indicating that one or more candidate tumor suppressor gene (TSG) in the two regions may be involved in NPC pathogenesis in an early clinical stage.

In this paper, waveguide mode conversions in a parallel plate waveguide, rectangular waveguide, and circular waveguide are all demonstrated at terahertz frequencies. Different from the traditional ways to realize mode conversions, an ultracompact design method based on the inner-embedded subwavelength metallic gratings is provided. The principle of the method relies on modulating the phase velocities of spoof surface plasmon polaritons (SSPPs) supported on the gratings to generate π phase difference. Owing to the gradient matching the phase velocities of the waveguide modes and SSPPs, the efficiencies of the mode conversions are considerable. The output mode purities of the both demonstrations are very good. Besides, waveguide bend is also achieved by this method. The work in this paper hopes to establish a universal technique for compact waveguide mode control, especially in the terahertz frequency range.

Approximately 30% of patients with Epstein-Barr virus (EBV)-positive advanced nasopharyngeal carcinoma (NPC) display chemoresistance to cisplatin-based regimens, but the underlying mechanisms are unclear. The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), a functional homologue of the tumor necrosis factor receptor family, contributes substantially to the oncogenic potential of EBV through the activation of multiple signaling pathways, and it is closely associated with a poorer prognosis for NPC. Recent studies show that EBV infection can induce the expression of many cellular miRNAs, including microRNA-21, a biomarker for chemoresistance. However, neither a link between LMP1 expression and miR-21 upregulation nor their cross talk in affecting chemoresistance to cisplatin have been reported. Here, we observed that stable LMP1-transformed NPC cells were less sensitive to cisplatin treatment based on their proliferation, colony formation, the IC50 value of cisplatin and the apoptosis index. Higher levels of miR-21 were found in EBV-carrying and LMP1-positive cell lines, suggesting that LMP1 may be linked to miR-21 upregulation. These data were confirmed by our results that exogenous LMP1 increased miR-21 in both transiently and stably LMP1-transfected cells, and the knock down of miR-21 substantially reversed the resistance of the NPC cells to cisplatin treatment. Moreover, the proapoptotic factors programmed cell death 4 (PDCD4) and Fas ligand (Fas-L), which were negatively regulated by miR-21, were found to play an important role in the program of LMP1-dependent cisplatin resistance. Finally, we demonstrated that LMP1 induced miR-21 expression primarily by modulating the PI3K/AKT/FOXO3a signaling pathway. Taken together, we revealed for the first time that viral LMP1 triggers the PI3K/Akt/FOXO3a pathway to induce human miR-21 expression, which subsequently decreases the expression of PDCD4 and Fas-L, and results in chemoresistance in NPC cells.

Objective: To study the relationship between p53 protein, proliferating cell nuclear antigen (PCNA) expression and benign or malignant gestational trophoblastic disease (MGTD). Methods: The histotomic sections of 48 patients with gestational trophoblastic disease and 24 patients of normal chorionic villi were stained using immunohistochemistry. The monoclonal antibodies were used to determine p53 protein and PCNA. Results: The frequency of p53 and PCNA positive expression were significantly different among the chorionic villi of normal pregnancy, hydratidiform mole (HM) and MGTD. But neither p53 nor PCNA has any relation with the clinical staging or metastasis of MGTD. Conclusion: Both P53 and PCNA are valuable in diagnosis of human gestational trophoblastic disease.

Serglycin is a proteoglycan that was first found to be secreted by hematopoietic cells. As an extracellular matrix (ECM) component, serglycin promotes nasopharyngeal carcinoma (NPC) metastasis and serves as an independent, unfavorable NPC prognostic indicator. The detailed mechanism underlying the roles of serglycin in cancer progression remains to be clarified. Here, we report that serglycin knockdown in NPC cells inhibited cell sphere formation and tumor seeding abilities. Serglycin downregulation enhanced high-metastasis NPC cell sensitivity to chemotherapy. It has been reported that serglycin is a novel ligand for the stem cell marker CD44. Interestingly, we found a positive correlation between serglycin expression and CD44 in nasopharyngeal tissues and NPC cell lines. Further study revealed that CD44 was an ERK-dependent downstream effector of serglycin signaling, and serglycin activated the MAPK/β-catenin axis to induce CD44 receptor expression in a positive feedback loop. Taken together, our novel findings suggest that ECM serglycin upregulated CD44 receptor expression to maintain NPC stemness by interacting with CD44 and activating the MAPK/β-catenin pathway, resulting in NPC cell chemoresistance. These findings suggest that the intervention of serglycin/CD44 axis and downstream signaling pathway is a rational strategy for targeting NPC cancer stem cell therapy.

Our previous study reported that Epstein-Barr virus(EBV)-encoded latent membrane protein 1 (LMP1) could induce development of CD44+/High stem-like cells in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms that underlie modulation of cancer stem cells (CSCs) in NPC remain unclear. Here, we show that LMP1 induced CSC-like properties through promotion of the expression of epithelial-mesenchymal transition (EMT)-like cellular markers and through alterations in differentiation markers. Furthermore, LMP1 activated and triggered PI3K/AKT pathway, which subsequently stimulated expression of CSC markers, development of side population (SP) and tumor sphere formation. This suggests that PI3K/AKT pathway plays an important role in the induction and maintenance of CSC properties in NPC. Similarly, PI3K/AKT pathway was also activated by phosphorylase in LMP1-induced CD44+/High cells. In addition, LMP1 greatly increased expression of miR-21 and down-regulated expression of the miR-21 target, PTEN. Overexpression of miR-21 by transfection of miR-21 mimics into LMP1-transformed cells led to phosphorylase-mediated activation of the PI3K/AKT pathway and induction of CSCs. On the contrary, phosphorylation of the PI3K/AKT pathway and the expression of CSC were reversed by a miR-21 inhibitor. The specific inhibitor (Ly294002) of PI3K/AKT pathway significantly decreased expression of miR-21 and CSC markers and up-regulated the expression of PTEN, which indicates that miR-21 and PTEN are the downstream effectors of PI3K/AKT and that expression of these two effectors are related to development of NPC CSCs. Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and play a key role in LMP1-induced CSCs in NPC. Citation Format: Chang-Fu Yang, Guang-Da Yang, Tie-Jun Huang, Jia-Ling Huang, Chao-Nan Qian, Bi-Jun Huang. EB-virus latent membrane protein 1 potentiates the stemness of nasopharyngealcarcinoma via preferential activation of PI3K/AKT pathway by a positive feedback loop. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3360.

To evaluate the therapeutic efficacy and safety of iodine-131 therapy for large goiter complicated by hyperthyroidism.After the diagnosis of large goiter complicated by hyperthyroidism was established, the weight of the patient's thyroid gland was determined, and the doses of iodine-131 calculated according to the formula currently available. After a single dose of oral iodine-131 capsule, the patients were observed for the therapeutic efficacy and side effects. Some patients were given the second or even the third dose of iodine-131.All of the 38 patients were cured by 1 to 3 single doses of iodine-131 therapy, of whom 23 (60.5%) needed only a single dose for the cure, 13 (34.2%) required the second dose, and 2 (5.3%) necessitate a third dose. Hypothyroidism occurred in 4 cases (10.5%), and none of the patients developed hyperthyroidism crisis and dyspnea.Iodine-131 therapy for serious goiter with hyperthyroidism is safe and effective, which can be used as a routine therapy for this condition.

Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to investigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological parameters and prognosis.Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene amplification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prognosis were analyzed statistically.HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patients with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated significantly with tumor size and postoperative survival time of HCC patients (P0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P=0.257), but not related to sex, age, AFP level, HBV infection, histopathological grading and clinical staging of HCC patients (P0.05). The HER-2 oncogene copy was examined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 patients with aneuploidy (52.4%). No significant relations were observed between the HER-2 oncogene copy, patient sex, tumor size, histopathological grading, clinical staging, postoperative relapse and survival time (P0.05); but the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P0.05).There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromosome 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and progression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the recurrence and poor survival in patients with large HCC.

Background Epstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies. EBV expresses different genes that are associated with three latency types. To date, as many as 44 EBV-encoded miRNA species have been found, but their comprehensive profiles in the three types of latent infection that are associated with various types of tumors are not well documented. Methods In the present study, we utilized poly (A)-tailed quantitative real-time RT-PCR in combination with microarray analysis to measure the relative abundances of viral miRNA species in a subset of representative lymphoid and epithelial tumor cells with various EBV latency types. Results Our findings showed that the miR-BHRF1 and miR-BART families were expressed differentially in a tissue- and latency type-dependent manner. Specifically, in nasopharyngeal carcinoma (NPC) tissues and the EBV-positive cell line C666-1, the miR-BART family accounted for more than 10% of all detected miRNAs, suggesting that these miRNAs have important roles in maintaining latent EBV infections and in driving NPC tumorigenesis. In addition, EBV miRNA-based clustering analysis clearly distinguished between the three distinct EBV latency types, and our results suggested that a switch from type I to type III latency might occur in the Daudi BL cell line. Conclusions Our data provide a comprehensive profiling of the EBV miRNA transcriptome that is associated with specific tumor cells in the three types of latent EBV infection states. EBV miRNA species represent a cluster of non-encoding latency biomarkers that are differentially expressed in tumor cells and may help to distinguish between the different latency types.