Expression of cytoskeleton-associated protein 4 is associated with poor prognosis and metastasis in nasopharyngeal carcinoma.

Cytoskeleton-associated protein 4 (CKAP4) acts as a key transmembrane protein that connects the endoplasmic reticulum (ER) to microtubule dynamics. Researchers have not examined the roles of CKAP4 in nasopharyngeal carcinoma (NPC). The study aimed at evaluating the prognostic value and metastasis-regulating effect of CKAP4 in NPC. CKAP4 protein could be observed in 86.36% of 557 NPC specimens but not in normal nasopharyngeal epithelial tissue. According to immunoblot assays, NPC cell lines presented high CKAP4 expression relative to NP69 immortalized nasopharyngeal epithelial cells. Moreover, CKAP4 was highly expressed at the NPC tumor front and in matched liver, lung, and lymph node metastasis samples. Furthermore, high CKAP4 expression reported poor overall survival (OS) and presented a positive relevance to tumor (T) classification, recurrence, and metastasis. According to multivariate analysis, CKAP4 could independently and negatively predict patients' prognosis. Stable knockdown of CKAP4 expression in NPC cells inhibited cell migration, invasion and metastasis in vitro and in vivo. Moreover, CKAP4 promoted epithelial-mesenchymal transition (EMT) in NPC cells. CKAP4 knockdown was followed by the downregulation of the interstitial marker vimentin, and upregulation of the epithelial marker E-cadherin. In NPC tissues, high CKAP4 expression exhibited a positive relevance to vimentin expression and a negative relevance to E-cadherin expression. In conclusion, CKAP4 is an independent predictor of NPC, and CKAP4 might contribute NPC progression and metastasis, which may be involved in EMT with vimentin and E-cadherin.

Expression of Programmed Death Ligand-2 is associated with Prognosis in Nasopharyngeal Carcinoma Microenviroment.

Background: Although immune checkpoint inhibitors have opened a new mode of treatment for solid tumors, their efficacy in nasopharyngeal carcinoma (NPC) needs to be further investigated. Inhibitors of the PD-1/PD-L1 immune checkpoint are one of the hot topics in tumor immunotherapy. Programmed death ligand-2 (PD-L2) is a less studied ligand of PD-1 and has not yet been fully explored, especially in NPC. Understanding the clinical significance of PD-L2 expression, together with immune cell infiltration, might provide clues for biomarker screening in NPC immunotherapy. This study aimed to evaluate the role of PD-L2 as a prognostic factor for NPC patients as well as its role in immune regulation. Methods: Immunohistochemistry (IHC) was performed on a tissue microarray including 557 NPC specimens using PD-L2 antibody. The immune cell markers CD4, FOXP3 and CD68 were also stained and quantified. The expression of PD-L2 exhibited different spatial patterns among NPC tumor and stromal tissues. Results: A total of 90.8% of the cases showed membranous PD-L2 expression in tumors, and 80.8% showed membranous PD-L2 expression in stromal tissue. High stromal expression of PD-L2 predicted favorable overall and disease-free survival of NPC patients and was negatively correlated with tumor size, recurrence or metastasis and clinical stage. In contrast, high tumor abundance of PD-L2 correlated with poor disease-free survival, but had no obvious correlation with clinicopathological parameters. Multivariate analysis indicated that stromal PD-L2 was an independent and favorable prognostic factor. Furthermore, we found a positive correlation between stromal PD-L2 expression and the infiltration of CD68+ macrophages and CD4+Foxp3+ Treg cells in NPC stromal tissues (Pearson correlation=0.181 and 0.098, respectively). Conclusions: Our results suggest that different PD-L2 expression patterns have distinct predictive values. PD-L2 expressed on stromal cells might play a role in the regulation of NPC progression, and involve in immune activation in the tissue microenvironment and have an independent good prognosis for NPC patients.

Design and analysis of transmission enhanced multi-segment grating in MZI configuration for slow light applications.

This paper proposes to use slow light effects near the Brillouin zone band edge of one-dimensional gratings for reducing the size of integrated electro-optic (EO) modulators. The gratings are built within the arms of a Mach-Zehnder Interferometer (MZI) for intensity modulation. To overcome the inherent high reflection and low extinction ratio, we introduce various multi-segment grating designs. We use coupled-mode theory and derive transfer matrices to analyze the spectral transmittance and phase delay of each arm of the interferometer. Calculations show that a size-reduction of a factor of 2 or more can be achieved at λ=1.574 µm with an insertion loss of 0.17 dB and an amplitude modulation extinction ratio of 18.84dB. The simulated structure is based on a Si slab-waveguide 0.2 µm thick with 30 nm deep grating groves on SiO(2)> substrate.

Design of a short electro-optic modulator based on SiGe HBT structure.

A SiGe electro-optic modulator operating at wavelength of 1.55 microm is proposed. The "ON" state voltage is set at 1.4V. The arm of the MZI waveguide required to generate a pi phase shift is 73.6 microm, and the total attenuation loss is 3.95 dB. The rise and fall delay time is 70.9 ps and 24.5 ps, respectively.

Design of high efficiency multi-GHz SiGe HBT electro-optic modulator.

We design and theoretically analyze a heterojunction bipolar transistor (HBT) electro-optic (EO) modulator with a composition graded SiGe base. The waveguide has a large cross-section of 1 microm for ease of fiber alignment. At a base-emitter bias of V BE = 2.5 V, a pi-phase shift requires 74.5 microm interaction length for TM polarization at lambda = 1.55 microm. The total optical attenuation is 3.9 dB to achieve a pi-phase shift in this condition. This device is expected to operate at a switching speed of 2.4 GHz.