The Role of Tumor Microenvironment in Mycosis Fungoides and Sézary Syndrome

( Zhaorui Liu ),( Xuesong Wu ),( Sam T. Hwang ),( Jie Liu ) 대한피부과학회 2021 Annals of Dermatology Vol.33 No.6

Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphomas (CTCLs). Most cases of MF display an indolent course during its early stage. However, in some patients, it can progress to the tumor stage with potential systematic involvement and a poor prognosis. SS is defined as an erythrodermic CTCL with leukemic involvements. The pathogenesis of MF and SS is still not fully understood, but recent data have found that the development of MF and SS is related to genetic alterations and possibly to environmental influences. In CTCL, many components interacting with tumor cells, such as tumor-associated macrophages, fibroblasts, dendritic cells, mast cells, and myeloid-derived suppressor cells, as well as with chemokines, cytokines and other key players, establish the tumor microenvironment (TME). In turn, the TME regulates tumor cell migration and proliferation directly and indirectly and may play a critical role in the progression of MF and SS. The TME of MF and SS appear to show features of a Th2 phenotype, thus dampening tumorrelated immune responses. Recently, several studies have been published on the immunological characteristics of MF and SS, but a full understanding of the CTCL-related TME remains to be determined. This review focuses on the role of the TME in MF and SS, aiming to further demonstrate the pathogenesis of the disease and to provide new ideas for potential treatments targeted at the microenvironment components of the tumor.

PANCHROMATIC OBSERVATIONS OF THE TEXTBOOK GRB 110205A: CONSTRAINING PHYSICAL MECHANISMS OF PROMPT EMISSION AND AFTERGLOW

Zheng, W.,Shen, R. F.,Sakamoto, T.,Beardmore, A. P.,De Pasquale, M.,Wu, X. F.,Gorosabel, J.,Urata, Y.,Sugita, S.,Zhang, B.,Pozanenko, A.,Nissinen, M.,Sahu, D. K.,Im, M.,Ukwatta, T. N.,Andreev, M.,Klun IOP Publishing 2012 The Astrophysical journal Vol.751 No.2

<P>We present a comprehensive analysis of a bright, long-duration (T-90 similar to 257 s) GRB 110205A at redshift z = 2.22. The optical prompt emission was detected by Swift/UVOT, ROTSE-IIIb, and BOOTES telescopes when the gamma-ray burst (GRB) was still radiating in the gamma-ray band, with optical light curve showing correlation with gamma-ray data. Nearly 200 s of observations were obtained simultaneously from optical, X-ray, to gamma-ray (1 eV to 5 MeV), which makes it one of the exceptional cases to study the broadband spectral energy distribution during the prompt emission phase. In particular, we clearly identify, for the first time, an interesting two-break energy spectrum, roughly consistent with the standard synchrotron emission model in the fast cooling regime. Shortly after prompt emission (similar to 1100 s), a bright (R = 14.0) optical emission hump with very steep rise (alpha similar to 5.5) was observed, which we interpret as the reverse shock (RS) emission. It is the first time that the rising phase of an RS component has been closely observed. The full optical and X-ray afterglow light curves can be interpreted within the standard reverse shock (RS) + forward shock (FS) model. In general, the high-quality prompt and afterglow data allow us to apply the standard fireball model to extract valuable information, including the radiation mechanism (synchrotron), radius of prompt emission (R-GRB similar to 3 x 10(13) cm), initial Lorentz factor of the outflow (Gamma(0) similar to 250), the composition of the ejecta (mildly magnetized), the collimation angle, and the total energy budget.</P>

Activation of Akt as a mechanism for tumor immune evasion.

Noh, Kyung Hee,Kang, Tae Heung,Kim, Jin Hee,Pai, Sara I,Lin, Ken Y,Hung, Chien-Fu,Wu, T-C,Kim, Tae Woo Academic Press 2009 Molecular therapy Vol.17 No.3

<P>Immune evasion is an important reason why the immune system cannot control tumor growth. To elucidate the mechanism for tumor immune evasion, we generated an immune-resistant human papillomavirus type 16 (HPV-16) E7-expressing tumor cell line by subjecting a susceptible tumor cell line to multiple rounds of in vivo immune selection with an E7-specific vaccine. Comparison of parental and immune-resistant tumors revealed that Akt is highly activated in the immune-resistant tumors. Retroviral transfer of a constitutively active form of Akt into the parental tumor significantly increased its resistance against E7-specific CD8(+) T-cell mediated apoptosis. The observed resistance against apoptosis was found to be associated with the upregulation of antiapoptotic molecules. We also observed that intratumoral injection of an Akt inhibitor enhanced the therapeutic efficacy of E7-specific vaccine or E7-specific CD8(+) T-cell adoptive transfer against the immune-resistant tumors. Thus, our data indicate that the activation of PI3K/Akt pathway represents a new mechanism of immune escape and has important implications for the development of a novel strategy in cancer immunotherapy against immune-resistant tumor cells.</P>

Long-lived K isomer and enhanced γ vibration in the neutron-rich nucleus ¹⁷²Dy: Collectivity beyond double midshell

Watanabe, H.,Zhang, G.X.,Yoshida, K.,Walker, P.M.,Liu, J.J.,Wu, J.,Regan, P.H.,Soderstrom, P.A.,Kanaoka, H.,Korkulu, Z.,Lee, P.S.,Nishimura, S.,Yagi, A.,Ahn, D.S.,Alharbi, T.,Baba, H.,Browne, F.,Bruce North-Holland Pub. Co 2016 Physics letters. Section B Vol.760 No.-

The level structure of <SUP>172</SUP>Dy has been investigated for the first time by means of decay spectroscopy following in-flight fission of a <SUP>238</SUP>U beam. A long-lived isomeric state with T<SUB>½</SUB>=0.71(5) s and K<SUP>π</SUP>=8<SUP>-</SUP> has been identified at 1278 keV, which decays to the ground-state and γ-vibrational bands through hindered electromagnetic transitions, as well as to the daughter nucleus <SUP>172</SUP>Ho via allowed β decays. The robust nature of the K<SUP>π</SUP>=8<SUP>-</SUP> isomer and the ground-state rotational band reveals an axially-symmetric structure for this nucleus. Meanwhile, the γ-vibrational levels have been identified at unusually low excitation energy compared to the neighboring well-deformed nuclei, indicating the significance of the microscopic effect on the non-axial collectivity in this doubly mid-shell region. The underlying mechanism of enhanced γ vibration is discussed in comparison with the deformed Quasiparticle Random-Phase Approximation based on a Skyrme energy-density functional.

Enhancement of Tumor-Specific T Cell–Mediated Immunity in Dendritic Cell–Based Vaccines by <i>Mycobacterium tuberculosis</i> Heat Shock Protein X

Jung, In Duk,Shin, Sung Jae,Lee, Min-Goo,Kang, Tae Heung,Han, Hee Dong,Lee, Seung Jun,Kim, Woo Sik,Kim, Hong Min,Park, Won Sun,Kim, Han Wool,Yun, Cheol-Heui,Lee, Eun Kyung,Wu, T.-C.,Park, Yeong-Min The American Association of Immunologists, Inc. 2014 JOURNAL OF IMMUNOLOGY Vol.193 No.3

<P>Despite the potential for stimulation of robust antitumor immunity by dendritic cells (DCs), clinical applications of DC-based immunotherapy are limited by the low potency in generating tumor Ag-specific T cell responses. Therefore, optimal conditions for generating potent immunostimulatory DCs that overcome tolerance and suppression are key factors in DC-based tumor immunotherapy. In this study, we demonstrate that use of the <I>Mycobacterium tuberculosis</I> heat shock protein X (HspX) as an immunoadjuvant in DC-based tumor immunotherapy has significant potential in therapeutics. In particular, the treatment aids the induction of tumor-reactive T cell responses, especially tumor-specific CTLs. The HspX protein induces DC maturation and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IFN-β) through TLR4 binding partially mediated by both the MyD88 and the TRIF signaling pathways. We employed two models of tumor progression and metastasis to evaluate HspX-stimulated DCs in vivo. The administration of HspX-stimulated DCs increased the activation of naive T cells, effectively polarizing the CD4<SUP>+</SUP> and CD8<SUP>+</SUP> T cells to secrete IFN-γ, as well as enhanced the cytotoxicity of splenocytes against HPV-16 E7 (E7)–expressing TC-1 murine tumor cells in therapeutic experimental animals. Moreover, the metastatic capacity of B16-BL6 melanoma cancer cells toward the lungs was remarkably attenuated in mice that received HspX-stimulated DCs. In conclusion, the high therapeutic response rates with tumor-targeted Th1-type T cell immunity as a result of HspX-stimulated DCs in two models suggest that HspX harnesses the exquisite immunological power and specificity of DCs for the treatment of tumors.</P>

PAWP, a Sperm-specific WW Domain-binding Protein, Promotes Meiotic Resumption and Pronuclear Development during Fertilization

Wu, Alexander T. H.,Sutovsky, Peter,Manandhar, Gaurishankar,Xu, Wei,Katayama, Mika,Day, Billy N.,Park, Kwang-Wook,Yi, Young-Joo,Xi, Yan Wei,Prather, Randall S.,Oko, Richard American Society for Biochemistry and Molecular Bi 2007 The Journal of biological chemistry Vol.282 No.16

Expression of Human Serum Albumin in Milk of Transgenic Mice Using Goat β-casein/Human Serum Albumin Fusion Gene

Wu, H.T.,Chou, C.K.,Huang, M.C. Asian Australasian Association of Animal Productio 2004 Animal Bioscience Vol.17 No.6

The gene encoding human serum albumin (HSA) was cloned from human liver cDNA library by PCR. The HSA cDNA in size of 2,176 bp, including 1,830 bp of open reading frame, was cloned into the plasmid carried with the 5'flanking sequence of goat $\beta$-casein gene (-4,044 to +2,025 bp) to get a tissue specific expression vector in mammary gland named pGB562/HSA (12.5 kb). A 9.6 kb DNA fragment in which the sequence is in order of goat $\beta$-casein gene regulatory sequence, HSA cDNA and SV40 polyadenylation signals was isolated from the pGB562/HSA by SacI and DraIII cutting, and used to microinject into the pronuclei of mouse fertilized eggs to produce transgenic mice. Three transgenic mice (2 female and 1 male) were identified by PCR and dot Southern blot analysis. The copy numbers of integrated transgene were more than 10 copies in line #21 and #26 as well as over 50 copies in line #31 of transgenic mice. HSA protein collected from the milk of lactating transgenic mice was confirmed by immuno-detection of Western and slot blot. The concentrations of HSA in the milk were from 0.05 to 0.4 mg/ml. An obvious antigen and antibody conjugate could be observed in immunohistochemical stain of mammary gland tissue from lactating day 11 of HSA transgenic mice. The transmission of transgene and its expression was recognized according to the results of RT-PCR and sequences analyses of their progeny.

Current Improvement for a 3∅ Bi-directional Inverter with Wide Inductance Variation

T.-F. Wu,L.-C. Lin,C.-H. Chang,Y.-L. Lin,Y.-R. Chang 전력전자학회 2011 ICPE(ISPE)논문집 Vol.2011 No.5

This paper presents current improvement for a 3? bi-directional inverter with wide inductance variation. A bi-directional inverter fulfilling grid connection and rectification with power factor correction has been designed and implemented in the laboratory. With a digital predictive current control, the inverter can accommodate wide inductance variation, improving current distortion in high power applications significantly. However, under low current levels, inductor currents have serious distortion. To improve current distortion, this paper presents four attempts, including mid-point current sampling, smooth region transition, current interleaving, and duty splitting. Theoretical analysis and experimental results are presented to verify the discussion.

Design and Implementation of 20 kVA D-Σ Digital Controlled Three-Phase Four-Wire Multi-Function Inverter System

T.-F. Wu,P.-H. Li,C.-W. Hsu,Y.-R. Chang 전력전자학회 2015 ICPE(ISPE)논문집 Vol.2015 No.6

This paper presents design and implementation of a 20 kVA division-summation (D-Σ) digital controlled three-phase four-wire multi-function inverter system. The inverter can be operated in grid-connected or stand-alone mode to act as a renewable- energy ac power-supply system. In the stand-alone mode, since the D-Σ digital control law includes load impedance estimation, the inverter can track sinusoidal output voltage under linear or nonlinear load. For the grid-connected mode and in order to achieve a specific PF and stabilize grid voltage and frequency, the D-Σ digital control law is supplemented by a droop control based linear P-Q compensation. Moreover, the D-Σ digital control law in this research is based on Two-Phase Modulation (TPM) scheme and associated with the switching sequence derived from space vector pulse width modulation (SVPWM) scheme. The inductance variation has been taken into account in the control-law derivation, reducing core size significantly. The analysis and discussion have been verified with measured results from a 20 kVA three-phase four-wire inverter system.

A Meshfree procedure for the microscopic analysis of particle-reinforced rubber compounds

Wu, C.T.,Koishi, M. Techno-Press 2009 Interaction and multiscale mechanics Vol.2 No.2

This paper presents a meshfree procedure using a convex generalized meshfree (GMF) approximation for the large deformation analysis of particle-reinforced rubber compounds on microscopic level. The convex GMF approximation possesses the weak-Kronecker-delta property that guarantees the continuity of displacement across the material interface in the rubber compounds. The convex approximation also ensures the positive mass in the discrete system and is less sensitive to the meshfree nodal support size and integration order effects. In this study, the convex approximation is generated in the GMF method by choosing the positive and monotonic increasing basis function. In order to impose the periodic boundary condition in the unit cell method for the microscopic analysis, a singular kernel is introduced on the periodic boundary nodes in the construction of GMF approximation. The periodic boundary condition is solved by the transformation method in both explicit and implicit analyses. To simulate the interface de-bonding phenomena in the rubber compound, the cohesive interface element method is employed in corporation with meshfree method in this study. Several numerical examples are presented to demonstrate the effectiveness of the proposed numerical procedure in the large deformation analysis.