Insight into the Surface Reconstruction-Induced Structure and Electrochemical Performance Evolution for Ni-Rich Cathodes with Postannealing after Washing.

Ni-rich layered LiNixCoyAlzO2 (NCA, x ≥ 0.8) oxides have attracted wide attention as cathode materials for lithium-ion batteries due to their higher energy density and lower cost. However, the increase in the capacity for Ni-rich cathodes can cause faster capacity decay and increase sensitivity to ambient air exposure during the storage process. Especially, the residual lithium on the surface of Ni-rich cathodes will cause severe flatulence during cycling which greatly reduces the safety performance of the battery. Washing is an effective method to reduce residual lithium, but it will seriously damage the surface phase structure of Ni-rich materials. Here, we introduce a designed method involving two steps, washing and high-temperature annealing, which can ingeniously modify the surface phase structure of Ni-rich cathodes. The results show that the residual lithium content can be significantly reduced. The thin NiO-like rock-salt phase formed on the surface of Ni-rich cathode annealed at 600 °C improves the diffusion kinetics of Li+, reduces the polarization, and improves the electrochemical performance of Ni-rich materials, while the thick spinel-like phase formed at 400 °C hinders the diffusion kinetics of Li+, significantly increases the polarization, and eventually leads to the structural degradation of Ni-rich materials. As a result, the discharge capacity of the cathode annealed at 600 °C still retains 174.48 mA h g-1 after 100 cycles, with a capacity retention of 92.04%, much larger than the cathode annealed at 400 °C, for which the discharge capacity drops to 107.77 mA h g-1, with a capacity retention of 65.78%.

Two stages of bandwidth scaling drives efficient neural coding of natural sounds.

Theories of efficient coding propose that the auditory system is optimized for the statistical structure of natural sounds, yet the transformations underlying optimal acoustic representations are not well understood. Using a database of natural sounds including human speech and a physiologically-inspired auditory model, we explore the consequences of peripheral (cochlear) and mid-level (auditory midbrain) filter tuning transformations on the representation of natural sound spectra and modulation statistics. Whereas Fourier-based sound decompositions have constant time-frequency resolution at all frequencies, cochlear and auditory midbrain filters bandwidths increase proportional to the filter center frequency. This form of bandwidth scaling produces a systematic decrease in spectral resolution and increase in temporal resolution with increasing frequency. Here we demonstrate that cochlear bandwidth scaling produces a frequency-dependent gain that counteracts the tendency of natural sound power to decrease with frequency, resulting in a whitened output representation. Similarly, bandwidth scaling in mid-level auditory filters further enhances the representation of natural sounds by producing a whitened modulation power spectrum (MPS) with higher modulation entropy than both the cochlear outputs and the conventional Fourier MPS. These findings suggest that the tuning characteristics of the peripheral and mid-level auditory system together produce a whitened output representation in three dimensions (frequency, temporal and spectral modulation) that reduces redundancies and allows for a more efficient use of neural resources. This hierarchical multi-stage tuning strategy is thus likely optimized to extract available information and may underlies perceptual sensitivity to natural sounds.

Dual-Modified Compact Layer and Superficial Ti Doping for Reinforced Structural Integrity and Thermal Stability of Ni-Rich Cathodes.

Nickel-rich layered oxides have been regarded as a potential cathode material for high-energy-density lithium-ion batteries because of the high specific capacity and low cost. However, the rapid capacity fading due to interfacial side reactions and bulk structural degradation seriously encumbers its commercialization. Herein, a highly stable hybrid surface architecture, which integrates an outer coating layer of TiO2&Li2TiO3 and a surficial titanium doping by incorporated Ti2O3, is carefully designed to enhance the structural stability and eliminate lithium impurity. Meanwhile, the surficial titanium doping induces a nanoscale cation-mixing layer, which suppresses transition-metal-ion migration and ameliorates the reversibility of the H2 → H3 phase transition. Also, the Li2TiO3 coating layer with three-dimensional channels promotes ion transportation. Moreover, the electrochemically stable TiO2 coating layer restrains side reactions and reinforces interfacial stability. With the collaboration of titanium doping and TiO2&Li2TiO3 hybrid coating, the sample with 1 mol % modified achieves a capacity retention of 93.02% after 100 cycles with a voltage decay of only 0.03 V and up to 84.62% at a high voltage of 3.0-4.5 V. Furthermore, the ordered occupation of Ni ions in the Li layer boosts the thermal stability by procrastinating the layered-to-rock salt phase transition. This work provides a straightforward and economical modification strategy for boosting the structural and thermal stability of nickel-rich cathode materials.

Distinct neural ensemble response statistics are associated with recognition and discrimination of natural sound textures.

The perception of sound textures, a class of natural sounds defined by statistical sound structure such as fire, wind, and rain, has been proposed to arise through the integration of time-averaged summary statistics. Where and how the auditory system might encode these summary statistics to create internal representations of these stationary sounds, however, is unknown. Here, using natural textures and synthetic variants with reduced statistics, we show that summary statistics modulate the correlations between frequency organized neuron ensembles in the awake rabbit inferior colliculus (IC). These neural ensemble correlation statistics capture high-order sound structure and allow for accurate neural decoding in a single trial recognition task with evidence accumulation times approaching 1 s. In contrast, the average activity across the neural ensemble (neural spectrum) provides a fast (tens of milliseconds) and salient signal that contributes primarily to texture discrimination. Intriguingly, perceptual studies in human listeners reveal analogous trends: the sound spectrum is integrated quickly and serves as a salient discrimination cue while high-order sound statistics are integrated slowly and contribute substantially more toward recognition. The findings suggest statistical sound cues such as the sound spectrum and correlation structure are represented by distinct response statistics in auditory midbrain ensembles, and that these neural response statistics may have dissociable roles and time scales for the recognition and discrimination of natural sounds.

Interfacial Regulation of Ni-Rich Cathode Materials with an Ion-Conductive and Pillaring Layer by Infusing Gradient Boron for Improved Cycle Stability.

Ni-rich cathodes LiNixCoyAl1-x-yO2 (0.8 < x < 1) with high energy density, environmental benignity, and low cost are regarded as the most promising candidate materials for next-generation lithium batteries. Unfortunately, capacity fading derived from unstable surface properties and intrinsic structural instability under extreme conditions limits large-scale commercial utilization. Herein, an interface-regulated Ni-rich cathode material LiNi0.87Co0.10Al0.03O2 with a layer (R3̅m) core, a NiO salt-like (Fm3̅m) phase, and an ultrathin amorphous ion-conductive LiBO2 (LBO) layer is constructed by gradient boron incorporation and lithium-reactive coating during calcination. The ultrathin LBO layer not only exhausts residual lithium species but also acts as a layer for Li+ transport and insulation of detrimental reaction. The NiO salt-like phase in the subsurface could enhance the structural stability of the layer core for the pillar effects. With the positive role provided by the functional hybrid surface layer and boron doping, the modified cathode exhibits enhanced Li+ conductivity, structural stability, reversibility of the H2-H3 phase transition, suppressed side reactions, ameliorated transition-metal dissolution, and excellent electrochemical performance. Especially, a 1% wt boron-modified cathode delivers a discharge capacity of 211.99 mA h g-1 in the potential range of 3.0-4.3 V at 0.2 C and excellent cycle life with a capacity retention of 89.43% after 200 cycles at 1 C.

Dual Elements Coupling Effect Induced Modification from the Surface into the Bulk Lattice for Ni-Rich Cathodes with Suppressed Capacity and Voltage Decay.

Injection of phase transition from a layered to rock-salt phase into the bulk lattice and side reactions on the interfacial usually causes structure degradation, quick capacity/voltage decay, and even thermal instability. Here, a self-formed interfacial protective layer coupled with lattice tuning was constructed for Ni-rich cathodes by simultaneous incorporation of Zr and Al in a one-step calcination. The migration energy between Zr and Al from the surface into the bulk lattice induces dual modifications from the surface into the bulk lattice, which effectively decrease the formation of cation mixing, the degree of anisotropic lattice change, and the generation of microcracks. With the stabilization role provided by the doped Zr-Al ions and protective function endowed by the surface layer, the modified cathode material exhibits significantly enhanced capacity and voltage retention. Specifically, the capacity retention for the modified cathode material reaches 99% after 100 cycles at 1 C and 25 °C in a voltage range of 3.0-4.3 V, which outperformed that for the pristine cathode (70%). The declination values of the average voltage for the modified cathode are only 0.025 and 0.097 V after 100 cycles at 1 C in voltage ranges of 3.0-4.3 and 2.8-4.5 V, respectively, which are much lower than those for the pristine cathode (0.230 and 0.405 V). The synchronous accomplishment of modification from the surface into the bulk lattice for Ni-rich materials with multiple elements in a one-step calcination process would provide some referenced value for the preparation of other cathode materials.

Synthesis of hierarchical Sn/SnO nanosheets assembled by carbon-coated hollow nanospheres as anode materials for lithium/sodium ion batteries.

Tin-based anode materials have aroused interest due to their high capacities. Nevertheless, the volume expansion problem during lithium insertion/extraction processes has severely hindered their practical application. In particular, nano-micro hierarchical structure is attractive with the integrated advantages of nano-effect and high thermal stability of the microstructure. Herein, hierarchical Sn/SnO nanosheets assembled by carbon-coated hollow nanospheres were successfully synthesized by a facile glucose-assisted hydrothermal method, in which the glucose served as both morphology-control agent and carbon source. The hierarchical Sn/SnO nanosheets exhibit excellent electrochemical performances owing to the unique configuration and carbon coating. Specifically, a reversible high capacity of 2072.2 mA h g-1 was observed at 100 mA g-1. Further, 964.1 mA h g-1 after 100 cycles at 100 mA g-1 and 820.4 mA h g-1 at 1000 mA g-1 after 300 cycles could be obtained. Encouragingly, the Sn/SnO also presents certain sodium ion storage properties. This facile synthetic strategy may provide new insight into fabricating high-performance Sn-based anode materials combining the advantages of both structure and carbon coating.

K2 Ti2 O5 @C Microspheres with Enhanced K+ Intercalation Pseudocapacitance Ensuring Fast Potassium Storage and Long-Term Cycling Stability.

Benefiting from the natural abundance and low standard redox potential of potassium, potassium-ion batteries (PIBs) are regarded as one of the most promising alternatives to lithium-ion batteries for low-cost energy storage. However, most PIB electrode materials suffer from sluggish thermodynamic kinetics and dramatic volume expansion during K+ (de)intercalation. Herein, it is reported on carbon-coated K2 Ti2 O5 microspheres (S-KTO@C) synthesized through a facile spray drying method. Taking advantage of both the porous microstructure and carbon coating, S-KTO@C shows excellent rate capability and cycling stability as an anode material for PIBs. Furthermore, the intimate integration of carbon coating through chemical vapor deposition technology significantly enhances the K+ intercalation pseudocapacitive behavior. As a proof of concept, a potassium-ion hybrid capacitor is constructed with the S-KTO@C (battery-type anode material) and the activated carbon (capacitor-type cathode material). The assembled device shows a high energy density, high power density, and excellent capacity retention. This work can pave the way for the development of high-performance potassium-based energy storage devices.

[Preparation of monoclonal antibodies against human interleukin-35 and their application in a quantitative ELISA for interleukin-35 detection].

To establish a quantitative ELISA for human interleukin-35 (IL-35) detection, we cloned cDNAs encoding the 2 subunits IL-27EBI3 and IL-12p35 of IL-35 by RT-PCR and transformed the cDNAs into Escherichia coli BL21 star (DE3) by recombinant DNA technology. IL-27EBI3 and IL-12p35 were expressed as recombinant proteins and used as immunogen to immunize Balb/c mice. Spleen cells from the positive serum mice were isolated and fused with SP-2/0 myeloma cells. We obtained the hybridoma cell lines stably secreting target antibodies by indirect ELISA screening of the cell supernatants with recombinant IL-27EBI3 and IL-12p35 as antigen and consecutive subcloning of the cells in the well with positive supernatant. Following further measurement of supernatant titers of the antibodies and identification of their antigen specificity, we obtained a hybridoma cell line 3B11 that stably secrets antibody against IL-27EBI3 and a hybridoma cell line 3A10 that secrets antibody against IL-12p35. Both monoclonal antibodies (mAbs) were identified as the subtype of IgG1. Finally, using the anti-IL-27EBI3 mAb from 3B11 as the capture antibody and the anti-IL-12p35 mAb from 3A10 as the secondary antibody, we established a quantitative double-antibodies sandwich ELISA for IL-35 detection with streptavidin-biotin amplification system. Results demonstrated that the quantitative assay had a detection range of 3.12-200 pg/mL, a detectability of 1.26 pg/mL, and a crossing-reactive rate of 0.1%. The intra-batch RSD and the inter-batch RSD of the quantitative assay were 5.1%-5.6% and 5.6%-7.2%, respectively, and the fortified recovery was 89%-103%. Therefore, the sandwich ELISA assay for IL-35 meets the qualification of quantitative analysis and laid a stable foundation for the development of quantitative ELISA kit for IL-35 detection.

miR-182-5p affects human bladder cancer cell proliferation, migration and invasion through regulating Cofilin 1.

BACKGROUND: Human bladder cancer is one of the common malignant tumors, and it mainly occurs in men. miR-182-5p, a member of miR-183 family, acts as tumor suppressor or oncogene in various kinds of tumors. In this study, we first investigate that the absence of miR-182-5p in human bladder cancer promotes tumor growth by regulating the expression of Cofilin 1, an actin modulating-protein. METHODS: Human bladder tumor tissue specimens were collected to detect the expression of miR-182-5p and Cofilin 1 by qRT-PCR. Luciferase activity assay was performed to demonstrate the regulation of Cofilin 1 mRNA 3'UTR by miR-182-5p. Then, cell experiments were performed to analysis the effect of miR-182-5p/Cofilin 1 pathway on tumor cell proliferation, migration, invasion and colony forming efficiency. Finally, xenograft tumor models were established to evaluate the role of miR-182-5p in tumorigenesis abilities in vivo. RESULTS: qRT-PCR and Western blotting analysis showed that Cofilin 1 expression was up-regulated in both bladder cancer tissues and cell lines compared with normal. Luciferase activity assay showed that miR-182-5p specifically targets Cofilin 1 mRNA 3'UTR and represses the expression of Cofilin 1. Also, miR-182-5p inhibited bladder tumor cell proliferation, migration, invasion and colony forming efficiency. Furthermore, xenograft tumor model assay showed that miR-182-5p plays a negative role in bladder cancer tumorigenesis abilities in vivo. CONCLUSION: Present results suggest that miR-182-5p could inhibit human bladder tumor growth by repressing Cofilin 1 expression. Our findings may provide a new horizon for exploring therapeutic target of bladder cancer.

Long non-coding RNA HOXA-AS2 promotes the migration, invasion and stemness of bladder cancer via regulating miR-125b/Smad2 axis.

Long non-coding RNA HOXA-AS2 (HOXA cluster antisense RNA 2) has been reported to function as an oncogene in different types of cancers including breast cancer, liver cancer, gastric cancer and colorectal cancer, etc. However, its role in the development and progression of bladder cancer remains unknown. This study aimed to examine the expression of HOXA-AS2 in bladder cancer, to explore its role in the migration, invasion and stemness of bladder cancer cells and to further identify the potential downstream target miRNAs of HOXA-AS2 in this type of cancer. Our results firstly demonstrated the upregulation of HOXA-AS2 in both bladder cancer cells and clinical bladder tumors. Such upregulation was also positively correlated with the advanced stage, invasion and lymph node metastasis of bladder cancer as well as the expression of cancer stem cell marker OCT4 in patients. After knockdown of HOXA-AS2 in bladder cancer 5637 and T24 cells, the migration, invasion and stemness of cancer cells were significantly inhibited, indicating the capability of HOXA-AS2 to promote the migration, invasion and stemness of bladder cancer cells. Knockdown of HOXA-AS2 also suppressed in vivo tumor growth in the nude mice. Furthermore, this study also identified miR-125b as a downstream target of HOXA-AS2 and revealed the downregulation of miR-125b by HOXA-AS2 as well as the involvement of HOXA-AS2/miR-125b/Smad2 interactions in the functional role of HOXA-AS2 in mediating the migration, invasion and stemness of bladder cancer cells. Together, our findings suggest that HOXA-AS2 might be a potential biomarker and target for the diagnosis, monitoring and treatment of bladder cancer.

High-Power and Ultralong-Life Aqueous Zinc-Ion Hybrid Capacitors Based on Pseudocapacitive Charge Storage.

Rechargeable aqueous zinc-ion hybrid capacitors and zinc-ion batteries are promising safe energy storage systems. In this study, amorphous RuO2·H2O for the first time was employed to achieve fast and ultralong-life Zn2+ storage based on a pseudocapacitive storage mechanism. In the RuO2·H2O||Zn zinc-ion hybrid capacitors with Zn(CF3SO3)2 aqueous electrolyte, the RuO2·H2O cathode can reversibly store Zn2+ in a voltage window of 0.4-1.6 V (vs. Zn/Zn2+), delivering a high discharge capacity of 122 mAh g-1. In particular, the zinc-ion hybrid capacitors can be rapidly charged/discharged within 36 s with a very high power density of 16.74 kW kg-1 and a high energy density of 82 Wh kg-1. Besides, the zinc-ion hybrid capacitors demonstrate an ultralong cycle life (over 10,000 charge/discharge cycles). The kinetic analysis elucidates that the ultrafast Zn2+ storage in the RuO2·H2O cathode originates from redox pseudocapacitive reactions. This work could greatly facilitate the development of high-power and safe electrochemical energy storage.

Cofilin 1 promotes bladder cancer and is regulated by TCF7L2.

Earlier reports demonstrated that Cofilin expression is increased in bladder cancer samples, though its function remains unknown. Here, we found that Cofilin 1 expression was higher in bladder cancer tissues than in paracancerous tissues. Overexpression of Cofilin 1 promoted, while Cofilin 1 knockdown inhibited, proliferation, migration, and invasion in the T24 and RT4 bladder cancer cell lines. In addition, Cofilin 1 overexpression increased, while Cofilin 1 knockdown decreased, bladder tumor volumes in mouse xenograft experiments. Transcription factor 7-like 2 (TCF7L2) targeted the promoter of the Cofilin 1 gene, and TCF7L2 knockdown or mutations in the Cofilin 1 promoter dramatically decreased Cofilin 1 transcription. TCF7L2 promoted cell proliferation and migration and increased Cofilin 1 protein levels in RT4 and T24 cells. Thus, TCF7L2 contributed to Cofilin 1-induced promotion of bladder cancer development by binding to the Cofilin 1 promoter and increasing its expression.

Study on the significance of Cofilin 1 overexpression in human bladder cancer.

PURPOSE: Cofilin 1 is a type of cytoskeletal protein. The overexpression of this gene has been regarded to hold a special relationship with the development and progress of some cancers. However, the detailed position of Cofilin 1 in human bladder cancer has not been investigated intensively. METHODS: In this study, we mainly explored the relationship between human bladder cancer and the expression of Cofilin 1. The expression of Cofilin 1 in bladder cancer tissues and paracancerous tissues of patients was evaluated with quantitative polymerase chain reaction, Western blot, and immunohistochemical staining. Downregulation of Cofilin 1 expression model was established with siRNA in human RT4 bladder cancer cell line, and the changing cell viability was analyzed to determine the role of Cofilin 1 in human bladder cancer. RESULTS: Our results showed that the expression of Cofilin 1 was much higher in both RNA level and protein level in human bladder cancer tissues than paracancerous tissues for 3 patients. Downregulation of Cofilin 1 expression could inhibit cell proliferation, cell migration, cell adhesion, and colony formation ability, and increase the percentage of cell apoptosis in RT4 cells. CONCLUSIONS: Our study indicates that Cofilin 1 holds an important position in the development and progression of human bladder cancer, and this gene might become a novel target in the diagnosis and treatment of human bladder cancer.

Demineralized dentin matrix composite collagen material for bone tissue regeneration.

Demineralized dentin matrix (DDM) had been successfully used in clinics as bone repair biomaterial for many years. However, particle morphology of DDM limited it further applications. In this study, DDM and collagen were prepared to DDM composite collagen material. The surface morphology of the material was studied by scanning electron microscope (SEM). MC3T3-E1 cells responses in vitro and tissue responses in vivo by implantation of DDM composite collagen material in bone defect of rabbits were also investigated. SEM analysis showed that DDM composite collagen material evenly distributed and formed a porous scaffold. Cell culture and animal models results indicated that DDM composite collagen material was biocompatible and could support cell proliferation and differentiation. Histological evaluation showed that DDM composite collagen material exhibited good biocompatibility, biodegradability and osteoconductivity with host bone in vivo. The results suggested that DDM composite collagen material might have a significant clinical advantage and potential to be applied in bone and orthopedic surgery.

Comparison of two functional kappa light-chain transcripts amplified from a hybridoma.

Three heavy-chain and three kappa (κ)-chain transcripts were amplified from hybridoma cells secreting a monoclonal antibody (mAb) against transferrin receptor. Sequence analysis via IMGT/V-QUEST yielded the functional/aberrant prediction. Two functional κ-chain transcripts, Vκ2 and Vκ3, and one functional VH1 were revealed. Comprehensive bioinformatics analyses including sequence alignment, phylogenetic tree, somatic hypermutation prediction, and three-dimensional-molecular structure modeling were used to predict the origin of the two κ-chain transcripts. The results of bioinformatics analysis suggest that Vκ3 is derived from the myeloma partner of the hybridoma; Vκ2 is derived from B-cell. Functional transcripts VH1 and Vκ2 and Vκ3 were then used to construct two chimeric antibodies chi-C2 (Vκ2-VH1) and chi-C3 (Vκ3-VH1), respectively. Antigen-binding experiments showed that only chi-C2 remained the same affinity as its parental mAb. Possible explanations for the coexistence of two functional κ-chain transcripts and the different affinity of the two chimeric antibodies are discussed.

Engineering and characterization of a baculovirus-expressed mouse/human chimeric antibody against transferrin receptor.

Transferrin receptor (TfR) has been explored as a target for antibody-based therapy of cancer. In the previous study, we reported a murine anti-TfR monoclonal antibody (mAb) 7579 had good anti-tumor activities in vitro. In an attempt to reduce its immunogenicity and enhance its ability to recruit immune effector mechanism in vivo, we herein developed its chimera in the baculovirus/insect cell expression system based on the mating-assisted genetically integrated cloning (MAGIC) strategy. The chimeric light and heavy chains, containing human IgG1 constant regions, were correctly processed and assembled in insect cells, and then secreted into the mediums as heterodimeric H(2)L(2) immunoglobulins. Furthermore, analyses of antigen-binding assay and competitive binding assay indicated that the chimeric antibody possessed specificity and affinity similar to that of its parental murine antibody. Results of the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assay verified that the chimeric antibody could efficiently mediate ADCC and CDC against TfR-overexpressing tumor cells. These results suggested that this baculovirus-expressed chimeric anti-TfR IgG1 might have the potential to be used for cancer immunotherapy. Meanwhile, the MAGIC strategy, facilitating the rapid generation of chimeric mAbs, could be one of the efficient strategies for antibody engineering.

B7-H4 transfection prolongs beta-cell graft survival.

B7-H4, a recently discovered member of B7 family, can negatively regulate T cell responses. However, it is not clear whether B7-H4 negatively function in cell transplantation. In this study we investigated the immunosuppressive effect of B7-H4 on beta-cell transplantation. An insulinoma cell line, NIT-1, transfected with B7-H4 (B7-H4-NIT) was established, and transplanted to diabetic C57BL/6 mice by intraperitoneal injection. Proliferation assay of splenocytes in vitro showed that B7-H4-NIT suppressed alloreactive T cell activation. The proportion of IFN-gamma-producing cells in recipient spleen was significantly reduced and the number of Treg cells was upregulated in B7-H4-NIT group compared to the control, EGFP-NIT. The expression of mRNA coding IFN-gamma was lower but that of IL-4 was higher in B7-H4-NIT transplanted recipients than in the control animals. The results of ELISA also revealed the same trends. Diabetic mice reached normalglycemic quickly and gained weight after transplantation of B7-H4-NIT. More importantly, the survival time for recipients transplanted with B7-H4-NIT cells was significantly longer than that with EGFP-NIT cells. These results indicate that B7-H4 transfection prolongs beta-cell graft survival.

The anti-tumor effect of human monocyte-derived dendritic cells loaded with HSV-TK/GCV induced dying cells.

Herpes simplex virus thymidine kinase (HSV-TK) gene and dendritic cells (DC) have been used as the pioneering in cancer therapy. HSV-TK gene can induce apoptosis and necrosis in tumor cells in the presence of the non-toxic prodrug ganciclovir (GCV). We investigated the anti-tumor effect of DC vaccination by introducing dying cells from HSV-TK gene treatment as an adjuvant. HepG(2)-TK cell line was established by transfecting human hepatoma cell line HepG(2) (HLA-A(2) positive) with HSV-TK gene. Dying tumor cells were generated by culturing HepG(2)-TK cells with GCV. After engulfed dying cells efficiently, immature DCs (imDC) derived from human monocytes were fully matured and elicited marked proliferation and cytotoxicity against HLA matched HepG(2) cells in autologous peripheral blood mononuclear cells (PBMC). It also implied that HepG(2) specific CTLs played an important role in the cytotoxicity which was primarily depended on Th1 responses. Given the feasibility of inducing dying cells by HSV-TK/GCV in vivo, our results suggest an effective method in clinical human hepatocellular carcinoma (HCC) treatment by an in vitro model of applying HSV-TK gene modified human tumor cells integrated with DC vaccination.

An anti-transferrin receptor antibody enhanced the growth inhibitory effects of chemotherapeutic drugs on human non-hematopoietic tumor cells.

Transferrin receptor (TfR) has been used as a target for antibody-based therapy of cancer. Combining anti-TfR antibodies with chemotherapeutic drugs shows potential as one of the strategies for cancer therapy. In this study, we investigated the effects of anti-TfR monoclonal antibody 7579 alone or in combination with chemotherapeutic drugs (5-fluorouracil or doxorubicin) on non-hematopoietic tumor cells (HepG2 and MCF-7) in vitro. We found that 7579 mAb alone could dramatically down-regulate surface TfR expression on tumor cells. Consequently, marked S phase arrest and apoptosis were observed in 7579 mAb-treated tumor cells. In combination with 5-fluorouracil or doxorubicin, 7579 mAb enhanced the growth inhibitory effects of chemotherapeutic drugs on tumor cells. Results of 7AAD/Annexin V staining demonstrated that 7579 mAb enhanced the cytotoxic effects of chemotherapeutic drugs on tumor cells by mainly promoting tumor cell necrosis. Using the median-effect/combination-index isobologram method, we further evaluated the nature of 7579 mAb/chemotherapeutic drug interactions. Synergistic interaction was observed for 7579 mAb combined with 5-fluorouracil whereas additive efficacy was observed for 7579 mAb plus doxorubicin. Our study provided the basis to further develop 7579 mAb-containing chemoimmunotherapy for non-hematopoietic malignancies.