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1.
Mater Horiz ; 10(10): 4488-4500, 2023 Oct 02.
Article in English | MEDLINE | ID: mdl-37534735

ABSTRACT

Al2O3 deposited via atomic layer deposition (ALD) has been used as an insulating and barrier film for thin-film transistors, organic electronics, and microelectromechanical systems. However, ALD Al2O3 films are easily degraded by hydrolysis under harsh hygrothermal conditions, owing to their poor environmental stability. In this study, the mechanical properties and water-vapor transmission rate (WVTR) of environmentally degraded Al2O3 films were investigated by varying the temperature and relative humidity (RH). The hygrothermal environment led to surface and pinhole-concentrated degradation based on aluminum hydroxide, which caused an increased WVTR and reduced elongation of the films in harsher environments. In particular, the elongation of the degraded Al2O3 films was reduced to 0.3%, which is one-third of that of as-deposited Al2O3, and their WVTR increased on the order of 10-1 g m-2 day-1, which is more than 1000 times that of as-deposited Al2O3. Therefore, we introduced a functional silane-based inorganic-organic hybrid layer (silamer) onto the Al2O3 films to improve their environmental stability. The silamer helped preserve the characteristics of Al2O3 films by forming a strong and continuous aluminate phase of Al-O-Si at their interface in hygrothermal environments. Furthermore, the silamer-capped Al2O3 was shown to be an environmentally stable encapsulation for application in wearable organic devices.

2.
Adv Sci (Weinh) ; 9(35): e2204622, 2022 12.
Article in English | MEDLINE | ID: mdl-36310107

ABSTRACT

Neonatal jaundice is a very common disease in newborns and can lead to brain damage or death in severe cases. Phototherapy with light-emitting diode (LED) arrays is widely used as the easiest and fastest way to relieve jaundice in newborns, but it has distinct disadvantages such as loss of water in the patient, damage to the retina, and separation from parents. In this paper, a novel light source-based phototherapy for neonatal jaundice is proposed using a textile-based wearable organic light-emitting diode (OLED) platform that can move flexibly and conform to the curvature of the human body. The soft and flexible textile-based blue OLED platform is designed to have a peak wavelength of 470 nm, suitable for jaundice treatment, and shows performance (>20 µW cm-2 nm- 1 ) suitable for intensive jaundice treatment even at low voltage (<4.0 V). The textile-based OLEDs fabricated in this study exhibit an operating reliability of over 100 h and low-temperature operation (<35 °C). The results of an in vitro jaundice treatment test using a large-area blue OLED confirm that the bilirubin level decreases to 12 mg dL-1 with 3 h of OLED irradiation.


Subject(s)
Jaundice, Neonatal , Jaundice , Wearable Electronic Devices , Humans , Infant, Newborn , Reproducibility of Results , Phototherapy/methods , Jaundice/therapy
3.
Micromachines (Basel) ; 13(9)2022 Sep 06.
Article in English | MEDLINE | ID: mdl-36144102

ABSTRACT

As the demand for flexible organic light-emitting diodes (OLEDs) grows beyond that for rigid OLEDs, various elements of OLEDs, such as thin-film transistors, electrodes, thin-film encapsulations (TFEs), and touch screen panels, have been developed to overcome OLEDs' physical and chemical limitations through material and structural design. In particular, TFEs, which protect OLEDs from the external environment, including reactive gases, heat, sunlight, dust, and particles, have technical difficulties to be solved. This review covers various encapsulation technologies that have been developed with the advent of atomic layer deposition (ALD) technology for highly reliable OLEDs, in which solutions to existing technical difficulties in flexible encapsulations are proposed. However, as the conventional encapsulation technologies did not show technological differentiation because researchers have focused only on improving their barrier performance by increasing their thickness and the number of pairs, OLEDs are inevitably vulnerable to environmental degradation induced by ultraviolet (UV) light, heat, and barrier film corrosion. Therefore, research on multi-functional encapsulation technology customized for display applications has been conducted. Many research groups have created functional TFEs by applying nanolaminates, optical Bragg mirrors, and interfacial engineering between layers. As transparent, wearable, and stretchable OLEDs will be actively commercialized beyond flexible OLEDs in the future, customized encapsulation considering the characteristics of the display will be a key technology that guarantees the reliability of the display and accelerates the realization of advanced displays.

4.
ACS Appl Mater Interfaces ; 13(14): 16650-16659, 2021 Apr 14.
Article in English | MEDLINE | ID: mdl-33788536

ABSTRACT

A fundamental understanding of the mechanical behavior of the indium tin oxide (ITO) layer is very important because cracking and delamination of the ITO layers have been a critical obstacle for mechanically robust flexible electronics. In this study, the intrinsic mechanical properties of ITO thin films without a substrate were measured by utilizing a freestanding tensile testing method. Young's modulus (89 ± 1 GPa), elongation (0.34 ± 0.02%), and tensile strength (293 ± 13 MPa) of amorphous as-deposited ITO thin films were successfully measured. The sheet resistance, transparency, and thickness of the as-deposited films were 32.9 ± 0.5 Ω/sq, 92.7% (400-700 nm), and 152 ± 6 nm, respectively. First, we investigated the effects of annealing temperature on the mechanical properties of ITO thin films. For 100- and 150 °C-annealed ITO thin films, which were amorphous, Young's modulus, elongation, and tensile strength were enhanced by increasing the packing density and reducing the structural defects. For 200 °C-annealed ITO thin films, which were polycrystalline, Young's modulus was further increased because of their highly packed crystalline nature. However, there was a significant decrease in elongation and tensile strength because grain boundaries act as critical defects. Next, the annealing time was varied from 0.5 to 6 h for a better understanding of the effects of the annealing time. As a result, the maximum elongation (0.54 ± 0.03%) and tensile strength (589 ± 11 MPa) were obtained at 150 °C for 1 h. Annealing for 1 h was appropriate for sufficient defect reduction; however, excessive annealing for more than 1 h increased the degree of partial crystallization of the ITO thin films. The proposed annealing conditions and the corresponding mechanical properties provide guidelines for the optimum annealing process of ITO thin films and quantitative data for mechanical analysis to design mechanically robust flexible electronics.

5.
Light Sci Appl ; 8: 114, 2019.
Article in English | MEDLINE | ID: mdl-31839934

ABSTRACT

Free-form optoelectronic devices can provide hyper-connectivity over space and time. However, most conformable optoelectronic devices can only be fabricated on flat polymeric materials using low-temperature processes, limiting their application and forms. This paper presents free-form optoelectronic devices that are not dependent on the shape or material. For medical applications, the transferable OLED (10 µm) is formed in a sandwich structure with an ultra-thin transferable barrier (4.8 µm). The results showed that the fabricated sandwich-structure transferable OLED (STOLED) exhibit the same high-efficiency performance on cylindrical-shaped materials and on materials such as textile and paper. Because the neutral axis is freely adjustable using the sandwich structure, the textile-based OLED achieved both folding reliability and washing reliability, as well as a long operating life (>150 h). When keratinocytes were irradiated with red STOLED light, cell proliferation and cell migration increased by 26 and 32%, respectively. In the skin equivalent model, the epidermis thickness was increased by 39%; additionally, in organ culture, not only was the skin area increased by 14%, but also, re-epithelialization was highly induced. Based on the results, the STOLED is expected to be applicable in various wearable and disposable photomedical devices.

6.
ACS Appl Mater Interfaces ; 11(18): 16776-16784, 2019 May 08.
Article in English | MEDLINE | ID: mdl-30977637

ABSTRACT

When placed in an outdoor environment, organic electronic devices (OEDs) can degrade on exposure to moisture, UV light, and heat, owing to the chemical sensitivity and decomposition of the organic materials. Therefore, to protect OEDs from outdoor environments, thin-film passivation, which can block harmful elements from reaching organic materials, is required. To meet the demands and trends in encapsulation technologies, in this study, we developed a low-temperature, simple, and effective gas diffusion multibarrier (GDM), which is UV and heat reflective as well as corrosion resistant. The designed UV- and heat-reflective GDM (UHGDM) has a multistacked structure in the form of a UV filter/Ag/gas diffusion barrier (GDB)/polymer based on a dielectric/metal/dielectric (DMD) configuration. First, the DMD structure was used as a heat mirror for infrared reflectance. Second, the bottom dielectric layer of the DMD structure was used as the UV filter, and it consisted of a ZnS/LiF multistacked structure with large differences in refractive indexes. Third, a nanolaminate-based GDB barrier with multi-interfacial and defect-decoupling systems, which achieved a water vapor transmission rate of 1.58 × 10-5 g/m2/day at a thickness of 60 nm, was used as the top dielectric layer of the DMD structure. Finally, an inorganic/organic hybrid polymer layer was coated on the DMD structure to provide corrosion-resistance and waterproofing properties. The fabricated UHGDM showed high transparency in the visible region and excellent reflectance in the UV and IR regions, resulting in excellent UV and heat rejection capability in practical UV and heat reflection tests. In addition to optical functionalities, the UHGDM maintained its functionality against harsh environmental conditions because of the GDB/polymer structure. Finally, the feasibility of the UHGDM was demonstrated using organic solar cells through water immersion and shelf lifetime tests.

7.
ACS Appl Mater Interfaces ; 11(3): 3251-3261, 2019 Jan 23.
Article in English | MEDLINE | ID: mdl-30189129

ABSTRACT

The lack of a transparent, flexible, and reliable encapsulation layer for organic-based devices makes it difficult to commercialize wearable, transparent, flexible displays. The reliability of organic-based devices sensitive to water vapor and oxygen must be guaranteed through an additional encapsulation layer for the luminance efficiency and lifetime. Especially, one of the major difficulties in current and future OLED applications has been the absence of thin-film encapsulation with superior barrier performance, mechanical flexibility, and water-resistant properties. In this work, we fabricated highly water-resistant, impermeable, and flexible inorganic/organic multilayers with optimized Al2O3 and functional organic layers. The key properties of the fabricated multilayers were compared according to the thickness and functionality of the inorganic and organic layers. Improvement of the barrier performance is mainly attributed to the optimized thickness of the Al2O3 films, and is additionally due to the increased lag time and effective surface planarization effects caused by the use of micrometer-thick organic layers. As a result, the 3-dyad multilayer structure composed of 60 nm-thick Al2O3 layers deposited at 70 °C and 2-µm-thick silane-based inorganic/organic hybrid polymer (silamer) layers with layered silica exhibited the lowest WVTR value of 1.11 × 10-6 g/m2/day in storage conditions of 30 °C/90% relative humidity. In addition, the multibarrier exhibited good mechanical stability through the use of alternating stacks of brittle inorganic and soft organic layers, without showing a large increase in the WVTR after bending tests. In addition, silamer layers improved the environmental stability of the Al2O3 ALD film. The silamer layer coated on the Al2O3 film effectively worked as a protective layer against harsh environments. The effective contact at the interface of Al2O3/silamer makes the barrier structure more impermeable and corrosion-resistant. In this study, we not only demonstrated an optimized multilayer based on functional organic layers but also provided a methodology for designing a wearable encapsulation applicable to wearable organic electronics.

8.
ACS Appl Mater Interfaces ; 10(38): 32387-32396, 2018 Sep 26.
Article in English | MEDLINE | ID: mdl-30141612

ABSTRACT

Thin-film encapsulation is strictly required to protect transparent, flexible organic light-emitting diodes (OLEDs) based on plastic substrates with poor moisture barrier performances against water vapor and oxygen. However, additional encapsulation process makes OLED fabrication complex and expensive, resulting in lower yield and higher costs for the manufacture of OLEDs. Therefore, to develop simple, transparent conductive gas diffusion barrier (TCGDB) technologies by providing barrier performances to electrodes can be alternatives. Furthermore, TCGDB based on dielectric/metal/dielectric structures exhibit not only excellent barrier performances to protect metallic and organic layers against the ambient environment but also mechanical flexibility overcoming the brittleness of oxides. In this work, to improve the moisture-resistant, electrical, and optical properties of ZnO film, periodical dopant layers were inserted during the deposition of atomic layer deposition ZnO film. These dopant layers make the intrinsic ZnO film more optically and electrically functional. The dopant of MgO with a wide band gap enables blue-shifted optical transmittance, and the dopant of Al atoms makes doped ZnO more electrically conductive. In addition, these dopant layers in the ZnO film interrupt the film crystallization, making the film less crystalline with fewer channels and grain boundaries. This effect results in significant improvement of its GDB properties. With a functional and material design that takes full advantage of the synergetic combination of highly flexible conductive Ag and a moisture-resistant MAZO layer, the MAZO/Ag/MAZO (MAM) multilayer with a thickness of approximately 110 nm achieves a sheet resistance of 5.60 Ω/sq, an average transmittance of 89.72% in the visible range, and a water vapor transmission rate on the order of 10-5 g/m2/day. In addition, OLEDs with the MAM electrode demonstrated a great potential of indium tin oxide- and encapsulation-free organic electronics.

9.
ACS Appl Mater Interfaces ; 10(18): 15829-15840, 2018 May 09.
Article in English | MEDLINE | ID: mdl-29672018

ABSTRACT

The lack of reliable, transparent, and flexible electrodes and insulators for applications in thin-film transistors (TFTs) makes it difficult to commercialize transparent, flexible TFTs (TF-TFTs). More specifically, conventional high process temperatures and the brittleness of these elements have been hurdles in developing flexible substrates vulnerable to heat. Here, we propose electrode and insulator fabrication techniques considering process temperature, transmittance, flexibility, and environmental stability. A transparent and flexible indium tin oxide (ITO)/Ag/ITO (IAI) electrode and an Al2O3/MgO (AM)-laminated insulator were optimized at the low temperature of 70 °C for the fabrication of TF-TFTs on a polyethylene terephthalate (PET) substrate. The optimized IAI electrode with a sheet resistance of 7 Ω/sq exhibited the luminous transmittance of 85.17% and maintained its electrical conductivity after exposure to damp heat conditions because of an environmentally stable ITO capping layer. In addition, the electrical conductivity of IAI was maintained after 10 000 bending cycles with a tensile strain of 3% because of the ductile Ag film. In the metal/insulator/metal structure, the insulating and mechanical properties of the optimized AM-laminated film deposited at 70 °C were significantly improved because of the highly dense nanolaminate system, compared to those of the Al2O3 film deposited at 70 °C. In addition, the amorphous indium-gallium-zinc oxide (a-IGZO) was used as the active channel for TF-TFTs because of its excellent chemical stability. In the environmental stability test, the ITO, a-IGZO, and AM-laminated films showed the excellent environmental stability. Therefore, our IGZO-based TFT with IAI electrodes and the 70 °C AM-laminated insulator was fabricated to evaluate robustness, transparency, flexibility, and process temperature, resulting in transfer characteristics comparable to those of an IGZO-based TFT with a 150 °C Al2O3 insulator.

10.
ACS Appl Mater Interfaces ; 9(50): 43983-43992, 2017 Dec 20.
Article in English | MEDLINE | ID: mdl-29185704

ABSTRACT

In this study, a structurally and materially designed thin-film encapsulation is proposed to guarantee the reliability of transparent, flexible displays by significantly improving their barrier properties, mechanical stability, and environmental reliability, all of which are essential for organic light-emitting diode (OLED) encapsulation. We fabricated a bioinspired, nacre-like ZnO/Al2O3/MgO laminate structure (ZAM) using atomic layer deposition for the microcrack toughening effect. The ZAM film was formed with intentional voids and defects through the formation of a quasi-perfect sublayer, rather than the simple fabrication of nanolaminate structures. The 240 nm thick ZAM-based multibarrier (ZAM-TFE) with a compressively strained organic layer demonstrated an optical transmittance of 91.35% in the visible range, an extremely low water vapor transmission rate of 2.06 × 10-6 g/m2/day, a mechanical stability enduring a strain close to 1%, and a residual stress close to 0, showing significant improvement of key TFE properties in comparison to an Al2O3-based multibarrier. In addition, ZAM-TFE demonstrated superior environmental resistance without degradation of barrier properties in a severe environment of 85 °C and 90% relative humidity (RH). Thus, our structurally and materially designed ZAM film has been well optimized in terms of its applicability as a gas diffusion barrier as well as in terms of its mechanical and environmental reliability. Finally, we confirmed the feasibility of the ZAM-TFE through application in OLEDs. The low-temperature ZAM-TFE technology showed great potential to provide a highly robust and flexible TFE of TFOLEDs.

11.
ACS Appl Mater Interfaces ; 9(32): 27062-27072, 2017 Aug 16.
Article in English | MEDLINE | ID: mdl-28718293

ABSTRACT

In this study, a new and efficient dielectric-metal-dielectric-based thin-film encapsulation (DMD-TFE) with an inserted Ag thin film is proposed to guarantee the reliability of flexible displays by improving the barrier properties, mechanical flexibility, and heat dissipation, which are considered to be essential requirements for organic light-emitting diode (OLED) encapsulation. The DMD-TFE, which is composed of Al2O3, Ag, and a silica nanoparticle-embedded sol-gel hybrid nanocomposite, shows a water vapor transmission rate of 8.70 × 10-6 g/m2/day and good mechanical reliability at a bending radius of 30 mm, corresponding to 0.41% strain for 1000 bending cycles. The electrical performance of a thin-film encapsulated phosphorescent organic light-emitting diode (PHOLED) was identical to that of a glass-lid encapsulated PHOLED. The operational lifetimes of the thin-film encapsulated and glass-lid encapsulated PHOLEDs are 832 and 754 h, respectively. After 80 days, the thin-film encapsulated PHOLED did not show performance degradation or dark spots on the cell image in a shelf-lifetime test. Finally, the difference in lifetime of the OLED devices in relation to the presence and thickness of a Ag film was analyzed by applying various TFE structures to fluorescent organic light-emitting diodes (FOLEDs) that could generate high amounts of heat. To demonstrate the difference in heat dissipation effect among the TFE structures, the saturated temperatures of the encapsulated FOLEDs were measured from the back side surface of the glass substrate, and were found to be 67.78, 65.12, 60.44, and 39.67 °C after all encapsulated FOLEDs were operated at an initial luminance of 10 000 cd/m2 for sufficient heat generation. Furthermore, the operational lifetime tests of the encapsulated FOLED devices showed results that were consistent with the measurements of real-time temperature profiles taken with an infrared camera. A multifunctional hybrid thin-film encapsulation based on a dielectric-metal-dielectric structure was thus effectively designed considering the transmittance, gas-permeation barrier properties, flexibility, and heat dissipation effect by exploiting the advantages of each separate layer.

12.
Epidemiol Health ; 38: e2016022, 2016.
Article in English | MEDLINE | ID: mdl-27283139

ABSTRACT

OBJECTIVES: We examined the associations between happiness and a wide range of health behaviors in South Korean adolescents. METHODS: Study data were derived from the ninth Korea Youth Risk Behavior Web-based Survey administered from June to July 2013. In addition to happiness levels, the questionnaire included items on sociodemographics and health-related lifestyle factors (smoking, drinking, eating breakfast, fruit and vegetable consumption, physical activity, sedentary behavior, and hours of sleep). RESULTS: The multivariate analysis revealed that higher levels of happiness were associated with not smoking or drinking, eating breakfast, eating fruits daily, vegetable consumption, participating in at least 60 minutes of physical activity a day, avoiding sedentary behavior, and hours of sleep. Additionally, sex differences were found in relationships between happiness and eating fruit daily, participation in physical activity, and sedentary behavior. CONCLUSIONS: These results encourage public health professionals to consider the psychological aspects of adolescent life in working to improve their health behaviors and outcomes.


Subject(s)
Adolescent Behavior/psychology , Happiness , Health Behavior , Healthy Lifestyle , Adolescent , Child , Cross-Sectional Studies , Female , Health Surveys , Humans , Male , Republic of Korea , Sex Factors
13.
Epidemiol Health ; 37: e2015030, 2015.
Article in English | MEDLINE | ID: mdl-26212505

ABSTRACT

OBJECTIVES: Little attention has been paid to levels of trust in online sources of health information. The objective of this study was to investigate levels of trust in various sources of health information (interpersonal channels, traditional media, and Internet media), and to examine the predictors of trust in health information available on the Internet. METHODS: A questionnaire was administered to 1,300 people (20 years of age or older), evaluating levels of trust in various sources of health information. RESULTS: The highest level of trust was expressed regarding interpersonal channels, with hospital physicians regarded as the most trusted source of information age and income showed an association with trust in online information sources. Elderly people were not likely to trust Internet news sources, and high incomes were found to be strongly associated with trust in online sources of information overall. CONCLUSIONS: Public health organizations must consider the predictors for trust in various sources of information in order to employ appropriate media when targeting vulnerable individuals or developing messaging strategies for health professionals.

14.
Asian Pac J Cancer Prev ; 16(2): 731-6, 2015.
Article in English | MEDLINE | ID: mdl-25684516

ABSTRACT

BACKGROUND: Little is known about the news coverage of cancer risk factors in Korea. This study aimed to examine how the news media encompasses a wide array of content regarding cancer risk factors and related cancer sites, and investigate whether news coverage of cancer risk factors is congruent with the actual prevalence of the disease. MATERIALS AND METHODS: A content analysis was conducted on 1,138 news stories covered during a 5-year period between 2008 and 2012. The news stories were selected from nationally representative media in Korea. Information was collected about cancer risk factors and cancer sites. RESULTS: Of various cancer risk factors, occupational and environmental exposures appeared most frequently in the news. Breast cancer was mentioned the most in relation to cancer sites. Breast, cervical, prostate, and skin cancer were overrepresented in the media in comparison to incidence and mortality cases, whereas lung, thyroid, liver, and stomach cancer were underrepresented. CONCLUSIONS: To our knowledge, this research is the first investigation dealing with news coverage about cancer risk factors in Korea. The study findings show occupational and environmental exposures are emphasized more than personal lifestyle factors; further, more prevalent cancers in developed countries have greater media coverage, not reflecting the realities of the disease. The findings may help health journalists and other health storytellers to develop effective ways to communicate cancer risk factors.


Subject(s)
Attitude to Health , Mass Media , Neoplasms/etiology , Humans , Neoplasms/epidemiology , Neoplasms/mortality , Prognosis , Republic of Korea/epidemiology , Risk Factors , Survival Rate
15.
BMC Med ; 10: 72, 2012 Jul 12.
Article in English | MEDLINE | ID: mdl-22788922

ABSTRACT

BACKGROUND: Probiotic lactic acid bacteria (LAB) support a functional and balanced immune system, and contribute to immune modulatory effects in combatting microbial pathogens, including viruses. Most cervical cancers are associated with anogenital region infection with high-risk (HR) human papillomavirus (HPV). In this study, we analyzed the antiviral activity of Bifidobacterium adolescentis SPM1005-A in the SiHa cervical cancer cell line expressing HPV type 16. METHODS: We assessed the cellular toxicity of B. adolescentis SPM1005-A in SiHa cells by the Trypan blue dye exclusion assay. Cells (3.6 × 105) in culture plates with or without B. adolescentis SPM1005-A in the same type of medium, were incubated with HPV type 16 at a concentration of 5.1 × 107 cfu/ml. For antiviral analysis, we performed quantitative real-time PCR (qRT-PCR) for E6 and E7 oncogene expressions and observed protein levels by immunoblotting. RESULTS: The qRT-PCR results showed that E6 and E7 mRNA levels decreased simultaneously. Western blot analysis revealed that the E6 protein expression slightly decreased after 24 and 48 h, but the level of E7 protein expression appear unaffected compared with that in the control. Decreased HPV16 E6 and E7 mRNA transcript and protein levels were not associated with cell morphology or significant cytotoxic effects. CONCLUSIONS: This study showed that B. adolescentis SPM1005-A had antiviral activity through suppression E6 and E7 oncogene expression. The results suggest that B. adolescentis SPM1005-A could be potential applications of HPV-associated cervical cancer prevention.


Subject(s)
Bifidobacterium/immunology , Human papillomavirus 16/immunology , Papillomavirus Infections/immunology , Probiotics , Uterine Cervical Neoplasms/immunology , Cell Line, Tumor , Cell Transformation, Neoplastic , Female , Gene Expression Regulation, Viral , Humans , Oncogene Proteins, Viral/antagonists & inhibitors , Oncogene Proteins, Viral/biosynthesis , Oncogene Proteins, Viral/genetics , Papillomavirus E7 Proteins/antagonists & inhibitors , Papillomavirus E7 Proteins/biosynthesis , Papillomavirus E7 Proteins/genetics , Repressor Proteins/antagonists & inhibitors , Repressor Proteins/biosynthesis , Repressor Proteins/genetics
16.
Cancer Chemother Pharmacol ; 65(6): 1029-37, 2010 May.
Article in English | MEDLINE | ID: mdl-19701751

ABSTRACT

PURPOSE: Recent studies have demonstrated that frequent, low-dose metronomic (MET) dosing of cytotoxic agents may not only be as efficient as conventional maximum tolerated dose (MTD) chemotherapy but also less toxic. In this study, we investigated the therapeutic effect and safety of MET chemotherapy using cyclophosphamide (CTX) in rats with chemically induced hepatocellular carcinoma (HCC). METHODS: Rats received weekly intraperitoneal (i.p.) injections of diethylnitrosamine during 16 weeks for induction of HCC. The rats were divided into three groups: MTD group received 40 mg/kg CTX i.p. injection on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received saline and 20 mg/kg CTX i.p. injection twice a week, respectively. The growth-modulating effects and overall survival were compared between the groups. Anti-angiogenic effects were evaluated by a measurement of endothelial cell and VEGFR-2 expression. RESULTS: At 6 weeks of therapy, MTD and MET chemotherapy resulted in a significant reduction in tumor number and size compared with Control group. MET chemotherapy showed more prolonged survival than MTD chemotherapy and Control groups (P < 0.05). MET chemotherapy resulted in a significant decrease in both the micro-vessel density and endothelial proliferation index (P < 0.01). Furthermore, MET chemotherapy led to a greater decrease in VEGFR-2 expression at the mRNA and protein levels (P < 0.01). CONCLUSIONS: MET scheduling not only exhibits anti-tumor and anti-angiogenic effects, but also prolongs survival without major toxicities in a rat model of HCC. Our results suggest that MET chemotherapy has a high therapeutic value and should be considered for future clinical trials.


Subject(s)
Cyclophosphamide/therapeutic use , Liver Cirrhosis/drug therapy , Liver Neoplasms, Experimental/drug therapy , Liver/drug effects , Animals , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/therapeutic use , Apoptosis/drug effects , Body Weight/drug effects , Cell Proliferation/drug effects , Cyclophosphamide/administration & dosage , Diethylnitrosamine , Dose-Response Relationship, Drug , Drug Administration Schedule , Endothelial Cells/cytology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Immunoblotting , Kaplan-Meier Estimate , Liver/metabolism , Liver/pathology , Liver Cirrhosis/chemically induced , Liver Neoplasms, Experimental/chemically induced , Proliferating Cell Nuclear Antigen/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Tumor Burden/drug effects , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolism , von Willebrand Factor/metabolism
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