Direct effects of alcohol on gut-epithelial barrier: Unraveling the disruption of physical and chemical barrier of the gut-epithelial barrier that compromises the host-microbiota interface upon alcohol exposure.

The development of alcohol-associated diseases is multifactorial, mechanism of which involves metabolic alteration, dysregulated immune response, and a perturbed intestinal host-environment interface. Emerging evidence has pinpointed the critical role of the intestinal host-microbiota interaction in alcohol-induced injuries, suggesting its contribution to disease initiation and development. To maintain homeostasis in the gut, the intestinal mucosa serves as the first-line defense against exogenous factors in the gastrointestinal tract, including dietary contents and the commensal microbiota. The gut-epithelial barrier comprises a physical barrier lined with a single layer of intestinal epithelial cells and a chemical barrier with mucus trapping host regulatory factors and gut commensal bacteria. In this article, we review recent studies pertaining to the disrupted gut-epithelial barrier upon alcohol exposure and examine how alcohol and its metabolism can affect the regulatory ability of intestinal epithelium.

Interleukin-1 receptor 1 deficiency worsens hepatocellular carcinoma, while gemcitabine treatment alleviates the hepatocellular carcinoma-induced increase in intra-hepatic immune cells.

BACKGROUND AND AIM: Primary liver cancer, particularly hepatocellular carcinoma (HCC), represents a substantial global health challenge. Although immune checkpoint inhibitors are effective in HCC treatment, several patients still experience disease progression. Interleukin-1 (IL-1) regulates immunity and inflammation. We investigate the role of IL-1 in HCC development and progression and determine the potential therapeutic impact of gemcitabine in treating HCC. METHODS: Hydrodynamics-based transfection, employing the sleeping beauty transposase system, delivered surrogate tumor antigens, NRAS (NRAS proto-oncogene, GTPase), ShP53, and SB100 to C57BL/6 mice. A basic HCC mouse model was established. Pathogen-free animals were tested for serum and hepatotoxicity. The HCC prognosis was monitored using alanine aminotransferase and aspartate aminotransferase levels. Liver histology immunohistochemistry and mouse splenocyte/intra-hepatic immune cell flow cytometry were conducted. IL-1ß levels in human and mouse serum were assessed. RESULTS: Interleukin-1ß levels were elevated in patients with HCC compared with those in non-HCC controls. Hepatic IL-1ß levels were higher in HCC mouse models than those in non-HCC mice, suggesting localized hepatic inflammation. IL-1 receptor type 1 (IL-1R1) knockout (IL-1R1-/-) mice exhibited less severe HCC progression than that in wild-type mice, despite the high intra-hepatic IL-1ß concentration. IL-1R1-/- mice exhibited increased hepatic levels of myeloid-derived suppressor cells and regulatory T cells, which may exacerbate HCC. Gemcitabine significantly reduced the HCC tumor burden, improved liver conditions, and increased survival rates in HCC mouse models. Gemcitabine reduced the hepatic levels of myeloid-derived suppressor cells and regulatory T cells, potentially alleviating immune suppression in the liver. CONCLUSIONS: Targeting IL-1 or combining gemcitabine with immunotherapy is a promising approach for treating advanced-stage HCC.

[Nursing Care Experiences of Periwound Moisture-Associated Dermatitis After Simultaneous Pancreas-Kidney Transplantation].

Simultaneous pancreas-kidney (SPK) transplantation is the primary surgical treatment for type I diabetes mellitus with end-stage renal disease. However, this transplant surgery has a high-risk of surgical complications, including duodenal anastomotic leakage, which may lead to pancreas transplantation failure if the leakage worsens. This case report describes a patient who suffered from duodenal anastomotic leakage after SPK transplantation. The digestive enzymes eroded the wound and skin around the wound, resulting in periwound moisture-associated dermatitis. During the period of nursing care, the wound-care intervention was determined by interdisciplinary cooperation. In our case report, the periwound moisture-associated dermatitis healed completely under inter-hospital care. In clinical nursing practice, periwound moisture-associated dermatitis should be cared in combination with macerated wounds. We suggest the following: (1) control the moisture source; (2) use advanced dressings as the primary dressing with sterile gauze as a secondary dressing and silver antimicrobial dressings for infected wounds; (3) consider using negative pressure wound therapy for complicated chronic wounds; and (4) use a pH-neutral skin cleanser with non-woven gauze to clean the periwound skin and keep the skin clean and dry. Finally, we suggest isolating and protecting the skin with No Sting Barrier Film and a hydrocolloid dressing. We hope this nursing care experiences serves as a reference for the nursing care of periwound moisture-associated dermatitis resulting from duodenal anastomotic leakage during / after SPK transplantation.

Postoperative Showering for Clean and Clean-contaminated Wounds: A Prospective, Randomized Controlled Trial.

OBJECTIVE: To evaluate wound infection rates, pain scores, satisfaction with wound care, and wound care costs starting 48 hours after surgery. BACKGROUND: Showering after surgery is a controversial issue for wound care providers and patients. We investigated the benefits and detriments of showering for postoperative wound care. METHODS: Patients undergoing thyroid, lung, inguinal hernia, and face and extremity surgeries with clean or clean-contaminated wounds were included. The patients were randomized to allow showering (shower group) or to keep the wound dry (nonshower group) for postoperative wound care starting 48 hours after surgery. The primary endpoint was the rate of surgical wound infection. The secondary endpoints included the wound pain score, satisfaction with wound care, and cost of wound care. RESULTS: Between May 2013 and March 2014, there were 222 patients randomized to the shower group and 222 to the nonshower group. Two patients in each group were lost to follow-up. There were 4 superficial surgical site infections in the shower group and 6 in the nonshower group (4/220, 1.8% vs 6/220, 2.7%, P = 0.751). Postoperative pain scores were comparable between the 2 groups. Patients in the shower group were more satisfied with their method of wound care, and their wound care costs were lower when compared with the nonshower group. CONCLUSIONS: Clean and clean-contaminated wounds can be safely showered 48 hours after surgery. Postoperative showering does not increase the risk of surgical site complications. It may increase patients' satisfaction and lower the cost of wound care.

Using induced electroosmotic micromixer to enhance the reproducibility of chemiluminescence intensity.

In this study, induced electroosmotic vortex flows were generated using an AC electric field by one pair of external electrodes to rapidly mix luminescence reagents in a 30 µL micromixer and enhance the reproducibility of chemiluminescence (CL) assays. A solution containing the catalyst reagent ferricyanide ions (4 µL) was pipetted into a reservoir containing luminol to produce CL in the presence of hydrogen peroxide. When the added ferricyanide aliquot contacted the reservoir solution, the CL began flashing, but rapidly diminished as the ferricyanide was consumed. In such a short illumination period, the solutes could not mix homogeneously. Therefore, the reproducibility of CL intensities collected using a CCD and multiple aliquot additions was determined to be inadequate. By contrast, when the solutes were efficiently mixed after adding a ferricyanide aliquot to a micromixer, the intensity reproducibility was significantly improved. When the CL temporal profile was analyzed using a PMT, a consistent improvement in reproducibility was observed between the CL intensity and estimated CL reaction rate. Replicating the proposed device would create a multiple well plate that contains a micromixer in each reservoir; this system is compatible with conventional CL instrumentation and requires no CL enhancer to slow a reaction.

Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies.

OBJECTIVE: Type 2 diabetes mellitus is associated with a higher risk of hepatocellular carcinoma (HCC), which is attenuated by the use of metformin. However, there are no studies addressing the effect of metformin on hepatocarcinoma cells from the antitumoural perspective. DESIGN: In the nationwide case-control study, the authors recruited 97,430 HCC patients and 19,860 age-, gender- and physician visit date-matched controls. The chemopreventive effects of metformin were examined by multivariate analysis and stratified analysis. The in vitro effects of metformin on cell proliferation and cell cycle were studied in HepG2 and Hep3B hepatoma cell lines. RESULTS: The OR of diabetes in HCC patients was 2.29 (95% CI 2.25 to 2.35, p<0.001). Each incremental year increase in metformin use resulted in 7% reduction in the risk of HCC in diabetic patients (adjusted OR=0.93, 95% CI 0.91 to 0.94, p<0.0001). In the multivariate stratified analysis, metformin use was associated with a reduced risk of HCC in diabetic patients in nearly all subgroups. Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53. Combined treatment of oral metformin with doxorubicin functioned more efficiently than either agent alone, in vivo. CONCLUSIONS: Use of metformin is associated with a decreased risk of HCC in diabetic patients in a dose-dependent manner, via inhibition of hepatoma cells proliferation and induction of cell cycle arrest at G0/G1 phase.

Osteopontin promoter polymorphisms are associated with susceptibility to gastric cancer.

GOALS: To evaluate the significance of osteopontin (OPN) genotypes in the susceptibility to gastric cancer. BACKGROUND: The expression of OPN has been correlated with development, invasiveness, metastasis, and survival of gastric cancer, but the role of polymorphisms in the OPN promoter has not been investigated. STUDY: We enrolled 146 gastric cancer patients and 128 controls. DNA was extracted from peripheral blood leucocytes. Single-nucleotide polymorphisms (SNPs) in the OPN promoter (-66, -156, -443, -616, -1748, and -1776) were analyzed by pyrosequencing and direct sequencing methods. Logistic regression analyses were used to evaluate the associations between SNPs and development of gastric cancer. RESULTS: SNP -443 C/C and -616 T/T of the OPN promoter were significantly associated with gastric cancer [odds ratio (OR)=2.88; 95% confidence interval (CI), 1.16-7.12 and OR=1.95; 95% CI, 1.35-2.82, respectively]. Analysis of the combined effect of OPN promoter SNPs revealed that the combination of SNP -443 (T/C or C/C) and SNP -616 (T/T or T/G) had the most significant association with gastric cancer (OR=3.95; 95% CI, 1.58-9.90). CONCLUSIONS: Our results suggest that polymorphisms in the OPN promoter are associated with the development of gastric cancer, and the combination of SNP -443 (T/C or C/C) and -616 (T/T or T/G) most significantly increases susceptibility to gastric cancer.

MMP-9 -1562 Promoter Polymorphism Associated with Gastric Cancer Risk in Females.

Background/Aims: C to T transition at the matrix metalloproteinase-9 (MMP-9) promoter site -1562 abolishes a binding site of a putative transcription repressor protein to the C allelic promoter. The aim of this study is to elucidate the significance of MMP-9 genotypes in clinicopathological manifestations of gastric cancer. Methodology: We conducted a case-control study based on previously stored peripheral blood samples from 263 gastric cancer patients and 354 controls. MMP-9 genotyping was analyzed by PCR-RFLP method. Stratified analysis, logistic regression and Cox proportional hazards analysis were used to evaluate the associations between polymorphisms and gastric cancer development, invasiveness, and survival. Results: There was significant correlation between female patients with MMP-9 -1562 C/T or T/T genotype and higher risk of gastric cancer (OR=2.12, p=0.02). On stratified analysis, only elderly females with T allele had higher risk of gastric cancer (OR=2.64, p=0.04). On Cox proportional hazards analysis, serosal invasion (adjusted HR=3.47, p<0.001) and lymph node metastasis (adjusted HR=2.31, p=0.003), but not MMP-9 polymorphism, were independent prognostic factors for survival. Conclusions: MMP-9 -1562 promoter polymorphism with T allele may be used as a marker to predict gastric cancer development in female subjects, especially in the elderly.

Experiences of Family Caregivers Providing Home Care to Older Patients With Cancer: A Qualitative Study.

BACKGROUND: Older patients with cancer receive anticancer therapy in outpatient settings, and care-related issues may occur after discharge, which often requires family caregivers (FCs) to play a significant role in providing cancer care at home. However, relatively few studies have been focused on exploring the care experiences of these FCs. PURPOSE: The aim of this study was to explore the care experiences of FCs caring for older family members with cancer at home. METHODS: A qualitative study design and in-depth individual interviews were used to explore the at-home care experiences of FCs of older patients with cancer. The research was conducted in chemotherapy outpatient settings of a medical center in northern Taiwan. Content analysis was used to analyze data. The analyses focused on first extracting meaningful units from the text and then inducting categories from these units and determining the major themes. RESULTS: Twenty FCs were interviewed. The three themes identified included (a) increased information needs and challenges in diet preparation and treatment decision making, (b) personal and patient-induced emotional stress, and (c) life rebalancing through the care experience. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings highlight the educational requirements, especially related to meeting personal dietary needs and obtaining psychological support, for FCs caring for older patients with cancer to help them rebalance their life.

Clinicopathological significance of urokinase-type plasminogen activator genotypes in gastric cancer.

BACKGROUND/AIMS: The roles of urokinase-type plasminogen activator (uPA) expression in tumor occurrence, invasion and prognosis have been established. However, how uPA genetic polymorphisms influence the occurrence and outcome of tumors is not as clear. METHODOLOGY: We conducted a case-control study based on previously stored peripheral blood samples from 237 gastric cancer patients and 242 healthy controls. uPA exon 6 and intron 7 genotypes were determined by direct DNA sequencing. Logistic regression analyses and Cox proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features, and survival. RESULTS: uPA exon 6 C/T and intron 7 T/C polymorphisms did not correlate well with gastric cancer susceptibility. uPA exon 6 T/C and T/T genotypes were associated with venous invasion and lymphatic invasion, but not with stage, serosal invasion or lymph node metastasis. uPA intron 7 T/C polymorphism did not correlate well with invasive phenotype of gastric cancer. On Cox proportional hazards analyses, uPA exon 6 and intron 7 polymorphisms were not independent prognostic factors for survival. CONCLUSIONS: uPA exon 6 C/T polymorphism is associated with invasive phenotype of gastric cancer, but not with susceptibility or survival of gastric cancer. uPA intron 7 is a silent polymorphism.

Clinicopathological significance of MMP-2 and TIMP-2 genotypes in gastric cancer.

AIMS: Single nucleotide polymorphisms in matrix metalloproteinase-2 (MMP-2) -1306 C/T and tissue inhibitor of metalloproteinase-2 (TIMP-2) -418 G/C abolish the Sp-1 binding site and down-regulate expression of these genes. We aim to elucidate the role of MMP-2 and TIMP-2 in clinicopathological manifestations of gastric cancer. METHODS: We enrolled 240 gastric cancer patients and 283 controls. DNA was extracted from peripheral blood leucocytes. MMP-2 and TIMP-2 genotypes were analysed by PCR-direct sequencing and PCR-RFLP method, respectively. RESULTS: MMP-2 and TIMP-2 genotypes were not associated with gastric cancer development. However, patients with MMP-2 -1306 C/C genotype showed higher risk of lymphatic invasion (odds ratio (OR)=2.77, p=0.01) and venous invasion (OR=2.93, p=0.012). TIMP-2 G/G genotype was associated with serosal invasion (OR=1.89, p=0.009), lymph node metastasis (OR=2.19, p=0.021), lymphatic invasion (OR=2.87, p=0.016) and venous invasion (OR=2.65, p=0.033). CONCLUSION: Our results suggest MMP-2 and TIMP-2 genotypes play a crucial role in gastric cancer invasion, but not with development of gastric cancer.

AC electro-osmotic mixing induced by non-contact external electrodes.

We demonstrate efficient mixing in a micro-fluidic reservoir smaller than 10 microL using ac electro-osmosis driven by field-induced polarization. Our mixing device, of that electrodes are outside of the mixing unit, consists of three circular reservoirs (3mm in diameter) connected by a 1 mm x 1 mm channel. Unlike dc electro-osmosis, whose polarization is from charged substrate functional groups, this new mechanism uses the external field to capacitively charge the surface and the surface capacitance becomes the key factor in the electrokinetic mobility. The charging and mixing are enhanced at tailor-designed channel corners by exploiting the high normal fields at geometric singularities. The induced surface dielectric polarization and the resulting electric counter-ion double layer produce an effective Zeta potential in excess of 1 V, over one order of magnitude larger than the channel Zeta potential. The resulting ac electro-osmotic slip velocity scales quadratically with respect to the applied field, in contrast to the linear scaling of dc electro-osmosis and at 1cm/s and larger, exceeds the classical dc values by two orders of magnitude. The polarization is non-uniform at the corners due to field leakage to the dielectric substrate and the inhomogeneous slip velocity produces intense mixing vortices that effectively homogenize solutes in 30s in a 3mm reservoir, in contrast to hour-long mixing by pure diffusion.

Thermoplastic microchannel fabrication using carbon dioxide laser ablation.

We report the procedures of machining microchannels on Vivak co-polyester thermoplastic substrates using a simple industrial CO(2) laser marker. To avoid overheating the substrates, we develop low-power marking techniques in nearly anaerobic environment. These procedures are able to machine microchannels at various aspect ratios. Either straight or serpent channel can be easily marked. Like the wire-embossed channel walls, the ablated channel surfaces become charged after alkaline hydrolysis treatment. Stable electroosmotic flow in the charged conduit is observed to be of the same order of magnitude as that in fused silica capillary. Typical dynamic coating protocols to alter the conduit surface properties are transferable to the ablated channels. The effects of buffer acidity on electroosmotic mobility in both bare and coated channels are similar to those in fused silica capillaries. Using video microscopy we also demonstrate that this device is useful in distinguishing the electrophoretic mobility of bare and latex particles from that of functionalized ones.

A magnetic vehicle realized tumor cell-targeted radiotherapy using low-dose radiation.

Radiotherapy, a common cancer treatment, often adversely affects the surrounding healthy tissue and/or cells. Some tumor tissue-focused radiation therapies have been developed to lower radiation-induced lesion formation; however, achieving tumor cell-targeted radiotherapy (i.e., precisely focusing the radiation efficacy to tumor cells) remains a challenge. In the present study, we developed a novel tumor cell-targeted radiotherapy, named targeted sensitization-enhanced radiotherapy (TSER), that exploits tumor-specific folic acid-conjugated carboxymethyl lauryl chitosan/superparamagnetic iron oxide (FA-CLC/SPIO) micelles to effectively deliver chlorin e6 (Ce6, a sonosensitizer) to mitochondria of HeLa cells under magnetic guidance. For the in vitro tests, the sensitization of Ce6 induced by ultrasound, that could weaken the radiation resistant ability of tumor cells, occurred only in Ce6-internalizing tumor cells. Therefore, low-dose X-ray irradiation, that was not harmful to normal cells, could exert high tumor cell-specific killing ability. The ratio of viable normal cells to tumor cells was increased considerably, from 7.8 (at 24h) to 97.1 (at 72h), after they had received TSER treatment. Our data suggest that TSER treatment significantly weakens tumor cells, resulting in decreased viability in vitro as well as decreased in vivo subcutaneous tumor growth in nude mice, while the adverse effects were minimal. Taken together, TSER treatment appears to be an effective, clinically feasible tumor cell-targeted radiotherapy that can solve the problems of traditional radiotherapy and photodynamic therapy.

Design of an Electronic Reminder System for Supporting the Integerity of Nursing Records.

The integrity of electronic nursing records (ENRs) stands for the quality of medical records. But patients' conditions are varied (e.g. not every patient had wound or need fall prevention), to achieve the integrity of ENRs depends much on clinical nurses' attention. Our study site, an one 2,300-bed hospital in northern Taiwan, there are a total of 20 ENRs including nursing assessments, nursing care plan, discharge planning etc. implemented in the whole hospital before 2014. It become important to help clinical nurses to decrease their human recall burden to complete these records. Thus, the purpose of this study was to design an ENRs reminder system (NRS) to facilitate nursing recording process. The research team consisted of an ENR engineer, a clinical head nurse and a nursing informatics specialist began to investigate NRS through three phases (e.g. information requirements; design and implementation). In early 2014, a qualitative research method was used to identify NRS information requirements through both groups (e.g. clinical nurses and their head nurses) focus interviews. According to the their requirements, one prototype was created by the nursing informatics specialist. Then the engineer used Microsoft Visual Studio 2012, C#, and Oracle to designed a web-based NRS (Figure 1). Then the integrity reminder system which including a total of twelve electronic nursing records was designed and the preliminary accuracy validation of the system was 100%. NRS could be used to support nursing recording process and prepared for implementing in the following phase.

Dependence of buffer acidity and surfactant chain-length on electro-osmotic mobility in thermoplastic microchannels.

In this paper, we report the dependence of buffer pH and coating surfactant chain-length on electro-osmotic (EO) mobility in co-polyester microchannels. Thermoplastics co-polyester hydrolyzes to anionic functionality to create electrical double layer on the micro-channel walls. These negatively charged sites are partially or completely screened when long-chain surfactants are added into the buffer. This ancillary technique to modify surface charge polarity to avoid analyte adsorption is known as dynamic coating. We develop a theory to predict the EO mobility tendency on buffer acidity considering the combination of pH-dependent surfactant aggregation and surface dissociation. Our findings of pH-dependent EO mobility in coated channels, using three types of quaternary ammonium surfactants, lauryltrimethyammonium bromide (LTAB), trimethyl (tetradecyl) ammonium bromide (TTAB), and cetyltrimethyammonium bromide (CTAB), agree with our theoretical prediction. We also explain the chain-length dependence of mobility with a collaborative adsorption mechanism of surfactant aggregates.

Frequency bandwidth limitation of external pulse electric fields in cylindrical micro-channel electrophoresis with analyte velocity modulation.

In capillary electrophoresis, effective optical signal quality improvement is obtained when high frequency (>100 Hz) external pulse fields modulate analyte velocities with synchronous lock-in detection. However, the pulse frequency is constrained under a critical value corresponding to the time required for the bulk viscous flow, which arises due to viscous momentum diffusion from the electro-osmotic slip in the Debye layer, to reach steady-state. By solving the momentum diffusion equation for transient bulk flow in the micro-channel, we show that this set-in time to steady-state and hence, the upper limit for the pulse frequency is dependent on the characteristic diffusion length scale and therefore the channel geometry; for cylindrical capillaries, the set-in time is approximately one half of that for rectangular slot channels. From our estimation of the set-in time and hence the upper frequency modulation limit, we propose that the half width of planar channels does not exceed 100 microm and that the radii of cylindrical channels be limited to 140 microm such that there is a finite working bandwidth range above 100 Hz and below the upper limit in order for flicker noise to be effectively suppressed.

Helicobacter pylori promote gastric cancer cells invasion through a NF-kappaB and COX-2-mediated pathway.

AIM: To examine the effects of Helicobacter pylori (H pylori) infection on the invasiveness of gastric cancer cells, and to elucidate its mechanism. METHODS: Gastric carcinoma cells, MKN-45, were incubated with CagA-positive H pylori, and cell invasion was determined by Matrigel analysis. The expression of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were assessed by Western-blot analysis, and transcriptional activation of the COX-2 promoter was examined by measuring luciferase and beta-galactosidase activities. Lastly, the protein-DNA interaction was confirmed by an electrophoretic mobility shift assay. RESULTS: The current studies showed that: (1) incubation of CagA-positive H pylori with MKN-45 cells significantly promotes gastric cancer cells invasion, and this effect is attenuated by pre-treatment with NS-398, a COX-2 inhibitor, or PDTC, a nuclear factor kappaB (NF-kappaB) inhibitor; (2) the induction of MKN-45 cells invasion by H pylori is associated with increases in COX-2, MMP-9, and VEGF protein expression, and co-incubation of NS-398 or PDTC significantly reduces these effects; (3) H pylori infection transactivates COX-2 promoter activity and increases the binding of NF-kappaB to this promoter. CONCLUSION: Our data demonstrate that H pylori infection promotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-kappaB and COX-2 mediated pathway, as COX-2 or NF-kappaB inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein.

A novel micelle-forming material used for preparing a theranostic vehicle exhibiting enhanced in vivo therapeutic efficacy.

A new micelle-forming material, folic acid-conjugated carboxymethyl lauryl chitosan (FA-CLC), and superparamagnetic iron oxide (SPIO) nanoparticles were used for preparing an imaging-guided drug vehicle (the FA-CLC/SPIO hybrid micelle) that demonstrates targeted delivery, imaging, and controlled release of hydrophobic agents. We found that the ratio of viable normal cells to tumor cells was increased prominently after delivery of camptothecin (CPT)-loaded FA-CLC/SPIO micelles and therapeutic sonication. In addition, a magnetic field could enhance the tumor-targeting effect of FA-CLC/SPIO micelles. Therefore, after sequential administration of magnetic attraction to CPT-loaded FA-CLC/SPIO micelles, and therapeutic sonication, the in vivo therapeutic efficacy of CPT was markedly enhanced. However, a nonfocused magnetic field could enhance the undesirable accumulation of iron-containing vehicles in the liver if the tumor (i.e., magnetic attraction site) is near the liver. We propose that magnetic attraction must be carefully applied, far from the liver.