To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy, we conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen ...(CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in the vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine efficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of vaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment.
Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic colorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic colorectal cancer with 1 × 10(6) CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 10(6) CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the final DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical status. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation responses against CEA.
No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC vaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically significant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients.
The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this protocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of patients. This treatment protocol should be further evaluated in additional colorectal cancer patients with modifications to enhance T cell responses.
ClinicalTrials.gov (identifier NCT00154713 ), September 8, 2005.
Human CO
respiration requires rapid conversion between CO
and HCO
Carbonic anhydrase II facilitates this reversible reaction inside red blood cells, and band 3 anion exchanger 1 (AE1) provides a ...passage for HCO
flux across the cell membrane. These 2 proteins are core components of the CO
transport metabolon. Intracellular H
O is necessary for CO
/HCO
conversion. However, abundantly expressed aquaporin 1 (AQP1) in erythrocytes is thought not to be part of band 3 complexes or the CO
transport metabolon. To solve this conundrum, we used Förster resonance energy transfer (FRET) measured by fluorescence lifetime imaging (FLIM-FRET) and identified interaction between aquaporin-1 and band 3 at a distance of 8 nm, within the range of dipole-dipole interaction. Notably, their interaction was adaptable to membrane tonicity changes. This suggests that the function of AQP1 in tonicity response could be coupled or correlated to its function in band 3-mediated CO
/HCO
exchange. By demonstrating AQP1 as a mobile component of the CO
transport metabolon, our results uncover a potential role of water channel in blood CO
transport and respiration.-Hsu, K., Lee, T.-Y., Periasamy, A., Kao, F.-J., Li, L.-T., Lin, C.-Y., Lin, H.-J., Lin, M. Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO
transport.
Moderate-intensity exercise improves insulin sensitivity, which may depend on the intensity, duration, and frequency of exercise. We examined the effects of a single bout of short-duration ...high-intensity exercise (HIE) and long-duration lowintensity exercise (LIE) on insulin sensitivity and the adiponectin/leptin ratio in individuals with different body mass indices (BMIs) who do not exercise regularly.
We enrolled 42 healthy volunteers aged 20–64 years and divided them into two groups based on BMI: BMI <24 kg/m2 and BMI ≥27 kg/m2. They were randomly assigned to either the short-duration (20 min) HIE (70%–80% heart rate reserve, HRR) or long-duration (60 min) LIE training groups (30%–40% HRR). Glucose, insulin, adiponectin, and leptin levels were assessed before training and at 0, 30, 60, and 120 min after training.
We finally analyzed 27 normal weight and 9 obese individuals. No significant differences were observed in the baseline information of both BMI groups. Homeostatic model assessment for insulin resistance significantly improved for both exercise patterns in the normal weight group and for the HIE pattern in the obese group (P < 0.01), whereas the adiponectin/leptin ratio increased significantly only among normal weight participants with the LIE intervention.
Both exercise patterns in BMI <24 kg/m2 and BMI ≥27 kg/m2 benefit on insulin resistance. Therefore, people can choose the way they can fit to improve insulin resistance both short-duration high-intensity exercise and long-duration low-intensity exercise.
High expression levels of cyclooxygenase-2 (COX-2) contribute a strong proliferative ability to human lung cancer cells, and this function is link to the epidermal growth factor receptor (EGFR) ...pathway, which was mediated by extracellular-signal-regulated kinase (ERK) and nuclear factor kappa B (NFκB). In this study, scutellarein, a flavonoid compound, was screened for proliferation inhibition at different concentrations (0, 5, 25 and 50 μM) at 24 h or 48 h in human lung cancer cell line A549. Results showed that A549 cell proliferation was inhibited by 50 μM scutellarein treatment in 24 h and 48 h of treatment. The expression levels of phosphorylated EGFR, phosphorylated ERK, phosphorylated NFκB and COX-2 were reduced in a dose-dependent manner after 24 h scutellarein treatments at different concentrations. Further, ERK inhibitor U0126 and NFκB inhibitor MG132 also inhibited A549 cell proliferation similar to 50 κM scutellarein treatment from 24 h to 48 h. The experimental results showed that scutellarein could inhibit proliferation of the human lung cancer cell line A549 through ERK and NFκB mediated by the EGFR pathway.
Abstract The aims of this preliminary study were to present a modified mandibular splint together with a treatment regimen and to evaluate their effects on the treatment of reciprocal joint sounds of ...the temporomandibular joint (TMJ). The study participants were recruited from 312 consecutive patients in the temporomandibular disorder clinic of a medical center in Taiwan from January 2003 to December 2003. From among these, 59 cases with typical reciprocal clicking were selected for this study. All participants were treated with a modified mandibular splint and then followed up for 6 months. Successful treatment was defined as leading to the disappearance of the joint sounds of TMJ, as described by patients. Based on clinical evaluation, the overall success rate was 71.2% (42/59) with minimal temporary complications. Patients with clicking at less than 3.5 cm of interincisal opening had a success rate of 92.5%, which was higher than the success rate of patients with clicking at a mouth opening of 3.5 cm or more. This study showed that a modified mandibular splint can be used to treat reciprocal clicking of the TMJ effectively and encouraged us to conduct further study on the efficacy of this splint to treat disc displacement with reduction of TMJ using magnetic resonance imaging examination.
Background: Thyroglobulin (TG) defect is a rare cause of congenital hypothyroidism. Although only 44 mutations of the human TG gene have been identified, we have suspected a TG defect in 38% of ...Taiwan Chinese children/adolescents presenting with moderate or severe thyroidal dyshormonogenesis.
Study Objective: The aim of the study is to report the discovery of new TG gene mutations and associated clinical manifestations of the defective TG protein.
Patients and Results: In seven patients from six families, we detected six new TG gene mutations, including c.1348delT, p.R432X (c.1351C>T), g.IVS3 + 2T>G, c.1712delT, p.Q1765X (c.5350C>T), and c.6047delA. The c.1348delT and p.R432X mutations were the most common, detected in 33 and 25%, respectively, of alleles studied. Haplotype analysis suggested that the c.1348delT and g.IVS3 + 2T>G mutations are due to founder effects, whereas p.R432X is probably due to independently recurrent de novo mutations. mRNA transcript of the g.IVS3 + 2T>G mutant, detected in whole blood by reverse transcription-nested PCR, showed skipping of exon 3 (98-bp deletion) and a frameshift, with a terminal signal after 17 altered amino acid residues.
Conclusions: TG defects have an important role in severe thyroidal dyshormonogenesis (pretreatment, or after a 3-wk T4 withdrawal, plasma T4 ≦ 30 nmol/liter) in Taiwanese. Its genetic characteristics are markedly different from those described in other populations presenting with mutations of the TG gene.
Thyroglobulin defects have an important role in severe thyroid dyshormonogenesis in Taiwanese, and its genetic characteristics are different from other populations that have been studied.
Gd-doped iron oxide nanoparticles were developed for use in tumour therapy via magnetic fluid hyperthermia (MFH). The nanoparticle composition was Gd0.02Fe2.98O4 as determined by ICP-AES. TEM image ...analysis showed the primary particles to be about 13 nm in diameter. The specific power adsorption rate (SAR) determined with a field strength of 246 Oe and 52 kHz was 36 W per gram of Fe. This value is about 4 times higher than the reported SAR values for Fe3O4. The heating rate for the nanoparticles in vivo and the potential for tumour therapy were determined in a mouse model. The mouse models treated with doped iron oxide displayed much slower tumour growth, the tumour doubled its mass after 7 days post-treatment compared to 4 days for those models treated with standard iron oxide or saline solution.
Tailored nanoparticles for tumour therapy Jiang, Pei-Shin; Drake, Philip; Cho, Hui-Ju ...
Journal of nanoscience and nanotechnology,
06/2012, Volume:
12, Issue:
6
Journal Article
Gd doped iron-oxide nanoparticles were developed for use in tumour therapy via magnetic fluid hyperthermia (MFH). The effect of the Gd3+ dopant on the particle size and magnetic properties was ...investigated. The final particle composition varied from Gd0.01Fe2.99O4 to Gd0.04Fe2.96O4 as determined by Inductively coupled plasma atomic emission spectroscopy (ICP-AES). TEM image analysis showed the average magnetic core diameters to be 12 nm and 33 nm for the lowest and highest Gd levels respectively. The specific power adsorption rate (SAR) determined with a field strength of 246 Oe and 52 kHz had a maximum of 38Wg(-1) Fe for the Gd0.03Fe2.97O4 sample. This value is about 4 times higher than the reported SAR values for Fe3O4. The potential for in vivo tumour therapy was investigated using a mouse model. The mouse models treated with Gd0.02Fe2.98O4 displayed much slower tumour growth after the first treatment cycle, the tumour had increased its mass by 25% after 7 days post treatment compared to a 79% mass increase over the same period for those models treated with standard iron-oxide or saline solution. After a second treatment cycle the mouse treated with Gd0.02Fe2.98O4 showed complete tumour regression with no tumour found for at least 5 days post treatment.
Endometrial cancer is one of the most common malignancy affecting women in developed countries. Resection uterus or lesion area is usually the first option for a simple and efficient therapy. ...Therefore, it is necessary to find a new therapeutic drug to reduce surgery areas to preserve fertility. Anticancer peptides (ACP) are bioactive amino acids with lower toxicity and higher specificity than chemical drugs. This study is to address an ACP, herein named Q7, which could downregulate 24-Dehydrocholesterol Reductase (DHCR24) to disrupt lipid rafts formation, and sequentially affect the AKT signal pathway of HEC-1-A cells to suppress their tumorigenicity such as proliferation and migration. Moreover, lipo-PEI-PEG-complex (LPPC) was used to enhance Q7 anticancer activity
and efficiently show its effects on HEC-1-A cells. Furthermore, LPPC-Q7 exhibited a synergistic effect in combination with doxorubicin or paclitaxel. To summarize, Q7 was firstly proved to exhibit an anticancer effect on endometrial cancer cells and combined with LPPC efficiently improved the cytotoxicity of Q7.
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