Triple modal treatment comprising with proton beam radiation, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer: a phase I/II study protocol (TT-LAP trial).

BACKGROUND: Locally advanced pancreatic ductal adenocarcinoma (PDAC), accounting for about 30% of PDAC patients, is difficult to cure by radical resection or systemic chemotherapy alone. A multidisciplinary strategy is required and our TT-LAP trial aims to evaluate whether triple-modal treatment with proton beam therapy (PBT), hyperthermia, and gemcitabine plus nab-paclitaxel is a safe and synergistically effective treatment for patients with locally advanced PDAC. METHODS: This trial is an interventional, open-label, non-randomized, single-center, single-arm phase I/II clinical trial organized and sponsored by the University of Tsukuba. Eligible patients who are diagnosed with locally advanced pancreatic cancer, including both borderline resectable (BR) and unresectable locally advanced (UR-LA) patients, and selected according to the inclusion and exclusion criteria will receive triple-modal treatment consisting of chemotherapy, hyperthermia, and proton beam radiation. Treatment induction will include 2 cycles of chemotherapy (gemcitabine plus nab-paclitaxel), proton beam therapy, and 6 total sessions of hyperthermia therapy. The initial 5 patients will move to phase II after adverse events are verified by a monitoring committee and safety is ensured. The primary endpoint is 2-year survival rate while secondary endpoints include adverse event rate, treatment completion rate, response rate, progression-free survival, overall survival, resection rate, pathologic response rate, and R0 (no pathologic cancer remnants) rate. The target sample size is set at 30 cases. DISCUSSION: The TT-LAP trial is the first to evaluate the safety and effectiveness (phases1/2) of triple-modal treatment comprised of proton beam therapy, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer. ETHICS AND DISSEMINATION: This protocol was approved by the Tsukuba University Clinical Research Review Board (reference number TCRB22-007). Results will be analyzed after study recruitment and follow-up are completed. Results will be presented at international meetings of interest in pancreatic cancer plus gastrointestinal, hepatobiliary, and pancreatic surgeries and published in peer-reviewed journals. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs031220160. Registered 24 th June 2022, https://jrct.niph.go.jp/en-latest-detail/jRCTs031220160 .

Contributions of the N-terminal flanking residues of an antigenic peptide from the Japanese cedar pollen allergen Cry j 1 to the T-cell activation by HLA-DP5.

Cry j 1 is a major allergen present in Japanese cedar (Cryptomeria japonica) pollens. Peptides with the core sequence of KVTVAFNQF from Cry j 1 ('pCj1') bind to HLA-DP5 and activate Th2 cells. In this study, we noticed that Ser and Lys at positions -2 and -3, respectively, in the N-terminal flanking (NF) region to pCj1 are conserved well in HLA-DP5-binding allergen peptides. A competitive binding assay showed that the double mutation of Ser(-2) and Lys(-3) to Glu [S(P-2)E/K(P-3)E] in a 13-residue Cry j 1 peptide (NF-pCj1) decreased its affinity for HLA-DP5 by about 2-fold. Similarly, this double mutation reduced, by about 2-fold, the amount of NF-pCj1 presented on the surface of mouse antigen-presenting dendritic cell line 1 (mDC1) cells stably expressing HLA-DP5. We established NF-pCj1-specific and HLA-DP5-restricted CD4+ T-cell clones from HLA-DP5 positive cedar pollinosis (CP) patients, and analyzed their IL-2 production due to the activation of mouse TG40 cells expressing the cloned T-cell receptor by the NF-pCj1-presenting mDC1 cells. The T-cell activation was actually decreased by the S(P-2)E/K(P-3)E mutation, corresponding to the reduction in the peptide presentation by this mutation. In contrast, the affinity of NF-pCj1·HLA-DP5 for the T-cell receptor was not affected by the S(P-2)E/K(P-3)E mutation, as analyzed by surface plasmon resonance. Considering the positional and side-chain differences of these NF residues from previously reported T-cell activating sequences, the mechanisms of enhanced T-cell activation by Ser(-2) and Lys(-3) of NF-pCj1 may be novel.

An Innovative Customized Biomimetic Hydrogel for Drug Screening Application Potential: Biocompatibility and Cell Invasion Ability.

The ability of Pluronic F127 (PF127) conjugated with tetrapeptide Gly-Arg-Gly-Asp (GRGD) as a sequence of Arg-Gly-Asp (RGD) peptide to form the investigated potential hydrogel (hereafter referred to as 3DG bioformer (3BE)) to produce spheroid, biocompatibility, and cell invasion ability, was assessed in this study. The fibroblast cell line (NIH 3T3), osteoblast cell line (MG-63), and human breast cancer cell line (MCF-7) were cultured in the 3BE hydrogel and commercial product (Matrigel) for comparison. The morphology of spheroid formation was evaluated via optical microscopy. The cell viability was observed through cell counting Kit-8 assay, and cell invasion was investigated via Boyden chamber assay. Analytical results indicated that 3BE exhibited lower spheroid formation than Matrigel. However, the 3BE appeared biocompatible to NIH 3T3, MG-63, and MCF-7 cells. Moreover, cell invasion ability and cell survival rate after invasion through the 3BE was displayed to be comparable to Matrigel. Thus, these findings demonstrate that the 3BE hydrogel has a great potential as an alternative to a three-dimensional cell culture for drug screening applications.

Suppression of amyloid-ß secretion from neurons by cis-9, trans-11-octadecadienoic acid, an isomer of conjugated linoleic acid.

Two common conjugated linoleic acids (LAs), cis-9, trans-11 CLA (c9,t11 CLA) and trans-10, cis-12 CLA (t10,c12 CLA), exert various biological activities. However, the effect of CLA on the generation of neurotoxic amyloid-ß (Aß) protein remains unclear. We found that c9,t11 CLA significantly suppressed the generation of Aß in mouse neurons. CLA treatment did not affect the level of ß-site APP-cleaving enzyme 1 (BACE1), a component of active γ-secretase complex presenilin 1 amino-terminal fragment, or Aß protein precursor (APP) in cultured neurons. BACE1 and γ-secretase activities were not directly affected by c9,t11 CLA. Localization of BACE1 and APP in early endosomes increased in neurons treated with c9,t11 CLA; concomitantly, the localization of both proteins was reduced in late endosomes, the predominant site of APP cleavage by BACE1. The level of CLA-containing phosphatidylcholine (CLA-PC) increased dramatically in neurons incubated with CLA. Incorporation of phospholipids containing c9,t11 CLA, but not t10,c12 CLA, into the membrane may affect the localization of some membrane-associated proteins in intracellular membrane compartments. Thus, in neurons treated with c9,t11 CLA, reduced colocalization of APP with BACE1 in late endosomes may decrease APP cleavage by BACE1 and subsequent Aß generation. Our findings suggest that the accumulation of c9,t11 CLA-PC/LPC in neuronal membranes suppresses the production of neurotoxic Aß in neurons.

Amelioration of Alzheimer's Disease by Gut-Pancreas-Liver-Brain Interaction in an App Knock-In Mouse Model.

In this study, we observed disease progression, changes in the gut microbiota, and interactions among the brain, liver, pancreas, and intestine in a mouse model of Alzheimer's disease (AD), in addition to attempting to inhibit disease progression through the dietary supplementation of L-arginine and limonoids. Wild-type mice (WC) and AD mice were fed a normal diet (AC), a diet supplemented with L-arginine and limonoids (ALA), or a diet containing only limonoids (AL) for 12-64 weeks. The normal diet-fed WC and AC mice showed a decrease in the diversity of the gut microbiota, with an increase in the Firmicutes/Bacteroidetes ratio, and bacterial translocation. Considerable bacterial translocation to the pancreas and intense inflammation of the pancreas, liver, brain, and intestinal tissues were observed in the AC mice from alterations in the gut microbiota. The ALA diet or AL diet-fed mice showed increased diversity of the bacterial flora and suppressed oxidative stress and inflammatory responses in hepatocytes and pancreatic cells, bacterial translocation, and neurodegeneration of the brain. These findings suggest that L-arginine and limonoids help in maintaining the homeostasis of the gut microbiota, pancreas, liver, brain, and gut in AD mice.

Magnetism and ion diffusion in honeycomb layered oxide [Formula: see text].

In the quest for developing novel and efficient batteries, a great interest has been raised for sustainable K-based honeycomb layer oxide materials, both for their application in energy devices as well as for their fundamental material properties. A key issue in the realization of efficient batteries based on such compounds, is to understand the K-ion diffusion mechanism. However, investigation of potassium-ion (K[Formula: see text]) dynamics in materials using e.g. NMR and related techniques has so far been very challenging, due to its inherently weak nuclear magnetic moment, in contrast to other alkali ions such as lithium and sodium. Spin-polarised muons, having a high gyromagnetic ratio, make the muon spin rotation and relaxation ([Formula: see text]SR) technique ideal for probing ions dynamics in these types of energy materials. Here we present a study of the low-temperature magnetic properties as well as K[Formula: see text] dynamics in honeycomb layered oxide material [Formula: see text] using mainly the [Formula: see text]SR technique. Our low-temperature [Formula: see text]SR results together with complementary magnetic susceptibility measurements find an antiferromagnetic transition at [Formula: see text] K. Further [Formula: see text]SR studies performed at higher temperatures reveal that potassium ions (K[Formula: see text]) become mobile above 200 K and the activation energy for the diffusion process is obtained as [Formula: see text] meV. This is the first time that K[Formula: see text] dynamics in potassium-based battery materials has been measured using [Formula: see text]SR. Assisted by high-resolution neutron diffraction, the temperature dependence of the K-ion self diffusion constant is also extracted. Finally our results also reveal that K-ion diffusion occurs predominantly at the surface of the powder particles. This opens future possibilities for potentially improving ion diffusion as well as K-ion battery device performance using nano-structuring and surface coatings of the particles.

Physical activity among patients with breast cancer receiving aromatase inhibitors is associated with bone health: a cross-sectional observational study.

PURPOSE: To examine the association of physical activity (PA) with bone health among patients with breast cancer receiving adjuvant aromatase inhibitor (AI) treatment. METHODS: In this single-center observational study, we enrolled postmenopausal women with primary hormone receptor-positive breast cancer who were receiving adjuvant AI treatment. We assessed patient bone health [bone mineral density (BMD) and biomarkers of bone turnover] as main outcomes. PA was assessed using Baecke physical activity questionnaires (BPAQ) and an accelerometer. Multiple regression analysis was performed after adjustment for age, body mass index, smoking history and duration of AI treatment. For missing data, multiple imputation analysis was adapted. RESULTS: The mean age of the 53 enrolled patients was 67.4 ± 8.4 years. The mean duration of AI administration was 25.7 ± 18.9 months. The most frequently administered AI was anastrozole (73.6%). Although not related to BMD, PA was related to bone turnover. Serum collagen type I amino-terminal propeptide, a bone formation marker, was associated with only light PA (t = - 2.55, p = 0.015), while tartrate-resistant acid phosphatase 5b, a bone absorption marker, was associated with work index in the BPAQ subscale and light PA (t = - 2.28, p = 0.028, t = - 2.26, p = 0.031, respectively). The results for all patients were similar to those observed in the multiple imputation analysis. CONCLUSION: PA was significantly associated with bone turnover among cancer patients receiving AI treatment. Light PA and PA in the work domain were the most important factors among various PA intensities and PA domains.

Astaxanthin Ameliorated Parvalbumin-Positive Neuron Deficits and Alzheimer's Disease-Related Pathological Progression in the Hippocampus of AppNL-G-F/NL-G-F Mice.

Growing evidence suggests that oxidative stress due to amyloid ß (Aß) accumulation is involved in Alzheimer's disease (AD) through the formation of amyloid plaque, which leads to hyperphosphorylation of tau, microglial activation, and cognitive deficits. The dysfunction or phenotypic loss of parvalbumin (PV)-positive neurons has been implicated in cognitive deficits. Astaxanthin is one of carotenoids and known as a highly potent antioxidant. We hypothesized that astaxanthin's antioxidant effects may prevent the onset of cognitive deficits in AD by preventing AD pathological processes associated with oxidative stress. In the present study, we investigated the effects of astaxanthin intake on the cognitive and pathological progression of AD in a mouse model of AD. The AppNL-G-F/NL-G-F mice were fed with or without astaxanthin from 5-to-6 weeks old, and cognitive functions were evaluated using a Barnes maze test at 6 months old. PV-positive neurons were investigated in the hippocampus. Aß42 deposits, accumulation of microglia, and phosphorylated tau (pTau) were immunohistochemically analyzed in the hippocampus. The hippocampal anti-oxidant status was also investigated. The Barnes maze test indicated that astaxanthin significantly ameliorated memory deficits. Astaxanthin reduced Aß42 deposition and pTau-positive areal fraction, while it increased PV-positive neuron density and microglial accumulation per unit fraction of Aß42 deposition in the hippocampus. Furthermore, astaxanthin increased total glutathione (GSH) levels, although 4-hydroxy-2,3-trans-nonenal (4-HNE) protein adduct levels (oxidative stress marker) remained high in the astaxanthin supplemented mice. The results indicated that astaxanthin ameliorated memory deficits and significantly reversed AD pathological processes (Aß42 deposition, pTau formation, GSH decrease, and PV-positive neuronal deficits). The elevated GSH levels and resultant recovery of PV-positive neuron density, as well as microglial activation, may prevent these pathological processes.

Increased Quinolone-Resistant Mutations of gyrA and parC Genes after Pouchitis Treatment with Ciprofloxacin.

BACKGROUND: Oral antibiotics, such as ciprofloxacin (CFX), are widely used for the treatment of acute and chronic pouchitis. Most bacterial mutations that confer quinolone resistance are at Ser-83 and Asp-87 in the gyrA gene and Ser-80 and Glu-84 in the parC gene. METHODS: We obtained 51 stool samples from 43 patients who were diagnosed with ulcerative colitis and underwent ileal pouch-anal anastomosis. Patients were divided into 2 groups: 13 patients with CFX treatment of pouchitis and 30 patients without pouchitis. After extraction of fecal DNA, the amount of Escherichia coli 16S rRNA, gyrA, and parC gene DNA were measured using real-time polymerase chain reaction (PCR). Possible mutations at gyrA 83 and 87 and at parC 80 and 84 were investigated by PCR cloning and sequencing, and mutation rates were quantified by rapid PCR-restriction fragment length polymorphism. RESULTS: Samples from both CFX-treated and -untreated patients had comparable levels of gyrA and parC gene DNA. Nucleic acid and amino acid mutations were identified at gyrA 83 and 87, and at parC 80 and 84. We successfully quantified mutation rates at gyrA 83 and 87, and at parC 84, all of which were significantly higher in samples from CFX-treated patients (70, 84, and 38%) than from CFX-untreated patients (13, 11, and 5%). CONCLUSION: E. coli in patient pouches may have mutations in their gyrA and parC genes that produce CFX resistance. Mutation rates of these genes were significantly higher in samples from CFX-treated patients. This study contributes to understanding the decrease and loss of CFX effectiveness against pouchitis.

Importance of Fc Receptor γ-Chain ITAM Tyrosines in Neutrophil Activation and in vivo Autoimmune Arthritis.

Activating Fcγ receptors associated with Fc receptor γ-chain (FcRγ) are critical for mediating neutrophil effector functions in immune complex-mediated autoimmune diseases. FcRγ contains ITAM tyrosines and the in vivo role of these tyrosines has not been defined in neutrophils and arthritis. In this study, the in vivo functions of FcRγ ITAM tyrosines were characterized using wild type and ITAM tyrosine mutant (Y65F/Y76F) transgenic mice crossed to an FcRγ-deficient genetic background. FcRγ-deficient neutrophils showed undetectable cell surface expression of the activating Fcγ receptor IV, defective immune complex-induced superoxide production, degranulation and spreading. Although the re-expression of both the wild type and the ITAM tyrosine mutant (Y65F/Y76F) FcRγ could restore activating Fcγ receptor expression of FcRγ-deficient neutrophils, only the wild type transgenic form could mediate Fcγ receptor-dependent effector functions. In contrast, neutrophils carrying ITAM tyrosine mutant FcRγ were unable to produce superoxide, mediate degranulation and perform active spreading. In addition, our results confirmed the protection of FcRγ-deficient mice from autoimmune arthritis. Importantly, the presence of the wild type FcRγ transgene, in contrast to the ITAM tyrosine mutant transgene, partially reversed autoimmune arthritis development. The reversing effect of the wild type transgene was even more robust when animals carried the wild type transgene in a homozygous form. Collectively, FcRγ ITAM tyrosines play a critical role in the induction of neutrophil effector responses, the initiation and progression of an autoantibody-induced experimental arthritis in vivo, indicating a signaling, rather than just a receptor stabilizing function of the molecule.

The in vitro effects of CCN2 on odontoblast-like cells.

OBJECTIVE: To investigate the in vitro effects of CCN2 on odontoblast-like cells proliferation and differentiation. DESIGN: MDPC-23 cells were cultured in DMEM supplemented with 5% FBS. CCN2 was either added to culture media or coated onto culture polystyrene, addition or coating of dH2O was served as control. In the addition group, CCN2 (100 ng/mL) was added into culture media. In the coating group, CCN2 at the concentration of 1000 ng/mL was employed. Cell proliferation was performed using CCK-8 assay. Cell differentiation and mineralization were analyzed by ALPase activity assay, real time RT-PCR and alizarin red staining. One-way ANOVA with post-hoc tukey HSD test was used for statistical analysis. RESULTS: MDPC-23 cells exhibited robust proliferative activity upon exposure to either soluble or immobilized CCN2. ALP activity of cells cultured on CCN2-modified surface was continuously strengthened from day six (0.831 ±â€¯0.024 units/µg protein versus 0.563 ±â€¯0.006 units/µg protein of control) till day eight (1.035 ±â€¯0.139 units/µg protein versus 0.704 ±â€¯0.061 units/µg protein of control). Gene expression of BSP, OCN and OPN were promoted by soluble CCN2 after 48 h exposure. Moreover, gene expression of BSP, OCN, OPN, ALP, COL1 A1, Runx-2, DSPP and DMP-1 was significantly enhanced by immobilized CCN2. Finally, mineralization of MDPC-23 cells was accelerated by both soluble and immobilized CCN2 to different extent. CONCLUSIONS: The findings indicate that CCN2 promoted proliferation, odontogenic gene expression and mineralization of MDPC-23 cells. It is proposed that CCN2 may be a promising adjunctive formula for dentin regeneration.

Multiple focal and macroreentrant left atrial tachycardias originating from a spontaneous scar at the contiguous aorta-left atrium area in a patient with hypertrophic cardiomyopathy: a case report.

BACKGROUND: Spontaneous scar-related left atrial tachycardia (AT) is a rare arrhythmia. We describe a patient with hypertrophic cardiomyopathy (HCM) who developed multiple, both focal and macroreentrant left ATs associated with a spontaneous scar located at the aorta-left atrium (LA) contiguous area. CASE PRESENTATION: A 65-year-old man with HCM complained of palpitations. Twelve-lead electrocardiogram showed narrow QRS tachycardia with 2:1 atrioventricular conduction. Two sessions of radiofrequency ablation (RFA) were required to eliminate all left ATs. In the first session, 3-dimensional electroanatomical mapping fused with the image constructed by multi-detector computed tomography showed a clockwise macroreentrant AT (AT1) associated with a low-voltage or dense scar area located along the aorta-LA contiguous area. AT1 was eliminated by RFA to the narrow isthmus with slow conduction velocity within the scar. Additional ATs (AT2-AT4) occurred 1 month after the first ablation. In the second session, AT2 and AT3 were identified as focal ATs with centrifugal propagation and few accompanying fragmentations, and AT4 as a macroreentrant AT with features similar to AT1. AT2 and AT3 were successfully eliminated by performing RFA to the earliest activation site, and AT4 was terminated by performing RFA to the narrow isthmus with slow conduction velocity. No ATs have recurred for 11 months after these RFAs. Interestingly, the substrate for all left ATs was associated with the aorta-LA contiguous area. CONCLUSION: To our knowledge, this is the first case of multiple, both focal and macroreentrant left ATs associated with a contiguous aorta-LA spontaneous scar area in a patient with HCM.

The possibility of genistein as a new direct pulp capping agent.

Genistein, kind of soy isoflavones, is well-known as natural ingredients and consumed as health foods and supplements. They are expected to improve renal function. They have high-affinity to estrogen receptor ß expressed predominantly in bone tissue, they prevent osteoporosis specifically and safely. We examined whether genistein can be a new direct capping agent. In this study, we examined the effect of genistein for the proliferation and differentiation of rat dental pulp cells in vitro and the ability of tertiary dentin formation in vivo. As a result, rat dental pulp cells with genistein were increased activity of ALPase and showed alizarin red positive-staining. Calcification-related genes expression has been confirmed by the addition of genistein. From in vivo study, high quality of tertiary dentin formation and minor pulp reaction were observed. From these findings, it was suggested that genistein may be useful agent for direct pulp capping.

A heat-stable extract from Mucuna stimulates the differentiation of bone marrow cells into dendritic cells and induces apoptosis in cancer cells.

Pine cone extract is known to induce differentiation of human mononuclear cells into dendritic cells (DCs) and also to induce apoptosis in human cancer cells. In the present study, we screened edible plants that contain components with biological activities similar to or more potent than those of pine cone extract. We found that Mucuna (Mucuna pruviens var. utilis) contains a DC differentiation/maturation-inducing activity and a component that induces apoptosis in human cancer cell lines. Mucuna extract specifically stimulated differentiation of BM cells to immature DCs. Marked production of IL-6 was observed by sequential treatment with at least 10 µg/mL of Mucuna extract followed by LPS. The sequential treatment with Mucuna extract followed by LPS produced a much higher ratio of IL-12 to IL-6 and a lower ratio of TNF-α to IL-6 than that obtained by sequential treatment with a medicinal mushroom Phellinus linteus extract and then LPS. The DC differentiation/maturation activity and the component inducing apoptosis in cancer cells were separable by column chromatography.

Bactericidal effect of Nd:YAG and Er:YAG lasers in experimentally infected curved root canals.

OBJECTIVE: The purpose of this study was to evaluate the bactericidal efficacy of Nd:YAG and Er:YAG laser in the experimentally infected curved root canals. BACKGROUND DATA: Previous studies revealed that laser systems have a significant bactericidal effect in both human and bovine infected straight root canals. MATERIALS AND METHODS: Sixty extracted single-rooted teeth with single root canals were selected and then instrumented with endodontic files to a size 60 (K-type file). The degree of root curvature was determined according to modified Schneider's method. Each of the specimens was incubated in a sterile centrifuge tube with 1 mL of the Enterococcus faecalis suspension at 37°C for 2 weeks under aerobic conditions. After laser irradiation at each of the two settings, 50 mJ, 10 pps (0.5 W) or 100 mJ, 10 pps (1.0 W), the number of E. faecalis in each root canal was examined. RESULTS: In the straight root canals, the Er:YAG laser showed higher bactericidal effects by 6.4-10.8% than did the Nd:YAG laser. Conversely, the bactericidal effect of Er:YAG laser in the curved root canals was higher by 1.5-3.1% than was that with the Nd:YAG laser. The bactericidal effect of the Er:YAG laser in the curved root canal is significantly lower than that in the straight root canal (p < 0.05). CONCLUSION: These results suggest that further development in the endodontic laser tip and technique is required to ensure its success in curved root canals sterilization.

Dendritic cell differentiation and tumor cell apoptosis induced by components of a poly-phenylpropanoid polysaccharide complex.

BACKGROUND: As part of the indigenous folk medicine in Japan, aqueous extracts of pine cones have been used for over a century to treat cancer and other illnesses and references to their use can be found in ancient Greek literature. However, the mechanisms by which such extracts work are largely unknown. MATERIALS AND METHODS: Murine bone marrow (BM)-derived dendritic cells (DCs) and human monocyte U937 cells were treated in vitro with an extract prepared from pine cones (termed poly-phenylpropanoid polysaccharide complex, PPC). RESULTS: The components of the PPC were separated into different molecular weight fractions with distinct biological activities. One fraction, consisting of relatively high molecular weight material, was found to induce the differentiation of murine BM cells into immature DC, as well as the maturation of immature DCs into mature DCs. A second fraction, consisting of low molecular weight material, was found to inhibit the in vitro growth of the U937 cells and two other human cancer cell lines. The inhibition of tumor cell growth was found to be associated with the generation of reactive oxygen species (ROS) and the induction of a mitochondria-dependent apoptotic pathway. CONCLUSION: The effects on dendritic cells and the inhibition of tumor growth, if they occur to a significant level in vivo, could help explain the apparent usefulness of PPC in the treatment of cancer.

In vitro heat generation by ferrimagnetic maghemite microspheres for hyperthermic treatment of cancer under an alternating magnetic field.

Ferrimagnetic materials can be expected to be useful as thermo seeds for hyperthermic treatment of cancer, especially where the cancer is located in deep parts of body, as they can generate heat by magnetic hysteretic loss when they are placed in an alternating magnetic field. Recently, it was reported that ferrimagnetic maghemite (gamma-Fe2O3) microspheres 20-30 microm in diameter prepared in aqueous solution can show excellent heat generating ability. However, these microspheres have many cracks on their surfaces. In this study, the preparation conditions for the microspheres was further optimized in order to obtain crack-free ferrimagnetic microspheres, and the in vitro heat generation of the obtained microspheres was measured in an agar phantom under an alternating magnetic field. Crack-free gamma-Fe2O3 microspheres 20-30 microm in diameter were obtained successfully. Their saturation magnetization and coercive force were 68 emu g(-1) and 198 Oe, respectively. Their heat generation under an alternating magnetic field of 300 Oe at 100 kHz was estimated to be 42 W g(-1). The microspheres showed in vitro heat generation when they were dispersed in an agar phantom and placed under an alternating magnetic field. It is believed that these microspheres may be useful for the in situ hyperthermic treatment of cancer.

Enzymatic preparation of hollow magnetite microspheres for hyperthermic treatment of cancer.

Ferrimagnetic materials can be expected to be useful as thermal seeds for hyperthermic treatment of cancer, especially where the cancer is located in deep parts of body, as they can generate heat by magnetic hysteretic loss when they are placed in an alternating magnetic field. In this study, hollow magnetite (Fe(3)O(4)) particles were prepared using an enzymatic reaction of urease. A hollow particle was obtained by using a Pasteur pipette. The particle was 500 microm in size and was composed of Fe(3)O(4). Its saturation magnetization and coercive force were 57 emuxg(-1) and 183 Oe, respectively. Its heat generation under an alternating magnetic field of 300 Oe at 100 kHz was estimated to be 45 Wxg(-1). Microspheres 30 microm in diameter were also successfully obtained by using a spray gun.

NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule that regulates B cell development and signaling.

A functional cDNA cloning system was developed by using a retrovirus library encoding CD8-chimeric proteins and a nuclear factor of activated T cells (NFAT)-GFP reporter cell line to identify molecules inducing NFAT activation. By using this strategy, NFAT activating molecule 1 (NFAM1) was cloned as an immunoreceptor tyrosine-based activation motif (ITAM)-bearing cell surface molecule belonging to the Ig superfamily and is predominantly expressed in spleen B and T cells. NFAM1 crosslinking induced ITAM phosphorylation, ZAP-70/Syk recruitment, NFAT activation, and cytokine production. In vivo overexpression of NFAM1 in bone marrow chimeras and transgenic mice induced severe impairment of early B cell development in an ITAM-dependent manner. In NFAM1-expressing B cells, B cell antigen receptor stimulation induced NFAM1 translocation to lipid raft, and NFAM1 co-crosslinking augmented B cell antigen receptor signaling. The results suggest that NFAM1 modulates B cell signaling through its ITAM, which regulates B cell development.