Sex-Driven Differences in the Effectiveness of Individualized Clinical Management of Alzheimer's Disease Risk.

BACKGROUND: The Comparative Effectiveness Dementia and Alzheimer's Registry (CEDAR) trial demonstrated that individualized, multi-domain interventions improved cognition and reduced the risk of Alzheimer's disease (AD). As biological sex is a significant risk factor for AD, it is essential to explore the differential effectiveness of targeted clinical interventions in women vs. men. METHODS: Patients were recruited from an Alzheimer's Prevention Clinic. Subjects with normal cognition, subjective cognitive decline, or asymptomatic preclinical AD were classified as "Prevention". Subjects with mild cognitive impairment due to AD or mild AD were classified as "Early Treatment." The primary outcome was the change from baseline to 18-months on the modified-Alzheimer's Prevention Cognitive Composite. Secondary outcomes included a cognitive aging composite, AD and cardiovascular (CV) risk scales, and serum biomarkers. Subjects who adhered to > 60% of recommendations in the CEDAR trial were included in this a priori sub-group analysis to examine whether individualized intervention effects were modified by sex (n=80). RESULTS: In the Prevention group, both women (p=0.0205) and men (p=0.0044) demonstrated improvements in cognition with no sex differences (p=0.5244). In the Early Treatment group, there were also no significant sex differences in cognition (p=0.3299). In the Prevention group, women demonstrated greater improvements in the Multi-Ethnic Study of Atherosclerosis risk score (MESA-RS) than men (difference=1.5, p=0.0013). Women in the Early Treatment group demonstrated greater improvements in CV Risk Factors, Aging and Incidence of Dementia (CAIDE) risk score (difference=2.3, p=0.0067), and the MESA-RS (difference=4.1, p<0.001). CONCLUSIONS: Individualized multi-domain interventions are equally effective at improving cognition in women and men. However, personally-tailored interventions led to greater improvements in calculated AD and CV risk, and CV blood biomarkers, in women compared to men. Future study in larger cohorts is necessary to further define sex differences in AD risk reduction in clinical practice.

Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary.

BACKGROUND: Cancer of unknown primary (CUP) has a poor prognosis. Given the recent approval of immune checkpoint inhibitors for several cancer types, we carried out a multicenter phase II study to assess the efficacy of nivolumab for patients with CUP. PATIENTS AND METHODS: Patients with CUP who were previously treated with at least one line of systemic chemotherapy constituted the principal study population. Previously untreated patients with CUP were also enrolled for exploratory analysis. Nivolumab (240 mg/body) was administered every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate in previously treated patients as determined by blinded independent central review according to RECIST version 1.1. RESULTS: Fifty-six patients with CUP were enrolled in the trial. For the 45 previously treated patients, objective response rate was 22.2% [95% confidence interval (CI), 11.2% to 37.1%], with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively. Similar clinical benefits were also observed in the 11 previously untreated patients. Better clinical efficacy of nivolumab was apparent for tumors with a higher programmed death-ligand 1 expression level, for those with a higher tumor mutation burden, and for microsatellite instability-high tumors. In contrast, no differences in efficacy were apparent between tumor subgroups based on estimated tissue of origin. Adverse events were consistent with the known safety profile of nivolumab. No treatment-related death was observed. CONCLUSIONS: Our results demonstrate a clinical benefit of nivolumab for patients with CUP, suggesting that nivolumab is a potential additional therapeutic option for CUP.

REVERCE: a randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for previously treated metastatic colorectal cancer patients.

BACKGROUND: The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. PATIENTS AND METHODS: Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence [cetuximab ± irinotecan followed by regorafenib (C-R arm)]. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins. RESULTS: One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P = 0.0293), with a hazard ratio (HR) of 0.61 for OS [95% confidence interval (CI) 0.39-0.96]. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61-1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17-0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib. CONCLUSIONS: The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.

Nanogel-based nasal ghrelin vaccine prevents obesity.

Obesity is associated with multiple comorbidities such as cardiovascular diseases and has a huge economic impact on the health-care system. However, the treatment of obesity remains insufficient in terms of efficacy, tolerability, and safety. Here we created a nasal vaccine against obesity for the first time. To avoid the injectable administration-caused pain and skin-related adverse event, we focused on the intranasal route of antigen delivery. We developed a vaccine antigen (ghrelin-PspA (pneumococcal surface protein A)), which is a recombinant fusion protein incorporating ghrelin, a hormone that stimulates food intake and decreases energy expenditure, and PspA, a candidate of pneumococcal vaccine as a carrier protein. Ghrelin-PspA antigen was mixed with cyclic di-GMP adjuvant to enhance the immunogenicity and incorporated within a nanometer-sized hydrogel for the effective antigen delivery. Intranasal immunization with ghrelin-PspA vaccine elicited serum immunoglobulin G antibodies against ghrelin and attenuated body weight gain in diet-induced obesity mice. This obesity-attenuating effect was caused by a decrease in fat accumulation and an increase in energy expenditure that was partially due to an increase in the expression of mitochondrial uncoupling protein 1 in brown adipose tissue. The development of this nasal vaccine provides a new strategy for the prevention and treatment of obesity.

Liposome chaperon in cell-free membrane protein synthesis: one-step preparation of KcsA-integrated liposomes and electrophysiological analysis by the planar bilayer method.

Chaperoning functions of liposomes were investigated using cell-free membrane protein synthesis. KcsA potassium channel-reconstituted liposomes were prepared directly using cell-free protein synthesis. In the absence of liposomes, all synthesized KcsA protein aggregated. In the presence of liposomes, however, synthesized KcsA spontaneously integrated into the liposome membrane. The KscA-reconstituted liposomes were transferred to the planar bilayer across a small hole in a thin plastic sheet and the channel function of KcsA was examined. The original electrophysiological activities, such as voltage- and pH-dependence, were observed. These results suggested that in cell-free membrane protein synthesis, liposomes act as chaperones, preventing aggregation and assisting in folding and tetrameric formation, thereby allowing full channel activity.

Effective CpG DNA delivery using amphiphilic cycloamylose nanogels.

Unmethylated CpG oligodeoxynucleotides induce inflammatory immune responses through cytokine production and have attracted increasing attention as an immunostimulator. However, there remains a challenging issue of the use of 'native CpG DNA'. In the present study, we prepared cationic nanometer-sized gels (nanogels) consisting of cycloamylose modified with cholesterol and diethylaminoethane to form hydrophobic cross-linking points and to add positively charged groups, respectively. The cationic nanogels and native CpG DNA formed nanometer-sized complexes. Complexes of native CpG DNA with cationic nanogels delivered native CpG DNA to macrophage-like cells and induced cytokine production. In addition, complexes of negative control oligonucleotides with cationic nanogels did not induce cytokine production, and the induction of cytokines using complexes of phosphorothioate-modified CpG with cationic nanogels was lower than that of native CpG DNA. These results suggest that the complex of native CpG DNA with cationic nanogels is a promising strategy for nucleic acid adjuvants.

Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques.

We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [(18)F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [(18)F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans.

Single molecular mechanics of a cholesterol-bearing pullulan nanogel at the hydrophobic interfaces.

The study of nanogel (hydrogel nanoparticle) has intensified in the last decade due to the enormous potential applications in biomimetics, biosensors, artificial muscles and drug delivery (or release) systems. Cholesterol-bearing pullulan (CHP) is composed of hydrophilic pullulan backbone and partly substituted hydrophobic cholesterol, and is capable of forming a stable hydrogel nanoparticle in aqueous solution due to the self-assembly of hydrophobic cholesterol moieties. The conformation of CHP changes dramatically at the hydrophobic interfaces. In order to understand the interfacial responses of CHP, the interaction forces of CHP nanogels to the hydrophobic HOPG (highly orientated pyrolytic graphite) or carbon-coated surfaces were measured using atomic force microscope. The freely jointed china model for CHP molecular elasticity was applied to the force-extension curves and debonding force-pull-off distance in order to estimate the contour lengths and the segment lengths of the CHP molecules. The segment length of CHP chains in aqueous solution was estimated 0.32+/-0.19 nm showing a very flexible chain. From our analysis of the dynamic force measurements, the debonding forces were shown to depend on the applied loading forces. The zero kinetic off-rate K(off)(0) and the transition state x(b) were estimated to be 1.1 x 10(-3)s(-1) and 2.9A, respectively.

Effect of coronary artery bypass grafting with gastroepiploic artery on gastric intramucosal pH and systemic inflammation.

BACKGROUND: The purpose of this study was to investigate the effect of coronary arterial bypass grafting (CABG) with gastroepiploic artery (GEA) on gastric intramucosal pH and systemic inflammation. DESIGN: retrospective study. SETTING: University hospital. PARTICIPANTS: 22 patients underwent CABG. INVESTIGATIONS: the GEA group (n=13) received CABG with the GEA graft. The non-GEA group (n=9) received conventional CABG without the GEA graft. MEASUREMENTS: gastric intramucosal pH (pHi) and carbon dioxide tension (PrCO(2)) were assessed by capnometric air tonometry. The difference between PrCO(2) and PaCO(2), PCO(2)-gap, was also determined. Systemic inflammatory responses were evaluated by serum interleukin-6 (IL-6) and leucocyte counts. Hemodynamics, oxygen delivery index (DO(2)I) and uptake index (VO(2)I) were monitored with catheters in the radial and pulmonary arteries (thermodilution). RESULTS: The duration of aortic cross-clamping and cardiopulmonary bypass was similar in both groups. Both groups did not show any significant difference in gastric pHi, PCO(2)-gap, systemic inflammation and hemodynamics. CONCLUSIONS: Our findings suggest that CABG using the GEA graft does not disturb gastric mucosal perfusion, and that laparotomy for the GEA graft does not aggravate systemic oxygen demand-supply imbalance or systemic inflammatory responses induced by hypothermic CPB. CABG with the GEA graft does not seem to pose an additional risk and is a safe technique compared with conventional CABG with regard to pHi and systemic inflammation.

Reduction of carotid artery blood flow in pediatric patients with syncope: evaluation with head-up tilt test.

We investigated the effect of postural changes on cerebral circulation by measuring carotid artery blood flow (CABF) in the supine position and during head-up tilt (HUT) test using a Doppler flow meter. Subjects included 10 patients with neurally mediated syncope, 10 patients with orthostatic intolerance, 8 with epilepsy, aged between 8 to 24 years (mean +/- SD, 13.9 +/- 4.1 years). The test caused pallor and dizziness in 16 patients (symptomatic), while no symptoms were recognized in the other 12 patients (asymptomatic). Significant reductions in the mean CABF (Fm), maximum CABF (Fs) and minimum CABF (Fd), components of the CABF waveform, were noticed during HUT compared to before HUT (supine), and these reductions in symptomatic patients were more severe than those in asymptomatic patients (Fm: - 2.8 +/- 2.0 SD vs - 0.7 +/- 1.4 SD; Fs: - 2.7 +/- 1.5 SD vs - 0.9 +/- 1.3 SD; Fd: - 4.5 +/- 2.8 SD vs - 2.2 +/- 2.1 SD). Reductions in Fm, Fs and Fd in the symptomatic patients during HUT lasted longer than those of the asymptomatic patients, being statistically significant for Fm and Fs (Fm: p < 0.01; Fs: p < 0.05). The criteria during HUT for distinguishing neurally mediated syncope (NMS) from others was Fs: < - 4 SD and Fd: < - 5 SD. Our data suggest that reduction of CABF should be carefully evaluated for the diagnosis of neurally mediated syncope in pediatric patients. Such a reduction might be an essential mechanism of syncopal attacks.

Outcome of acute lymphoblastic leukemia in children with AL90 regimen: impact of response to treatment and sex difference on prognostic factors.

BACKGROUND: In our previous studies, the outcome of high-risk ALL was still poor. In the present study, all children with ALL were classified into three groups and treated with a new regimen (AL90). PATIENTS AND METHODS: Between 1990 and 1996, 220 children with ALL, treated with the AL90 regimen, were classified into three risk groups: low, intermediate, and high: LR, IR, and HR, respectively. The protocol consisted of three- to five-drug induction, consolidation with intermediate-dose methotrexate and/or cytarabine, mercaptopurine and cyclophosphamide, four-drug intensification, and sequential maintenance therapies. Only intrathecal chemotherapy was used for CNS prophylaxis in the LR group, whereas cranial irradiation was added for the IR and HR groups. RESULTS: The number of eligible patients was 91: LR group, 71: IR group, and 58: HR group. Complete remission (CR) was obtained in > 98% of the LR and IR groups, while only 88% achieved CR in the HR group. The 5-year event-free survival (EFS) rate was 67.4% in all patients: 70.4% in the LR group, 71.7% in the IR group, and 57.5% in the HR group. With respect to the previous study, EFS in the HR group who showed positive residual leukemia at 14 days was improved, whereas EFS in boys versus girls was significantly lower (48.8% : 85.7%, P = 0.02). CONCLUSIONS: In high-risk ALL, the rate of induction failure was high and boys had a worse outcome, calling for improvements in induction therapy and a specific approach for boys.

Long-term outcome of treatment with protocols AL841, AL851, and ALHR88 in children with acute lymphoblastic leukemia: results obtained by the Kyushu-Yamaguchi Children's Cancer Study Group.

We analyzed the long-term outcome and late effects of treatment in 187 patients with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and 1990. Overall survival and event-free survival rates were 68.2% +/- 3.7% and 63.2% +/- 3.6% at 15 years, respectively. Of 55 patients who relapsed after achieving the first complete remission (CR), only 17.4% were rescued by salvage therapy. The advantage of stem cell transplantation over chemotherapy was observed only in those patients with bone marrow relapse during therapy. The SD for score height in patients maintaining the first CR significantly decreased at the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P < .0001). The decrease was remarkable in patients younger than 5 years at diagnosis. Other late effects included mild liver dysfunction in 18% and hepatitis C virus infection in 9%. Congestive heart failure was observed in only 2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2). Although the survival rates of patients on our protocols were comparable to those of other study groups, some modification, including reduction in dose of cranial irradiation and/or anticancer drugs, should be considered to reduce late adverse effects in survivors of childhood ALL.

Effect of low-dose milrinone on gastric intramucosal pH and systemic inflammation after hypothermic cardiopulmonary bypass.

OBJECTIVE: To investigate the usefulness of low-dose milrinone on gastric intramucosal pH (pHi) and systemic inflammation in patients undergoing hypothermic cardiopulmonary bypass (CPB). DESIGN: Prospective randomized study. SETTING: University hospital. PARTICIPANTS: Twenty patients scheduled for cardiac surgery. INTERVENTIONS: Ten patients were administered a low dose of milrinone, 0.25 microg/kg/min, from the initiation of CPB to 1 hour after admission to the intensive care unit. The other patients were administered saline. Supplemental inotropes and intravenous fluid were given to obtain adequate mean arterial blood pressure and pulmonary artery occlusion pressure. MEASUREMENTS AND RESULTS: Gastric pHi and carbon dioxide pressure (PCO2) were assessed by capnometric air tonometry. The difference between PCO2 and arterial carbon dioxide pressure (PaCO2), PCO2-gap, was also examined. Systemic inflammatory responses were evaluated by serum interleukin-6 and leukocyte counts. Hemodynamics, oxygen delivery index, and oxygen uptake index were monitored with catheters in the radial and pulmonary arteries (thermodilution). The hepatic venous blood flow and left ventricular flow were measured using transesophageal echocardiography. Milrinone prevented gastric intramucosal acidosis, detected as a decrease in pHi or an increase in PCO2-gap, without affecting hepatic venous blood flow. Increases in interleukin-6, leukocyte count, and oxygen uptake index, all of which developed after CPB, were significantly less in the milrinone group than in the control group. CONCLUSION: These results suggest that in patients undergoing hypothermic CPB, supplemental low-dose milrinone prevents gastric intramucosal acidosis and increases in some markers of systemic inflammation.

Effects of olprinone, a new phosphodiesterase inhibitor, on gastric intramucosal acidosis and systemic inflammatory responses following hypothermic cardiopulmonary bypass.

BACKGROUND: Phosphodiesterase (PDE) III inhibitors have both an inotropic and a peripheral vasodilatory effect, and also inhibit the activation of macrophages. Thus a newly developed PDE III inhibitor, olprinone, could modify gastric intramucosal pH (pHi), systemic oxygen consumption, and systemic inflammatory responses in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: We studied 23 patients. In 15 patients, olprinone (0.1 or 0.2 microg x kg(-1) x min(-1)) was administered from the commencement of CPB until their admission to the ICU. The other 8 patients received placebo. The pHi and regional CO2 tension (PrCO2) were assessed by a capnometric air tonometry. Systemic inflammatory responses were evaluated by serum interleukin-6 (IL-6), IL-10, and leucocyte counts. RESULTS: The pHi and PCO2-gap, the difference between PrCO2 and arterial CO2 tension (PaCO2), showed a transient decrease and an increase after CPB, respectively. Although olprinone did not affect pHi, olprinone at 0.2 microg x kg(-1) x min(-1) significantly lessened post-CPB increase in PCO2-gap. Olprinone at 0.2 microg x kg(-1) x min(-1) significantly increased IL-10 and reduced the extent of leucocytosis, while it did not affect IL-6 levels. At the same dosage, olprinone also lessened the surge in systemic oxygen uptake index (VO2) and augmented the increase in mixed oxygen saturation (SvO2) both of which occurred after CPB. At 0.1 microg x kg(-1) x min(-1), however, olprinone did not show any significant effect. CONCLUSION: Our results suggest that olprinone at 0.2 microg x kg(-1) x min(-1) suppresses gastric intramucosal acidosis and systemic inflammation following CPB.

Pulmonary lipiodol embolism during transcatheter arterial chemoembolization for hepatoblastoma under general anaesthesia.

We present a case of pulmonary embolism that occurred during the injection of lipiodol during transcatheter arterial chemoembolization under general anaesthesia. A 7-year-old child suffering from a large hepatoblastoma was admitted for arterial chemoembolization and carcinostatic administration. Pulmonary embolism due to lipiodol during arterial chemoembolization was evident by a sudden fall in oxyhaemoglobin saturation from 100 to 90%. This was associated with a spread of lipiodol into both lungs, particularly the middle lung zones and detected by chest fluoroscopy. Arterial blood gases returned to normal values 1 day later but pulmonary infiltration persisted for 7 days before final clearance. Pulmonary embolism caused by lipiodol during arterial chemoembolization is infrequent, but such a complication could prove fatal. Understanding the risk of pulmonary embolism in patients receiving lipiodol, during and after arterial chemoembolization, and late onset pulmonary injury is important and a close follow-up for several days after arterial chemoembolization is advisable.

Selective uptake by cancer cells of liposomes coated with polysaccharides bearing 1-aminolactose.

We investigated the selective uptake of liposomes chemically modified by polysaccharides-cholesterol derivatives with 1-aminolactose (lactose) in two human hepatoma cell lines (HUH7 and Alexander), a human colon cancer cell line (FCC) and a human lung cancer cell line (KNS). The uptakes of the labeled liposomes alone (conventional liposomes), those with cholesterol pullulan (CHP) and with lactose (lactose CHP) were compared in four cancer cells and normal rat hepatocytes after 3 hours of incubation. The radioactivities of the lactose CHP were 4.4, 4, 3.4 and 4.4 times greater than those of CHP in HuH7, Alexander, FCC and KNS cells, respectively, after 3 hours of incubation. All the above differences were statistically significant (p < 0.01). No statistically significant differences were seen in the case of hepatocytes. Thus, cancer cells have a common affinity with lactose CHP liposomes, however, these mechanisms appear to have no connection with the galactose-specific asialoglycoprotein receptors of hepatocytes.

Development of a cancer vaccine: peptides, proteins, and DNA.

Genetic changes leading to protooncogene activation qualitatively and/or quantitatively alter their gene products and are exclusively or largely restricted to transforming cells and their precursors. The overexpression of HER2 is among those changes and is often detected in adenocarcinomas such as breast, ovarian, lung, and gastric cancer. This provides a rationale for exploring the possibility that HER2 is a target of host immune responses against cancer cells. We have recently demonstrated that HER2 can be a target for tumor-rejecting immune responses against syngeneic murine HER2+ tumor cells. We defined two different peptides, HER2p63-71 and HER2p780-788, with a Kd anchor motif that can induce CD8+ cytotoxic T lymphocytes (CTLs). The growth of HER2+ syngeneic tumors was suppressed in mice immunized with HER2p63-71 or p780-788. Since murine Kd and human HLA-A24 share a similar anchor motif for peptides, HER2p63 71 and HER2p780-788 were examined for induction of CTLs in HLA-A24+ individuals. CD8+ CTL clones specific for these peptides were established and they lysed HER2+ tumor cells in a human leukocyte antigen (HLA)-A24-restricted manner. To elicit specific CD8+ T cell immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the major histocompatibility complex (MHC) class I pathway constitutes a central issue. We have developed a novel formula of hydrophobized polysaccharide nanoparticles which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway. We designed a simple protein delivery system: cholesteryl group-bearing polysaccharides, mannan or pullulan (CHM or CHP, respectively), complexed with the truncated HER2 protein containing the 147 N-terminal amino acids. These complexes were able to induce CD8+ CTLs against HER2+ tumors. CTLs were MHC class I restricted and specifically recognized HER2p63-71, a part of a truncated HER2 protein used as an immunogen. The complete rejection of tumors also occurred when CHM-HER2 was applied early after tumor implantation. In the effector phase of in vivo tumor rejection, CD8+ T cells played a major role. The results suggest that this unique hydrophobized polysaccharide may help soluble proteins to induce cellular immunity. Such a novel vaccine may be of potential benefit in cancer prevention and cancer therapy.

Ganglioside patterns in neuroepithelial tumors of childhood.

To elucidate a relationship between neuronal anaplasia, tumor proliferation, and ganglioside contents, we quantified gangliosides by HPTLC in tumors of neuroepithelial tissues at different grade, i. e. peripheral primitive neuroectodermal tumor (PPNET, grade IV), ependymoma (EPEN, grade III), neuroblastoma (NB, grade IV), and dysembryoplastic neuroepithelial tumor (DNT, grade I). PPNET, the most undifferentiated tumor examined had lowest concentration of total lipid-bound sialic acid. GM3 was the major ganglioside in all undifferentiated tumors (46-72.7% of total lipid-bound sialic acid). GD3 was an another component in PPNET and EPEN (7.2-17.3%). Concentration of a complex gangliosides GM1 was decreased in all tumor tissues and those of GT1a, GD1b and GT1b were decreased in tumors of high grade. The results suggest that the composition of gangliosides could be of considerable value in refining the classification of neuroepithelial tumors in infancy and childhood.

Capillary hemangioma of the liver with Kasabach-Merritt syndrome in a neonate: report of a case.

Hepatic hemangiomas are benign tumors, and therefore minimally invasive treatment such as irradiation or steroid therapy is often recommended. However, in patients who have a hemangioma complicated by Kasabach-Merritt syndrome, surgical intervention should also be considered because of its confirmative therapeutic effect. We present herein the case of a 32-day-old male infant in whom a huge hepatic hemangioma associated with Kasabach-Merritt syndrome was treated by surgical intervention together with strong antidisseminated intravascular coagulation therapy.

Changes in left ventricular end-diastolic area, end-systolic wall stress, and fractional area change during anesthetic induction with propofol or thiamylal.

PURPOSE: To elucidate the mechanisms of the more profound hypotensive effects of propofol relative to thiamylal, we monitored changes in left ventricular (LV) preload, afterload, and contractility during the course of anesthetic induction with propofol and thiamylal. METHODS: Thirty-two patients (ASA I) were randomly assigned into two groups and injected with propofol (2 mg.kg(-1)) or thiamylal (4 mg.kg(-1)) as anesthetic induction agents. Transthoracic echocardiography (TTE) was used to assess LV performance before and during induction by the two anesthetics. The LV end-diastolic area (EDA) and LV end-systolic wall stress (ESWS) were used as indices of LV preload and LV afterload, respectively, while LV contractility was assessed by the fractional area change (FAC). RESULTS: Both propofol and thiamylal significantly reduced EDA and ESWS without significant change in FAC. Propofol-induced reductions in EDA and ESWS were significantly greater than those of thiamylal. CONCLUSION: The more profound hypotension observed during induction of anesthesia with propofol is due to the greater decrease in preload and afterload than with thiamylal, but not to a decrease in LV contractility.