Enhanced antitumour immunity by combined use of temozolomide and TAT-survivin pulsed dendritic cells in a murine glioma

Although chemotherapy remains among the best treatment options for most cancers, adjuvant therapies such as dendritic cell (DC)-based immunotherapy have been added to treatment protocols to destroy residual tumour cells. Combination treatment with low-dose temozolomide (TMZ) chemotherapy followed by vaccination with TAT-survivin-pulsed DCs enhanced T-cell responses specific for survivin and improved survival rate, as compared with DC alone or TMZ alone. Moreover, antigen-specific immunity appears to be mediated by CD8(+) T cells, as determined by in vitro T-cell subset depletion. These studies demonstrated that a combination of low-dose TMZ chemotherapy and TAT-based DC immunotherapy may be a novel strategy for safe and effective treatment of malignant gliomas.     

Dysbindin gene variants are associated with bipolar I disorder in a Korean population

The dysbindin gene (DTNBP1) has been associated with schizophrenia in several populations. Because the clinical characteristics of schizophrenia and bipolar disorder overlap in many respects and findings from genetic studies have suggested common genes between them, we conducted a case control association study of bipolar disorder in Korea to investigate the genetic association between DTNBP1 and bipolar disorder. In total, 163 patients with bipolar disorder and 350 controls were evaluated. We genotyped three single nucleotide polymorphisms of DTNBP1 (SNP A, P1763, and P1320) and analyzed the allele, genotype, and haplotype associations with bipolar disorder. We found significant genotypic associations with P1763 and P1320, but no association with SNP A in the bipolar I group. When we included bipolar II and schizoaffective disorder in the affected phenotype, the significance decreased. A positive association was observed between the SNP A-P1763 haplotype and the bipolar I phenotype. This haplotype association was lost when we either broadened our phenotype or included P1320 in a haplotype. The positive results of the present study lost significance after a Bonferroni correction for multiple testing. These findings are consistent with previous findings that showed a positive association of DTNBP1 with bipolar disorders. Moreover, our results suggest that DTNBP1 may contribute more to bipolar I disorder than bipolar II disorder or schizoaffective disorder. Further comprehensive studies will be required to clarify these association, however, it seems likely that DTNBP1 is a susceptibility gene for bipolar disorder.     

Expression of nuclear and cytoplasmic phosphorylated FADD in gastric cancers

Fas-associated death domain (FADD) plays a crucial role during death receptor-mediated apoptosis. In addition, FADD possesses apoptosis-independent activities, including cell-cycle regulation and cell proliferation regulated by the phosphorylation of FADD at Ser194. The aim of this study was to explore the possibility whether alteration of phosphorylated FADD (p-FADD) expression might be a characteristic of gastric cancer. We analyzed the expression of p-FADD protein in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. In the normal gastric mucosal cells, surface and glandular epithelial cells evenly expressed p-FADD in the nuclei but not in the cytoplasm. In the cancers, p-FADD expression was detected in 38 cases (63%) of the gastric carcinomas, but there was no p-FADD immunostaining in the remaining 22 cancers (37%). Of note, p-FADD immunostaining was observed in cytoplasm/nuclei (20 cancers; 33%) and cytoplasm (18 cancers; 30%). There was no significant association of p-FADD expression with clinocopathological characteristics, including invasion, metastasis, and stage. Our data showed that the expression of p-FADD in gastric cancers was heterogenous in its location compared to the uniform nuclear expression of p-FADD in normal gastric cells. Many of the cancers (67%) were devoid of nuclear p-FADD, suggesting that p-FADD functions in the nucleus may be perturbed in the cancers. Also, p-FADD expression in the cytoplasm in a large fraction of the cancers (63%), not seen in the normal cells, suggested that the cell death functions of p-FADD could be altered in the cancer cells.     

The impact of unrecognized bipolar disorders among patients treated for depression with antidepressants in the fee-for-services California Medicaid (Medi-Cal) program: a 6-year retrospective analysis

INTRODUCTION: The cost of unrecognized bipolar disorders over time is unknown. METHODS: Ten years of data from the California Medicaid program were used to identify depressed patients initiating new episodes of antidepressant therapy and with 6+ years of post-treatment data. Recognized bipolar (RBP) patients received a BP diagnosis or used mood stabilizers in the pre-index period. Unrecognized bipolar (UBP) patients received an initial BP diagnosis or used a mood stabilizer in the post-index period. Depression-only (MDD) patients had no BP diagnosis or mood stabilizer use. Three analyses were conducted: (1) regression models of cost per year, (2) a regression model of aggregate cost over 6 years and (3) a time trend analysis of the costs for UBP patients. RESULTS: 14,809 patients were identified: RBP 14.5%, UBP 28.2% and MDD 57.3%. The growth in costs per month for UBP patients over 6 years (171%) far exceeds the growth for RBP and MDD patients (82% and 95%, respectively). RBP and MDD patients cost 2316 dollars and 1681 dollars less per year in the 6th year relative to UBP patients (p<0.0001 for both estimates). The cost per month increased by 91 dollars for each month of delayed diagnosis (p=0.011). Costs for UBP patients increased by 10 dollars per month prior to their initial BP diagnosis (p<0.001) and by -1.01 dollars thereafter (p=0.006 for the change in slope). LIMITATIONS: Classification of patients based on diagnosis or mood stabilizer use using paid claims data is inexact. CONCLUSIONS: Early diagnosis of bipolar disorders may significantly reduce health care cost.     

The use of HPV Linear Array Assay for multiple HPV typing on archival frozen tissue and DNA specimens

Accurate HPV typing is important for natural history and epidemiology studies. With the introduction of prophylactic multivalent HPV vaccines, there is also the need to determine the dominant genotypes in different populations and the effect of a vaccination programme on infection profiles. The interplay between multiple infection, viral persistence and implementation of interventions is a complicated one and therefore requires a reliable and accurate HPV detection and typing method. The Linear Array HPV genotyping test is a PCR-based HPV detection kit which can detect qualitatively Multiple HPV Infection in cervical cells collected in PreservCyt Solution. The utility of this kit for multiple HPV typing of archival frozen tissue and cervical cells not collected in PreservCyt are described.     

A prospective, multicenter, open-label trial of zoledronic acid in patients with hormone refractory prostate cancer

PURPOSE: The short-term safety and efficacy of zoledronic acid for the treatment of skeletal metastasis was evaluated in patients with hormone-refractory prostate cancer. PATIENTS AND METHODS: A total of 19 hormone-refractory prostate cancer patients with bone metastases were enrolled. All patients received up to six infusions of zoledronic acid (4 mg, given intravenously over 15 minutes, every 3-4 weeks). Safety was assessed by monitoring adverse events and serum creatinine levels. Efficacy was assessed by monitoring skeletal-related events, brief pain inventory score, quality of life score, type of pain medication, and analgesic score. Mean age of patients was 67.3 years (46-86 years), mean time from diagnosis of bone metastases was 27.6 months (0-117 months), and mean time from diagnosis of hormone-refractory disease was 7.5 months (0-26 months). RESULTS: There was no clinically significant change in serum creatinine levels. Eleven adverse events (musculoskeletal disorders and systemic disorders) in 8 patients were classed as having a possible relationship to study drug. Fifteen patients completed six courses of zoledronic acid infusion. There were no significant changes in the brief pain inventory composite scores, quality of life questionnaire scores or analgesic score. No new skeletal-related events developed during the treatment period. CONCLUSION: Zoledronic acid administered in this study as a 15-minute infusion demonstrated an acceptable and well-known safety profile in patients with refractory prostate cancer with bone metastases. However, prospective placebo- controlled clinical trials are required to elucidate the efficacy of zoledronic acid.     

Spontaneous Regression of a Cystic Tumor in a Postpartum Woman; Is It A Cystic Lymphangioma?

Spontaneous regression of intra-abdominal cystic tumors in adults is unusual. Here, we present the case of an apparently spontaneous regression of a large intra-abdominal cystic mass found in the postpartum period of an 18-year-old woman. The regression was demonstrated using serial computed tomography (CT) examinations over a two-year period.     

Vaccination against murine toxoplasmosis using recombinant Toxoplasma gondii SAG3 antigen alone or in combination with Quil A

PURPOSE: Surface antigen 3 (SAG3) of Toxoplasma gondii is very similar in structure to the major surface antigen 1 (SAG1). Although numerous studies have supported the importance of SAG1 in protection against T. gondii infection, few reports exist on SAG3. MATERIALS AND METHODS: Glutathione-S-transferase (GST)-fused SAG3 of T. gondii (rSAG3) were immunized into BALB/c mice alone or in combination with Quil A (rSAG3/Quil A), and then evaluated the protective immunity in vivo and in vitro against murine toxoplasmosis. RESULTS: Immunization with rSAG3 or rSAG3/Quil A resulted in significantly more survival days and fewer brain cysts after challenge with T. gondii compared to an infected control group. Mice immunized with rSAG3 alone or in combination with Quil A produced significantly more specific IgG2a antibody, whereas specific IgG1 antibody titers did not increase. The percentage of CD8+ T cells, IFN-gamma mRNA expression, and nitric oxide production significantly increased in rSAG3- and rSAG3/Quil A-immunized mice. CONCLUSION: These results indicate that vaccination with Toxoplasma rSAG3 results in partial protective immunity against T. gondii infection through induction of a Th1-type immune response, and that protective immunity is accelerated by the modulating effects of Quil A.