Comparison of chemosensitivity tests: clonogenic assay versus MTT assay.

When the development of chemotherapeutic agents reaches the clinical trial stage, it is necessary to perform drug sensitivity tests quickly in order to select the most promising agents for the treatment of cancer. In order to assess the possibility of using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as a substitute for the human tumor clonogenic assay (HTCA), we evaluated the correlation between the results obtained by these 2 assays in 5 human lung cancer cell lines. The correlation coefficient between the results of the HTCA and the MTT assay was 0.673, indicating a relatively good correlation. The correlation was most prominent in platinum analogues (r = 0.939) and good in anthracyclines/anthracenedione (r = 0.611). However, no significant correlation was observed in vinca alkaloids, etoposide, irinotecan, SN-38 (an active metabolite of irinotecan), and rhizoxin. The results of the MTT assay showed a high degree of correlation with those of the HTCA in predicting the sensitivity of cancer cell lines to platinum analogues, and anthracyclines/anthracenedione. These results suggest that the MTT assay may be more convenient and quickly performed than the HTCA and can replace HTCA in evaluating the effects of anticancer agents, especially the platinum analogues and anthracyclines/anthracenedione.</p

Effect of juggling therapy on anxiety disorders in female patients

<p>Abstract</p> <p>Aims</p> <p>The aim of this study was to investigate the effect of juggling therapy for anxiety disorder patients.</p> <p>Design and Method</p> <p>Subjects were 17 female outpatients who met the DSM-IV diagnostic criteria for anxiety disorders. Subjects were treated with standard psychotherapy, medication and counseling for 6 months. For the last 3 months of treatment, subjects were randomized into either a non-juggling group (n = 9) or a juggling therapy group (juggling group: n = 8). The juggling group gradually acquired juggling skills by practicing juggling beanbags (<it>otedama </it>in Japan) with both hands. The therapeutic effect was evaluated using scores of psychological testing (STAI: State and Trate Anxiety Inventry, POMS: Profile of Mood Status) and of ADL (FAI: Franchay Activity Index) collected before treatment, 3 months after treatment (before juggling therapy), and at the end of both treatments.</p> <p>Results</p> <p>After 6 months, an analysis of variance revealed that scores on the state anxiety, trait anxiety subscales of STAI and tension-anxiety (T-A) score of POMS were significantly lower in the juggling group than in the non-juggling group (p < 0.01). Depression, anger-hostility scores of POMS were improved more than non-jugglers. In the juggling group, activity scores on the vigor subscale of POMS and FAI score were significantly higher than those in the non juggling group (p < 0.01). Other mood scores of POMS did not differ between the two groups.</p> <p>Conclusion</p> <p>These findings suggest that juggling therapy may be effective for the treatment of anxiety disorders.</p

Is the number of covered intercostal arteries a predictor of postoperative spinal cord ischemia after thoracic endovascular aortic repair?

Objective: The purpose of this study was to investigate the impact of the number of covered intercostal arteries (ICAs) on postoperative spinal cord ischemia (SCI) after Thoracic endovascular aortic repair (TEVAR).Methods: A retrospective review of a collected database was performed for all patients who underwent TEVAR at the Sapporo Medical University between January 2006 and February 2016. The pre- and post-operative thin slice contrast-enhanced computed tomography was performed, and ICAs were evaluated. Preoperative demographics, procedure-related variables, and clinical details related to SCI were examined. Logistic regression analysis was performed to identify risk factors for the development of SCI.Results: Of the 263 patients who underwent TEVAR during the study period, 11 patients (4.1%) developed SCI. The number of patent preoperative ICAs was 10.1 ± 4.4. There was no significant difference in the number of patent ICAs between the SCI and No SCI groups. On the other hand, the number of postoperative covered ICAs was 4.8 ± 3.3. The number of covered ICAs was higher in the SCI than No SCI group (8.3 ± 2.9 vs 4.7 ± 3.2, p = 0.001). The cut-off value was set at 6 ICAs by ROC curve analysis. Multivariate analysis demonstrated that in TEVAR, the covering of 6 or more ICAs by stent grafts became a significant risk factor for SCI (odds ratio, 10.9; p = 0.029).Conclusions: The number of covered ICAs becomes a predictor of postoperative SCI after TEVAR. The patient with 6 or more ICAs covered by stent grafts is deemed to require a more careful perioperative management

Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI

The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL

Prognostic impact of complex and/or monosomal karyotypes in post‐transplant poor cytogenetic acute myeloid leukaemia: A quantitative approach

To evaluate the prognostic impact of complex karyotype (CK) and/or monosomal karyotype (MK) in combination with various clinical factors on allogeneic stem cell transplantation (HSCT) outcomes of patients with acute myeloid leukaemia (AML), we analysed the registry database of adult AML patients who underwent allogeneic HSCT between 2000 and 2019 in Japan. Among 16 094 patients, those with poor cytogenetic risk (N = 3345) showed poor overall survival (OS) after HSCT (25.3% at 5 years). Multivariate analyses revealed that CK and/or MK (hazard ratio [HR], 1.31 for CK without MK; 1.27 for MK without CK; and 1.73 for both), age at HSCT ≥50 years (HR, 1.58), male sex (HR, 1.40), performance status ≥2 (HR, 1.89), HCT-CI score ≥3 (HR, 1.23), non-remission status at HSCT (HR, 2.49), and time from diagnosis to HSCT ≥3 months (HR, 1.24) independently reduced post-HSCT OS among patients with poor cytogenetic risk AML. A risk scoring system based on the multivariate analysis successfully stratified patients into five distinct groups for OS. This study confirms the negative effects of CK and MK on post-HSCT outcomes, and offers a powerful risk scoring system for predicting prognoses after HSCT among AML patients with unfavourable cytogenetics

Functional Evolution of Duplicated Odorant-Binding Protein Genes, Obp57d and Obp57e, in Drosophila

Odorant-binding proteins (OBPs) are extracellular proteins found in insect chemosensilla, where they participate in the sensing of odors, tastes, and pheromones. Although a large number of OBP genes have been identified in insect genomes, their molecular functions and biological roles have been clarified in limited cases. Two OBP genes, Obp57d and Obp57e, were involved in the evolution of host-plant preference in Drosophila sechellia. Comparative analyses of the Obp57d/e genomic sequences from 27 closely related species suggested that the two genes arose by tandem gene duplication and functionally diverged from each other. In this study, the functional evolution of Obp57d and Obp57e was examined by in vitro binding assays using recombinant proteins synthesized in a bacterial system. Compared to the ancestral Dpse\OBP57de, Dmel\OBP57d was more specialized to tridecanoic acid while Dmel\OBP57e was generalized regarding their binding affinity, suggesting that the two OBP genes underwent subfunctionalization and neofunctionalization. A behavioral analysis using knockout flies supported that the biological role is different between OBP57d and OBP57e in vivo. Site-directed mutagenesis of the evolutionarily conserved amino acids revealed that these residues play an important role in protein folding. These findings provide a clue to understanding how the repertoire of OBP genes is maintained in a genome under natural selection