Gadolinium-DTPA enhanced magnetic resonance imaging of bone and soft tissue sarcomas in comparison with pathological findings.

We compared gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced T1-weighted images (T1-Gd) with the histopathological findings in 13 patients with bone or soft tissue sarcomas. Signal intensity of the viable tumor tissue was increased in T1-Gd in 92% of the patients. The necrotic or cystic areas in the tumor were not enhanced, rendering them distinctly. The degree of enhancement of the edematous area around the tumor was similar to or more marked than that of the tumor in 54% of the patients. Area showing inflammatory cells infiltration and edematous areas in the tumor tissue were also enhanced. Thus, the effect of preoperative chemotherapy in tumor tissues other than necrotic and cystic areas tended to be underestimated in T1-Gd. Its effect should be comprehensively evaluated based on not only T1-Gd but also T2-weighted images and findings of other imaging techniques.</p

A clinical analysis of malignant schwannoma

In this study, we reviewed the clinical features of 11 patients with malignant schwannoma who were treated in our institute. Five patients had coexistent von Recklinghausen's disease and one of them showed multifocal occurrence. Patients with the centrally located tumors had a poorer prognosis than those with the others. The overall 3-year survival rate was 36%; 40% in patients with von Recklinghausen's disease and 33% in the others. At the time of the last follow-up, 9 patients had died of the tumor, one continued to be tumor free, and one was alive with tumor. Postoperative local recurrence developed in 5 patients (45%); 4 out of 6 patients (67%) who underwent a marginal excision and one out of 3 (33%) who underwent primary amputation. There was no local recurrence in patients after a wide excision with at least 3cm of normal tissue removed surrounding the tumor in all directions. Nine patients (82%) developed pulmonary metastasis. The effect of adjuvant chemotherapy was not clear in this study. The high risk of pulmonary metastasis in this disease indicates the necessity of more effective adjuvant chemotherapy.</p

Radiofrequency Ablation with the Real-Time Virtual Sonography System for Treating Hepatocellular Carcinoma Difficult to Detect by Ultrasonography

Radiofrequency ablation has been applied to treat hepatocellular carcinoma, with favorable therapeutic outcomes. Nevertheless, practitioners have approached radiofrequency ablation with some reluctance due to the difficulty of identifying isoechoic tumors and recurrent tumors. The aim of the present study is to investigate the efficacy of Real-time Virtual Sonography to treat hepatocellular carcinoma difficult to detect by conventional ultrasonography. Real-time Virtual Sonography is a system generating multiplanar reconstruction images in real-time using the Hitachi medico EUB-8500 equipped with a probe. The system included following components: 1) digital imaging and communications in medicine (DICOM) data from dynamic CT, 2) a magnetic field generator to match the multiplanar reconstruction image on the monitor and the actual ultrasonography image, 3) the cross section with the tumor displayed as a multiplanar reconstruction image. Total twenty-five nodules of twenty-one patients underwent radiofrequency ablation monitored by Real-time Virtual Sonography. All nodules difficult to detect via conventional ultrasonography were clearly visualized in real-time. The average nodule diameter was 2.4 ± 1.6 cm, and punctures and coagulation were performed an average of 2.2 and 3 times per session. Dynamic CT after session confirmed effective coagulation of each nodule. In conclusion, this study demonstrates that the present system is capable of effectively and accurately treating tumors difficult to detect by conventional ultrasonography

Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders

Elucidating the neural and genetic factors underlying psychiatric illness is hampered by current methods of clinical diagnosis. The identification and investigation of clinical endophenotypes may be one solution, but represents a considerable challenge in human subjects. Here we report that mice heterozygous for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII+/-) have profoundly dysregulated behaviours and impaired neuronal development in the dentate gyrus (DG). The behavioral abnormalities include a severe working memory deficit and an exaggerated infradian rhythm, which are similar to symptoms seen in schizophrenia, bipolar mood disorder and other psychiatric disorders. Transcriptome analysis of the hippocampus of these mutants revealed that the expression levels of more than 2000 genes were significantly changed. Strikingly, among the 20 most downregulated genes, 5 had highly selective expression in the DG. Whereas BrdU incorporated cells in the mutant mouse DG was increased by more than 50 percent, the number of mature neurons in the DG was dramatically decreased. Morphological and physiological features of the DG neurons in the mutants were strikingly similar to those of immature DG neurons in normal rodents. Moreover, c-Fos expression in the DG after electric footshock was almost completely and selectively abolished in the mutants. Statistical clustering of human post-mortem brains using 10 genes differentially-expressed in the mutant mice were used to classify individuals into two clusters, one of which contained 16 of 18 schizophrenic patients. Nearly half of the differentially-expressed probes in the schizophrenia-enriched cluster encoded genes that are involved in neurogenesis or in neuronal migration/maturation, including calbindin, a marker for mature DG neurons. Based on these results, we propose that an "immature DG" in adulthood might induce alterations in behavior and serve as a promising candidate endophenotype of schizophrenia and other human psychiatric disorders

Glycolysis Inhibition Inactivates ABC Transporters to Restore Drug Sensitivity in Malignant Cells

Cancer cells eventually acquire drug resistance largely via the aberrant expression of ATP-binding cassette (ABC) transporters, ATP-dependent efflux pumps. Because cancer cells produce ATP mostly through glycolysis, in the present study we explored the effects of inhibiting glycolysis on the ABC transporter function and drug sensitivity of malignant cells. Inhibition of glycolysis by 3-bromopyruvate (3BrPA) suppressed ATP production in malignant cells, and restored the retention of daunorubicin or mitoxantrone in ABC transporter-expressing, RPMI8226 (ABCG2), KG-1 (ABCB1) and HepG2 cells (ABCB1 and ABCG2). Interestingly, although side population (SP) cells isolated from RPMI8226 cells exhibited higher levels of glycolysis with an increased expression of genes involved in the glycolytic pathway, 3BrPA abolished Hoechst 33342 exclusion in SP cells. 3BrPA also disrupted clonogenic capacity in malignant cell lines including RPMI8226, KG-1, and HepG2. Furthermore, 3BrPA restored cytotoxic effects of daunorubicin and doxorubicin on KG-1 and RPMI8226 cells, and markedly suppressed subcutaneous tumor growth in combination with doxorubicin in RPMI8226-implanted mice. These results collectively suggest that the inhibition of glycolysis is able to overcome drug resistance in ABC transporter-expressing malignant cells through the inactivation of ABC transporters and impairment of SP cells with enhanced glycolysis as well as clonogenic cells

Combination of Defucosylated AHM plus Lenalidomide

The immunomodulatory drug lenalidomide (Len) has drawn attention to potentiate antibody-dependent cellular cytotoxicity (ADCC)-mediated immunotherapies. We developed the defucosylated version (YB-AHM) of humanized monoclonal antibody against HM1.24 (CD317) overexpressed in multiple myeloma (MM) cells. In this study, we evaluated ADCC by YB-AHM and Len in combination against MM cells and their progenitors. YB-AHM was able to selectively kill via ADCC MM cells in bone marrow samples from patients with MM with low effector/target ratios, which was further enhanced by treatment with Len. Interestingly, Len also up-regulated HM1.24 expression on MM cells in an effector-dependent manner. HM1.24 was found to be highly expressed in a drug-resistant clonogenic ‘‘side population’’ in MM cells; and this combinatory treatment successfully reduced SP fractions in RPMI 8226 and KMS-11 cells in the presence of effector cells, and suppressed a clonogenic potential of MM cells in colony-forming assays. Collectively, the present study suggests that YB-AHM and Len in combination may become an effective therapeutic strategy in MM, warranting further study to target drug-resistant MM clonogenic cells

Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors

<p>Abstract</p> <p>Background</p> <p>The clinical course of human papillomavirus (HPV) associated with Bowenoid papulosis and condyloma acuminatum of anogenital tumors are still unknown. Here we evaluated molecules that are relevant to cellular proliferation and regulation of apoptosis in HPV associated anogenital tumors.</p> <p>Methods</p> <p>We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity.</p> <p>Results</p> <p>Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (<it>p </it>< 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (<it>p </it>< 0.001, <it>p </it>< 0.001, <it>p </it>= 0.022, respectively) and normal skin (<it>p </it>< 0.001, <it>p </it>= 0.002, <it>p </it>= 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression.</p> <p>Conclusion</p> <p>Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors.</p

Reinvestigation of the β‑to‑α Crystal Phase Transition of Poly(butylene adipate) by the Time-Resolved X‑ray Scattering and FTIR Spectral Measurements in the Temperature-Jump Process

Poly­(butylene adipate) (PBA) exhibits the two types of crystal modification, the α and β forms, depending on the sample preparation conditions. They show the different degree of biodegradability. A majority of papers published so far reported that the phase transition from the β-form to the α-form occurs as the direct solid-to-solid process when the sample is heated up to the high temperature of around 55 °C. We have reinvestigated this β-to-α phase transition by performing the temperature-jump time-resolved measurement of the FTIR, WAXD, and SAXS measurements. This transition has been found to be not a solid-to-solid phase transition but the combined phenomena of the melting of the β-phase followed by the recrystallization to the high-temperature α-phase