Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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Increased accumulation of iodine-123-IMP in the pulmonary inflammatory lesion surrounding a lung cancer

In a patient with primary lung cancer, increased accumulation of I-123-IMP was observed in a pulmonary inflammatory lesion surrounding a lung cancer which was delineated as a photon deficient area. Ga-67-citrate uptake was observed in both the inflammatory and cancerous areas. These findings suggest that I-123-IMP may have the potential to accumulate differently in a variety of pathological conditions of the lung and thus may be a clinically useful lung imaging agent.     

Locally-Delivered T-Cell-Derived Cellular Vehicles Efficiently Track and Deliver Adenovirus Delta24-RGD to Infiltrating Glioma

Oncolytic adenoviral vectors are a promising alternative for the treatment of glioblastoma. Recent publications have demonstrated the advantages of shielding viral particles within cellular vehicles (CVs), which can be targeted towards the tumor microenvironment. Here, we studied T-cells, often having a natural capacity to target tumors, for their feasibility as a CV to deliver the oncolytic adenovirus, Delta24-RGD, to glioblastoma. The Jurkat T-cell line was assessed in co-culture with the glioblastoma stem cell (GSC) line, MGG8, for the optimal transfer conditions of Delta24-RGD in vitro. The effect of intraparenchymal and tail vein injections on intratumoral virus distribution and overall survival was addressed in an orthotopic glioma stem cell (GSC)-based xenograft model. Jurkat T-cells were demonstrated to facilitate the amplification and transfer of Delta24-RGD onto GSCs. Delta24-RGD dosing and incubation time were found to influence the migratory ability of T-cells towards GSCs. Injection of Delta24-RGD-loaded T-cells into the brains of GSC-bearing mice led to migration towards the tumor and dispersion of the virus within the tumor core and infiltrative zones. This occurred after injection into the ipsilateral hemisphere, as well as into the non-tumor-bearing hemisphere. We found that T-cell-mediated delivery of Delta24-RGD led to the inhibition of tumor growth compared to non-treated controls, resulting in prolonged survival (p = 0.007). Systemic administration of virus-loaded T-cells resulted in intratumoral viral delivery, albeit at low levels. Based on these findings, we conclude that T-cell-based CVs are a feasible approach to local Delta24-RGD delivery in glioblastoma, although efficient systemic targeting requires further improvement.     

Predicting sustained virological response in chronic hepatitis C patients treated with pegylated interferon and ribavirin using a novel highly sensitive Real-time detection PCR assay

The Abbott Real Time HCV assay (lower limit of detection 12 IU/ml) was developed as a highly sensitive HCV RNA quantitative assay using real-time detection PCR(RTD-PCR). We assessed whether the new assay more effectively predicts sustained virological response (SVR) than conventional PCR (PCR) in 38 chronic hepatitis patients infected with HCV genotype 1b and treated with pegylated interferon alpha2b plus ribavirin. Sixteen patients reached SVR, 10 patients relapsed, 9 patients did not respond, 3 patients discontinued treatment. Positive predictive value (PPV) for SVR of undetectable HCV RNA at W4, 8, 12 by RTD-PCR and PCR was (100% vs. 100% at W4), (100% vs. 100% at W8), (83.3% vs. 72.7% at W12). HCV RNA undetectable at W12 had a higher PPV for SVR when measured by RTD-PCR than by conventional PCR.     

Changes in body surface potential distributions induced by isoproterenol and Na channel blockers in patients with the Brugada syndrome

BACKGROUND: The characteristics of unique ECG findings in the Brugada syndrome have not been well explained. METHODS: To clarify their characteristics and mechanisms, body surface maps (BSM) were recorded from patients with the Brugada syndrome (13 cases; a mean age of 48 years) before and after administration of isoproterenol (ISP) or Na channel blockers (12 cases). RESULTS: ST elevation in V1-V3 was decreased by 0.1 mV or more after ISP infusion in 8 of 11 cases and elevated after Na channel blockers in 8 of 12. In ventricular activation time (VAT) isochronal map, delayed conduction was noted on upper anterior chest in 11 and on anterior left chest in two. Delayed conduction areas were decreased by ISP and expanded by Na channel blockers. QRST isointegral map showed normal findings in baseline with minimal changes after ISP or Na channel blockers. Activation recovery interval (ARI) isochronal map showed prolonged area on upper anterior chest in baseline, being reduced by ISP and expanded by Na channel blockers. ARI dispersion (ARI-d), defined as difference between the maximum and minimum value of ARI, was larger in Brugada patients than that of normal subjects in baseline, and decreased after ISP and increased after Na channel blockers. CONCLUSION: ST elevation in the Brugada syndrome is primarily caused by abnormality in depolarization rather than in repolarization. BSM can provide better information to clarify a mechanism of ECG changes adding its diagnostic value for this unique syndrome.     

Scrobiculosides A and B from the deep-sea sponge Pachastrella scrobiculosa

Journal of Natural Medicines - Two new steroidal saponins, scrobiculosides A and B, were isolated from the deep-sea sponge Pachastrella scrobiculosa, collected at a depth of 200 m off...     

Preparation of oligozoospermic and/or asthenozoospermic semen for intrauterine insemination using the SpermPrep semen filtration column.

OBJECTIVE: To improve the quality of oligozoospermic and/or asthenozoospermic semen by the SpermPrep (Fertility Technologies Inc., Natick, MA) semen filtration column. DESIGN: The SpermPrep column was applied for semen manipulation in oligozoospermia and/or asthenozoospermia (sperm count less than 20 x 10(6)/mL, sperm motility less than 40%). After concentration of motile sperm using a 40% Percoll density gradient centrifugation, the sperm suspension was filtered through the SpermPrep column. The percentage yield of motile sperm by the SpermPrep method was compared with those by a two-layer Percoll density gradient (Pharmacia, Uppsala, Sweden) centrifugation and a swim-up method. Infertile couples with poor quality semen were treated with intrauterine insemination (IUI) with motile sperm by the three preparations through three cycles. SETTING: Department of Obstetrics and Gynecology, Osaka University Hospital. PATIENTS: Twenty-one couples with long-standing infertility because of poor quality semen. MAIN OUTCOME MEASURE: Recovery of motile sperm, sperm motility, and outcome of IUI were evaluated among three semen preparations. RESULTS: Motility was improved by the SpermPrep method in 32 of 33 cases of oligozoospermia and/or asthenozoospermia. Percentage yield of motile sperm by the SpermPrep method was significantly greater than those by the two-layer Percoll density gradient and swim-up methods (42.7 +/- 4.6 versus 22.1 +/- 3.1 and 13.8 +/- 3.5), but there is no significant difference in the sperm motility among three semen preparations. After one treatment cycle for each preparation, 2 of 21 women conceived after IUI with motile sperm separated in the SpermPrep method. CONCLUSIONS: The SpermPrep method is an improved semen manipulation method for oligozoospermia and/or asthenozoospermia.