Results of definitive radiotherapy with concurrent chemotherapy for maxillary sinus carcinomas with neck lymph node metastasis

The purpose of this study was to describe the results of definitive radiotherapy (RT) with concurrent chemotherapy for maxillary sinus carcinomas (MSCs) with neck lymph node metastasis to clarify its limitation. Local control (LC), progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan–Meier method and were compared between subgroups using the log rank test. Toxicity was classified using common terminology criteria of adverse events version 5.0. Eighteen patients with inoperable MSC with neck lymph node metastasis including 12 men and 6 women with a median age of 67 years were analyzed. The histologic diagnoses were as follows: 16 patients had squamous cell carcinomas and 2 had other histology. Four patients had stage T3 MSC, 6 had T4a and 8 had T4b. Among 18 patients, 7 received concurrent systemic chemotherapy and 11 received selective arterial chemo-infusion. The median follow-up period was 17 months. The 2-year LC, PFS and OS rates for the entire cohort were 34, 31 and 46%, respectively. No significant differences were observed for LC, PFS and OS rates between systemic chemotherapy and selective arterial chemo-infusion cohorts. Grade 3 or higher acute toxicity, including both non-hematological and hematological, was observed in nine patients (50%), while no grade 3 or higher late toxicity was observed. In conclusion, we described the results of definitive RT for MSCs with neck lymph node metastasis. Local recurrence of primary tumor was a frequent pattern of failure and it should be addressed in future study.     

Induction of HIV-specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV-capturing nanospheres in macaques

We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and that intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody response in mice. In this study, to evaluate the protective effect of immunization, each three macaques was intranasally immunized with Con A-NS or inactivated simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) and then intravaginally challenged with a pathogenic virus, SHIV KU-2. After a series of six immunizations, vaginal anti-HIV-1 gp120 IgA and IgG antibodies were detected in all SHIV-NS-immunized macaques. After intravaginal challenge, one of the three macaques in each of the Con A-NS- and SHIV-NS-immunized groups was infected. Plasma viral RNA load of infected macaque in SHIV-NS-immunized macaques was substantially less than that in unimmunized control macaque and reached below the detectable level. However, it could not be determined whether intranasal immunization with SHIV-NS is effective in giving complete protection against intravaginal challenge. To explore the effect of the SHIV-NS vaccine, the remaining non-infected macaques were rechallenged intravenously with SHIV KU-2. After intravenous challenge, all macaques became infected. However, SHIV-NS-immunized macaques had lower viral RNA loads and higher CD4(+) T cell counts than unimmunized control macaques. Plasma anti-HIV-1 gp120 IgA and IgG antibodies were induced more rapidly in the SHIV-NS-immunized macaques than in the controls. The rapid antibody responses having neutralizing activity might contribute to the clearance of the challenge virus. Thus, SHIV-NS-immunized macaques exhibited partial protection to vaginal and systemic challenges with SHIV KU-2.     

Influence of 1 alpha,25-dihydroxyvitamin D-3 on growth regulation through epidermal growth factor receptor in human breast cancer cell lines

We investigated the relationship between epidermal growth factor (EGF) dependent cell growth and antiproliferative effects of 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) in hormone responsive breast cancer cell lines in vitro. MCF-7 breast cancer cells and GMC-M, which is a serum-independent, hormone receptor-positive subtype derived from MCF-7, were used in this study. EGF stimulated the growth Of both cell lines, and 1,25(OH)(2)D-3 inhibited the EGF-stimulated cell growth in a dose dependent fashion. But treatment with 1,25(OH)(2)D-3 did not change the EGF receptor (EGFR) level significantly in either cell line. GMC-M had a higher level of EGFR and was more sensitive to EGF than MCF-7. These results suggest that other mechanisms of action, which are different from EGFR modulation, concern with the growth inhibitory effect of 1,25(OH)(2)D-3, and that 1,25(OH)(2)D-3 will be a new effective treatment for breast cancer irrespective of EGFR.     

A Simple and Rapid Fluorometric Determination Method of α1-Acid Glycoprotein in Serum Using Quinaldine Red

We examined different fluorescent probes suitable for fluorometric determination of ₁-acid glycoprotein (AGP) in serum. Quinaldine red (QR) was shown to bind strongly and selectively to AGP. Taking advantage of the enhanced fluorescence of QR in the presence of AGP, we developed a direct method for the determination of serum AGP without removal of other serum proteins such as albumin. AGP concentrations in serum of healthy volunteers and patients correlated well with results from the conventional single radial immunodiffusion (SRID) method (r = 0.93, slope = 1). The newly developed method is faster and has a larger analytical concentration range than the SRID method. This method can also be used to determine AGP in serum of experimental animals, and it can serve to monitor AGP serum concentrations for pharmacokinetic evaluation of basic drugs.     

Finger bougie method compared with pyloroplasty in the gastric replacement of the esophagus

To elucidate the necessity of pyloroplasty for the gastric tube through the posterior mediastinum in esophageal surgery, gastric emptying and duodenogastric reflux (DGR) were evaluated in 16 cases undergoing an anterior pylorectomy (group P) and in 16 cases treated by the finger bougie method (group F). First, the obstruction and reflux symptoms were examined based on a patient questionnaire using a brief scoring system. The median value of the symptom score showed the patients in P to have more symptoms than those in F; however, the difference was not significant (8.0 vs 6.0). Secondly, the swallowed Tc O₄ ⁻ (85 MBq) was counted using a gamma camera at three sites on the sternal bone in the upright position based on a gastric transit scintigram. Both the descending time of the RI peak and the clearance rates were similar between the two groups. Thirdly, intragastric 24-h pH monitoring was carried out. Antimony pH sensors were anchored 5 and 15 cm below the esophagogastrostomy. We could not find any difference between the two groups in both the % time pH>4 and %time pH>7. These findings thus revealed no big difference between groups P and F. The finger bougie method to drain the vagotomized posterior mediastinal stomach was found to achieve results similar to conventional pyloroplasty, while it was also simpler and safer.     

Postsynaptic expression of Ca2+-permeable AMPA-type glutamate receptor channels by viral-mediated gene transfer

The ability to artificially express a particular receptor protein in the postsynaptic sites of neurons in the central nervous system (CNS) would be useful for the study of synaptic function of cloned receptor genes as well as for gene therapy of neurological disorders caused by dysfunction of postsynaptic receptors. In this study, we aimed to express the cDNA of unedited GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor that forms inwardly rectifying and Ca2+-permeable channel in CNS neurons by using adenoviral-mediated gene transfer. For this purpose, we have constructed a recombinant adenovirus bearing an expression-switching unit, where the unedited GluR2 cDNA can be activated by the Cre recombinase-mediated excisional deletion of a stuffer DNA interposed between the promotor and the coding region. When PC12 cells were infected with this recombinant adenovirus together with an adenovirus expressing Cre recombinase, the inwardly rectifying and Ca2+-permeable AMPA receptor channels were expressed in nearly 100% of infected cells. Two days after co-infection of cultured rat hippocampal neurons with these adenoviruses, fast excitatory neurotransmission in the glutamatergic synapse was mediated predominantly by the inwardly rectifying and Ca2+-permeable AMPA receptor channels. This indicates that the native AMPA receptors in the postsynaptic sites of the glutamatergic synapse are replaced rapidly with recombinant receptors newly produced by the viral-mediated gene transfer.