A new therapy for highly effective tumor eradication using HVJ-E combined with chemotherapy

<p>Abstract</p> <p>Background</p> <p>Inactivated HVJ (hemagglutinating virus of Japan; Sendai virus) particles (HVJ envelope vector; HVJ-E can incorporate and deliver plasmid DNA, siRNA, antibody and peptide and anti-cancer drugs to cells both <it>in vitro </it>and <it>in vivo</it>. We attempted to eradicate tumors derived from mouse colon cancer cells, CT26, by combining bleomycin (BLM)-incorporated HVJ-E (HVJ-E/BLM) with cisplatin (CDDP) administration.</p> <p>Methods</p> <p>CT-26 tumor mass was intradermally established in Balb/c mice. HVJ-E/BLM was directly injected into the tumor mass with or without intraperitoneal administration of CDDP. The anti-tumor effect was evaluated by measuring tumor size and cytotoxic T cell activity against CT26. Re-challenge of tumor cells to treated mice was performed 10 days or 8 months after the initial tumor inoculation.</p> <p>Results</p> <p>We found that three intratumoral injections of HVJ-E/BLM along with a single intraperitoneal administration of CDDP eradicated CT26 tumors with more than 75% efficiency. When tumor cells were intradermally re-injected on day 10 after the initial tumor inoculation, tumors on both sides disappeared in most of the mice that received the combination therapy of HVJ-E/BLM and CDDP. Eight months after the initial tumor eradication, surviving mice were re-challenged with CT26 cells. The re-challenged tumors were rejected in all of the surviving mice treated with the combination therapy. Cytotoxic T lymphocytes specific for CT26 were generated in these surviving mice.</p> <p>Conclusion</p> <p>Combination therapy consisting of HVJ-E and chemotherapy completely eradicated the tumor, and generated anti-tumor immunity. The combination therapy could therefore be a promising new strategy for cancer therapy.</p

Okayama University Survey of the current situation of community-based medical facilities supported by part-time work by physicians

　We investigated the situation of how physicians at Okayama University support local medical institutions by serving as a part-time worker, and analyzed the difference between the five medical districts of Okayama prefecture and other prefectures. Many physicians (actual number of physicians, full-time equivalent number of physicians) served in the southeastern region of the Okayama prefecture (339, 82.2). On the other hand, fewer physicians (42, 11.4) served in Takahashi・Niimi in the northwestern region of Okayama. Many physicians also served in Hiroshima prefecture (193, 48.8), Hyogo prefecture (109, 26.7), and the four prefectures of Shikoku Island (81, 23.6). 　It has been clarified that many physicians at Okayama University are working on a part-time basis to support local and community medical institutions in the wide area of Okayama prefecture, Hiroshima prefecture, Hyogo prefecture and the four prefectures of Shikoku Island

Role of the rasGAP-associated docking protein p62^(dok) in negative regulation of B cell receptor-mediated signaling

Antigenic stimulation of the B-cell receptor (BCR) is a central event in the immune response. In contrast, antigen bound to IgG negatively regulates signals from the BCR by cross-linking it to the inhibitory receptor FcγRIIB. Here we show that upon cross-linking of BCR or BCR with FcγRIIB, the rasGAP-associated protein p62^(dok) is prominently tyrosine phosphorylated in a Lyn-dependent manner. Inactivation of the dok gene by homologous recombination has shown that upon BCR cross-linking, p62^(dok) suppresses MAP kinase and is indispensable for FcγRIIB-mediated negative regulation of cell proliferation. We propose that p62^(dok), a downstream target of many PTKs, plays a negative role in various signaling situations

Reading development in bilingual pupils

The subjects are a group of bilingual pupils in 3rd grade. They live in an area dominated by Norwegian, but their parents have chosen Sámi as their first language in school. The pupils communicate in Sámi with one or both parents, the teacher, classmates during lessons, and in some cases other family members. In play, both in their neighbourhood and school, the children use Norwegian. Earlier research has showed that bilingualism for some groups has a positive effect on education, for other a negative effect. The motivation for this study is to describe the language environment and the pupils' reading competence in the context described above. The most of the children manage decoding rather well, and the decoding mistakes are of the same types in both languages. There is a connection between decoding proficiency and understanding of the text, but this is complex. The reading comprehension for all the children was at least twice as good for Norwegian texts compared with Sámi texts, for some of the children more than three times better. There was a clear connection between the children's language environment and their comprehension of the texts from school books written for the class level

A new therapy for highly effective tumor eradication using HVJ-E combined with chemotherapy-2

<p><b>Copyright information:</b></p><p>Taken from "A new therapy for highly effective tumor eradication using HVJ-E combined with chemotherapy"</p><p>http://www.biomedcentral.com/1741-7015/5/28</p><p>BMC Medicine 2007;5():28-28.</p><p>Published online 21 Sep 2007</p><p>PMCID:PMC2039728.</p><p></p>and one (single) or three (multiple) injections of HVJ-E/BLM were intradermally re-challenged with 5 × 10parental CT-26 cells on day 10 after CDDP administration (arrow). The initial (upper) and re-challenged (lower) tumor volumes per mouse were assessed (mean value ± standard deviation). p < 0.05, single vs multiple injection, Student's test. The control mice were age-matched mice that were intradermally inoculated with CT-26 cells. (B) Eradication rate of initial or re-challenge tumor. On day 31 after CDDP administration (on day 16 after re-challenge) the tumors – whether visible or invisible – were examined

A new therapy for highly effective tumor eradication using HVJ-E combined with chemotherapy-0

<p><b>Copyright information:</b></p><p>Taken from "A new therapy for highly effective tumor eradication using HVJ-E combined with chemotherapy"</p><p>http://www.biomedcentral.com/1741-7015/5/28</p><p>BMC Medicine 2007;5():28-28.</p><p>Published online 21 Sep 2007</p><p>PMCID:PMC2039728.</p><p></p>n the dorsa of BALB/c mice reached 5 mm in diameter, HVJ-E (5000 HAU, i.t.), HVJ-E/BLM (5000 HAU, i.t.), CDDP (i.p.), or CDDP (i.p.) plus HVJ-E/BLM (5000 HAU, i.t.) was administered. The tumor diameter was measured every 3 days. Results are expressed as the mean (n = 8 per group). Data are representative of each group. Two independent experiments were performed. CDDP and HVJ-E/BLM treated tumor growth was strongly suppressed compared with saline treated tumors (control). *p < 0.05. By contrast, no significant difference (NS) was seen between control and CDDP alone. Results were statistically analyzed using the Steel-Dwass test. (B) The body weight of each groups. Data are expressed as means ± SD. No significant difference was seen in all groups

Novel Anti-Microbial Peptide SR-0379 Accelerates Wound Healing via the PI3 Kinase/Akt/mTOR Pathway

<div><p>We developed a novel cationic antimicrobial peptide, AG30/5C, which demonstrates angiogenic properties similar to those of LL-37 or PR39. However, improvement of its stability and cost efficacy are required for clinical application. Therefore, we examined the metabolites of AG30/5C, which provided the further optimized compound, SR-0379. SR-0379 enhanced the proliferation of human dermal fibroblast cells (NHDFs) via the PI3 kinase-Akt-mTOR pathway through integrin-mediated interactions. Furthermore SR-0379 promoted the tube formation of human umbilical vein endothelial cells (HUVECs) in co-culture with NHDFs. This compound also displays antimicrobial activities against a number of bacteria, including drug-resistant microbes and fungi. We evaluated the effect of SR-0379 in two different would-healing models in rats, the full-thickness defects under a diabetic condition and an acutely infected wound with full-thickness defects and inoculation with <i>Staphylococcus aureus</i>. Treatment with SR-0379 significantly accelerated wound healing when compared to fibroblast growth factor 2 (FGF2). The beneficial effects of SR-0379 on wound healing can be explained by enhanced angiogenesis, granulation tissue formation, proliferation of endothelial cells and fibroblasts and antimicrobial activity. These results indicate that SR-0379 may have the potential for drug development in wound repair, even under especially critical colonization conditions.</p></div

<i>In vitro</i> activities of SR-0379 against Gram-positive and Gram-negative bacteria and fungi.

<p>The scores indicate the MICs (mg/ml) for gram-positive and gram-negative bacteria and fungi. MICs represent the individual data from two independent experiments.</p><p>NT: Not tested.</p