Recent studies have suggested that photo-oxidative lesions produced by photodynamic therapy (PDT)-treated tumors are recognized by the host as altered self, (4) prompting a strong inflammatory and immune response.(5) In addition, the use of PDT vaccines has been studied to generate antitumor immunity and control tumor growth, suggesting that further improvements can be achieved in the optimization of the protocols for the generation of PDTgenerated cancer vaccines.(6,7) Because of the inflammatory/immune response triggered by PDT, this therapy has been shown to be particularly suitable for combination with a variety of immunotherapy based treatments, including angiogenic growth factors, matrix metalloproteinases, cytokines and adoptive transfer of immune cells. (8 -12) Overexpression of these molecules within PDTtargeted tissue can adversely affect tumor response. Therefore, experimental protocols combining PDT with procedures targeting these molecules are being examined in an effort to improve treatment efficacy.Oligodeoxynucleotide (ODN) containing unmethylated cytosine-phosphate-guanosine (CpG) motifs was originally isolated from components of bacterial DNA.(13) CpG-ODN immunotherapy has been studied as a strategy for tumor prevention as well as for treatment of immune disorders. (14,15) A variety of studies have shown that CpG-ODN can activate B cells, monocytes and natural killer cells, and induce a Th1-like pattern of cytokine production.(16-18) The CpG sequences drive macrophages to secrete interleukin-12, a potent inducer of interferon-γ (IFN-γ) production in vivo from natural killer cells. IFN-γ production drives Th1-type immune responses by inducing differentiation of type-1 Th cells, which see antigen in the presence of IFN-γ from the uncommitted T-cell pool. (19,20) Moreover, ODN enhances humoral responses and induces the development of enhanced cytotoxic T lymphocytes (CTL) activity. (17,21) ODN has been studied extensively as a strong immunomodulatory agent. (22)(23)(24) The aim of the present study was to further characterize the immunotherapeutic significance of the combination of CpGoligodeoxynucleotide and TC-1 tumor cell lysates induced by PDT. We examined the in vivo antitumor effect of PDT (or freezing/thawing)-generated cell lysates plus ODN injection and the immune response in a mouse model. Our results showed that PDT-cell lysates plus ODN showed a significant suppression of tumor growth at both prophylactic and therapeutic levels, compared to PDT (or F/T)-cell lysates or ODN alone. Materials and MethodsPreparation of PDT-generated tumor cell lysates. Radachlorin (25) was purchased from RADA-PHARMA group (RADA-PHARMA, Moscow, Russia). The light source was a diode laser with a 662 ± 3 nm wavelength (Won-PDT D662, Won Technology, Daejeon, Korea). The irradiation power in vitro was fixed to be 6.25 J/cm 2 at 20 mW/cm 2 for 5 min irradiation measured at a distance of 3 cm from the exit slit.To generate cell lysates by Radachlorin/PDT, TC-1 cells carrying human papillomavirus (HPV) 16 E7 (ATC...

Background/AimsChronic intestinal pseudo-obstruction (CIPO) is a disorder characterized by recurrent symptoms suggestive of obstruction such as abdominal pain, proximal distension with extremely suppressed motility in the absence of lumen-occluding lesion, whose etiology/pathophysiology is poorly understood. In this study we investigated a functionally obstructive lesion that could underlie symptoms of CIPO. MethodsWe studied colons surgically removed from 13 patients exhibiting clinical/pathological features of pseudo-obstruction but were unresponsive to standard medical treatments. The colons were characterized morphologically, functionally and molecularly, which were compared between regions and to 28 region-matched controls obtained from colon cancer patients. ResultsThe colons with pseudo-obstruction exhibited persistent luminal distension proximally, where the smooth muscle was hypertrophied with changes in the cell phenotypes. Distinct luminal narrowing was observed near the distal end of the dilated region, close to the splenic flexure, previously referred to as the "transition zone (TZ)" between the dilated and non-dilated loops. Circular muscles from the TZ responded less to depolarization and cholinergic stimulation, which was associated with downregulation of L-type calcium channel expression. Smooth muscle contractile protein was also downregulated. Myenteric ganglia and neuronal nitric oxide synthase (nNOS) positive cells were deficient, more severely in the TZ region. Interstitial cells of Cajal was relatively less affected. 561 ConclusionsThe TZ may be the principal site of functional obstruction, leading to proximal distension and smooth muscle hypertrophy, in which partial nNOS depletion could play a key role. The neuromuscular abnormalities probably synergistically contributed to the extremely suppressed motility observed in the colonic pseudo-obstruction.(J Neurogastroenterol Motil 2015;21:560-570)

Purpose: Screening in cervical cancer is now progressing to discover candidate genes and proteins that may serve as biological markers and that play a role in tumor progression. W e examined the protein expression patterns of the squamous cell carcinoma (SCC) tissues from Korean women with using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometer.Materials and Methods: Normal cervix and SCC tissues were solubilized and 2-DE was performed using pH 3～10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software TM . The differentially expressed protein spots were identified with a MALDI-TOF mass spectrometer, and the peptide mass spectra identifications were performed using the Mascot program and by searching the Swiss-prot or NCBInr databases.Results: A total of 35 proteins were detected in SCC.17 proteins were up-regulated and 18 proteins weredownregulated. Among the proteins that were identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, α-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were protein previously known to be involved in tumor, and 21 proteins were newly identified in this study. Conclusion