Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses

<p>Abstract</p> <p>Background</p> <p>Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA.</p> <p>Results</p> <p>In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed <it>in vitro</it>. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (<it>P </it>< 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220⁺cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-A^d) were increased on CD11c⁺dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice.</p> <p>Conclusion</p> <p>These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.</p

Primary Polymorphous Low-Grade Adenocarcinoma of Lung Treated by Sleeve Bronchial Resection : A Case Report

We report a surgical case of primary polymorphous low-grade adenocarcinoma (PLGA) of the minor salivary gland-type of the lung. A PLGA originating from the right upper lobar bronchial inlet was successfully treated by sleeve right upper lobectomy. PLGAs are thought to be indolent tumors that are preferentially localized to the palate, and they affect the minor salivary glands almost exclusively. Until now, two cases of distant metastases to the lung have been reported in the English literature. To the best of our knowledge, only one case of PLGA of minor salivary gland-type of the lung without evidence of a previous oropharyngeal primary tumor has been reported in the English literature. But the case was not a single lesion; it was bilateral tumors accompanied by tumors of the cervical lymph nodes. We report here the first case of a single primary PLGA of the minor salivary gland-type of the lung, which was successfully treated by sleeve bronchial resection of right upper lobe

Xylitol production is increased by expression of codon-optimized Neurospora crassa xylose reductase gene in Candida tropicalis

Xylose reductase (XR) is the first enzyme in d-xylose metabolism, catalyzing the reduction of d-xylose to xylitol. Formation of XR in the yeast Candida tropicalis is significantly repressed in cells grown on medium that contains glucose as carbon and energy source, because of the repressive effect of glucose. This is one reason why glucose is not a suitable co-substrate for cell growth in industrial xylitol production. XR from the ascomycete Neurospora crassa (NcXR) has high catalytic efficiency; however, NcXR is not expressed in C. tropicalis because of difference in codon usage between the two species. In this study, NcXR codons were changed to those preferred in C. tropicalis. This codon-optimized NcXR gene (termed NXRG) was placed under control of a constitutive glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter derived from C. tropicalis, and integrated into the genome of xylitol dehydrogenase gene (XYL2)-disrupted C. tropicalis. High expression level of NXRG was confirmed by determining XR activity in cells grown on glucose medium. The resulting recombinant strain, LNG2, showed high XR activity (2.86 U (mg of protein)−1), whereas parent strain BSXDH-3 showed no activity. In xylitol fermentation using glucose as a co-substrate with xylose, LNG2 showed xylitol production rate 1.44 g L−1 h−1 and xylitol yield of 96% at 44 h, which were 73 and 62%, respectively, higher than corresponding values for BSXDH-3 (rate 0.83 g L−1 h−1; yield 59%)

Immunohistochemical Analysis of Non-Small Cell Lung Cancer: Correlation with Clinical Parameters and Prognosis

Non-small cell lung cancers (NSCLC) vary in their biologic behavior. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors. This study evaluated such immunophenotypes with regard to cell cycle regulation and proliferation, apoptosis, and angiogenesis, to determine their significance for patient outcome. Core biopsies from 219 patients with NSCLC were assembled on tissue microarrays, and the expressions of p16, p21, p27, cyclin B1, cyclin E, Ki-67, caspase-3, survivin, bcl-2, VEGF, and endostatin were evaluated by immunohistochemistry. Despite previously described prognostic relevance of some of the investigated molecules, many of those markers were not directly associated with recurrence or survival. However, there was a trend for p16 immunoreactivity to be associated with a good prognosis (57% vs. 42% in 5-yr survival) (p=0.071). bcl-2 expression was strongly correlated with a better outcome (65% vs. 45% in 5-yr survival) (p=0.029), and the hazard of death for bcl-2 positive patients was 0.42 times of that for bcl-2 negative patients (p=0.047). A multivariate analysis with Cox proportional hazards model confirmed that the lymph node status (p=0.043) and stage (p=0.003) were other independent prognostic factors. Our results suggest that p16 and bcl-2 provide prognostic information independent of the TNM stage in NSCLC

RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer

PURPOSE The phase III RESILIENT trial compared second-line liposomal irinotecan with topotecan in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS Patients with SCLC and progression on or after first-line platinum-based chemotherapy were randomly assigned (1:1) to intravenous (IV) liposomal irinotecan (70 mg/m(2) every 2 weeks in a 6-week cycle) or IV topotecan (1.5 mg/m(2) daily for 5 consecutive days, every 3 weeks in a 6-week cycle). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) and objective response rate (ORR). RESULTS Among 461 randomly assigned patients, 229 received liposomal irinotecan and 232 received topotecan. The median follow-up was 18.4 months. The median OS was 7.9 months with liposomal irinotecan versus 8.3 months with topotecan (hazard ratio [HR], 1.11 [95% CI, 0.90 to 1.37]; P = .31). The median PFS per blinded independent central review (BICR) was 4.0 months with liposomal irinotecan and 3.3 months with topotecan (HR, 0.96 [95% CI, 0.77 to 1.20]; nominal P = .71); ORR per BICR was 44.1% (95% CI, 37.6 to 50.8) and 21.6% (16.4 to 27.4), respectively. Overall, 42.0% and 83.4% of patients receiving liposomal irinotecan and topotecan, respectively, experienced grade >= 3 related treatment-emergent adverse events (TEAEs). The most common grade >= 3 related TEAEs were diarrhea (13.7%), neutropenia (8.0%), and decreased neutrophil count (4.4%) with liposomal irinotecan and neutropenia (51.6%), anemia (30.9%), and leukopenia (29.1%) with topotecan. CONCLUSION Liposomal irinotecan and topotecan demonstrated similar median OS and PFS in patients with relapsed SCLC. Although the primary end point of OS was not met, liposomal irinotecan demonstrated a higher ORR than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged

Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data

Background/AimsWhile gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.MethodsThe data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.ResultsThe initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).ConclusionsThe clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis