PURPOSE: To develop paclitaxel carried by injectable PEGylated emulsions, an artificial neural network (ANN) was used to optimize the formulation--which has a small particle size, high entrapment efficiency, and good stability--and to investigate the role of each ingredient in the emulsion. METHODS: Paclitaxel emulsions were prepared by a modified ethanol injection method. A computer optimization technique based on a spherical experimental design for three-level, three factors [soybean oil (X1), PEG-DSPE (X2) and polysorbate 80 (X3)] were used to optimize the formulation. The entrapment efficiency of paclitaxel (Y1) was quantified by HPLC; the particle size of the emulsions (Y2) was measured by dynamic laser light scattering and the stability of paclitaxel emulsions was monitored by the changes in drug concentration (Y3) and particle size (Y4) after storage at 4 degrees C. RESULTS: The entrapment efficiency, particle size and stability of paclitaxel emulsions were influenced by PEG-DSPE, polysorbate 80, and soybean oil. Paclitaxel emulsions of small size (262 nm), high entrapment efficiency (96.7%), and good stability were obtained by the optimization. CONCLUSIONS: A novel formulation for paclitaxel emulsions was optimized with ANN and prepared. The contribution indices of each component suggested that PEG-DSPE mainly contributes to the entrapment efficiency and particle size of paclitaxel emulsions, while polysorbate 80 contributes to stability. 相似文献
Sialyl-Tn (STn), overexpressed on various tumors, has been investigated for its application in anti-cancer vaccine therapy. However, Theratope, an STn-based vaccine, failed in the phase III clinical trial due to poor immunogenicity and epitope suppression by the foreign carrier protein. We therefore developed a self-adjuvanting STn based-vaccine, a conjugate of clustered STn (triSTn) antigen, TLR1/2 ligand (Pam3CSK4), and T-helper (Th) cell epitope, and found that this three-component self-adjuvanting vaccine effectively resulted in the production of anti-triSTn IgG antibodies. We herein analyzed immune responses induced by this self-adjuvanting vaccine in detail. We newly synthesized two-component vaccines, i.e., Pam3CSK4- or Th epitope-conjugated triSTn, as references to evaluate the immune-stimulating functions of Pam3CSK4 and Th epitope. Immunological evaluation of the synthesized vaccine candidates revealed that Pam3CSK4 was essential for antibody production, indicating that the uptake of triSTn antigen by antigen-presenting cells (APCs) was promoted by the recognition of Pam3CSK4 by TLR1/2. The function of the Th epitope was also confirmed. Th cell activation was important for boosting antibody production and IgG subclass switching. Furthermore, flow cytometric analyses of immune cells, including T cells, B cells, dendritic cells, and other monocytes, were first employed in the evaluation of self-adjuvanting vaccines and revealed that the three-component vaccine was able to induce antigen-specific immune responses for efficient antibody production without excessive inflammatory responses. Importantly, the co-administration of Freund''s adjuvants was suggested to cause excessive myeloid cell accumulation and decreased plasma cell differentiation. These results demonstrate that vaccines can be designed to achieve the desired immune responses via the bottom-up construction of each immune element.Detailed analysis of a three-component self-adjuvanting vaccine revealed that conjugate vaccines can be designed to achieve the desired immune responses via bottom-up construction of the necessary immune elements.相似文献
Objective: To compare treatment patterns, persistence and adherence between fixed-dose combinations (FDCs) and two-pill combinations (TPCs) of oral antidiabetic drug (OAD) classes in Japanese patients with type 2 diabetes mellitus (T2DM) using administrative claims databases (Japan Medical Data Center [JMDC] and Medical Data Vision [MDV]).
Methods: This was a retrospective, longitudinal cohort analysis conducted between 2011 and 2015, in patients with T2DM receiving OADs as FDC or TPC. Outcomes included prescribing patterns, treatment persistence and adherence.
Results: Data from 3474 and 3066 patients receiving FDCs, and 4325 and 5192 patients receiving TPCs from the JMDC and MDV databases, respectively, was extracted. The most common OAD combination received by over half of all patients was dipeptidyl peptidase-4 inhibitor (DPP-4i) + thiazolidinediones (TZDs) (64.1% [JMDC] and 70.5% [MDV]). Overall, 12-month persistence rates were higher in patients receiving FDCs compared with TPCs (70.4 vs. 66.2% [JMDC], 75.6 vs. 55.7% [MDV]). In the JMDC population receiving FDCs or TPCs, persistence rates were highest with DPP-4i schedules (67.5–83.5%). Median time to discontinuation was significantly longer with biguanide?+?TZD, and DPP-4i?+?TZD FDC schedules (p < .05) than TPC; adherence rates were ≥80% across all antidiabetic drug classes in both database populations.
Conclusions: Persistence with and adherence to OADs in Japanese patients with T2DM were greater with FDCs than with TPCs, which may suggest increased patient satisfaction due to reduced treatment burden. Further studies are warranted to investigate the impact of adherence and persistence of FDCs of OADs on glycemic control. 相似文献
AIM: To investigate features of Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) among a Mexican population. METHODS: Cases of primary gastric adenocarcinoma were retrieved from the files of the Departments of Pathology at the Instituto Nacional de Cancerologia and the Instituto Nacional de la Nutricion in Mexico City. The anatomic site of the gastric neoplasia was identified, and carcinomas were histologically classified as intestinal and diffuse types and subclassified as proposed by the Japanese Research Society for Gastric Cancer. EBV-encoded small non-polyadenylated RNA-1 (EBER-1) in situ hybridization was conducted to determine the presence of EBV in neoplastic cells. RESULTS: We studied 330 consecutive, non-selected, primary gastric carcinomas. Among these, there were 173 male and 157 female patients (male/female ratio 1.1/1). EBER-1 was detected in 24 (7.3%) cases (male/female ratio: 1.2/1). The mean age for the entire group was 58.1 years (range: 20-88 years), whereas the mean age for patients harboring EBER-1-positive gastric carcinomas was 65.3 years (range: 50-84 years). Age and histological type showed statistically significant differences, when EBER-1-positive and -negative gastric carcinomas were compared. EBER-1 was detected in hyperplastic- and dysplastic-gastric mucosa surrounding two EBER-1-negative carcinomas, respectively. CONCLUSION: Among Latin-American countries, Mexico has the lowest frequency of EBVaGC. Indeed, the Mexican population >50 years of age was selectively affected. Ethnic variations are responsible for the epidemiologic behavior of EBVaGC among the worldwide population. 相似文献
The gastrointestinal tract is a rare site for metastatic lung cancer. Programmed cell death-ligand 1 (PD-L1) expression in lung cancer is a biomarker for the response to anti-PD-1/PD-L1 therapy. We investigated clinicopathological features and PD-L1 expression in 25 gastrointestinal metastatic tumors from the lung and primary adenocarcinoma of the small bowel. The small bowel was the most common site (16/25; 64%) of gastrointestinal tract lung cancer metastasis. A total of 19 (76%) of the gastrointestinal metastasis showed PD-L1 expression in ≥5% of tumor cells, with 14 (56%) showing high expression levels (≥50%). In contrast, 21 (84%) expressed PD-L1 in ≥5% immune cells, including 4 (16%) showing a high expression levels (≥50%). The PD-L1 expression on tumor cells and immune cells in primary lung cancer and corresponding gastrointestinal metastasis was concordant in 13 (68%) and 11 (58%) of the 19 paired cases, respectively. Small-bowel metastasis of lung cancer was characterized by a higher incidence of perforation (31% vs. 0%), ulcerated mass (83% vs. 60%), and neoplastic PD-L1 expression (75% vs. 0%) compared to primary small-bowel adenocarcinoma. Gastrointestinal metastasis from lung cancer might be a potential target for immune checkpoint inhibitor therapy, given its high expression of PD-L1. 相似文献