6623 research outputs found
Sort by
PD-L1-specific helper T-cells exhibit effective antitumor responses: new strategy of cancer immunotherapy targeting PD-L1 in head and neck squamous cell carcinoma.
Get PDFBACKGROUND:
Head and neck squamous cell carcinoma (HNSCC) originates from squamous epithelium of the upper aerodigestive tract and is the most common malignancy in the head and neck region. Among HNSCCs, oropharynx squamous cell carcinoma (OSCC) has a unique profile and is associated with human papillomavirus infection. Recently, anti-programmed cell death-1 monoclonal antibody has yielded good clinical responses in recurrent and/or metastatic HNSCC patients. Therefore, programmed death-ligand 1 (PD-L1) may be a favorable target molecule for cancer immunotherapy. Although PD-L1-expressing malignant cells could be targeted by PD-L1-specific CD8+ cytotoxic T lymphocytes, it remains unclear whether CD4+ helper T lymphocytes (HTLs) recognize and kill tumor cells in a PD-L1-specific manner.
METHODS:
The expression levels of PD-L1 and HLA-DR were evaluated using immunohistochemical analyses. MHC class II-binding peptides for PD-L1 were designed based on computer algorithm analyses and added into in vitro culture of HTLs with antigen-presenting cells to evaluate their stimulatory activity.
RESULTS:
We found that seven of 24 cases of OSCC showed positive for both PD-L1 and HLA-DR and that PD-L1241-265 peptide efficiently activates HTLs, which showed not only cytokine production but also cytotoxicity against tumor cells in a PD-L1-dependent manner. Also, an adoptive transfer of the PD-L1-specific HTLs significantly inhibited growth of PD-L1-expressing human tumor cell lines in an immunodeficient mouse model. Importantly, T cell responses specific for the PD-L1241-265 peptide were detected in the HNSCC patients.
CONCLUSIONS:
The cancer immunotherapy targeting PD-L1 as a helper T-cell antigen would be a rational strategy for HNSCC patients.博士（医学）旭川医科大
White coat status is a predictive marker for post-esophageal endoscopic submucosal dissection stricture: a retrospective study
Get PDFThis article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://creat iveco
mmons .org/licen ses/by/4.0/)BACKGROUND:
Steroid therapy is primarily used to prevent esophageal stricture after endoscopic submucosal dissection (ESD). However, esophageal stricture can still occur after preventive therapy, and the effect of preventive steroid therapy cannot be predicted before stricture formation. This study aimed to clarify the risk factors for esophageal stricture after preventive steroid therapy.
METHODS:
This was a retrospective study conducted at three institutions. From January 2011 to February 2018, 28 large-sized SENs in 26 patients who had a mucosal defect that involved more than three-quarters of the esophageal circumference were enrolled. We classified white coats on artificial ulcers after esophageal ESD into three groups (thin, moderately thick, thick) based on endoscopic images obtained on postoperative day 7.
RESULTS:
The white coat status on the artificial ulcer after ESD was a significant risk factor for post-ESD stricture (p < 0.05). The stricture rates in patients with thin, moderately thick and thick white coats were 10.0, 36.4 and 85.7%, respectively. When thin and moderately thick white coats were combined, the stricture rate was 23.8%. The rate of stricture in lesions with thick white coats was significantly higher than that in patients with thin white coats or thin to moderately thick white coats (p < 0.05). The multivariate analysis revealed that the white coat status was an independent factor related to esophageal stricture (odds ratio 13.70, 95% confidence interval 1.22-154.0; p = 0.034).
CONCLUSIONS:
The thickness of the white coat is a useful marker for predicting the risk of post-ESD stricture and the effectiveness of preventive steroid therapy
Learning and developing scanning electron microscopy (SEM) techniques for biological research
Get PDFImpact is published under a CC-BY Creative Commons licence
A nationwide comparison between Sepsis-2 and Sepsis-3 definition in Japan
Get PDFBACKGROUND::
Currently, it remains controversial whether the Sepsis-3 definition provides the most appropriate criteria for clinical use. The purpose of this study was to compare between the Sepsis-2 and Sepsis-3 definitions using Japan's nationwide registry.
METHODS::
Data were obtained from a multicenter registry conducted at 42 intensive care units (ICUs) throughout Japan, in which patients received treatment for severe sepsis or septic shock between January 2011 and December 2013.
RESULTS::
A total of 2797 patients diagnosed using the Sepsis-2 criteria were included in the present study. These patients were categorized into "Severe sepsis" (n = 1154) and "Sepsis-2 shock" (n = 1643) groups. Among the "Sepsis-2 shock" group, patients who did not meet the Sepsis-3 criteria for septic shock were categorized into the "Sepsis-2 shock-only" (n = 448, 27.3%) group, while patients who met the Sepsis-3 criteria for septic shock were categorized into "Sepsis-3 shock (n = 1195, 72.7%)" group. The ICU mortality in the "Sepsis-3 shock" group, "Sepsis-2 shock-only" group, and "Severe sepsis" group was 28.5%, 10.9%, and 14.1%, respectively. We observed no significant difference between the "Severe sepsis" and "Sepsis-2 shock-only" groups in terms of in-hospital survival ( P = .098), while the "Sepsis-3 shock" group had the highest in-hospital mortality rate ( P < .001). In a multivariate logistic regression analysis, liver insufficiency and immunocompromised status were independent prognostic factors in the "Sepsis-2 shock-only" group. In contrast, chronic heart disease and chronic hemodialysis were independent prognostic factors in the "Sepsis-3 shock" group.
CONCLUSIONS::
The ICU mortality of the "Sepsis-2 shock-only" group was significantly low. Besides septic shock diagnosed by the Sepsis-3 definition selects patients with more severe cases of sepsis among the "Sepsis-2 shock" group