HU may be a useful objective marker of bone remodeling in chronic rhinosinusitis.
In order to explore the potential patient population who could benefit from anti PD-1/PD-L1 mono or combination therapies, this study aimed to profile a panel of immunotherapy related biomarkers (PD-1, PD-L1, CTLA-4 and CD8) and targeted therapy biomarkers (EGFR, KRAS, ALK, ROS1 and MET) in NSCLC.Tumor samples from 297 NSCLC patients, including 156 adenocarcinomas (AD) and 129 squamous cell carcinomas (SCC), were analyzed using immunohistochemistry, immunofluorescence, sequencing and fluorescence in situ hybridization.43.1% of NSCLC patients had PD-L1 positive staining on ≥ 5% tumor cells (TC). Furthermore, dual color immunofluorescence revealed that the majority of PD-L1/CD8 dual positive tumor infiltrating lymphocytes (TIL) had infiltrated into the tumor core. Finally, combined analysis of all eight biomarkers showed that tumor PD-L1 positivity overlapped with known alterations in NSCLC oncogenic tumor drivers in 26% of SCC and 76% of AD samples.Our illustration of the eight biomarkers’ overlap provides an intuitive overview of NSCLC for personalized therapeutic strategies using anti-PD-1/PD-L1 immune therapies, either as single agents, or in combination with targeted therapies. For the first time, we also report that PD-L1 and CD8 dual positive TILs are predominantly located within the tumor core.
The signal transducer and activator of the transcription (Stat)-family of proteins are latent cytoplasmic transcription factors that transmit signals from cytokines and growth-factor receptors to the nucleus. Stat proteins, especially Stat3 and Stat5, are constitutively activated in various solid tumors and hematological malignancies. However, the role of Stat3 signaling in gastric carcinoma has not yet been fully determined. This study was conducted to investigate the clinical value of phospho-Stat3 expression in gastric carcinoma. Expression of phospho-Stat3 (Tyr705), vascular endothelial growth factor (VEGF), p53, and Bcl-2 was determined by immunohistochemical staining of tissue microarrays from 137 cases of resected gastric cancer specimens. We evaluated the relationships among phospho-Stat3, VEGF, p53, and Bcl-2 expression and the correlation between expression of these proteins and various clinicopathological factors, including overall survival. Phospho-Stat3 nuclear expression was observed in 18.2% of the cases. Of the total number of cases, 68.6% were positive for VEGF, 40.1% for p53, and 11.7% for Bcl-2. Phospho-Stat3 expression correlated with VEGF (p=0.021) and Bcl-2 (p=0.005) expression. Positive phospho-Stat3 staining was significantly associated with poor pathological grade. However, there was no significant difference in other clinicopathological parameters, such as tumor stage (T, N, M), pathological type, relapse-free survival, and overall survival between the phospho-Stat3-positive and -negative groups. Co-expression of phospho-Stat3 and VEGF was found in many patients with N3 and Stage IV disease. These results suggest that phospho-Stat3 expression might be associated with angiogenesis, anti-apoptosis, and tumor progression. Further studies are needed to determine the role of phospho-Stat3 in gastric cancer.
PurposeGlucose uptake and glycolytic metabolism are enhanced in cancer cells, and increased expression of glucose transporter 1 (GLUT1) has also been reported. The aim of this study was to investigate GLUT1 expression in human breast tissues and invasive ductal carcinomas.MethodsWe used tissue microarrays consisting of normal breast tissue, ductal hyperplasia, ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastases. We examined GLUT1 expression in the microarrays by immunohistochemistry, reviewed the medical records and performed a clinicopathological analysis.ResultsMembranous GLUT1 expression was observed in normal and tumor cells. GLUT1 expression was higher in ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastasis than in normal tissue and ductal hyperplasia (p=0.002). Of 276 invasive ductal carcinomas, 106 (38.4%) showed GLUT1 expression. GLUT1 expression was correlated with higher histologic grade (p<0.001), larger tumor size (p=0.025), absence of estrogen receptor (p<0.001), absence of progesterone receptor (p<0.001), and triple-negative phenotype (p<0.001). In univariate survival analysis, patients with GLUT1 expression had poorer overall survival and disease-free survival (p=0.017 and p=0.021, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, GLUT1 expression was an independent prognostic factor of poorer overall survival and disease-free survival (p=0.017 and p=0.019, respectively).ConclusionGLUT1 expression seems to play an important role in malignant transformation, and the glycolytic phenotype in invasive ductal carcinoma may indicate aggressive biological behavior and a worse prognosis.
A typical and protracted clinical course, unusual gross features of the appendix and the characteristic histologic features are a clue in the diagnosis of appendiceal CD.
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