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Katharina Kessel ◽  
Robert Seifert ◽  
Matthias Weckesser ◽  
Martin Boegemann ◽  
Sebastian Huss ◽  

Abstract Introduction Fibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue. FAP tracer uptake has been reported in various tumor entities. The aim of this study was to compare FAP and Prostate-specific membrane antigen (PSMA) expression in primary prostate cancer employing histological analyses and PET imaging in two small patient collectives. Methods Two independent small patient collectives were included in this study. For cohort A, data of 5 prostate cancer patients and 3 patients with benign prostate hyperplasia were included. Patients with prostate cancer were initially referred for PSMA PET staging. Radical prostatectomy was performed in all patients and prostate specimen of patients and biopsies of healthy controls were available for further evaluation. Histological workup included HE and immunohistochemistry using PSMA Ab, FAP Ab. Cohort B consists of 6 Patients with diagnosed mCRPC and available PSMA as well as FAP PET. Results Patients with proven prostate cancer infiltration exhibited strong positivity for PSMA in both primary tumors and lymph node metastases while stainings for FAP were found positive in some cases, but not all (2/5). Controls with BPH presented moderate PSMA staining and in one case also with a positive FAP staining (1/3). PET imaging with FAP seemed to result in more precise results in case of low PSMA expression than PSMA-PET. Conclusions While PSMA staining intensity is a valid indicator of prostate cancer in both primary tumor and lymph node metastases, the expression of FAP seems to be heterogeneous but not necessarily linked to cancer-associated fibroblasts. It is also present in inflammation-associated myofibroblasts. Therefore, its ultimate role in prostate cancer diagnosis remains a subject of discussion.

2021 ◽  
Masayoshi Kawakubo ◽  
Josh Glahn ◽  
Shadmehr Demehri ◽  
Dieter Manstein

While ablative fractional photothermolysis (aFP) with a 10,600 nm CO2 laser is employed for a wide variety of dermatologic conditions, its applications in oncology are relatively unexplored. Building off our previous work, we investigated the effect of unilateral aFP treatment in combination with anti-PD-1 blocking antibody and OX40 agonist on bilateral tumor growth and remission. A CT26 wild type (CT26WT) colon carcinoma cell line was established bilaterally on the hind flanks of a standardized mouse model and tumor characteristics were investigated on aFP treated and untreated sides. Remarkably, triple therapy with fractional CO2 laser in combination with anti-PD-1 antibodies and OX40 agonists resulted in significantly slower tumor growth and complete remissions on bilateral tumors. Flow cytometric analysis showed the triple treatments elicited an increase of granzyme B+ CD8+T cells due to synergistic effect of aFP treatment and the checkpoint molecules, including the induction of CD103+ CCR7+ dendritic cells (DCs) in aFP-treated tumor by aFP treatment, XCR1+ DCs in drainage lymph node by anti-PD-1 inhibitor and OX40+ Ki67+ CD8+ T cells in the lymph node by OX40 agonist. Triple therapy-mediated tumor regression and survival was abrogated upon CD8+ T cell depletion. Importantly, when two mismatched cancer cells were implanted into mice, the effect of the triple therapy on distant tumor was abrogated, showing antigen specificity of the T cell immunity induced by triple therapy. This study highlights the efficacy of aFP a novel adjuvant for current cancer immunotherapeutics.

2021 ◽  
Kosuke Narumiya ◽  
Kenji Kudo ◽  
Yosuke Yagawa ◽  
Shinsuke Maeda ◽  
Yukinori Toyoshima ◽  

Abstract BackgroundIncidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing in Japan as well as Western Country. However, there is no consensus on treatment strategy. The purpose of this study was to determine the optimal range of resection and lymph node dissection for Siewert type II AEG and to develop a strategy for treatment that includes adjuvant therapy to improve the survival rate. MethodsWe retrospectively investigate 88 cases of advanced AEG in patients who underwent surgery with lymph node dissection with 52 cases of superficial AEG, 23 of whom underwent endoscopic treatment (endoscopic mucosal resection [EMR] or endoscopic submucosal dissection [ESD]), and 29 of whom underwent surgery with lymph node dissection. ResultsThe optimal lymph nodes to resect for advanced AEG were in the inferior mediastinum (No. 110), in the lesser curvature (Nos. 1, 3, 7), No. 2, and No 11. According to area of actual lymph node metastasis, lymphadenectomy of lymph nodes 1, 2, 3, 7, and 11 was sufficient to improve survival of patients with superficial AEG. If esophageal involvement was >40 mm, we performed esophagectomy through right thoracotomy. The 5-year overall survival rates were 88% for patients treated with ESD, 78% for those with superficial AEG who under-went surgery, and 24% for those with advanced AEG (p = 0.011). Despite of lymph node dissection, twenty-five patients experienced lymph node metastasis after operation in advanced AEG and there were many disseminations in advanced AEG. There were no differences in survival between patients who received postoperative adjuvant therapy with S-1 for advanced AEG and those who received surgery alone (p = 0.5192).Conclusion Although surgical procedures of superficial and locally advanced AEG are standardized, the role of adjuvant therapy for AEG is still controversial. We recommend nab-paclitaxel plus radiotherapy for advanced AEG as neoadjuvant therapy.

2021 ◽  
Zirui Jia ◽  
Yuhang Wang ◽  
Jiacheng Gao ◽  
Guo Zu

Abstract Background:The relationship between PROX1 expression and clinicopathological characteristics and prognosis in patients with gastric cancer (GC) is hotly contested and continues to be so. The aim of this study is to determine the clinicopathological and prognostic significance of PROX1 expression in patients with GC.Methods:PROX1 expression in GC patients was evaluated clinicopathologically and in terms of overall survival (OS) using a systematic literature search and meta-analysis. Additionally, the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) datasets were utilized to examine the relationship between PROX1 expression and clinicopathological significance and overall survival (OS) in GC patients.Results:A total of 8 studies pooling 1289 GC patients were included in the assessment. PROX1 expression, in GC patients, was shown to be unrelated to gender (odds ratio (OR) : 1.234, 95%CI: 0.958-1.590, P = 0.104), depth of tumor invasion (OR: 0.742, 95%CI:0.428-1.287, P = 0.289), lymph node metastasis (OR: 2.161, 95%CI: 0.808-5.779, P = 0.125), TNM stage (OR: 1.324, 95%CI: 0.572-3.066, P = 0.513), tumor size (OR: 0.889, 95%CI: 0.502-1.576, P = 0.687), metastasis (OR: 1.096, 95%CI: 0.470-2.555, P= 0.763), 1-year OS (OR: 0.908, 95%CI: 0.631-1.306, P = 0.602), 3-years OS (OR: 1.234, 95%CI: 0.482-3.160, P = 0.661) and 5-years OS (OR: 0.853, 95%CI: 0.266-2.736, P = 0.790). Patients with high PROX1 expression had a worse OS than those with low PROX1 expression, according to TCGA analyses, however the difference was not statistically significant (p=0.119).Conclusion:The expression of PROX1 was shown to be unrelated to gender, TNM stage, depth of invasion, tumor size, stage, tumor cell metastasis, or lymph node metastasis. The expression of PROX1 was also unrelated to OS and it failed to be a meaningful biomarker to prevent and diagnose GC.

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