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Wednesday, November 25, 2020

Vaccines, Vol. 8, Pages 706: DC-Based Vaccines for Cancer Immunotherapy

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Vaccines, Vol. 8, Pages 706: DC-Based Vaccines for Cancer Immunotherapy

Vaccines doi: 10.3390/vaccines8040706

Authors: Chunmei Fu Li Zhou Qing-Sheng Mi Aimin Jiang

As the sentinels of the immune system, dendritic cells (DCs) play a critical role in initiating and regulating antigen-specific immune responses. Cross-priming, a process that DCs activate CD8 T cells by cross-presenting exogenous antigens onto their MHCI (Major Histocompatibility Complex class I), plays a critical role in mediating CD8 T cell immunity as well as tolerance. Current DC vaccines have remained largely unsuccessful despite their ability to potentiate both effector and memory CD8 T cell responses. There are two major hurdles for the success of DC-based vaccines: tumor-mediated immunosuppression and the functional limitation of the commonly used monocyte-derived dendritic cells (MoDCs). Due to their resistance to tumor-mediated suppression as inert vesicles, DC-derived exosomes (DCexos) have garnered much interest as cell-free therapeutic agents. However, current DCexo clinical trials have shown limited clinical benefits and failed to generate antigen-specific T cell r esponses. Another exciting development is the use of naturally circulating DCs instead of in vitro cultured DCs, as clinical trials with both human blood cDC2s (type 2 conventional DCs) and plasmacytoid DCs (pDCs) have shown promising results. pDC vaccines were particularly encouraging, especially in light of promising data from a recent clinical trial using a human pDC cell line, despite pDCs being considered tolerogenic and playing a suppressive role in tumors. However, how pDCs generate anti-tumor CD8 T cell immunity remains poorly understood, thus hindering their clinical advance. Using a pDC-targeted vaccine model, we have recently reported that while pDC-targeted vaccines led to strong cross-priming and durable CD8 T cell immunity, cross-presenting pDCs required cDCs to achieve cross-priming in vivo by transferring antigens to cDCs. Antigen transfer from pDCs to bystander cDCs was mediated by pDC-derived exosomes (pDCexos), which similarly required cDCs for cross-priming of an tigen-specific CD8 T cells. pDCexos thus represent a new addition in our arsenal of DC-based cancer vaccines that would potentially combine the advantage of pDCs and DCexos.

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LncRNA MEG8 plays an oncogenic role in hepatocellular carcinoma progression through miR-367-3p/14-3-3 ζ/TGFβR1 axis.

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Via Neoplasma
In conclusion, this work exposed a novel role and regulatory mechanism of MEG8 in HCC and provided new insight into the treatment of HCC. PMID: 33147050 [PubMed - as supplied by publisher] (Source: Neoplasma)
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The mechanism of ABL1 upregulating the expression of PD-L1 and the therapeutic effect of PD-L1 and STAT3 inhibitors in lung adenocarcinoma.

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Authors: Tang D, Jiang H, Li Z, Gao W, Sun Y Abstract The upregulation of programmed cell death-ligand 1 (PD-L1) and continuous mutation of EGFR could induce chemoresistance in somatic cancers, however, the molecular mechanism of oncogene ABL1 in regulating the expression of PD-L1 in lung adenocarcinoma (LAD) remains unclear. In addition, the therapeutic effect of STAT3 and PD-L1 inhibitors in LAD is not fully understood. The ABL1 lentiviruses were used to transfect LAD cell lines (H1975, PC-9) with different EGFR mutation subtypes. Next, the expression of the JAK/STAT3 and PD-L1 pathway was detected followed by the treatment with STAT3 and PD-L1 inhibitors. Lastly, we observed the apoptosis and expression of STAT3 and PD-L1 before and after treatments in transfected and knocked do...
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Expression of COX-2, p16, and Ki67 in the range from normal breast tissue to breast cancer.

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The objective of the study was to examine COX-2, p16, and Ki67 expression in a broad spectrum of breast lesions in order to define the proteins' phenotype throughout the tumorigenesis. Expression was studied by immunohistochemistry in 308 human breast samples divided into 7 subgroups - flat epithelial atypia (FEA), atypical hyperplasia (ADH), intraductal carcinoma (DCIS), invasive cancer (IC), benign lesions (BLs), normal tissue adjacent to breast cancer (CANT), and fatty tissue (FT). Analysis among 4 subgroups - premalignant lesions (DIN), IC, BLs, and normal tissue was also performed. High prevalence of COX-2 overexpression was found in all breast lesions including BLs (70% FEA, 89% ADH, 86% DCIS, 81% IC, 44% CANT, 92% BLs, 29% FT). Significant dominance of p16 overexpression was found i...
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Quantitative CT Detects Undiagnosed Low Bone Mineral Density in Oncologic Patients Imaged With 18F-FDG PET/CT

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Purpose We assessed the prevalence of low bone mineral density (BMD) in oncologic patients undergoing 18F-FDG PET/CT. Patients and Methods This is a retrospective analysis of 100 patients who underwent 18F-FDG PET/CT at a single center from October 2015 till May 2016. Quantitative CT (QCT) was used to assess BMD at the lumbar spine (BMDQCT) and femoral necks (BMDCTXA). SUVmax was used to evaluate metabolic activity of the bone marrow. Risk of osteoporosis-related fractures was calculated with femoral neck BMDCTXA and the FRAX algorithm, which was compared against measurements of CT attenuation of the trabecular bone at L1 (L1HU). Results Osteoporosis and osteopenia were respectively present in 16% and 46% of patients 50 years and older. Bone marrow SUVmax was correlated with BMD at the lumbar spine (ρ = 0.36, P
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Usual and Rare Abdominal Location of Giant Cell Arteritis Diagnosed and Follow-up With 18F-FDG PET/CT

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Giant cell arteritis is not an uncommon disease, and its extension is furthermore finely assessed with new-generation PET/CT system. 18F-FDG PET/CT is increasingly used in case of large-vessel vasculitis for optimal diagnosis, activity monitoring (even when treated with interleukin 6 receptor inhibitor), and evaluation damage progression. We reported the case of a 61-year-old woman with common giant cell arteritis pattern on 18F-FDG PET/CT (aorta and large arteries) and uptakes in all aorta branches, mainly impressive and uncommon in the abdomen. After 2 years of therapeutic optimization including IV tocilizumab and monitoring with 18F-FDG PET/CT, a complete metabolical response was assessed. Received for publication July 8, 2020; revision accepted October 6, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Pierre-Benoît Bonnefoy, MD, MS, Service de Médecine Nucléaire, CHU de Saint-Etienne – Hôpital Nord, Avenue Albert Raymond, 42055, Saint-E[Combining Acute Accent]tienne, France. E-mail: p.benoit.bonnefoy@chu-st-etienne.fr. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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Rapidly Evolving Diffuse Omental Carcinomatosis of Prostate Cancer in 68Ga-PSMA PET/CT

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An 81-year-old man received androgen deprivation therapy for a locally advanced prostate cancer and, 6 months later, a curative radiation therapy. Half a year later, the patient presented with a steeply increased PSA value (32 ng/mL) and a suppressed testosterone level (0.48 nmol/L). The consecutively performed 68Ga-PSMA PET/CT revealed, besides local tumor remains and several PSMA-positive lymph node and soft tissue metastases, an extensive, diffuse PSMA ligand accumulation in the omentum, which was immunohistochemically proven to be a carcinomatosis of prostate cancer. None of the extraprostatic lesions were present in the pretherapeutic PSMA PET 1 year ago. Received for publication July 6, 2020; revision accepted October 6, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Sebastian Hoberück, MD, Department of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany. E-mail: Sebastian.Hoberueck@uniklinikum-dresden.de. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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Diffuse Subcutaneous Metabolic Activity in Post Bone Marrow Transplant Hodgkin Lymphoma

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We present a 14-year-old adolescent boy with Hodgkin lymphoma. He had prior completed chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen followed by bone marrow transplantation 6 months ago. Currently, he has neither specific clinical complaint nor receiving any specific medication. Follow-up FDG PET/CT scan demonstrated diffuse increased metabolic activity in the entire body subcutaneous tissue. This finding is rarely reported in the literature and may represent an underlying active inflammatory process, most likely attributed to the received treatments. This could impair the diagnostic quality of the scan, affecting the image interpretation, and should be recognized when present. Received for publication July 10, 2020; revision accepted October 6, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Abtin Doroudinia, MD, PET/CT Unit, Department of Radiology, Masih Daneshvari Hospital, Niyavaran Street, Dar Abad, Tehran, Iran 19569-44413. E-mail: abtin1354@gmail.com. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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99mTc-PSMA SPECT/CT Versus 68Ga-PSMA PET/CT in the Evaluation of Metastatic Prostate Cancer

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Background 99mTc–prostate-specific membrane antigen (PSMA) SPECT/CT is less expensive and readily available modality compared with 68Ga-PSMA PET/CT for imaging prostate cancer (PC). The aim of this study is to compare the value of these 2 modalities in patients confirmed or suspicious to have metastatic prostate cancer. Patients and Methods Twenty-two patients with the mean age of 66.6 ± 10.1 years were studied using 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT, with less than 7 days interval between the 2 imaging procedures. Whole-body PET/CT was done 60 minutes after IV injection of 185 MBq (5 mCi) of 68Ga-PSMA. 99mTc-PSMA SPECT/CT was performed 3 hours after IV injection of 555 to 740 MBq (15–20 mCi) of 99mTc-PSMA. The images of each modality were interpreted independently, and the results were compared according to patient-based as well as region-based analyses. Results In patient-based evaluation, both 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT scans were positive in 95.45% (21/22). In region-based evaluation, 68Ga-PSMA PET/CT detected 53 regions (median of 2 regions per patient; range, 0–5), whereas 43 (median of 2 regions per patient; range, 0–5) were detected by 99mTc-PSMA SPECT/CT. Most of these differences could be explained by lower detection rate of 99mTc-PSMA SPECT/CT in prostate bed (n = 6). PET/CT detected more involved regions than SPECT/CT (P = 0.007), whereas similar frequency of extraprostatic lesions were diagnosed in both modalities (P = 0.102). Significant correlation was also demonstrated between serum prostate-specific antigen level and imaging parameters of disease extension detected by 2 modalities. Conclusions 99mTc-PSMA SPECT/CT could be a potential substitute for 68Ga-PSMA PET/CT in high-risk patients, except when evaluation of prostate bed is of major concern. Received for publication June 6, 2020; revision accepted October 5, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Davood Beiki, PhD, Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, North Kargar Ave 1411713135, Tehran, Iran. E-mail: beikidav@sina.tums.ac.ir. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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18F-FDG PET and 18F-FDG PET/CT in Vulvar Cancer: A Systematic Review and Meta-analysis

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Aim The aims of this study were to determine the role of 18F-FDG PET/CT in vulvar cancer patients and to extract summary estimates of its diagnostic performance for preoperative lymph node staging. Patients and Methods PubMed/Medline and Embase databases were searched to identify studies evaluating 18F-FDG PET/CT in vulvar cancer patients. The assessment of methodological quality of the included articles was performed. Per-patient and per-groin pooled estimates, with 95% confidence intervals (CIs), of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR) were calculated. Results Ten articles were included in the systematic review, 7 among which evaluated the diagnostic performance of preoperative 18F-FDG PET/CT for lymph node staging. Qualitative per-patient analysis (72 patients from 4 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.70 (95% CI, 0.44–0.95), 0.90 (95% CI, 0.76–1.04), 0.86 (95% CI, 0.66–1.06), 0.77 (95% CI, 0.56–0.97), and 10.49 (95% CI, 1.68–65.50), respectively. Qualitative per-groin analysis (245 groins from 5 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.76 (95% CI, 0.57–0.94), 0.88 (95% CI, 0.82–0.94), 0.70 (95% CI, 0.55–0.85), 0.92 (95% CI, 0.86–0.97), and 19.43 (95% CI, 6.40–58.95), respectively. Conclusions Despite limited literature data, this systematic review and meta-analysis revealed that a negative preoperative PET/CT scan may exclude groin metastases in at least early-stage vulvar cancer patients currently unfit for sentinel node biopsy and select those eligible for a less invasive surgical treatment. A positive PET/CT result should otherwise be interpreted with caution. Larger prospective studies are needed to confirm these results and to evaluate the diagnostic value of standardized semiquantitative analysis compared with the qualitative one. Received for publication August 13, 2020; revision accepted October 2, 2020. Conflicts of interest and sources of funding: none declared. Correspondence to: Vittoria Rufini, MD, UOC Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli, 8-00168 Rome, Italy. E-mail: vittoria.rufini@unicatt.it. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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Comparative Performance of 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT Imaging in Patients With Parkinson’s Disease, Parkinson-Plus Syndrome, and Essential Tremor

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Purpose The aim of this study was to assess the utility of presynaptic dopaminergic imaging using 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT and compare their performance in Parkinson's disease (PD), Parkinson-plus syndrome (PPS), and essential tremor (ET). Patients and Methods A total of 103 patients (PD = 48, PPS = 19, and ET = 36) were enrolled prospectively. Hoehn and Yahr (H&Y) staging and MDS-UPDRS (Movement Disorder Society–Sponsored Revision of Unified Parkinson's Disease Rating Scale) were done for PD and PPS cases. All the patients underwent 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT brain scan. The scans were analyzed visually and semiquantitatively. Average pixel count and SUVmean of the striatum were calculated in SPECT and PET images, respectively, to calculate the specific uptake ratio of striatum (SUR). Comparison of scan findings and SURs among different groups and correlation with clinical characteristics was done. Results Symmetrical comma-shaped uptake was seen in bilateral striatum in ET cases with mean SURs significantly higher than in cases of early PD (H&Y stage I and II, n = 37), PD and PPS both on SPECT and PET images (P ≤ 0.001). The mean SURs between PD and PPS showed no significant difference (SPECT, P = 0.17; PET, P = 0.61). Substantial agreement (weighted κ = 0.659) was found between 99mTc-TRODAT-1 and 18F-FDOPA for the detection of presynaptic dopaminergic dysfunction. Specific uptake ratio of striatum correlation between SPECT and PET was statistically significant (r = 0.67; P
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90Y Radiosynovectomy in Persistent Synovitis Caused by Knee Replacement: Long-Term Outcome

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Introduction After knee replacement, therapy resistant, persistent synovitis is a common issue, which causes effusion and pain, and leads to loosing. It has been hypothesized that radiosynovectomy (RSO) is useful in these patients. Materials and Methods A cohort of 55 patients with 57 knee replacements and persistent synovitis underwent RSO using 4.9 ± 0.24 mCi (182 ± 9 MBq) of 90Y-citrate. The number of RSOs ranged from 1 to 4. Bone scans before and 3 months after every RSO were performed. Long-term follow-up ranged from 0.8 to 7.6 years with a mean of 23.2 months. For qualitative analysis, an established 4 steps scoring was used. For quantification, the uptake was determined within the 99mTc-MDP scintigraphy blood pool phase before and after therapy. Results Long-term response was in 27% with excellent, 24% good, 30% weak, and 20% no response. The duration of response was 12.0 ± 12.0 months (maximum, 54 months). In patients with repeated treatment, the effect after the first therapy was lesser than in patients who received a single treatment in total. However, 3 months after the last RSO, patients with repeated treatment showed a similar effectiveness than single treated patients. At the end of long-term follow-up, patients with repeated RSOs had a higher effectiveness at similar duration response. In bone scan, 65% of patients showed a reduction of uptake. When comparing subjective and objective response, 78% of patients showed a concordance in both symptoms and scintigraphy. Pilot histological analysis revealed that the synovitis is triggered by small plastic particles. Conclusions We concluded that RSO is an effective therapy in patients with knee replacement and persistent synovitis with high long-term response. Repeated treatment leads to a stronger long-time response. Received for publication August 21, 2020; revision accepted October 2, 2020. K.L. and M.B. equally contributed. Conflicts of interest and sources of funding: K.L. is a consultant of Serene LCC. M.B. declares that no funding was applicable. The authors declare that no ethics approval and consent to participate were necessary. The authors have consent of publication for their data. The used data and materials are available and can be requested. The licenses of used software are available. Correspondence to: Knut Liepe, MD, PhD, MHBA, Department of Nuclear Medicine, Klinikum Frankfurt (Oder), Muellroser Chaussee 7, 15236 Frankfurt (Oder), Germany. E-mail: knut.liepe@klinikumffo.de. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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