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programmed death ligand 1 pd l1 Passaporto Falso Reato Penale, Il Ballo Delle Incertezze Chords, Il Nome Della Rosa, La Serie, Si Muove La Città, Matrimonio A Prima Vista 1, Canzoni D'amore 2020 Rap, Domenica In Oggi E In Diretta, Maestra'' In Francese, 150 Frasi In Inglese Parte 3, Spartiti Musicali Per Strumenti In Do, " /> Passaporto Falso Reato Penale, Il Ballo Delle Incertezze Chords, Il Nome Della Rosa, La Serie, Si Muove La Città, Matrimonio A Prima Vista 1, Canzoni D'amore 2020 Rap, Domenica In Oggi E In Diretta, Maestra'' In Francese, 150 Frasi In Inglese Parte 3, Spartiti Musicali Per Strumenti In Do, " /> Passaporto Falso Reato Penale, Il Ballo Delle Incertezze Chords, Il Nome Della Rosa, La Serie, Si Muove La Città, Matrimonio A Prima Vista 1, Canzoni D'amore 2020 Rap, Domenica In Oggi E In Diretta, Maestra'' In Francese, 150 Frasi In Inglese Parte 3, Spartiti Musicali Per Strumenti In Do, "/>

Oncotarget. All residues important for the interaction are highlighted as sticks.  DW, Kaumaya PTP, Guo L, Overholser J, Penichet ML, Bekaii-Saab T. Oncoimmunology. Dr Suda reported receiving grants from Boehringer Ingelheim, AstraZeneca, Takeda Pharmaceutical Company, Kyorin Pharmaceutical Company, Shionogi and Co, Taiho Phamaceutical Co, Daiichi Sankyo Healthcare, and Pfizer outside the submitted work. In this study, a selection of patients with NSCLC based on PD-L1 amplification was associated with greater durable benefit from nivolumab.  et al.  |  In contrast to our hypothesis that low-grade PD-L1 CNGs represented as polysomy would derive limited benefit from nivolumab therapy, no benefit in response and survival was observed, suggesting distinct roles for PD-L1 amplification and polysomy in tumor immune evasion.  PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. , Barrett First, it is shown that the ligand binding to human PD-1 is associated with significant plasticity within the receptor.  CA, Vokes  PD-1 blockade induces responses by inhibiting adaptive immune resistance. , Riaz 細胞質内に ITSM … All patients received nivolumab monotherapy at a dose of 3 mg/kg; the dosage was changed to a flat 240-mg dose in August 2018, according to the renewed approval by the Japanese Ministry of Health, Labor, and Welfare. There was a positive and statistically significant correlation between PD-L1 signals and the PD-L1 to CEP9 ratio (ρ = 0.61; 95% CI, 0.51-0.70; P < .001) (eFigure 1C in the Supplement).  et al.  Pembrolizumab versus chemotherapy for, Antonia  B, Kim Sequential nivolumab was given on day 1 of a 14-day cycle.  KN,  et al. Water molecules are shown as red spheres. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. In contrast, the 1-year PFS and 1-year OS rates were only 18.5% (95% CI, 6.7%-34.8%) and 46.0% (95% CI, 26.4%-63.6%) for patients with PD-L1 polysomy and 20.8% (95% CI, 14.8%-27.4%) and 57.6% (95% CI, 49.6%-64.8%) for patients with PD-L1 disomy, respectively. Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1).  MA.  A, Tay Progression-Free Survival of Patients Stratified by PD-L1 Protein Expression, eFigure 8.  Genomic correlates of response to immune checkpoint blockade. , Green  JP; STROBE Initiative.  Clinical significance of PD-L1 and PD-L2 copy number gains in non–small cell lung cancer. , Ikeda Nivolumab was repeatedly administered intravenously on day 1 of each 14-day cycle until progressive disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; discontinuation as a result of unacceptable adverse event; or withdrawal of consent. We excluded patients with concomitant autoimmune diseases, interstitial lung diseases, uncontrolled symptomatic brain metastases, or other severe uncontrolled complications. Immune checkpoint inhibitors (ICIs) targeting programmed death 1 (PD-1) or its ligand (PD-L1) have offered a subset of cancer patients profound and durable survival benefit and transformed the therapeutic landscape of multiple tumor types, particularly in non–small cell lung cancer (NSCLC).1-6 However, the proportion of patients with NSCLC who respond to ICIs is low; response to the anti–PD-1 antibody nivolumab was confirmed in only approximately 20% of patients in the pivotal randomized phase 3 clinical trials.1,2 More troublesome, PD-1/PD-L1 inhibitors can cause immune-related adverse effects7 as well as hyperprogressive disease.8 Therefore, there have been substantial attempts to discover and validate predictive biomarkers to identify patients who may benefit from PD-1/PD-L1 inhibitors by integrating information from tumors, the tumor microenvironment (TME), and the host immune system.9 To date, tumor PD-L1 expression using companion diagnostics is the only approved biomarker to indicate NSCLC patients for PD-1 axis blockade.  I, Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model. Genomic amplification of 9p24.1 targets Janus kinase 2 (JAK2) as well as PD-L1 and PD-L2, resulting in enhanced expression of JAK2 that further augments PD-L1 induction.36 This positive circuit makes the amplification of this locus more impactful in terms of constitutive PD-L1 expression and provides a rationale for response to anti–PD-1/PD-L1 inhibitors. Other names: anti-programmed cell death-1 (PD-1) monoclonal antibodies, immune checkpoint inhibitors, programmed death-ligand 1 (PD-L1) blocking antibodies What are Anti-PD-1 monoclonal antibodies? Overall response rate (ORR) according to the.  DM, Gly124 Cleft ( L Tyr123-Accommodating…, Figure 3.  CF, Proverbs-Singh  Y, Karayama PD-1/PD-L1は、がん免疫療法のターゲット分子として注目されています。 Cloud-Clone(WLS)社では、PD-1とPD-L1に関する製品を数多く取り扱っております。 【関連情報】特集:PD-1(Programmed death 1) / PD-L1 / PD-L2 (PD ligand 1 … First, definite conclusions are still precluded because of the small number of patients with PD-L1 amplification.  H, Paz-Ares Correlative Analysis of Response and PD-L1 Expression. Apo-hPD1 (PDB: 3RRQ) was overlaid on hPD-1 within the complex, and residues 62–82 of the former are shown (yellow ribbon).  Patient and Tumor Characteristics at Baseline, Brahmer  Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer. , Inoue However, the ORR among patients with PD-L1 amplification was high (80.0%; 95% CI, 28.4%-99.5%), which was a contrast with the low ORR (18.5%; 95% CI, 6.3%-38.1%) among patients with PD-L1 polysomy (Figure 3B).  Genomic features of response to combination immunotherapy in patients with advanced non–small cell lung cancer. , Rizvi Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has recently provided breakthrough progress in the treatment of melanoma, non-small cell lung cancer, and other types of cancer. Please allow up to 2 business days for review, approval, and posting. Correlation coefficients between continuous variables of biomarkers were calculated according to Spearman. Importance  PD-L1 and CEP9 signals are shown in red and green, respectively. 2016 May 24;7(21):30323-35. doi: 10.18632/oncotarget.8730. Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2. Is the copy number status of the programmed death ligand 1 (PD-L1) gene in non–small cell lung cancer associated with response to nivolumab monotherapy? These results justify the clinical application of PD-L1 FISH, considering the strong association of PD-L1 amplification with response to PD-1/PD-L1 blockade. 3D rendering. Conclusions and Relevance  Of these, 155 (79.9%) were men, with a median (range) age of 69 (43-83) years. Programmed Cell Death Ligand-1 (PD-L1) and CD8 Expression Profiling Identify an Immunologic Subtype of Pancreatic Ductal Adenocarcinomas with Favorable Survival Ludmila …  N, Hellmann  C, Findings   K,  F, Goldberg Response was assessed every 4 cycles using Response Evaluation Criteria in Solid Tumors version 1.1. With the planned sample size, the ORR would be estimated with the half width of the 95% CI within 15%.  Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. , Friedman The mechanisms by which PD-L1–amplified tumors are associated with long-lasting responses to nivolumab remain unclear.  P,  et al. This study reveals the molecular details of the human PD-1/PD-L1 interaction based on an X-ray structure of the complex.  L, Ammari sign up for alerts, and more, to access your subscriptions, sign up for alerts, and more, to download free article PDFs, sign up for alerts, customize your interests, and more, to make a comment, download free article PDFs, sign up for alerts and more, Archives of Neurology & Psychiatry (1919-1959), Sign Up for Emails Based on Your Interests, FDA Approval and Regulation of Pharmaceuticals, 1983-2018, Global Burden of Skin Diseases, 1990-2017, Health Care Spending in the US and Other High-Income Countries, Life Expectancy and Mortality Rates in the United States, 1959-2017, Medical Marketing in the United States, 1997-2016, Practices to Foster Physician Presence and Connection With Patients in the Clinical Encounter, US Burden of Cardiovascular Disease, 1990-2016, US Burden of Neurological Disease, 1990-2017, Waste in the US Health Care System: Estimated Costs and Potential for Savings, Register for email alerts with links to free full-text articles. Of note, the 5 PD-L1–amplified tumors exhibited various PD-L1 TPS values, ranging from 4% to 95% (eTable in the Supplement). doi:10.1001/jamanetworkopen.2020.11818, Is the copy number status of the programmed death ligand 1 (, In this cohort study of 194 patients with non–small cell lung cancer who were treated with nivolumab monotherapy, the proportion of patients with.  RM, Pedrero This study reveals the molecular details of the human PD-1/PD-L1 interaction based on an X-ray structure of the complex.  Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. , Le This cohort study evaluates whether the programmed death ligand 1 (PD-L1) gene copy number gains, comprising amplification and polysomy, in pretreatment specimens are associated with … The Kruskal-Wallis test was used for continuous variables, followed by adjustment using the method of Holm. In terms of survival outcome, we observed only 1 event of progression (Figure 4A) and no deaths (Figure 4B) among patients with PD-L1 amplification, with a 1-year PFS rate of 80.0% (95% CI, 20.4%-96.9%) and 1-year OS rate of 100%. To evaluate whether PD-L1 (CD274) copy number gains (CNGs), comprising amplification and polysomy, in pretreatment specimens assessed by fluorescence in situ hybridization are associated with response to nivolumab monotherapy in NSCLC.  et al; OAK Study Group.  JC, Postel-Vinay An OS benefit for patients with high expression of PD-L1 compared with those with low expression of PD-L1 was observed at the PD-L1 TPS threshold of 50% (HR, 0.44; 95% CI, 0.23-0.84; P = .01) (eFigure 8A in the Supplement), but again, no significant benefit was observed at lower PD-L1 TPS thresholds (eFigures 8B, 8C, and 8D in the Supplement). For the overall population, the ORR and disease control rate was 19.6% (95% CI, 14.2%-25.9%) and 50.5% (95% CI, 43.3%-57.8%), respectively.  AM, Borrello Identify all potential conflicts of interest that might be relevant to your comment.  et al. Three Main Hot Spots on the PD-L1 Surface, NLM 2017 May 2;13(5):892-900. doi: 10.1039/c7mb00036g.  K, Inoue  D, Kato  Y.  A, Soria 2017 Jul 13;60(13):5857-5867. doi: 10.1021/acs.jmedchem.7b00293. Recently, a single-nucleotide polymorphism (SNP) in the programmed death ligand 1 (PD-L1) gene has been associated with Graves’ disease (GD) in a Japanese patient cohort. Tumor specimens that contained fewer than 100 tumor cells or showed low quality were excluded from FISH and IHC analyses.  H.  E, BMC Bioinformatics. Genomic amplification of this locus is associated with distinct features in multiple tumor types.19-21 We previously reported that PD-L1 copy number gains (CNGs), including amplification and polysomy, as determined by fluorescence in situ hybridization (FISH), were associated with greater PD-L1 expression in NSCLC,22 suggesting that PD-L1 CNGs are responsible for innate immune resistance through constitutive upregulation of PD-L1. The interaction between PD … to download free article PDFs,  AG,  et al.  et al. Additional Contributions: The authors would like to acknowledge patients and their families and Naoko Yoshida and Hisaki Igarashi (Hamamatsu University School of Medicine) for their excellent technical assistance. No other disclosures were reported.  V, Baseline patient and tumor characteristics are given in the Table. 2020 Nov 5;11:598556. doi: 10.3389/fimmu.2020.598556. Median (interquartile range) duration of follow-up was 12.6 (5.6-20.4) months. Corresponding Author: Naoki Inui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan (inui@hama-med.ac.jp).  A,  JN, Smith Targeting programmed death-1 and programmed death-ligand 1 (PD-1/PD-L1) in breast cancer appears increasingly appealing after the success of such an approach in other cancers. PD-L1 CNGs were identified in 32 patients (16.5%), including 5 (2.6%) with amplification and 27 (13.9%) with polysomy.  et al. Representative images of fluorescence in situ hybridization analysis of tumors carrying PD-L1 disomy, polysomy, or amplification obtained from patients enrolled in this study (original magnification ×100).  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. , von Elm In addition, the benefit observed in patients with PD-L1–amplified tumors irrespective of PD-L1 expression levels suggests other mechanisms that render PD-L1–amplified tumors sensitive to ICIs, including the link with known predictive factors such as TMB.  PD-1 blockade in tumors with mismatch-repair deficiency. , Rizvi Descriptive Statistics for PD-L1 FISH, eFigure 2. We thank the Edanz Group for editing a draft of this article.  MR, Monti 2020 Nov 20;23(12):101835. doi: 10.1016/j.isci.2020.101835. Not all submitted comments are published.  L, Tumor PD-L1 protein expression was assessed in sections adjacent to those used for FISH by IHC using the E1L3N antibody (Cell Signaling Technology) or the 22C3 pharmDX assay (Agilent) before and after the approval of the 22C3 assay in Japan, respectively, followed by calculation of the tumor proportion score (TPS). Kuang Z, Heng Y, Huang S, Shi T, Chen L, Xu L, Mei H. ACS Omega. Hydrogen bonds are depicted as black dashed lines. To validate the performance of E1L3N, we used positive and negative controls as follows: (1) immunocytochemistry and immunoblot analyses of PD-L1 in PD-L1–negative NCI-H1299 cells in which PD-L1 was exogenously expressed using the p3 × FLAG-CMV-14 vector (Sigma-Aldrich) and (2) IHC of PD-L1 using SignalSlide PD-L1 IHC Controls (Cell Signaling Technology).  L, Horn PD-L1 is encoded by the PD-L1 gene (CD274; OMIM 605402) located on the chromosome band 9p24.1. JAMA Netw Open. All Rights Reserved, Challenges in Clinical Electrocardiography, Clinical Implications of Basic Neuroscience, Health Care Economics, Insurance, Payment, Scientific Discovery and the Future of Medicine, United States Preventive Services Task Force, 2020;3(9):e2011818. First, it is shown that the ligand binding to human PD-1 is associated with … ¥çš„に作った抗体で蓋をしてしまうことで結合を阻害しT細胞を抑制させない薬が認可され …  Heterogeneity analysis of PD-L1 expression and copy number status in EBUS-TBNA biopsy specimens of non–small cell lung cancer: comparative assessment of primary and metastatic sites. , Ready Close-Up Views of the hPD-1/hPD-L1 Interface, hPD-1 and hPD-L1 are represented by blue…, Figure 3. JAMA Network Open. Indeed, previously treated patients with NSCLC who had PD-L1 expression of at least 50% had more response to pembrolizumab compared with those with PD-L1 expression between 1% and 50%.3 However, in our study, PD-L1 expression was relatively low (TPS, ≤15%) in 2 of 5 PD-L1–amplified tumors.  Predictive biomarkers of response for immune checkpoint inhibitors in non-small-cell lung cancer. , Le Get free access to newly published articles.  First-line nivolumab plus ipilimumab in advanced non–small-cell lung cancer (CheckMate 568): outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. , Davoli  Pembrolizumab versus docetaxel for previously treated, Rittmeyer Programmed death-ligand 1, commonly abbreviated PD-L1, is a protein with an important role in immune system regulation and cancer. Overall, 3 PD-L1-amplified tumors (60.0%) showed PD-L1 TPS of at least 80%, but 2 (40.0%) had PD-L1 TPS of 15% or less. Median (interquartile range) duration of follow-up was 12.6 (5.6-20.4) months.  B, Califano  D, Robinson  SM, Lesokhin  |   S,  PC, Harview Adverse events were graded based on the National Cancer Institute Common Toxicity Criteria version 4.0. Several other predictors of responsiveness have also been identified, including mismatch repair deficiency,10,11 tumor mutation burden (TMB),12-14 and tumor-infiltrating immune cells.15-17 However, none of these factors appear to be satisfactorily sensitive or specific, even when multiple factors are combined,18 in part owing to technical issues, the dynamic nature of the TME, and the complexity and heterogeneity of cancer cells.  PC, Vandenbroucke Please see our commenting policy for details.  K, They were not compensated for their time.  et al.  J, Bockmayr COVID-19 is an emerging, rapidly evolving situation.  et al; PACIFIC Investigators. R21 GM087617/GM/NIGMS NIH HHS/United States, R01 GM097082/GM/NIGMS NIH HHS/United States, P41 GM094055/GM/NIGMS NIH HHS/United States, 1P41GM094055/GM/NIGMS NIH HHS/United States, 1R21GM087617/GM/NIGMS NIH HHS/United States, 1R01GM097082/GM/NIGMS NIH HHS/United States, NCI CPTC Antibody Characterization Program. As a result, median duration of response was not reached (range, 17.7 [ongoing] to 33.7 [ongoing] months) for patients with PD-L1 amplification who responded, which was longer than that among patients with PD-L1 polysomy who responded (14.9 months; 95% CI, 4.6 months to not reached) or those with disomy who responded (16.8 months; 95% CI, 8.1 months to not reached) (eFigure 3A in the Supplement). Patients with PD-L1 amplification showed excellent survival outcomes for progression-free and overall survival.  T, Rizvi Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PD-L1) inhibitors are the therapeutic candidates or drugs, popularly known as checkpoint inhibitors, used most commonly for …  TA, Postow Inoue Y, Yoshimura K, Nishimoto K, et al. Programmed cell death 1 (PD-1), a member of the B7 receptor family, is an inhibitory receptor expressed on the surface of T cells. Statistical analyses were carried out using EZR statistical software29 version 1.35 (Saitama Medical Center, Jichi Medical University) and GraphPad Prism version 8.2.1 (GraphPad Software).  D, The "Programmed Death-Ligand 1 (PD-L1) Non-Small Cell Lung Cancer (NSCLC)-Market Insights, Epidemiology and Market Forecast - 2030" drug pipelines has been added to …  Comparison of biomarker modalities for predicting response to PD-1/PD-L1 checkpoint blockade: a systematic review and meta-analysis. , Budczies  Cancer immunology: mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. , Tumeh Representative computed tomography scans demonstrating response in a patient with PD-L1–amplified adenocarcinoma are shown in eFigure 4 in the Supplement. Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. Copyright © 2015 Elsevier Ltd. All rights reserved. The associations of tumor PD-L1 protein expression with PD-L1 copy number and outcomes were also included in the secondary end points. B, Scatterplot depicting PD-L1 tumor proportion score and PD-L1 to CEP9 ratio (Spearman ρ = 0.12; 95% CI, −0.025 to 0.26; P = .10). (B) hPD-1 complexed with hPD-L1.  et al; KEYNOTE-024 Investigators.  S.  F, Waterkamp A 2-tailed P < .05 was considered statistically significant. Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1.  MD, Nathanson Conflict of Interest Disclosures: Dr Inui reported receiving grants from Chugai Pharmaceutical Co, Eli Lilly Japan, and MSD KK outside the submitted work.  et al. Terms of Use|  MD, Awad Programmed death-ligand 1 (PD-L1) protein. Â, Ock  Nivolumab versus docetaxel in advanced nonsquamous non–small cell lung cancer. .  H, This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.27. Main Outcomes and Measures   R, Ferrara Nivolumab was discontinued in 178 patients (91.8%), mainly due to disease progression (135 [69.6%]) and adverse events (37 [19.1%]). Of the 4 patients with PD-L1 amplification who responded to therapy, 3 patients were still receiving study treatment at the final database lock. eCollection 2020 Oct 20. PD-L1 copy number was assessed by centrally performed FISH using the Histra PD-L1 FISH kit (Jokoh, Tokyo, Japan) as described elsewhere.22,28 This kit contains the spectrum orange-labeled bacterial artificial chromosome clone RP11-599H20 (9p24.1, PD-L1; Advanced GenoTechs) and the spectrum green-labeled control centromere enumeration probe for chromosome 9 (CEP9; RP11-113O24; Advanced GenoTechs) as PD-L1 locus–specific and referenced chromosome 9 FISH probes, respectively. Within the complex structure, hPD-1 is colored blue and hPD-L1 is colored green; both are shown in stereo view in ribbon representation. Supervision: Inui, Karayama, Hozumi, Suzuki, Enomoto, Sugimura, Suda. In this prospective study, we demonstrated that FISH-based PD-L1 amplification but not polysomy was associated with durable responses to nivolumab among patients with NSCLC.  R, Chaput Although somatic genomic features, such as variations and copy number alterations, have been associated with response and resistance to ICIs,30,31 tumor PD-L1 copy number status has received limited attention in solid tumors. Our aim was …  H, Sanchez-Vega  Mutational landscape and sensitivity to immune checkpoint blockers. , Goodman  A, Barlesi External validation with a larger sample size is warranted.  AM, Piccioni Programmed cell death 1 ligand 1 (synonym CD274, B7 Homolog 1) ist ein Oberflächenprotein und beteiligt an der Hemmung der Immunantwort. © 2020 American Medical Association.  A transcriptionally and functionally distinct PD-1, Lu This multicenter cohort study enrolled 200 patients, of whom 194 had assessable tumors, with advanced or recurrent NSCLC who were treated with nivolumab after progression following prior treatment at 14 institutions in Japan between July 2016 and December 2018.

Passaporto Falso Reato Penale, Il Ballo Delle Incertezze Chords, Il Nome Della Rosa, La Serie, Si Muove La Città, Matrimonio A Prima Vista 1, Canzoni D'amore 2020 Rap, Domenica In Oggi E In Diretta, Maestra'' In Francese, 150 Frasi In Inglese Parte 3, Spartiti Musicali Per Strumenti In Do,

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