scholarly journals Programmed death-ligand 1 expression and its correlation with clinicopathological parameters in gallbladder cancer

2020 ◽  
Vol 54 (2) ◽  
pp. 154-164
Author(s):  
Ji Hye Kim ◽  
Kyungbin Kim ◽  
Misung Kim ◽  
Young Min Kim ◽  
Jae Hee Suh ◽  
...  
Author(s):  
Moomal Aslam Khan ◽  
Serajuddaula Syed ◽  
Noor Ul Wahab ◽  
Saima Akram Butt ◽  
Jabbar Ahmed Qureshi

Background: Oral squamous cell carcinoma is prevalent in South Asian countries with rising cases of its incidence and mortality. Despite advancements in treatment, survival and recurrence rates are poor. Immunotherapy is a novel therapeutic modality in immunooncology. Immune checkpoint proteins are under investigation for clinical implications amongst which Programmed Death Ligand-1 has shown valuable results in certain malignancies. Aims: To determine the immunohistochemical expression of Programmed Death Ligand-1(PD-L1) in oral squamous cell carcinoma and to find an association of Programmed Death Ligand-1 with stage and clinicopathological parameters of oral squamous cell carcinoma. Study Design: Cross-sectional study. Place and Duration of Study: Ziauddin Medical University, Karachi, 1 Year duration during 2018-2019. Methods: A total number of 140 biopsy confirmed cases of oral squamous cell carcinoma were recruited in the study. Immunohistochemical expression of Programmed Death Ligand-1 was evaluated and associated with the clinicopathological parameters of oral squamous cell carcinoma (OSCC). The data was statistically analyzed through Descriptive statistics and Chi square test by using SPSS v.20. Results: Out of 140 participants, 74% were males (n=103) and 26% were females (n=37). Programmed Death Ligand-1 positivity was observed in 62.1% of cases (n=87). The Mean age of the participants was 48.91 ± 11.7 years.  The most common site of cancer involvement was buccal mucosa and majority of participants were habitual of consuming chewable products i.e. Pan, Gutka and betel nut (89; 64%). Stage III and IV tumours comprised a major portion of cases in our study. (52; 37%), (56; 40%). A statistically significant p-value was noted for the association of Programmed Death Ligand-1 with stage II and IV tumours. (P-values: 0.029, 0.001)The association of Programmed Death Ligand-1 with other variables such as age, gender, ethnicity, sites or habits was not statistically significant. Conclusion: This study concludes that the statistical significance of Programmed Death Ligand-1 expression with tumour stage is suggestive of worsening prognosis and might have detrimental effects as tumour progresses in advanced stage. Programmed Death Ligand-1 positivity in patients having oral squamous cell carcinoma could be useful in future research in the light of cancer immunotherapy which has shown success in oncology.


Author(s):  
Steven Banik ◽  
Kayvon Pedram ◽  
Simon Wisnovsky ◽  
Nicholas Riley ◽  
Carolyn Bertozzi

<p>Targeted protein degradation is a powerful strategy to address the canonically undruggable proteome. However, current technologies are limited to targets with cytosolically-accessible and ligandable domains. Here, we designed and synthesized conjugates capable of binding both a cell surface lysosome targeting receptor and the extracellular domain of a target protein. These lysosome targeting chimeras (LYTACs) consist of an antibody fused to agonist glycopeptide ligands for the cation-independent mannose-6-phosphate receptor (CI-M6PR). LYTACs enabled a CRISPRi knockdown screen revealing the biochemical pathway for CI-M6PR-mediated cargo internalization. We demonstrated that LYTACs mediate efficient degradation of Apolipoprotein-E4, epidermal growth factor receptor (EGFR), CD71, and programmed death-ligand 1 (PD-L1). LYTACs represent a modular strategy for directing secreted and membrane proteins for degradation in the context of both basic research and therapy. <b></b></p>


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