Abstract Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches. 

Regulatory mechanisms of PD-1/PD-L1 in cancers

Pancreatic cancer (PC) is a fatal disease with high malignancy and difficult for early diagnosis. PC causes more than 400,000 patient deaths world widely and becomes the severe health problems. The tumor microenvironment (TME) is comprised of acellular stroma, pancreatic stellate cells, immune cells, and soluble factors. TME is maintained by continuous cell-matrix and cell-cell interactions. TME induced by the interaction among pancreatic cancer cells, epithelial cells and stromal cells is essential for the progression of PC and leads to resistance to chemotherapy. Components in the microenvironment can also promote the formation of connective tissue in the primary or metastatic site, or promote the metastatic ability of PC by enhancing angiogenesis, epithelial-mesenchymal transformation, and lymph angiogenesis. In addition, the TME also leaves pancreatic cancer unsusceptible to different immunotherapeutic strategies. In this review, we summarized the current knowledge about TME in PC. And the focus was placed on the role of TME in chemotherapeutic resistance and metastasis in the field of PC. And we also paid attention to the immunological therapy targeting the TME, aiming to provide the novel therapy for pancreatic cancer.

Tumor microenvironment in chemoresistance, metastasis and immunotherapy of pancreatic cancer.

The acetylation of histone and non-histone proteins has been implicated in several disease states. Modulation of such epigenetic modifications has therefore made histone deacetylases (HDACs) important drug targets. HDAC3, among various class I HDACs, has been signified as a potentially validated target in multiple diseases, namely, cancer, neurodegenerative diseases, diabetes, obesity, cardiovascular disorders, autoimmune diseases, inflammatory diseases, parasitic infections, and HIV. However, only a handful of HDAC3-selective inhibitors have been reported in spite of continuous efforts in design and development of HDAC3-selective inhibitors. In this Perspective, the roles of HDAC3 in various diseases as well as numerous potent and HDAC3-selective inhibitors have been discussed in detail. It will surely open up a new vista in the discovery of newer, more effective, and more selective HDAC3 inhibitors.

Dissecting Histone Deacetylase 3 in Multiple Disease Conditions: Selective Inhibition as a Promising Therapeutic Strategy.

Contemporary clinical trials in pancreatic cancer immunotherapy targeting PD-1 and PD-L1

Immune checkpoint blockade in pancreatic cancer: trudging through the immune desert.

Autophagy inhibition and ferroptosis activation during atherosclerosis: Hypoxia-inducible factor 1α inhibitor PX-478 alleviates atherosclerosis by inducing autophagy and suppressing ferroptosis in macrophages.

PURPOSE
To investigate the demographics, clinical features, radiologic measurement, treatment, and outcomes of symptomatic spontaneous isolated superior mesenteric artery dissection (SISMAD) according to computed tomography (CT) classification.


METHODS
This retrospective study included 201 patients diagnosed with symptomatic SISMAD from November 2014 to December 2020. Symptomatic spontaneous isolated superior mesenteric artery dissection was categorized into four types based on CT images by Yun's angiographic classification. Their clinical characteristics, images features, treatment methods, and radiological outcomes were comparatively analyzed by CT angiographic types.


RESULTS
SISMADs were categorized into type I (13.9%) patent false lumen (FL) with both entry and re-entry; type IIa (37.3%), blind pouch of FL; type IIb (43.3%), thrombosed FL; and type III (5.5%), and the occlusion of superior mesenteric artery (SMA). Type IIb, the most common SISMAD, showed the largest true lumen (TL) residual diameter and the lowest percentage of TL stenosis. Type III positioned most proximally to SMA origin and had the maximum dissection length. Symptomatic spontaneous isolated superior mesenteric artery dissections underwent conservative (75.1%), endovascular (22.4%), and surgical (2.5%) treatment. Conservative treatment was more frequent in type I (85.7%) and type IIb (83.9%) than in type IIa (65.3%) and type III (45.5%). Endovascular intervention was more commonly utilized in type IIa (32.0%) and type III (36.4%) than in type I (14.3%) and type IIb (14.9%). Conservative patients achieved FL vanishment/shrinkage (57.8%), stabilization (26.6%), and enlargement (15.6%). After conservative treatment, type I showed angiographic FL stabilization; type IIa achieved FL shrinkage (48.1%), stabilization (22.2%), and enlargement (29.6%); type IIb exhibited FL vanishment/shrinkage (92.0%) and enlargement (8.0%). Cumulative rate of stent patency was 92.3% during 6-year follow-up.


CONCLUSIONS
Conservative management with close follow-up is initially provided especially for types I and IIb. Morphological stabilization is more frequent in type I of patent FL with entry and re-entry. False lumen vanishment or shrinkage was more likely to occur in type IIb due to the thrombus absorption. Endovascular intervention has excellent long-term in-stent patency and is predominantly utilized in types IIa and III. Blood flow sustained into a blind-ending FL causes the TL compression and stenosis in type IIa. Type III with the occlusion of SMA has the high risk of bowel ischemia.


CLINICAL IMPACT
According to Yun's angiographic classification of spontaneous isolated superior mesenteric artery dissection (SISMAD), type I (13.9%) has patent true and false lumen and the morphological pattern is maintained stable; type IIa (37.3%) possesses a patent blind-ending false lumen which might shrink, remain unchanged, or enlarge; and endovascular intervention is suggested when conservative treatment failed; type IIb (43.3%) recovers spontaneously due to the absorption of false lumen thrombus and conservative treatment is preferentially considered; type III (5.5%) with the occlusion of main trunk carries a high risk of bowel necrosis, early endovascular intervention is proposed, and open surgery might be necessary.

Management Strategy and Radiologic Outcomes of Symptomatic Spontaneous Isolated Superior Mesenteric Artery Dissection Based on Angiographic Classification: The Follow-Up Experience in a Single Center.

HDAC3 modulates cancer immunity via increasing PD-L1 expression in pancreatic cancer

Vascular cellular senescence in human atherosclerosis: The critical modulating roles of CDKN2A and CDK4/6 signaling pathways.

Background Deep vein thrombosis (DVT) of the lower extremity (LE) might lead to pulmonary embolism (PE) and post-thrombolytic syndrome (PTS). Recently, percutaneous endovenous intervention (PEVI) has been advocated for early removal of thrombus clot and restoration of venous patency. This study aims to review the safety and efficacy outcomes of PEVI versus anticoagulation in the treatment of acute LE-DVT. Methods We searched the databases of PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing catheter-directed thrombolysis (CDT) and/or pharmacomechanical thrombectomy (PMT) versus anticoagulation for acute proximal LE-DVT, published before August 2022. Efficacy outcomes were PTS and venous patency. Safety outcomes included recurrent thromboembolism, bleeding complications, and PE. Results Overall, 1,266 patients were included from 6 RCTs. The overall risk of bias was small due to enrolled high-quality RCTs. Compared to anticoagulation, PEVI moderately reduced PTS incidence [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.23–0.99], obviously inhibited moderate–to–severe PTS (OR 0.60, 95% CI: 0.40–0.88), significantly decreased PE (OR 0.16, 95% CI: 0.05–0.48), and substantially increased venous patency (OR 7.95, 95% CI: 1.00–63.16). There was no significant difference in recurrent thromboembolism between PEVI and anticoagulation (OR 0.76, 95% CI: 0.34–1.73). Bleeding events did not differ statistically between PEVI and anticoagulation (OR 1.36, 95% CI: 0.87–2.11). We conducted single-arm meta-analysis of the PEVI or anticoagulation. Pooled proportion of PTS was less after PEVI (0.295, 95% CI: 0.123–0.505) than after anticoagulation (0.459, 95% CI: 0.306–0.616). Pooled proportion of moderate-to-severe PTS was lower after PEVI (0.098, 95% CI: 0.033–0.191) than after anticoagulation (0.183, 95% CI: 0.126–0.247). Pooled proportion of PE was smaller after PEVI (0.006, 95% CI: 0.00–0.020) as compared to anticoagulation (0.075, 95% CI: 0.038–0.122). Pooled proportion of recurrent thromboembolism was similar between PEVI (0.095, 95% CI: 0.054–0.146) and anticoagulation (0.124, 95% CI: 0.061–0.206). Pooled proportion of bleeding was not different statistically between PEVI (0.026, 95% CI: 0.00–0.131) and anticoagulation (0.008, 95% CI: 0.00–0.094). Conclusions PEVI, consisting of PMT and/or CDT, is an extremely effective and feasible approach for patients with acute LE-DVT. In comparison to therapeutic anticoagulation, PEVI restores venous patency, inhibits the PTS development, reduces the PE occurrence, does not markedly increase the bleeding risk, but does not reduce recurrent thromboembolism.

/pdf/percutaneous-endovenous-intervention-versus-anticoagulation-1j3wphmq.pdf

Percutaneous endovenous intervention versus anticoagulation in the treatment of lower extremity deep vein thrombosis: a systematic review and meta-analysis

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Guofu Hu

Author Tools

Chat about Author