Poly(<scp>ADP</scp>‐ribose) polymerase inhibition in pancreatic cancer

Singh, Hans Martin; Bailey, Peter J.; Hübschmann, Daniel; Berger, Anne; Neoptolemos, John P.; Jäger, Dirk; Siveke, Jens T.; Springfeld, Christoph

doi:10.1002/gcc.22932

Cited by 15 publications

(10 citation statements)

References 82 publications

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“…Due to the dreadful aggressiveness and the difficulty of early detection, PaCa is one of the malignant tumors with the worst prognosis and accounts for almost as many deaths as new cases [2]. In contrast to most other cancer types, improvement of the therapeutic options and prognosis over the last decades has been quietly limited [3,4].…”

Section: Introductionmentioning

confidence: 99%

Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer

et al. 2022

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Background B7 molecules play significant roles in regulating tumor immunity, but their expression patterns and immuno-biological correlations in pancreatic cancer (PaCa) have not been fully discussed. Methods RNA-sequencing data of B7 molecules of PaCa samples in the Cancer Genome Atlas (TCGA) dataset was downloaded from the UCSC Xena to assess the expression, correlation, and mutation of the B7 family in PaCa. Next, two PaCa tissue microarrays (TMAs, Cat. HPanA150CS02 and HPanA120Su02) were obtained from Outdo BioTech (Shanghai, China). To detect the expression levels of PD-L1, B7-H3 and B7-H4, immunohistochemistry (IHC) staining was performed on these TMAs. Results Most B7 molecules, including B7–1, B7–2, PD-L1, B7-DC, B7-H2, and B7-H5 exhibited similar expression patterns, but B7-H3, B7-H4, B7-H6, and B7-H7 showed outlier expression patterns compared with other B7 molecules. Besides, B7 molecules were genetically stable and exhibited low alteration frequency. IHC staining indicated PD-L1, B7-H3, and B7-H4 were up-regulated in PaCa tissues and showed uncorrelated expression patterns. Furthermore, high expression of PD-L1 and B7-H3 indicated poor-differentiated grades in PaCa. PD-L1 was positively, but B7-H4 was negatively correlated with CD8+ TILs infiltration in PaCa. Moreover, combined PD-L1 and B7-H4 expression was a novel subtyping strategy in PaCa, namely patients with both high PD-L1 and B7-H4 expression exhibited decreased CD8+ TILs infiltration in tumor tissues. Conclusion Overall, we systemically analyzed the expression patterns of B7 molecules and proposed a novel subtyping strategy in PaCa. Patients with both high PD-L1 and B7-H4 expression exhibited the immuno-cold phenotype, which may be not suitable for immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer

et al. 2022

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“…Phase II precision oncology trials are now assessing whether single agent Olaparib therapy is effective in advanced PDAC patients that do not harbour germline BRCA1/2 mutations (NCT02677038). In addition, several early phase clinical trials are testing whether PARP inhibitors in combination with either standard chemotherapy (NCT03337087; NCT04228601) or other targeted therapies (NCT03842228; NCT04005690; NCT03682289) are effective in treating germline and/or somatic HRD in advanced PDAC ( Singh et al, 2021 ).…”

Section: Genomic Profiling Identifies Driver Events and Actionable Mutations In Pdacmentioning

confidence: 99%

Deconstructing Pancreatic Cancer Using Next Generation-Omic Technologies–From Discovery to Knowledge-Guided Platforms for Better Patient Management

Schreyer

Neoptolemos

Barry

et al. 2022

Front. Cell Dev. Biol.

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Comprehensive molecular landscaping studies reveal a potentially brighter future for pancreatic ductal adenocarcinoma (PDAC) patients. Blood-borne biomarkers obtained from minimally invasive “liquid biopsies” are now being trialled for early disease detection and to track responses to therapy. Integrated genomic and transcriptomic studies using resectable tumour material have defined intrinsic patient subtypes and actionable genomic segments that promise a shift towards genome-guided patient management. Multimodal mapping of PDAC using spatially resolved single cell transcriptomics and imaging techniques has identified new potentially therapeutically actionable cellular targets and is providing new insights into PDAC tumour heterogeneity. Despite these rapid advances, defining biomarkers for patient selection remain limited. This review examines the current PDAC cancer biomarker ecosystem (identified in tumour and blood) and explores how advances in single cell sequencing and spatially resolved imaging modalities are being used to uncover new targets for therapeutic intervention and are transforming our understanding of this difficult to treat disease.

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“…Notably, the PDE sub-fractions induced apoptosis in PC-3 cells, as indicated by increase in sub-G1 peaks in flow cytometry histograms; with dichloromethane (DCM) sub-fraction achieving this by increasing the Bax/Bcl-2 ratio by 650% compared to negative control, and cleaving poly (ADP-ribose) polymerase (PARP). Overexpression of PARP has been shown to contribute to the promotion of carcinogenesis and survival of cancer cells, hence, its inhibition is a major current target of managing ovarian [ 65 ], prostate, breast [ 66 ], renal [ 67 ], pancreatic [ 68 ], and other cancers. Hence, phytochemicals responsible for the above bioactivity by PDE sub-fractions should be isolated via activity-guided fractionation and should be further explored as broad-spectrum anticancer entities.…”

Section: Application Of Salvia Species In Cancer P...mentioning

confidence: 99%

Therapeutic benefits of Salvia species: A focus on cancer and viral infection

Ezema

Ezeorba

Aguchem

et al. 2022

Heliyon

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Man is increasingly being faced with many health conditions, including viral infection, some of which increases the risk to cancer. These infectious agents contribute to the large number of persons with cancer and the worrisome number that die from the diseases. A good range of drugs are currently in place for treating patients infected with viruses, however, some of the drugs' effectiveness are limited by the emergence of drug-resistant strains of the viruses, as well as adverse effects of the drugs. Similarly, the inability of many anticancer drugs to selectively kill cancer cells while sparing hosts’ normal cells limit their use. This warrants more research for newer drugs, especially from chemicals naturally encrypted in plants with anticancer and antiviral activities. In response to infection with cancer-inducing viruses, plants such as Salvia species synthesize and store secondary metabolites to protect themselves and kill these viruses as well as inhibit their ability to induce carcinogenesis. Hence, this review presented a discussion on the potential application of Salvia species in the prevention and management of cancer and viral infection. The study also discusses the cellular mechanisms of action of these herbal products against cancer cells and viruses, where available and provided suggestions on future research directions. The study is believed to spur more research on how to exploit Salvia phytochemicals as candidates for the development of nutraceuticals and drugs for managing cancers and viral infection.

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Poly(ADP‐ribose) polymerase inhibition in pancreatic cancer

Cited by 15 publications

References 82 publications

Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer

Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer

Deconstructing Pancreatic Cancer Using Next Generation-Omic Technologies–From Discovery to Knowledge-Guided Platforms for Better Patient Management

Therapeutic benefits of Salvia species: A focus on cancer and viral infection

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