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  • 1
    Online Resource
    Online Resource
    Cannabinoids in the landscape of cancer
    Springer Science and Business Media LLC ; 2021
    In:  Journal of Cancer Research and Clinical Oncology Vol. 147, No. 9 ( 2021-09), p. 2507-2534
    Details
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 147, No. 9 ( 2021-09), p. 2507-2534
    Abstract: Cannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. There is a growing body of evidence from cell culture and animal studies in support of cannabinoids possessing anticancer properties. Method A database search of peer reviewed articles published in English as full texts between January 1970 and April 2021 in Google Scholar, MEDLINE, PubMed and Web of Science was undertaken. References of relevant literature were searched to identify additional studies to construct a narrative literature review of oncological effects of cannabinoids in pre-clinical and clinical studies in various cancer types. Results Phyto-, endogenous and synthetic cannabinoids demonstrated antitumour effects both in vitro and in vivo. However, these effects are dependent on cancer type, the concentration and preparation of the cannabinoid and the abundance of receptor targets. The mechanism of action of synthetic cannabinoids, (−)-trans-Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD) has mainly been described via the traditional cannabinoid receptors; CB 1 and CB 2 , but reports have also indicated evidence of activity through GPR55, TRPM8 and other ion channels including TRPA1, TRPV1 and TRPV2. Conclusion Cannabinoids have shown to be efficacious both as a single agent and in combination with antineoplastic drugs. These effects have occurred through various receptors and ligands and modulation of signalling pathways involved in hallmarks of cancer pathology. There is a need for further studies to characterise its mode of action at the molecular level and to delineate efficacious dosage and route of administration in addition to synergistic regimes.
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    URL: Article
    DOI: 10.1007/s00432-021-03710-7
    RVK:
    XA 52301
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 2
    Online Resource
    Online Resource
    Abstract PO-101: Characterization of longitudinally collected fine needle aspiration biopsies of pancreatic ductal adenocarcinoma upon endoscopic ultrasound guided radiofrequency ablation
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 22_Supplement ( 2021-11-15), p. PO-101-PO-101
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 22_Supplement ( 2021-11-15), p. PO-101-PO-101
    Abstract: Background: Most patients with pancreatic ductal adenocarcinoma (PDAC) are metastatic at presentation with dismal prognosis warranting improved systemic therapy options. Longitudinal sampling for assessment of treatment response poses a challenge for validating novel therapies. In this proof-of-principle study, we evaluate the role of endoscopic ultrasound (EUS)-guided serial fine-needle aspiration biopsies (FNABs) to study the mechanism of action of radiofrequency ablation (RFA). Methods: Patients with stage III inoperable PDAC with prior exposure to gemcitabine were selected into ARDEO (ethically approved Phase-II prospective clinical study of EUS-RFA). Post examination, targeted RF was delivered thrice and sequential FNABs of tumor were taken before and after treatment. Transcriptomic profiling of 6 FNABs from 2 patients was performed using a custom NanoString gene panel (144 genes) consisting of cancer and cancer-associated fibroblast (CAFs) subtypes along with immune changes. CAF culture was established from one FNAB and characterised by immunofluorescence and immunoblotting. Results: RFA treatments were well tolerated without any complications and both patients had stable disease immediately after EUS-RFA. Two-course RFA led to upregulation of CD1E gene (participates in antigen presentation) in both, patient 1 and 2 (4.5 and 3.9-fold) compared to baseline. Patient 1 showed increased expression of T cell genes (CD4 – 8.7-fold, CD8 – 35.7-fold), cytolytic function (6.4-fold) and inflammatory response (8-fold) post-RFA. Greater than 2-fold upregulation of CD274 (PDL1), IDO1, PDCD1 and TNFRSF18 (GITR) was observed post 2nd RFA in both the patients. Further, two-course RFA led to increased PDGFRa (4.5 and 9-fold) in both patients along with enrichment of pCAF subtypes B and C in patient 1 and subtypes A, B and D in patient 2. Immunofluorescence staining revealed expression of PDGFRa, aSMA, VIM, POSTN and MYH11 on patient2-derived CAFs post 1st RFA; validated by immunoblotting. Finally, RFA led to downregulation of classical PDA subtype in both patients. Conclusions: This feasibility study validates longitudinal sampling by EUS-FNABs as an appropriate research tool to study tumor microenvironmental changes associated with local pancreatic immunomodulatory techniques like RFA. Citation Format: Krisha Desai, Patrick Varun Lawrence, Christopher Wadsworth, Nagina Mangal, Nagy Habib, Anguraj Sadanandam, Mikael Sodergren. Characterization of longitudinally collected fine needle aspiration biopsies of pancreatic ductal adenocarcinoma upon endoscopic ultrasound guided radiofrequency ablation [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-101.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.PANCA21-PO-101
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
    Online Resource
    Online Resource
    A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from Pancreatic Cancer Patients Treated with Endoscopic Ultrasound Guided Radiofrequency Ablation
    MDPI AG ; 2022
    In:  Current Oncology Vol. 29, No. 10 ( 2022-09-21), p. 6754-6763
    Details
    In: Current Oncology, MDPI AG, Vol. 29, No. 10 ( 2022-09-21), p. 6754-6763
    Abstract: Background: Most patients with pancreatic ductal adenocarcinoma (PDAC) are metastatic at presentation with dismal prognosis warranting improved systemic therapy options. Longitudinal sampling for the assessment of treatment response poses a challenge for validating novel therapies. In this case study, we evaluate the feasibility of collecting endoscopic ultrasound (EUS)-guided longitudinal fine-needle aspiration biopsies (FNABs) from two PDAC patients and conduct gene expression studies associated with tumour microenvironment changes associated with radiofrequency ablation (RFA). Methods: EUS-guided serial/longitudinal FNABs of tumour were collected before and after treatment from two stage III inoperable gemcitabine-treated PDAC patients treated with targeted RFA three times. Biopsies were analysed using a custom NanoString panel (144 genes) consisting of cancer and cancer-associated fibroblast (CAFs) subtypes and immune changes. CAF culture was established from one FNAB and characterised by immunofluorescence and immunoblotting. Results: Two-course RFA led to the upregulation of the CD1E gene (involved in antigen presentation) in both patients 1 and 2 (4.5 and 3.9-fold changes) compared to baseline. Patient 1 showed increased T cell genes (CD4—8.7-fold change, CD8—35.7-fold change), cytolytic function (6.4-fold change) and inflammatory response (8-fold change). A greater than 2-fold upregulation of immune checkpoint genes was observed post-second RFA in both patients. Further, two-course RFA led to increased PDGFRα (4.5-fold change) and CAF subtypes B and C genes in patient 1 and subtypes A, B and D genes in patient 2. Patient 2-derived CAFs post-first RFA showed expression of PDGFRα, POSTN and MYH11 proteins. Finally, RFA led to the downregulation of classical PDAC subtype-specific genes in both patients. Conclusions: This case study suggests longitudinal EUS-FNAB as a potential resource to study tumour and microenvironmental changes associated with RFA treatment. A large sample size is required in the future to assess the efficacy and safety of the treatment and perform comprehensive statistical analysis of EUS-RFA-based molecular changes in PDAC.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    URL: Article
    DOI: 10.3390/curroncol29100531
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2270777-3
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